Osmoregulation

Question 1

Where in the brain is osmolality detected?

Answer 1

In the anteroventral third ventricle (AV3V), where the blood-brain barrier is incomplete.

Question 2

Into which area of the brain do neurones originating in the anteroventral third ventricle (AV3V) project?

With which neurones does it synapse here?

Answer 2

The supraoptic and paraventricular regions of the hypothalamus.

• Here, it synapses with neurones that will lead to the posterior pituitary.

Question 3

What type of change in osmolality stimulates the neurones that detect osmolality?

Answer 3

The neurones only respond to an increase in osmolality.

Question 4

What is the result of stimulation of the neurones that detect osmolality?

Answer 4

ADH release from neurones in the posterior pituitary / neurohypophysis.

Question 5

Where does the ADH that is released by neurones in the posterior pituitary / neurohypophysis originate?

Answer 5

It is produced in the cell bodies of the neurones that have their cell bodies in the anteroventral third ventricle (AV3V) as a prohormone, which is cleaved as it descends to the pituitary.

Question 6

What is co-released with ADH?

Answer 6

Its carrier peptide neurophysin.

Question 7

What is the half life of ADH in the circulation?

Answer 7

~10 minutes.

Question 8

Which hormone is produced in the same place as ADH?

Answer 8

Oxytocin.

Question 9

What is the name of the tract that connects the hypothalamus to the pituitary gland?

What does it contains?

Answer 9

• The infundibulum.

- It contains axons of nerves originating in the hypothalamus and vessels.

Question 10

To which receptors does ADH bind?

Where are these receptors found?

Answer 10

• V1 and V2 receptors.
• V1 receptors are found on the smooth muscle of veins, causing venoconstriction.
• V2 receptors are found on the basolateral membrane of cortical collecting ducts.

Question 11

Through which pathway do V1 receptors mediate their effects?

Answer 11

The Gq pathway.

Question 12

Through which pathway do V2 receptors mediate their effects?

Answer 12

The Gs pathway.

Question 13

What is the name of the protein that is regulated by ADH?

Answer 13

AQP2.

Question 14

Describe the structure of AQP1.

Answer 14

• It is a multisubunit oligomer.
• It is organised as a tetramer of four identical subunits.
• One of the subunits has a large glycan chain attached.

Question 15

List 2 functions of oxytocin.

Answer 15

1 - It is a trigger of the milk let-down reflex during breastfeeding.

2 - It is an agonist of V1 and V2 receptors.

Question 16

Describe the mechanism by which thirst comes about.

Answer 16

• A loss of water increases tissue osmolality (normally 285 mOsm kg^-1).
• This change in osmolality is detected in the anteroventral third ventricle (AV3V) of the brain.
• This stimulates the nerves originating in the anteroventral third ventricle (AV3V) which project into the median preoptic region of the hypothalamus.
• Stimulation of this pathway increases thirst.

Question 17

What is the effect of decreased plasma osmolality on ADH release and thirst?

Answer 17

• ADH release is decreased.

- Thirst is decreased.

Question 18

What is the relationship between the rate of secretion of ADH and tissue osmolality?

Answer 18

The relationship is directly proportional.

Question 19

What is the urine production rate and osmolality when ADH is secreted at the maximum rate?

What about when no ADH is secreted?

Answer 19

• When ADH secretion rate is maximum, urine production rate is 300-400ml/day and urine osmolality is 1400mOsmkg^-1.
• When ADH secretion rate is 0, urine production rate is 25L/day and urine osmolality is 60-90mOsmkg^-1.

Question 20

Why does drinking sea water cause dehydration?

Answer 20

• The osmolality of sea water is 2000mOsmkg^-1.
• The maximum osmolality of urine that the kidneys can produce is 1400mOsmkg^-1.
• So to completely clear 1kg of sea water, 2000/1400 = 1.4kg of water needs to be cleared.

Question 21

Why is it important that infant formula feeds have a relatively low concentration?

Answer 21

Because infants can only produce urine with a maximum osmolality of 500mOsmkg^-1.

Question 22

Why is the contribution of carbohydrates to plasma osmolality low?

Under which conditions might the contribution of carbohydrates to plasma osmolality be too high?

Answer 22

• Because glucose is converted into CO2 (which is rapidly excreted) and water.
• It is usually only a problem with diabetes mellitus, where glucose concentration can exceed 33mM, giving an osmolality of around 320mOsmkg^-1.

Question 23

Why is the contribution of proteins to plasma osmolality low?

Answer 23

• Because the amino acids into which the proteins are broken down are rapidly taken up by cells.
• The nitrogen is converted into urea, which has a high renal clearance.

Question 24

Define clearance.

Answer 24

The volume of body fluid that is completely cleared of a substance per unit time.

Question 25

What is the difference between creatinine clearance and para-aminohippurate (PAH) clearance?

Explain the reasons for this difference.

Answer 25

• Creatinine clearance is equal to the GFR.
• PAH clearance is equal to renal plasma flow.
• This is because all PAH in the plasma that reaches the kidney is cleared, whereas only the creatinine that is contained in the filtered plasma (~20% of all plasma flow) is cleared.
• All PAH that reaches the kidney is cleared because it is secreted (by peritubular capillaries) into the renal tubular lumen, so the remaining PAH that is not filtered is secreted into the kidney.
• Creatinine is neither secreted nor reabsorbed.

Question 26

Why is the contribution of K+ to plasma osmolality lower than that of Na+?

Answer 26

• Because all cells are relatively permeable to K+, which allows a large reservoir of K+ to form in the tissues (rather than in the plasma).
• K+ is cleared from the kidney more quickly than Na+.
• Na+ is absorbed in the gut more efficiently than K+ (only relevant for oral K+ ingestion).

Question 27

What is a risk of clearing high blood glucose by increasing water intake?

Answer 27

Hyponatraemia.

Question 28

Why does hyperglycaemia increase clotting risk?

Answer 28

Because hyperglycaemia increases blood viscosity.

Question 29

What is the side effect of intranasal delivery of ADH?

Why?

Answer 29

• Nasal necrosis.

- Caused by vasoconstriction secondary to V1 receptor stimulation.

Question 30

What is the current drug for ADH supplementation?

Answer 30

Desmopressin (an ADH analogue).