Vasopressin disorders final

Question 1

What is the posterior pituitary anatomically continuous with?

Answer 1

Hypothalamus

Question 2

What neurons are found in the hypothalamus

Answer 2

Parvocellular that terminate at median eminence ( anterior pit)
Magnocellular neurons ( long) that travel into the pit stalk and into the posterior pit

Question 3

what do you magnocellular neurons originate and what do they contain

Answer 3

Superoptic ( AVP)

Oxytocin ( paraventricular)

Question 4

How is the posterior pit regulated

Answer 4

Hypothalamic secretory neurons make AVP ( superoptic) and oxytocin ( paraventricular . Excitation of these neurons releases these into the post pit

Question 5

What is the function of Vasopressin or ADH

Answer 5

1) stimulation of water reabsorption in renal collecting duct via V2 receptor in kidney. This concentrates the urine
2) Vasoconstrictor via V1 receptor. it stimulated ACTH release from anterior pit

Question 6

How does vasopressin concentrate urine?

Answer 6

AVP binds to V2 receptors which cause intracellular signalling cascade. This causes aquaporins to bind to cell membrane on the apical membrane ( tubular side). Water reabsorbed through aquaporin II and leaves to basolateral side ( plasma side) through Aquaporin III . See image in notes

Question 7

How is the posterior pit visualised on an MRI

Answer 7

Post pit is seen as a bright spot on MRI. Though not present in all healthy individuals so expect variation

Question 8

What are the two stimuli for vasopressin release ( aka what things increase vasopressin release)

Answer 8

1) osmotic –> increase in plasma osmolarity ( increase in concentration of plasma ) sensed by osmoreceptors
2) Non osmotic –> decrease in atrial pressure sensed by atrial stretch receptors

Question 9

Where are osmoreceptors found

Answer 9

organum vasculosum and subfornical organ ( both nuclei are found around the 3rd ventricle aka circumventricular). Both have no blood brain barrier and are highly vascularised so neurons in them can respond to changes in systemic circulation . The neurons here project into the supraoptic nucleus where vasopressinergic neuros are found

Question 10

How do osmoreceptors regulate vasopressin

Answer 10

When there is an increase in extracellular Na+ . H2O moves out the osmoreceptor by osmosis causing it to shrink. When it shrinks there is increased osmoreceptor firing –> more AVP release

See how osmotic stimulation causes vasopressin release

Question 11

How does non osmotic stimulation affect vasopressin release?

Answer 11

1) If Atrial stretch receptors detect increase pressure right atrium
2) Vasopressin release is inhibited via afferent vagus nerves to hypothalamus

Note remember vasopressin is a vasoconstrictor so it would increase pressure
3) Reduction in circulating volume

Question 12

Where are stretch receptors found

Answer 12

Right atrium

Question 13

what happens to vasopressin release during a haemorrhage

Answer 13

Less stretch of atrial stretch receptors leasing to less inhibition of vasopressin

Question 14

Why is vasopressin released following a haemorrhage ( ie reduction in circulating blood volume)

Answer 14

1) Increases water absorption in kidney via V2 receptors ( allows some restoration of circulating volume)
2) Vasoconstriction via V1 receptors ( not renin - aldosterone system will also help this)

Question 15

What is the physiological response to water deprivation

Answer 15

1) increased plasma osmolality
2) Stimulation of osmoreceptors –> thirst and increased AVP rate

3) Increased AVP –> increased water reabsorption from renal collecting ducts
4) reduced urine volume , increase in urine osmolality
5) reduction in plasma osmolality

Question 16

symptoms of diabetes insipidus

Answer 16

Polyuria + hypo- osmolar ( dilute) urine
Nocturia

Extreme thirst ( Polydipsia)
Plasma:
increase conc ( hyper-osmolar) as patient becomes dehydrated
increased sodium ( hypernatremia)

REMEMBER GLUCOSE is normal ( only high in Diabetes mellitus)

