Disorders of Vasopressin

Question 1

Describe the structure of post pit magnocellular neurones?

Answer 1

Hypothalamic magnocellular neurons containing AVP or oxytocin:
Long, originate in supraoptic and paraventricular hypothalamic nuclei
Nuclei → stalk →posterior pituitary

Question 2

What is the physiological action of vasopressin/ADH?

• refer to previous cc for how ADH does this

Answer 2

stimulation of water reabsorption in the RENAL COLLECTING DUCT

This concentrates urine
Acts through the V2 receptor in the kidney

Also a vasoconstrictor (via V1 receptor)
Stimulates ACTH release from anterior pituitary

Question 3

How does pituitary look on MRI?

Answer 3

Posterior pituitary ‘bright spot’ on MRI

Not visualised in all healthy individuals, so absence may be normal variant

Question 4

Describe the osmotic stimuli for vasopressin release?

Answer 4

Rise in plasma osmolality sensed by osmoreceptors

Question 5

Describe the non- osmotic stimuli for vasopressin release?

Answer 5

Decrease in atrial pressure sensed by atrial stretch receptors

Question 6

Which nuclei sit around the 3rd ventricle and stimulate vasopressin release?

Answer 6

organum vasculosum and subfornical organ

Question 7

How do osmoreceptors regulate vasopressin

Answer 7

increase in sodium, increase osmolality down gradient out of receptor, shape changes of osmoreceptor triggering receptor firing which stimulates vasopressin release from hypothalamus

Question 8

What do atrial stretch receptors do?

Answer 8

Detect pressure in right atrium
and
inhibit vasopressin release via vagal afferents to hypothalamus

Question 9

Descrive atrial stretch receptors involved with haemorrhage?
/
Why is vasopressin reeased following a haemorrage?

Answer 9

in response to reduction in circulating volume

Vasopressin release results in increased water reabsorption in the kidney (some restoration of circulating volume) V2 receptors
vasoconstriction via V1 receptors
(NB renin-aldo system will also be important, sensed by JG apparatus)

Question 10

Physiological response to water deprivation? (6)

Answer 10

• > Plasma osmolality increases
• > Stimulate osmoreceptors

-> Causes:
Thirst + Increased AVP release

• > Increased water reabsorption from renal collecting ducts
• > decrease urine volume + increase urine osmolality

==> reduction in plasma osmolality

Question 11

What are clinical symptoms of diabetes insipidus?

Answer 11

Polyuria
Nocturia
Thirst – often extreme
Polydispia

Question 12

Although the symptoms are same as Diabetes Mellitus, what makes Diabetes Insipidus different?

Answer 12

In diabetes mellitus (hyperglycaemia), these symptoms are due to osmotic diuresis

In diabetes insipidus, these symptoms are due to a problem with arginine vasopressin

• Diabetes M is more common

Question 13

What is cranial /central diabetes inspidus?

Answer 13

Problem with hypothalamus &/or posterior pituitary
Unable to make arginine vasopressin
‘VASOPRESSIN INSUFFICIENCY’

Question 14

What is nephrogenic diabetes inspidus?

Answer 14

Can make arginine vasopressin (normal hypothalamus & posterior pituitary)
Kidney (collecting duct) unable to respond to it
‘VASOPRESSIN RESISTANCE

Question 15

What are the causes of cranial diabetes insipidus?

Answer 15

Acquired causes:

• Traumatic brain injury
• Pituitary surgery
• Pituitary tumours
• Metastasis to the pituitary gland eg breast
• Granulomatous infiltration of pituitary stalk eg TB, sarcoidosis
• Autoimmune

Or congenital although very rare

Question 16

What are the causes of nephrogenic diabetes inspidus?

Answer 16

less common than cranial

• Congenital:

rare (e.g. mutation in gene encoding V2 receptor, aquaporin 2 type water channel)

• Acquired:
  Drugs (e.g. lithium)

Question 17

Urine trends in diabetes I?

Answer 17

Very dilute (hypo osmolar) large volumes of urine

Question 18

Plasma trends seen in Diabetes I?

Answer 18

Hyper-osmolar so increased concentration due to dehydration

Increased Na = hypernatraemia

Normal glucose!

Question 19

Why do DI patients have their symptoms?

Answer 19

->ARGININE VASOPRESSIN PROBLEM
Not enough (CDI)
Not responding (NDI)

• > imapired concentrations of urine in renal collecting duct
• > large volumes of dulite urine
• increase in plasma osmlality including Na
• > stimulation of osmoreceptors
• > thirst
• > drink water - maintain circulating volume

Question 20

Why can DI be a cause of death?

Answer 20

If there is no access to water to maintain circulating volume due to dehydration

Question 21

What is psychogenic polydipsia?

Answer 21

Unlike DI - no problem with arginine vasopressin

problem is px drinks all the time = large volumes of dilute urine

• Has similar presentation as DI
• can be in mental health px

Question 22

How do we distinguish between diabetes insipidus & psychogenic polydipsia?

Answer 22

Water deprivation test :

No access to anything to drink
Over time, measure
- Urine volumes  
- Urine concentration (osmolality)
- Plasma concentration through blood sample ( osmolality )

Question 23

What indicator as a part of the water deprivation test marks DI?

Answer 23

Weigh regularly : stop test if lose >3% body weight (a marker of significant dehydration which can occur in diabetes insipidus)

Question 24

What do you expect to see in a px with DI during a water deprivation test?

Answer 24

progressive increase in plasma osmolality

Question 25

How do we distinguish between cranial & nephrogenic diabetes insipidus?

Answer 25

Give ddAVP

will work like vasopressive

Cranial : urine will concentrate

Nephrogenic : no incease in urine osmality so nothing happens

Question 26

Plasma osmolality in DI vs psychogenic polydipsia?

Answer 26

290 DI
270 PSYCHOGENIC POLYDIPSIA

normal range is around 280

Question 27

treatment of CDI?

Answer 27

Cranial DI:

Replace vasopressin

= Desmopressin
Selective for V2 receptor

Tablets OR Intranasal

Question 28

Treatment of NDI?

Answer 28

Thiazide diuretics eg bendofluazide

Mechanism unclear

Question 29

What is SIADH?

Answer 29

Syndrome of Inappropriate Anti-Diuretic Hormone

Too much Arginine vasopressin:

Reduced urine output
Water retention

High urine osmolality
Low plasma osmolality
Dilutional hyponatraemia

Question 30

What are the causes of SIADH?

Answer 30

CNS:
Head injury, stroke, tumour,

Pulmonary disease:
Pneumonia, bronchiectasis

Malignancy:
Lung cancer (small cell)

Drug-related:
Carbamazepine, Serotonin Reuptake Inhibitors (SSSRIs)

Idiopathic

Question 31

How to manage SIADH?

Answer 31

Long hospital stays - need to get hyponatraemia back to normal

Fluid restriction

Can use a vasopressin antagonist (vaptan) – binds to the V2 receptors in the kidney (£)