Regulation of osmolarity

Question 1

Water regulation is controlled by which hormone?

Answer 1

Anti-diuretic hormone (ADH) - vasopressin

ADH can change the collecting duct’s permability to water

Question 2

Where is ADH synthesised?

Answer 2

In the hypothalamus - more specifically from the supraoptic (SO) and paraventricular (PVN) nuclei

Question 3

Where is ADH released from?

Answer 3

Posterior pituitary

Question 4

What’s the half life of ADH?

Answer 4

10 minutes

It can rapidly be adjusted depending on the body’s need for H20 conservation

Question 5

What is the primary control of ADH secretion?

Answer 5

Plasma osmolarity

Question 6

How does plasma osmolarity control ADH secretion?

Answer 6

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

Question 7

Function of osmoreceptors?

Answer 7

Detect changes in osmolarity

Found in the anterior hypothalamus near the SO and PVN

Question 8

How do osmoreceptors respond to an increase in osmolarity?

Answer 8

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

Question 9

How do osmoreceptors respond to an decrease in osmolarity?

Answer 9

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

Question 10

The volume change experienced by the cell is connected to electrical/neural discharge. How is this mediated?

Answer 10

By stretch sensitive ion channels. These channels produce an AP in response to stretch

Question 11

How much does the concentration of ADH increase for a 2.5% increase in osmolality

Answer 11

10 times - a very high gain system + very sensitive

Question 12

What does the term ‘effective osmolarity’ mean?

Answer 12

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

Question 13

What does the amount of urine that is excreted depend on? (2)

Answer 13

Concentration of ADH and the amount of solute to be excreted

Question 14

Permeability is a property of what?

Answer 14

The cell type not the substance itself

Question 15

Why do you pee more when you’ve eaten a lot of salt?

Answer 15

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.

Question 16

Site of water regulation in the nephron?

Answer 16

Collecting duct

Question 17

Difference between osmolarity and osmolality

Answer 17

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.

Question 18

How does vasopressin work on collecting duct cells to bring about increased permeability to H2O?

Answer 18

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

Question 19

What happens once ADH has allowed H2O movement?

Answer 19

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.

Question 20

What happens in the situation of maximum ADH concentration? (water deficit)

Answer 20

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.

Question 21

How is water reabsorbed into the blood at the collecting duct?

Answer 21

By the oncotic pressure of the vasa recta (this will be even greater than usual in the presence of the H20 deficit

Question 22

What happens in the collecting duct in the absence of ADH?

Answer 22

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.

Question 23

How can the osmolarity of urine sometimes fall below 100 right down to 30-50 mOsmM?

Answer 23

Might still be reabsorbing some other substances over the membrane into the interstitium – so it might decrease to about 30-50 mOsmM

Question 24

Look

Answer 24

So in a water deficit we conserve water.

In water excess, we lose it.

Question 25

What is an important role of urea?

Answer 25

Production of concentrated urine.

Question 26

What happens to urea in the presence of ADH?

Answer 26

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

Question 27

What happens if urea stays in the collecting duct?

Answer 27

It would retain H2O in the collecting duct due to osmotic effect. Wouldn’t be able to produce as concentrated urine

Question 28

Why is urea so important in dehydrated state

Answer 28

Urea reinforces the ability to reabsorb H2O from the collecting duct and produce a maximum concentrated urine

Question 29

What is an alternative control mechanism of ADH secretion?

Answer 29

ECF volume

Question 30

As ECF increases what happens to the concentration of ADH?

Answer 30

[ADH] decreases

Question 31

As ECF decreases what happens to the concentration of ADH?

Answer 31

[ADH] increases

Question 32

Where are the low pressure receptors located?

Answer 32

In the L and R atria and great veins

Question 33

Where are the high pressure receptors located? What type of receptor are they?

Answer 33

In the carotid and aortic arch

They are baroreceptors

Question 34

What do low pressure receptors do?

Answer 34

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.

Question 35

How do low pressure receptors react in high ECF states?

Answer 35

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.

Question 36

A moderate decrease in ECF volume would primarily affect which pressure receptors? What is their response?

Answer 36

Atrial receptors

Normally they exert tonic inhibitory discharge of ADH secreting neurones via the vagus nerve.

Question 37

What happens if the volume changes enough to affect BP?

Answer 37

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.

Question 38

What other stimuli cause an increase in ADH?

Answer 38

Pain, emotion, stress, exercise, nicotine, morphine. Following traumatic surgery, inappropriate ADH secretion occurs, need to be careful about monitoring H2O intake.

Question 39

What other stimuli cause a decrease in ADH?

Answer 39

Alcohol (makes us go to the toilet more – interferes with ADH system), suppresses ADH release.

Question 40

When might the hypothalamic areas synthesising ADH become diseased or damaged?

Answer 40

Diseased - tumours, meningitis

Damaged - surgery

Question 41

Diabetes insipidus and ADH

Answer 41

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.

Question 42

Central diabetes insipidus can be treated with what?

Answer 42

ADH

Question 43

Peripheral DI common cause?

Answer 43

Usually 2° to hypercalcaemia or hypokalaemia so resolves when ion disorders corrected.

Question 44

Which 3 key situations stimulate the hypothalamic neurons to synthesise vasopressin (promote increase in [ADH])

Answer 44

Osmolarity greater than 280 mOsM

Decreased atrial stretch due to low blood volume

Decreased BP

Question 45

Look

Answer 45

A higher water concentration increases the volume and pressure of your blood.