Question 17

How are the symptoms of diabetes insipidus different to diabetes mellitus

Answer 17

In DM ( hyperglycaemia) symptoms caused due to osmotic diuresis

In DI symptoms due to problem with arginine vasopressin

REMEMBER DM IS MORE COMMON THAN DI

Question 18

what are the 2 types of diabetes insipidus

Answer 18

Cranial / central ( VASOPRESSIN INSUFFICIENCY )
( More common than nepherogenic)

Nepherogenic ( VASOPRESSIN RESISTANCE)

Question 19

What is cranial diabetes insipidus caused by

Answer 19

Problem with post pituitary or hypothalamus –> unable to make AVP , VASOPRESSIN INSUFFICEINCY

Question 20

What is Nephrogenic DI caused by

Answer 20

Can make AVP ( normal post pit + hypothalamus ) but kidney ( collecting duct ) unable to respond to it ( VASOPRESSIN RESISTANCE)

Question 21

Causes of Cranial Diabetes Insipidus

Answer 21

1) Congenital ( rare)
2) Acquired –> trauma to brain , pit surgery / tumours . metastasis to pit gland (ie from breast cancer) , granulomatous infiltration of pit stalk (ie TB , Sarcoidosis) , autoimmune

Question 22

Causes of nephrogenic DI

Answer 22

1) Congenital ( rare) –> mutation of gene encoding V2 receptor ( aquaporin 2 water channel)
2) Drugs ( lithium)

Question 23

What causes symptoms of DI/ Why does DI cause death

BONUS: and what happens if the patients has no water

Answer 23

1) Problem in AVP ( not enough CDI / not responding NDI)
2) Impaired conc of urine in renal collecting duct

3) Large volumes or dilute urine
4) Increase in plasma conc + Na+
5) stimulation of osmoreceptors
6) Thirst
7) body maintains circuiting blood volume as long as patient has access to water

if no water leads to dehydration and death

Question 24

What is psychogenic polydipsia

Answer 24

patient drinks all the time so passes large volumes of dilute urine

similar presentation to DI :
- Polydipsia , polyuria , Nocturia

Remember unlike DI not problem with AVP

Question 25

What are the symptoms of psychogenic polydipsia and why do they occur

Answer 25

• Polydipsia , polyuria , Nocturia

1) increased drinking
2) fall in plasma osmolality
3) Less AVP secreted by post pit
4) large volumes of dilute urine
5) plasma osmolality returns to normal

Question 26

How do we test between DI and Psychogenic polydipsia

Answer 26

Water deprivation test
1) No access to fluids

2) measure : Urine volume , urine osmolality , plasma osmolality over time
3) Weigh regularly –> stop test if >3% body weight loss ( sign of dehydration )

after few hours of water deprivation:
Normal –> urine osmolality high
Psychogenic –> medium
DI – >low

Question 27

How to distinguish between cranial and nephrogenic DI

Answer 27

1) give ddAVP ( works like AVP)
2) Measure urine osmolality

cranial –> urine concentrates in response to ddAVP

nephro –> no increase in urine osmolality as kidney’s can’t respond

Question 28

How does plasma osmolality compare btwn Di and Psyco Polydipsia

Answer 28

normal is 280 mOSM/Kg H2o

DI –> above range

PP–> below range

Question 29

Treatment of cranial DI

Answer 29

Replace AVP using demopressin
can take tablets / intranasal

Treatment must be selective for V2 receptor ( V1 receptor activation unhelpful)

Question 30

Treatment of nephrogenic DI

Answer 30

Difficult to treat as v rare.

Thiazide diuretics is bendofluazide

Question 31

What is SIADH ( syndrome of inappropriate ADH) and symptoms

Answer 31

Too much AVP causes reduced urine output , water retention , high urine osmolality , low plasma osmolality , dilutional hyponatraemia

Question 32

Causes of SIADH

Answer 32

1) CNS –> head injury , stroke , tumour
2) Pulmonary disease –> pneumonia , bronchiectasis

3) Malignancy –> lung cancer
4) Drug related –> Carbamazepine , serotonin reuptake inhibitors (SSSRIs)
5) Idiopathic

Question 33

Management of SIADH

Answer 33

Fluid restriction in hospital

can use vasopressin antagonist ( vaptan) that binds to V2 receptors in kidney but v expensive