Regulation of Osmolality Flashcards
What are 2 other names for ADH?
Vasopressin
Arginine vasopressin (AVH)
Which nuclei of the hypothalamus is ADH synthesised in?
Supraoptic + paraventricular (SO + PVN)
Which type of pituitary hormone is ADH?
Posterior pituitary
What is the half life of ADH? What is the benefit of this?
~10 mins
Can be rapdly adjusted depending on the body’s needs for H2O conservation
What is the primary control of ADH secretion?
Plasma osmolarity
When the effective OP (osmotic pressure) of the plasma increases, what happens to ADH release?
Rate of discharge of ADH-secreting neurons in the SO and PVN is increased, leading to an increased release of ADH from the posterior pituitary
What are changes in neuronal discharge mediated by?
Osmoreceptors
Where are osmoreceptors found?
Anterior hypothalamus
Close to the SO and PVN
What do other receptors in the lateral hypothalamus mediate?
Thirst
Describe the mechanism of osmoreceptors in situations of both 1. increased and 2.decreased osmolarity
- Increased osmolarity = H2O leaves the cell, cell shrinks/stretch sensitive ion channel is activated = increased neuronal discharge = increased ADH secretion
- Decreased osmolarity = H2O enters the cell, cell swells = decreased neural discharge = decreased ADH secretion
What is normal plasma osmolality?
280-290mOsm/kg H2O
It is regulated very precisely
What do small changes in either direction of osmolality result in?
Rapid changes in ADH
For example, if the system has a very high ‘gain’ of 2.5% increase in osmolality, what increase in ADH would be stimulated?
10x increase in ADH
Why do we talk about effective OP rather than just OP?
An increase in osmolarity that does not cause an increase in tonicity is ineffective in causing an increase in [ADH]
[sidenote] Difference between osmolarity, osmolality and tonicity?
Tonicity is the term used to encompass solutes that are non-penetrating and therefore produce an osmotic drag
Solutes that can penetrate membranes move together with water and don’t produce any what?
‘osmotic drag’ or tonicity
The concentrating ability of the human kidney is relatively limited and the amount of urine produced depends on what 2 things?
[ADH]
Amount of solute to be excreted
Maximally concentrated urine is 1200-1400mOsm/l, so even if the amount was 2400mOsm, this would mean excretion of how much urine?
2L of urine
Ingestion of hypertonic solutions, such as seawater, increase the solute load to be excreted and therefore do what to urine flow?
Increase it, leading to dehydration because more H2O is required to excrete the solute load than was ingested with it
(shipwrecked sailors die if they drink seawater!!)
Is urea an effective osmole?
NO!
Where is the site of water regulation?
the collecting duct
The permeability of the collecting duct is under control of what?
ADH
Whether or not the dilute urine delivere to the distal tubule is conentrated and to what extent depends on the presence or absence of what?
ADH
Lovely wee diagram of the tubule system
How does ADH increase permeability of collecting ducts to H2O?
By incorporating H2O channels into the luminal membrane (aquaporins)
What are the 3 steps following the vasopressin binds to membrane receptor on the kidney tubule?
- Receptor activates cAMP second messenger system
- Cell inserts AQP2 water pores into apical membrane
- Water is absorbed by osmosis into the blood
Describe the process of ADH and AQP2 again - diagram
If ADH is present then H2O is able to leave the collecting duct, what does this mean for the cortical CD? Then what happens after?
It becomes equilibriated with that of the cortical interstitium i.e. 300mOsm/l
The CD then passes through the hypertonic medullary interstitial gradient
What is the hypertonic medullary interstitial gradient created by?
Countercurrent multiplier of the loop of Henle
If maximum ADH is present, what do the contents of the CD do with the medullary interstitium?
The contents equilibriate with that of the medullary interstitium via osmotic efflux of H2O and thus become highly oncentrated at the tip of the medulla
(effectively anti-diuretic effect)
With maximal [ADH], what is the nature of the urine produced, to compensate for water deficit?
