Regulation of Osmolarity

Question 1

Describe ADH

Answer 1

• Polypeptide, synthesised in the supraoptic (SO) and paraventricular (PVN) nuclei of the hypothalamus in the brain
• Posterior pituitary hormone
• Half-life is ~10mins, so can rapidly be adjusted depending on the body’s needs for H2O conservation.

Question 2

What is the primary control of osmolarity?

Answer 2

ADH secretion

Question 3

When is ADH secretion stimulated?

Answer 3

When the effective oncotic pressure of the plasma ↑ (high protein conc.), the rate of discharge of ADH-secreting neurones in the SO and PVN is ↑ → ↑ release of ADH from the posterior pituitary (to eventually stimulate reabsorption of H2O from the nephron tubules)

Question 4

How are ADH-secreting neurones in the SO and PVN stimulated to release ADH?

Answer 4

Changes in neuronal discharge are mediated by osmoreceptors in the anterior hypothalamus

Changes in the volume of the osmoreceptors → changes in osmoreceptor discharge – linked to stretch-sensitive ion channels.

Question 5

What is the effect of increase in ECF osmolarity on osmoreceptors in the hypothalamus?

Answer 5

• ↑ H2O diffuses out of cell
• Cell shrinks/stretch sensitive ion channel activated
• ↑neural discharge
• ↑ADH secretion

Question 6

What is the effect of decrease in ECF osmolarity on osmoreceptors in the hypothalamus?

Answer 6

• H2O enters cells (moves out of low osmotic environment as will have high water content)
• Cells swell
• ↓neural discharge
• ↓ ADH secretion

Question 7

What is the normal plasma osmolality?

Answer 7

280-290 mOsm/kg H2O -> small changes results in changes in ADH

Question 8

If an increase in osmolarity that does not cause an increase in tonicity, will it effect [ADH]?

Answer 8

No

Question 9

What is tonicity?

Answer 9

Measure of osmotic pressure gradient between two solutions; only influenced by solutes that are impermeable

Question 10

Do permeable solutes effect tonicity?

Answer 10

No

Question 11

Does urea effect tonicity?

Answer 11

No, as it is freely permeable and so causes no change in volume -> therefore no change in discharge -> therefore no change in ADH

Question 12

What does the concentrating ability of the kidneys depend on?

Answer 12

ADH and the amount of solute to be excreted

Question 13

What is the effect of hypertonic solution (i.e. seawater)?

Answer 13

Increases solute load to be excreted and therefore ↑ urine flow -> dehydration, because more H2O required to excrete the solute load than was ingested with it (so H2O excreted with urine)

Question 14

Where in the nephron does ADH’s action take place?

Answer 14

In the collecting duct, site of water regulation

Question 15

What is the effect of ADH on the collecting duct?

Answer 15

Increases the permeability of the collecting ducts to H2O by increasing the number of H2O channels (aquaporins into the luminal membrane)

Question 16

How does vasopressin (ADH) increase number of aquaporins on the luminal membrane?

Answer 16

1. ADH binds to membrane receptor
2. Receptor activates cAMP second messenger system
3. Cell inserts AQP2 water pores into apical membrane
4. Water is absorbed by osmosis into the blood

Question 17

What are the effects if ADH is present?

Answer 17

• H2O is able to be reabsorbed from the collecting duct.
• This causes the collecting duct to become equilibrated with the interstitium – 300mOsm/L
• The CD gradient passes through the hypertonic medullary interstitial gradient, created by the countercurrent multiplier of the Loop of Henle.

Question 18

What are the effects of maximum ADH release?

Answer 18

• Contents equilibrates with the medullary interstitium via osmotic efflux of H2O from the CD and thus urine becomes highly concentrated at the tip of the medulla
• Produces small volume of highly concentrated urine, which contains less of the filtered H2O than of solute, therefor compensating for water deficit.
• H2O is reabsorbed by the oncotic pressure of vasa recta, which will be even greater than usual due to H2O deficit in the CD.

Question 19

What is the effect of absent ADH?

Answer 19

• CD is impermeable to H2O
• 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 osmolaity can fall to 30-50mOsm/L (can be lower if ions are reabsorbed)

Question 20

What is the role of urea?

Answer 20

The production of concentrated urine. In the presence of ADH, movement of H2O out of the collecting ducts concentrates urea remaining in the CD.

As it increases its concentration gradient so as it approaches the medullary tips, there is an increasing tendency for it to move down its conc. gradient and into the ISF.

Question 21

What is the effect of ADH on urea?

Answer 21

The permeability of the late medullary collecting ducts to urea is enhanced by ADH.

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.

Question 22

What happens to urea during maximum anti-diuresis (high ADH)?

Answer 22

Urea is retained (loss of water increased [urea] causing it to diffuse out of CD) in order to save water and reinforce medullary gradient in region of thin ascending limb of LoH -> ureamia occurs

Question 23

Why is it important that urea is reabsorbed?

Answer 23

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.

Question 24

Effect of increased ECF volume on ADH?

Answer 24

Decreased

Question 25

Effect of decreased ECF volume on ADH?

Answer 25

Increased

Question 26

What are the two types of osmoreceptors that change ADH secretion in response to change in ECF VOLUME?

Answer 26

• Low P receptors: in L and R atria and great veins
• High P receptors: carotid and aortic arch baroreceptors

↑ ECF volume → ↓ [ADH]
↓ ECF volume → ↑ [ADH]

Question 27

What is the relationship between ECF, atrial receptors and ADH release?

Answer 27

↓ ECF volume → ↓ atrial receptor discharge and therefore ↑ ADH release (vagus nerve to ADH secreting neurones).

Question 28

What are the effects of ADH in haemorrhage?

Answer 28

Stronger response to maintain CO and BP -> massive increase in ADH

Even when going from lying down to standing up, there is an ↑ ADH release. The inverse of these changes occur on volume expansion

Question 29

What are other stimuli increasing ADH?

Answer 29

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

Question 30

What are other stimuli decreasing ADH?

Answer 30

Alcohol (causes diuresis), suppresses ADH release.

Question 31

What are causes of diabetes insidipidus?

Answer 31

The hypothalamic areas synthesising ADH may become diseased due to tumours, or in meningitis. They may be “damaged” during surgery -> Central DI.
• Central DI can be treated by giving ADH (AVP)

The Collecting duct may be insensitive to ADH -> Peripheral DI.

Question 32

What is the presentation of diabetes insipidus?

Answer 32

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.

• For Peripheral DI, importance of the thirst mechanism for survival, can’t give ADH. Usually secondary to hypercalcaemia or hypokalaemia so resolves when ion disorders corrected.