Regulation of Osmolarity

Question 1

Water regulation is controlled by…

Answer 1

ADH/Vasopressin

Question 2

What is ADH?

Answer 2

A 9 amino acid chain polypeptide hormone made in the supraoptic and paraventricular nuclei of the hypothalamus and released from the posterior pituitary gland

Question 3

What is the 1y control of ADH secretion?

Answer 3

Plasma osmolarity - when this increases the rate of ADH discharge also increases

Question 4

What are changes in neuronal discharge of ADH mediated by?

Answer 4

Osmoreceptors in the anterior hypothalamus - close to the supraoptic and paraventricular nuclei

Question 5

What other receptors are there in the lateral hypothalamus?

Answer 5

Ones that mediate thrist

Question 6

How do osmoreceptors work?

Answer 6

If osmolarity increases, H2O leaves the cell causing it to shrink and activate stretch sensitive ion channels

This increases neural discharge which increases ADH secretion

If osmolarity decreases, cells swell and neural discharge decreases

Question 7

So changes in the BLANK of the osmoreceptors leads to changes in…

Answer 7

Volume

Leads to changes in osmoreceptor discharge

Question 8

What is normal plasma osmoLALity?

Answer 8

280-290 mOsm/kg H2O

It is very precisely regulated

Question 9

What happens if small changes in plasma osmolality occurs?

Answer 9

Leads to rapid changes in ADH

Even a 2.5% increase in osmolality leads to 10x more ADH

Question 10

If osmolarity increases but tonicity doesn’t - does this still entice a ADH response? Explain

Answer 10

No - because solutes that penetrate membranes without need of transporters move together with water and do not create any osmotic drag like ions do

Question 11

Give examples of a substance that changes osmolarity but not tonicity.

Answer 11

Urea can move in and out of the cell changing osmolarity but it doesn’t create any water gradients so tonicity stays the same

Question 12

Is the concentrating ability of the kidney high or limited? What does this mean for the amount of urine produced?

Answer 12

Limited

The amount of urine produced depends not only on the [ADH] but also on the amount of solute to be excreted

Question 13

If 2400 mOsm of solutes needed excreted, how much urine would need to be made to get rid of this?

Answer 13

Even at max concentrated urine - 1200/1400 you would need at least 2L to get rid of it

Question 14

So why is ingestion of hypertonic solutions dangerous? Give an example.

Answer 14

Leads to rapid dehydration as the body needs to get rid of these extra solutes via urine

Drinking seawater will cause to to increase urine flow to get rid of salt meaing you excrete more water to do so and you will die of dehydration

Question 15

How does ADH work?

Answer 15

Binds to membrane receptors in the collecting duct which activates aquaporins increases permeability of H2O

This allows the CORTICAL collecting duct to become equilibrated with the interstitial at 300 mOsm/L

The collecting duct then passes through the hypertonic medullary interstitial gradient and water is removed or retained as needed, dictated by ADH

Question 16

What happens in the hypertonic medullary area if max. ADH is present?

Answer 16

then the contents equilibrates with the medullary interstitium with water with moving out making the collecting duct contents highly concentrated at the tip of the medulla

Question 17

How is H2O reabsorbed from the interstitium?

Answer 17

By the oncotic pressure of the vasa recta

Question 18

What happens to oncotic pressure in the vasa recta if there is a H2O deficit in the body?

Answer 18

Will be greater to = more reabsorption

Question 19

What happens in the absence of ADH?

Answer 19

Collecting ducts are impermeable to H2O and it is excreted as waste

Further ions can be reabsorbed from the collecting ducts leaving urine osmolarity sometimes at 30-50!!!

Question 20

What is the role of urea?

Answer 20

In the presence of ADH - when water moves out of the collecting duct - it concentrates urea levels.

SO when urea approaches medullary tips it leaves the collecting ducts down its conc. gradient and gets reabsorbed which helps reinforce the interstitial gradient in the loops of henle area

Question 21

What would happen if urea was not reabsorbed?

Answer 21

Would exert an osmotic effect and hold water in the collecting ducts stopping rehydration

Question 22

If urea is a waste product why is it reabsorbed?

Answer 22

The conservation of water is more important than any effects of high urea

Question 23

What else besides plasma osmolarity affects ADH secretion?

Answer 23

ECF volume

An increase in volume = a decrease in ADH and vice versa

Question 24

An inverse relationship exists between…

Answer 24

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 25

Low P receptors are located in….

Answer 25

L and R atria and great veins

Question 26

What are L pressure receptors often called? Why?

Answer 26

Volume receptors because they monitor the return of blood to the heart and the “fullness” of the circulation.

Question 27

Where are high P receptors located and what are they called?

Answer 27

Carotids and aortic arch

baroreceptors

Question 28

What are moderate decreases in ECf volume picked up by?

Answer 28

The low P atrial receptors

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

But ECF volume decreases, the activity of atrial receptors decreases and ADH is released

Question 29

If volume changes are enough to change mean BP - what is the system to correct this? When is this particularly important

Answer 29

Carotid and aortic receptors will also contribute to changes in ADH secretion

Drop in BP increases ADH

Very important in haemorrhage

Question 30

What are some other stimuli affecting ADH?

Answer 30

Increases in - pain, stress, morphine. Following traumatic surgery inappropriate ADH secretion can occur

Decreases with alcohol

Question 31

Recap the 3 main things that stimulate ADH release.

Answer 31

Osmolarity greater than 280-290
Decrease in atrial stretch due to low blood volumes
Decrease in BP

Question 32

What is diabetes insipidus?

Answer 32

An ADH deficiency

Question 33

Causes of central DI?

Answer 33

Hypothalmic damage or disease (surgery, tumours or meningitis)

Question 34

Causes of peripheral DI?

Answer 34

Collecting duct insensitivity

Question 35

Characteristics of DI?

Answer 35

Very large volumes of very dilute urine = polyuria

Polydipsia

Question 36

How to treat central DI?

Answer 36

Give ADH

Question 37

How can peripheral DI be managed?

Answer 37

Cannot give ADH so must be managed via the thirst mechanism

Treat the cause if known

Question 38

What are some causes of peripheral DI?

Answer 38

Usually 2y to hypercalcaemia or hypokalaemia