Regulation of Osmolality Flashcards
water retention is contorlled by what? where is it made? and what sits half-life?
Water Regulation controlled by ADH (Vasopressin) = arginine vasopressin (AVP)
Polypeptide (9aas), synthesized in the supraoptic (SO) and paraventricular (PVN) nuclei of the hypothalamus in the brain
Posterior pituitary hormone
Half-life around 10 minutes, so can rapidly be adjusted depending on the body’s needs for H2O conservation
what is the primary control of ADH secretion?
plasma osmolarity
When the effective OP of the plasma increases, what happens to the rate of discharge of ADH?
the rate of discharge of ADH-secreting neurones in the SO and PVN is increases = increased release of ADH from the posterior pituitary.
Changes in neuronal discharge of ADH are mediated by what?
Changes in neuronal discharge are mediated by osmoreceptors in the anterior hypothalamus, close to the SO and PVN
Other receptors in the lateral hypothalamus mediate thirst
if Osmolarity ↑, what happens to osmoreceptors?
if Osmolarity ↓, what happens to osmoreceptors?
Water flows inside as it follows its gradient and the cells swell
Changes in the volume of the osmoreceptors = changes in osmoreceptor _________ (Stretch-sensitive ion channels)
discharge
Normal plasma osmolality is 280-290mOsm/kg H2O
how do changes in osmolarity affect ADH levels?
It is regulated very precisely
Small changes in either direction results in rapid changes in ADH. System has a very high “gain” a 2.5% increase in osmolality can produce a 10x increase in ADH
10 times increase in [ADH] for a 2.5% increase in osmolality
Means it’s a very high gain system and very sensitive
why effective osmolarity pressure?
An increase in osmolarity that does not cause an increase in tonicity is ineffective in causing an increase in [ADH]
Remember the difference between osmolarity and tonicity!
Solutes that can penetrate membranes move together with water and don’t produce any “osmotic drag” or tonicity
Urea is freely permeable on these osmoreceptors so it doesn’t matter and it moves freely and doesn’t create any osmotic drag
what does the amount of urine produce depend on?
The concentrating ability of the human kidney is relatively limited and the amount of urine produced depends not only on the [ADH] but also on the amount of solute to be excreted
If the amount were 2400mOsm, then even with maximally concentrated urine (1200-1400mOsm/l), this would mean excretion of 2 l of urine
what does the ingestion of hypertonic solutions cause?
Ingestion of hypertonic solutions, such as seawater, increase the solute load to be excreted and therefore increased urine flow = dehydration, because more H2O is required to excrete the solute load than was ingested with it
Shipwrecked sailors die if they drink seawater
what is the site of water regulation? what is responsible for it?
The site of water regulation is the Collecting duct, whose permeability is under the control of ADH = Anti-Diuretic Hormone (Vasopressin)
Whether or not the dilute urine delivered to the distal tubule is concentrated and to what extent depends on the presence or absence of the posterior pituitary hormone, ADH
How does ADH increase water permeability in order for it to be reabsorbed?
This increases the permeability of the collecting ducts to H2O, by incorporating H2O channels into the luminal membrane, (aquaporins)
Mediated by aquaporins and can be stored as vesicles
ADH = exocytosis of vesicles to membrane so increases permeability of the membrane for water and the water pass on to the interstitium
H20 channels are mainly recuted by ADH on what side of the membrane?
On luminal side there is a pretty constant amount of aquaporin and little on the basolateral side
what happens to the collecting duct if ADH is present?
If ADH is present then H2O is able to leave the collecting duct (CD). That means that the cortical CD becomes equilibrated with that of the cortical interstitium ie 300 mOsm/l. The CD then passes through the hypertonic medullary interstitial gradient, created by the countercurrent multiplier of the loop of Henle
What happens to the contents of the CD if maximum AD is present?
If Maximum ADH is present then the contents equilibrates with that of the medullary interstitium via osmotic efflux of H2O and thus becomes highly concentrated at the tip of the medulla
how does maximal [ADH] compensate for a water deficit?
With maximal [ADH] produce a small volume of highly concentrated urine, which contains relatively less of the filtered H2O than of solute, therefore compensating for water deficit
Effectively adds pure H2O to the ECF
H2O is reabsorbed by the oncotic P of vasa recta, which will be even greater then usual in the presence of the H2O deficit
Equilibrate with the maximum amount of 1200 mOsmol
Describe what happens to the collecting ducts and urine if ADH is not present?
