Regulation of Osmolarity

Question 1

Where is ADH produced?

Answer 1

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

Posterior pituitary hormone.

Question 2

What is the half life of ADH?

Answer 2

Half-life » 10 minutes, so can rapidly be adjusted depending on the body’s needs for H2O conservation.

Question 3

What is the primary control of plasma osmolarity?

Answer 3

Plasma osmolarity - increase means increase in ADH prouction by the supraoptic and paraventricular nuclei

Question 4

What causes the change in neuronal discharge in the SO and PVN?

Answer 4

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

Question 5

Where are the receptors that mediate thirst?

Answer 5

Lateral hypothalamus

Question 6

What happens to osmoreceptors when the osmolarity is high?

Answer 6

H2O moves out of the cell

Cell shrinks / stretch sensitive ion channel is activated

Increase in neural discharge

Increase in ADH secretion

Question 7

What happens to osmoreceptors when osmolarity is decreased?

Answer 7

H2O enters cells

Cells swell

↓neural discharge

↓ ADH secretion

Question 8

What is normal plasma osmolarity?

Answer 8

280-290mOsm/kg H2O

Question 9

Describe the ‘gain’ in the ADH system

Answer 9

Small changes in either direction results in rapid changes in ADH. System has a very high “gain” a 2.5% ­increase in osmolality can produce a 10x increase­ in ADH.

Question 10

What must the increase in osmolarity include in order to create an increase in ADH concentration?

Answer 10

Must also have an increase in tonicity

(Tonicity is the term used to encompass solutes that are non-penetrating and therefore produce an osmotic drag)

Question 11

Does urea affect tonicity?

Answer 11

No! It is permeable

Question 12

Why do shipwrecked sailors die of they drink sea water?

Answer 12

Seawater increases the solute load to be excreted

More water is required to excrete the solute than was ingested with it

The maximum concentration of urine is 1200-1400 mOsmoles/l

Question 13

What happens after vasopressin binds to the membrane receptor on the kidney tubule?

Answer 13

Receptor activates cAMP second messenger system

Cell inserts AQP2 water pores into apical membrane (increases the permeability of the collecting ducts to H2O)

Water is absorbed by osmosis into the blood

Question 14

If ADH is present and water is able to leave the collecting duct - what does the cortical collecting duct become equilibrated with?

Answer 14

The cortical interstitium (300 mOsmoles/l)

CD then passes through the hypertonic medullary interstitial gradient created by the countercurent multiplier of the loop of henle

Question 15

What does the contents of the collecting duct equilibrate with if maximum ADH is present?

Answer 15

Equilibrates with that of the medullary interstitium - via osmotic efflux of H2O and thus becomes highly concentrated at the tip of the medulla

Question 16

Describe the volume and concentration of urine when there is maximal ADH

Answer 16

Small volume of highly concentrated urine

This in essence adds pure H2O to the ECF

Question 17

How is water reabsorbed in the presence of high ADH?

Answer 17

H2O is reabsorbed by the oncotic P of vasa recta, which will be even greater then usual in the presence of the H2O deficit.

Question 18

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

Answer 18

Collecting ducts are impermeable to water (medullary interstitial gradient is ineffective in inducing H2O movements out of the collecting duct)

Large volume of dilute urine is excreted - compensating for H2O excess

Question 19

What is the role of urea in anti-diuresis (high levels of ADH)

Answer 19

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

Urea is reabsorbed from the collecting duct into the interstitium, where it acts to reinforce the interstitial gradient in the region of the thin ascending loops of henle

Question 20

Besides reinforcing the interstitial gradient - what is the other effect of the urea being reabsorbed?

Answer 20

If it remained in the tubule it would exert an osmotic effect to hold H2O in the tubule - therefore reduce potential rehydration

Question 21

What is the effect of ECF volume on ADH?

Answer 21

Increased ECF volume = decreased ADH

Decreased ECF volume = increase in ADH

Question 22

Where are the low pressure receptors and the high pressure receptors?

Answer 22

Low pressure: Located in the left and right atria and great veins

High pressure: Carotid and aortic arch baroreceptors

Question 23

What is the action of the low volume receptors in the atria / great veins when there is low ECF volume?

Answer 23

Primarily affects the atrial receptors

Normally (when ECF volume is within normal limits) there is an inhibatory effect on ADH production via the vagus nerve

(The atrial receptors constantly send signals saying ‘we don’t need any ADH’)

So when there is a decrease in the ECF volume there is a decrease in atrial receptor discharge

(The lecture also says that if the change in volume is enough to affect mean blood pressure then the carotid and aortic receptors will also contribute to changes in ADH secretion)

Question 24

What happens to ADH secretion when you stand up?

Answer 24

There is an increase in ADH secretion

Question 25

What are ADH secreting cells?

Answer 25

Neurones - they receive multiple inputs which they integrate to determine ADH

Question 26

What other stimuli increase ADH production?

Answer 26

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

Question 27

What other stimuli redeuce ADH secretion?

Answer 27

Alcohol

Question 28

Summary

Question 29

What is diabetes insipidus?

Answer 29

When hypothalamic areas become damaged and cannot produce sufficient ADH - central

The collecting duct may become impermeable to ADH - peripheral ADH

Question 30

How is diabetes insipidus characterised?

Answer 30

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 31

How is central DI treated?

Answer 31

By giving ADH

Question 32

How is peripheral DI treated?

Answer 32

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

(May arise as a genetic defect in the V2 (ADH) receptor or in gene for aquaporins (H2O channels).

Question 33

Which part of the nephron can you find osmolarity of 300 mosmoles/l?

Answer 33

Bowman’s capsule

End of proximal tubule

Question 34

Where in the nephron can you find fluid with the osmolarity of 100 mosmoles/l?

Answer 34

End of loop of henle (100 mOsmoles/L)

End of collecting duct (50 - 1200 mOsmoles/L)