Regulation of Osmolarity

Question 1

What is water regulation controlled by?

Answer 1

ADH

Question 2

What is ADH?

Answer 2

Polypeptide (9amino acids)

Synthesised in the supraoptic (SO) and paraventricular (PVN) nuclei of the hypothalamus in the brain.

Posterior pituitary hormone

Question 3

WHat is the half life of ADH?

Answer 3

Around 10mins

So can be rapidly adjusted depending on the body’s needs for H2O conservation

Question 4

What is the primary control of ADH secretion?

Answer 4

Plasma osmolarity

When the EFFECTIVE osmilarity of the plasma increases the rate of discharge of ADH- secreting neurones in the SO and PVN is increased

Increased release of ADH from the posterior pituitary

Question 5

What receptors detect incraesed plasma osmolarity?

Answer 5

Osmoreceptors in the anterior hypothalamus, close to the SO and PVN.

Other receptor in the lateral hypothalamus mediate thirst.

Question 6

How do osmoreceptor work?

Answer 6

• Increased osmolarity
• Incaresed H2O outside cell
• Cell shrinks/ stretch sensitive ion channel activated
• Incraesed neural discharge
• Incraesed ADH secretion
• Decreased osmolarity
• H2O enters and cell swells
• Decreased neural discharge
• Decreased ADH secretion

Question 7

What is normal plasma osmolarity?

Answer 7

280-290mOsm/kg H2O.

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 osmolarity can produce a 10x increase in ADH.
-Very sensitive

Question 8

What do we mean by effective osmolarity?

Answer 8

Osmolality is a measure of the number of particles present in solution and is independent of the size or weight of the particles. It can be measured only by use of a property of the solution that is dependent solely on the particle concentration.

Tonicity is the effective osmolality and is equal to the sum of the concentrations of the solutes which have the capacity to exert an osmotic force across the membrane.

Question 9

Is urea tonic?

Does it have an effective osmolarity?

Answer 9

Urea increased

Urea can pass through most cells. So will equilibriate

Concentration of urea in ECF relative to intracellular fluid doesnt change.

No water movement so no tonicity.
Ineffective osmolarity

Question 10

What does the amount of urine produced depend on?

Answer 10

[ADH]

Amount of solute to be excreted.

Question 11

Whay does the amount of solute to be excreted effect the amount of urine we must produce?

Answer 11

If the amount were 2400mOsm, then even with maximally concentrated urine (1200-1400mOsm/l), this would mean excretion of 2L of urine.

Limit on concentration so more solute = more water

This is why you cant hydrate with salt water. Have to excrete salt and will always excrete more than you gain.

Question 12

How does ADH increase the permeability of collecting duct cells to water?

Answer 12

ADH receptor causes storage vesicles to deposit H2O channels into the apical membrane.

These H2O channels are called aquaporins

Question 13

How does the collecting duct continue to reabsorb water past normal plasma levels?

Answer 13

Collecting duct becomes equilibriated with the cortical interstitium (300mOsm/l)

Then the collecting duct passes through the hypertonic medullary interstitial gradient, created by the countercurrent multiplies of the loop of Henle

Question 14

How does the absence of ADH effect water reabsorption?

Answer 14

Collecting ducts are impermeable to H2O, so that the medullary interstitial gradient is ineffective in inducing H2O movements out of the collecting ducts and therefore a large volume of dilute urine is excreted, compensating for H2O excess.

Question 15

What is the most dilute urine you can produce?

Answer 15

Since further ions are reabsorbed from the collecting duct in addition to maximum reabsorption urine osmolarity can fall to 30-50mOsm/l

Question 16

What is the role of Urea in producing concentrated urine?

Answer 16

In the presence of ADH, movement of H2O out of the colleccting ducts greatly concentrates the urea remaining in the ducts.

Collecting duct membranes are relatively permeable to urea, particularly towards medullary tips.

So as urea approaches the medullary tips, there is an increased tendancy for it to move out down its concentration gradient.
The permeability of the late medullary CD to urea is enhanced by ADH.

So in antidiuresis with high levels of ADH, urea will be reabsorbed from the collecting duct into the interstitium

Question 17

How does ECF volume affect ADH secretion?

Answer 17

Increase in ECF volume = decrease in [ADH]

Decrease in ECF volume = increase in [ADH]

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

Question 18

Where are stretch receptors found in the circulation?

Answer 18

Low P receptors are located in the L and R atria and great veins.

Sometimes called “volume receptors” because they monitor the return of blood to the heart and the “fullness” of the circulation

High P receptors are the carotid and aortic arch baroreceptors

Question 19

Moderate decreases in ECF volume primarily effect what receptors?

Answer 19

Atrial receptors

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

Decrease ECF volume ->
Decrease atrial receptor discharge ->
Incraesed ADH release

Question 20

Volume changes enough to effect MBP effect what receptors?

Answer 20

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 increased ADH release

The inverse of these changes occur on volume expansion

Question 21

What other stimuli may increase ADH release?

Answer 21

Pain
Emotion
Stress
Exercise
Nicotine
Morphine

Following traumatic surgery -> inappropriate ADH secretion occurs -> monitor H2O intake and output

Question 22

What may damage hypothalamic areas leading to cranial diabetes insipidus?

Answer 22

Tumours
Meningits
Surgery

Question 23

How do patients solve peripheral diabetes insipidus?

Answer 23

Importance of the thirst mechanism for survival because you cant give ADH.

Usually secondary to hypercalcaemia or hypokalaemia so resolves when ion disorders corrected