Regulation of osmolarity Flashcards
Water regulation is controlled by which hormone?
Anti-diuretic hormone (ADH) - vasopressin
ADH can change the collecting duct’s permability to water
Where is ADH synthesised?
In the hypothalamus - more specifically from the supraoptic (SO) and paraventricular (PVN) nuclei
Where is ADH released from?
Posterior pituitary
What’s the half life of ADH?
10 minutes
It can rapidly be adjusted depending on the body’s need for H20 conservation
What is the primary control of ADH secretion?
Plasma osmolarity
How does plasma osmolarity control ADH secretion?
As the osmolarity of the plasma increases, the rate of discharge of ADH-secreting neurones in the SO and PVN nuclei in the hypothalamus increases too => increasing the release of ADH from the posterior pituitary
Function of osmoreceptors?
Detect changes in osmolarity
Found in the anterior hypothalamus near the SO and PVN
How do osmoreceptors respond to an increase in osmolarity?
Following an increase in osmolarity water follows its own gradient and flows out of the cell causing the cell to shrink.
This results in increased neural discharge and increased ADH secretion
How do osmoreceptors respond to an decrease in osmolarity?
Following a decrease in osmolarity water follows its own gradient and flows into cell causing the cell to swell.
This results in decreased neural discharge and decreased ADH secretion
The volume change experienced by the cell is connected to electrical/neural discharge. How is this mediated?
By stretch sensitive ion channels. These channels produce an AP in response to stretch
How much does the concentration of ADH increase for a 2.5% increase in osmolality
10 times - a very high gain system + very sensitive
What does the term ‘effective osmolarity’ mean?
Effective osmolarity is tonicity.
Non-penetrating particles cannot move together with water - this causes the change in osmolarity. If substance moved with H2O there would be no change in osmolarity
What does the amount of urine that is excreted depend on? (2)
Concentration of ADH and the amount of solute to be excreted
Permeability is a property of what?
The cell type not the substance itself
Why do you pee more when you’ve eaten a lot of salt?
A big salt load on the body causes the osmolarity to increase – the body needs to get rid of the salt and the only way to do that is to excrete it. Need water to do this though.
Site of water regulation in the nephron?
Collecting duct
Difference between osmolarity and osmolality
Osmolarity refers to the number of solute particles per 1 L of solvent,
whereas osmolality is the number of solute particles in 1 kg of solvent.
How does vasopressin work on collecting duct cells to bring about increased permeability to H2O?
It moves from the blood and binds to vasopressin receptor on the collecting duct cell. This activates cAMP.
The cell inserts/incorporates AQP2 water pores into the apical/ luminal membrane and so now H2O can move across and is absorbed by osmosis into the blood
What happens once ADH has allowed H2O movement?
The cortical Collecting Duct 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 in the situation of maximum ADH concentration? (water deficit)
You produce a small vol of highly concentrated urine, which contains relatively less of the filtered H2O than of the solute (therefore compensating for a water deficit)
We want to reabsorb as much H2O into the blood as we can from collecting duct.
This is mediated by maximising the permeability to H2O on the membranes.
When fluid passes from the distal tubule into the CD it equilibrates by moving H2O into the interstitium.
We see increasing concentration as you move down the collecting duct.
How is water reabsorbed into the blood at the collecting duct?
By the oncotic pressure of the vasa recta (this will be even greater than usual in the presence of the H20 deficit
What happens in the collecting duct in the absence of ADH?
If you are hydrated and healthy then your ADH production is down to a minimum.
This means your collecting ducts are impermeable to H2O, so that the medullary intersitial gradient is ineffective in inducing H2O movements. No chance for water exchange despite the gradient – no permeability => no equilibrium 100 mOsm stays the same. This is how we produce very diluted urine.
therefore a large vol of dilute urine is excreted, compensating for H20 excess.
How can the osmolarity of urine sometimes fall below 100 right down to 30-50 mOsmM?
Might still be reabsorbing some other substances over the membrane into the interstitium – so it might decrease to about 30-50 mOsmM
Look
So in a water deficit we conserve water.
In water excess, we lose it.
What is an important role of urea?
Production of concentrated urine.
What happens to urea in the presence of ADH?
Movement of H2O out of the collecting duct greatly concentrates the remaining urea (50% remains).
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 - facilitates the uptake of H2O.
It stays in the interstitium to an extent.
Some urea is taken up by the vasa recta with water (freely permeable on VR) => uraemia
What happens if urea stays in the collecting duct?
It would retain H2O in the collecting duct due to osmotic effect. Wouldn’t be able to produce as concentrated urine
Why is urea so important in dehydrated state
Urea reinforces the ability to reabsorb H2O from the collecting duct and produce a maximum concentrated urine
What is an alternative control mechanism of ADH secretion?
ECF volume
As ECF increases what happens to the concentration of ADH?
[ADH] decreases
As ECF decreases what happens to the concentration of ADH?
[ADH] increases
Where are the low pressure receptors located?
In the L and R atria and great veins
Where are the high pressure receptors located? What type of receptor are they?
In the carotid and aortic arch
They are baroreceptors
What do low pressure receptors do?
They are stretch receptors.
They are sometimes called “volume receptors” because they monitor the return of blood to the heart and the “fullness” of the circulation.
How do low pressure receptors react in high ECF states?
If body has a fuller CVS – there is increased venous return causing the atria to stretch.
This tells the system that the circulation is full.
A moderate decrease in ECF volume would primarily affect which pressure receptors? What is their response?
Atrial receptors
Normally they exert tonic inhibitory discharge of ADH secreting neurones via the vagus nerve.
What happens if the volume changes enough to affect BP?
The 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 increase in ADH release.
What other stimuli cause an increase in ADH?
Pain, emotion, stress, exercise, nicotine, morphine. Following traumatic surgery, inappropriate ADH secretion occurs, need to be careful about monitoring H2O intake.
What other stimuli cause a decrease in ADH?
Alcohol (makes us go to the toilet more – interferes with ADH system), suppresses ADH release.
When might the hypothalamic areas synthesising ADH become diseased or damaged?
Diseased - tumours, meningitis
Damaged - surgery
Diabetes insipidus and ADH
The Collecting duct may be insensitive to ADH => Peripheral DI.
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.
Central diabetes insipidus can be treated with what?
ADH
Peripheral DI common cause?
Usually 2° to hypercalcaemia or hypokalaemia so resolves when ion disorders corrected.
Which 3 key situations stimulate the hypothalamic neurons to synthesise vasopressin (promote increase in [ADH])
Osmolarity greater than 280 mOsM
Decreased atrial stretch due to low blood volume
Decreased BP
Look
A higher water concentration increases the volume and pressure of your blood.