A small volume of highly concentrated urine, which contains relatively less H2O than of solute
In maximal ADH, effectively pure H2O is added to the ECF, how is this then reabsorbed?
By the oncotic P of vasa recta, which will be even greater than usual in the presence of the H2O deficit
What happens to collecting ducts in the absence of ADH? So how does the medullary interstitial gradient affect them?
They are impermeable to H2O, so that the medullary interstitial gradient is ineffective in inducing H2O movements out of the CD
How does the nature of urine produced in absence of ADH compensate for H2O excess?
Large volume of dilute urine is excreted, compensatng for H2O excess
Why then in the absence of CD can urine osmolarity even fall to 30-50 mOsm/l?
Further ions are absorbed in the CD and no water is lost
What happens to urea in the CD in the presence of ADH?
Movement of H2O out of the CDs greatly concentrates the urea remaining in the ducts
CD membranes are relatively permeable to urea, particularly towards the medullary tips, so what happens as urea approaches these tips?
There is an increasing tendency for it to move out down its concentration gradient; permeability of late medullary CD to urea is enhanced by ADH
So in antidiuresis, what happens to urea in the CD and what does this act to reinforce?
In antidiuresis w high ADH levels, urea will be reabsorbed from CD into the interstitium, where it reinforces the interstitial gradient in the region of the thin ascending loops of Henle
In max ADH, what then happens with urea? (one word)
Uraemia
Why is it so important that urea should be reabsorbed?
If it remained in the tubule, it would exert an osmotic effect to hold H2O in the tubule and therefore reduce the potential for rehydration
(conservation of H2O is more important than the associated retention of urea)
Any level of ADH between the extremes of [max] and absence is possible, so that…
the CD permeability can be precisely graded to meet the demands of the body for H2O regulation
How does an increase v decrease in ECF volume affect ADH secretion?
Increased ECF vol = decreased [ADH]
Decreased ECF vol = increased [ADH]
What is the relationship between the rate of ADH secretion and the rate of discharge of stretch receptor afferents in the low and high P areas of circulation?
Inverse relationship
Where are the low P receptors and high P receptors?
Low P receptors = L and R atria and great veins
High P receptors = caroitic and aortic arch baroreceptors
Moderate decreases in ECF volume primarly affect what?
The atrial receptors
When ECF volume is within normal limits, what do low P atrial receptors do?
Exert tonic inhibitory discharge of ADH secreting neurones via the vagus nerve (the atrial receptors constantly send signals saying ‘we don’t need any ADH’)
Decreased ECF volume = decreased atrial receptor discharge and therefore…
increased ADH release
If volume changes enough to affect MBP - then what else gets involved?
Carotid (and aortic) receptors (high P) which will also contribute to changes in ADH secretion
On volume expansion, what occurs?
The inverse of these changes
What happens to ADH secretion when you go from lying down to standing up?
increase in ADH release
Try to name stimuli which increase ADH release (7)
Pain
Stress
Emotion
Exercise (sweat - body loses fluid - pre-emptive ADH release)
Nicotine
Morphine
Traumatic surgery (innapropriate - need to be careful about monitoring H2O intake)
Give a factor which decreases ADH release
Alcohol (diuretic)
What type of cells are ADH secreting cells?
Neurones - receive multiple inputs which they integrate to dermine [ADH]
Summary of receptor function
What is diabetes insipidus?
ADH deficiency
Why might the hypothalamic areas synthesising ADH become diseased/damaged? (central DI)
Due to tumours or in meningitis
Surgery (central DI)
What is the pathology of peripheral DI?
CD may be insensitive to ADH
How are DI patients characterised?
Passage of v large volumes of v dilure urine (generally >10l/day) = POLYURIA
Drink large volumes of water = POLYDIPSIA
How can central DI be treated?
Giving ADH (AVP)
How can peripheral DI be treated?
Importance of thirst mechanism for survival - cant give ADH
Usually secondary to hypercalcaemia/hypokalaemia so resolves when ion disorders corrected
May arise as a genetic defect in the V2 (ADH) receptor or in gene for aquaporins
Changes in filtrate volume and osmolarity along the nephron graph