In the absence of ADH collecting ducts are impermeable to H2O, so that the medullary interstitial gradient is ineffective in inducing H2O movements out of the CD and therefore a large volume of dilute urine is excreted, compensating for H2O excess
Since further ions are reabsorbed from the CD, urine osmolarity can fall to 30-50 mOsm/l
So in water deficit ________ water
In water excess, ____ it
conserve
lose
what does urea play an important part in?
Urea plays an important part in the production of concentrated urine
how does urea play an important part in the production of concentrated urine?
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 medullary tips
So as urea approaches the medullary tips, there is an increasing tendency for it to move out down its concentration gradient. The permeability of the late medullary CD to urea is enhanced by ADH
So, in an antidiuresis with high levels of ADH, urea will be reabsorbed from the CD into the interstitium, where it acts to reinforce the interstitial gradient in the region of the thin ascending loops of Henle
In an anti-diuresis with high levels of ADH, what happens to urea in the collecting duct?
In an anti-diuresis with high levels of ADH, urea is retained in order to save water and reinforce medullary gradient in region of thin ascending limb of LoH
Uraemia occurs
what would happen is urea remained in the tubule?
It is important that urea should be reabsorbed because 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
The conservation of H2O is more important than the associated retention of ____
urea
Any level of ADH between the extremes of [max] and absence is _______, so that the CD permeability can be precisely graded to meet the _______ of the body for H2O regulation
possible
demands
apart form osmolarity, what else affects ADH secretion?
ECF volume
how does increased and decreased ECF volume affect ADH?
increase ECF volume = decreased [ADH]
decrease ECF volume = increased [ADH]
There is an inverse relationship between the rate of ADH secretion and the rate of discharge of stretch receptor afferents in the low and high P areas of the circulation
where are low P receptors found?
Low P receptors are located in the L and R atria and great veins
They are sometimes called “volume receptors” because they monitor the return of blood to the heart and the “fullness” of the circulation
stretch receptors, high ECF then bigger blood volume, more plasma for the vascular system is fuller and bigger venous return so atria stretch so tells the system that it is full and there is too much fluid
where are high P receptors found
High P receptors are the carotid and aortic arch baroreceptors
sense pressure changes by responding to change in the tension of the arterial wall
what hapens if ECF volume decreases and what controls this?
Moderate decreases in ECF volume 1°ily affect the atrial receptors
Normally they exert tonic inhibitory discharge of ADH secreting neurones via the vagus nerve
decreased ECF volume = decreased atrial receptor discharge and therefore increases ADH release
However if volume changes enough to affect MBP, then carotid (and aortic) receptors will also contribute to changes in ADH secretion.
Very important in haemorrhage. Even when going from lying down to standing up, there is an ADH release
The inverse of these changes occur on volume expansion
ADH secreting cells are _______ and receive multiple inputs which they integrate to determine [ADH]
neurones
what are other sitmuli that increase ADH?
Pain, emotion, stress, exercise, nicotine, morphine. Following traumatic surgery, inappropriate ADH secretion occurs, need to be careful about monitoring H2O intake
name other sitmuli that decrease ADH release
Alcohol, suppresses ADH release
summary diagram showing the different release mechanisms and action of ADH
Diabetes Insipidus is a what deficiency?
ADH
what is Central DI?
The hypothalamic areas synthesizing ADH may become diseased due to tumours, or in meningitis. They may be “damaged” during surgery
what is Peripheral DI?
The Collecting duct may be insensitive to ADH
What are DI patients characterised by?
Patients are characterised by the passage of very large volumes of very dilute urine, generally > 10 l/day = polyuria. They drink large volumes of H2O = polydipsia
what is the treatment of DI?
Central DI can be treated by giving ADH (AVP)
For Peripheral DI, importance of the thirst mechanism for survival, can’t give ADH. Usually 2° to hypercalcaemia or hypokalaemia so resolves when ion disorders corrected
(May arise as a genetic defect in the V2 (ADH) receptor or in gene for aquaporins (H2O channels)
summary of volume and osmolarity of fluid
