3. Neurohypophysial disorders

Question 1

how can you visualise the pituitary gland?

Answer 1

pituitary MRI scan

Question 2

what does the posterior pituitary look like on an MRI scan?

Answer 2

bright spot

Question 3

where is the posterior gland located?

Answer 3

in the sella turcica

Question 4

what nuclei are present in the hypothalamus and where do the axons project to?

Answer 4

• paraventricular nucleus
• supraoptic nucleus

axons project to the neurohypophysis

Question 5

what do the paraventricular and supraoptic nuclei release?

Answer 5

oxytocin and vasopressin

Question 6

what is the principle effect of vasopressin (ADH)?

Answer 6

anti-diuretic

- increases water reabsorption from the renal cortical and medullary collecting ducts via V2 receptors

Question 7

how does vasopressin increase water reabsorption?

Answer 7

binds to V2 receptors in the basolateral membrane -> activates adenylate cyclase -> ATP to cAMP -> cAMP activates protein kinase A -> synthesis of aquaporin 2 molecules stimulated -> aquaporins assemble into aggraphores which migrate to the apical membrane (side of collecting duct) -> water moves into the cells through channels and instransported into the blood via AQP3 and AQP4.

Question 8

what is vasopressin release regulated by?

Answer 8

osmoreceptors (neurones) located in the organum vasculosum which doesn’t have a BBB so can communicate directly with the blood and detect its osmolality

Question 9

how do osmoreceptors regulate vasopressin?

Answer 9

water leaves osmoreceptor (down osmotic gradient) -> osmoreceptor shrinks -> osmoreceptor becomes more excitable and starts firing more -> vasopressin neurones in the hypothalamic nuclei are stimulated to release vasopressin -> vasopressin travels to the pituitary via supraoptic and paraventricular nuclei

Question 10

what is the normal response to water deprivation?

Answer 10

you become slightly dehydrated -> increased serum osmolality -> osmoreceptors are stimulated -> thirst -> signals the nuclei to release VP which stimulates water reabsorption across the collecting durct

you excrete a smaller volume of more concentrated urine

Question 11

what is diabetes insipidus?

Answer 11

when someone has insufficient ADH or ADH isn’t able to work

Question 12

what are the 2 types of diabetes insipidus?

Answer 12

1. cranial (most likely)

2. nephrogenic (less likely)

Question 13

what is cranial DI and what is it caused by?

Answer 13

damage to the neurohypophysial system resulting in not enough ADH being made because of problems with the posterior pituitary

may be due to:

• traumatic brain injury
• pituitary surgery
• pituitary tumours
• metastasis to the pituitary gland
• granulomatous infiltration of the median eminence (e.g. TB)

Question 14

what is nephrogenic DI and what is it caused by?

Answer 14

vasopressin resistance where the end organ (kidney) won’t respond even though vasopressin is being made

may be:

• congenital - rare (e.g. mutation in gene encoding V2 receptor)
• acquired - drugs (e.g. lithium given for bipolar disorder)

Question 15

what are the signs and symptoms of DI?

Answer 15

• polyuria (large volumes of urine)
• dilute urine
• thirst and increased drinking (polydipsia)
• dehydration
• disruption to sleep

Question 16

what is the consequence of no access to water if you have DI?

Answer 16

dehydration and death

Question 17

what is psychogenic polydipsia?

Answer 17

mostly seen in psychiatric patients who drink lots because of anti-cholinergic effects of medication (dry mouth) or because they have been told to ‘drink plenty’ by healthcare professionals - results in polydipsia and polyuria but their vasopressin secretion is normal

Question 18

what is the normal range for plasma osmolality?

Answer 18

270-290mOsm/kg H2O

Question 19

what test can be done to distinguish between psychogenic polydipsia and diabetes insipidus?

Answer 19

water deprivation test - patient is kept in a room without access to water. they are weighed periodically but if they lose >2% body weight the test is stopped (clinical dehydration)

Question 20

compare the results from a water deprivation test of healthy people with people that have DI

Answer 20

in healthy people (including psychogenic polydipsia) vasopressin is produced when access to water is restricted, so osmolality is maintained and you produce very small amounts of concentrated urine

in people with DI they cannot make/respond to ADH so they continue to produce large volumes of dilute urine

Question 21

how can you distinguish between nephrogenic and cranial DI?

Answer 21

DDAVP mimics vasopressin and can be administered as the 2nd part of the test - it binds specifically to the V2 receptors (like vasopressin) therefore patients with cranial DI (who don’t make enough vasopressin) will respond to DDAVP and begin to regulate plasma osmolality but patients with nephrogenic DI still can’t respond with DDAVP

Question 22

what are the biochemical features of DI?

Answer 22

• hypernatraemia (high sodium due to dehydration)
• raised urea
• increased plasma osmolality
• dilute urine

Question 23

what are the biochemical features of psychogenic polydipsia?

Answer 23

• mild hyponatraemia (due to excess water intake)
• low plasma osmolality
• dilute urine

Question 24

why is vasopressin not given to treat DI?

Answer 24

vasopressin has other effects via the V1 receptors (vasoconstriction) which are unwanted

Question 25

what are the selective vasopressin receptor peptidergic agonists used to treat?

Answer 25

V1 - terlipressin (stimulates V1 receptors) used for upper GI bleeds (vasoconstrictor)
V2 - desmopressin (DDAVP) used to treat cranial DI

Question 26

how is desmopressin administered?

Answer 26

1. nasally
2. orally
3. subcutaneously

Question 27

how is nephrogenic DI treated?

Answer 27

thiazides e.g. bendroflumethiazide

Question 28

what is the production of excess ADH called?

Answer 28

syndrome of inappropriate ADH (SIADH)

Question 29

what are the signs of SIADH?

Answer 29

• raised urine osmolality
• decreased urine volume
• hyponatraemia due to water reabsorption
• euvolemia (you don’t hold onto excess fluid)

Question 30

why can hyponatraemia in SIADH patients sometimes be worsened?

Answer 30

due to increased EC volume, stretch-sensitive receptors in the right atrium are stimulated and release atrial naturietic peptide. this causes sodium loss from the urine (water follows - osmotic gradient) and this worsens the already low sodium

Question 31

in SIADH patients, what is the result of natriuresis due to atrial natriuretic peptide (ANP) stimulation?

Answer 31

euvolaemia - because the water follows the sodium there is no fluid overload, peripheral oedema and they are not dehydrated

Question 32

what are the symptoms of SIADH?

Answer 32

if sodium concentration <120mM = weakness, poor mental function, nausea and confusion (CNS dulling)

if sodium concentration <110mM = confusion leading to coma and death

Question 33

what are the causes of SIADH?

Answer 33

• CNS: subarachnoid haemorrhage, stroke, tumour, traumatic brain injury
• pulmonary disease: pneumonia
• malignancy: small cell lung cancer (can cause XS secretion of ADH)
• drug-related: carbamazepine
• idiopathic

Question 34

what is the treatment of SIADH?

Answer 34

• surgery for tumour

- to reduce hyponatraemia: fluid restriction and drugs that prevent vasopressin action in kidneys (demeclocycline)

Question 35

what are VAPTANS?

Answer 35

non-competitive V2 receptor antagonists that inhibit aquaporin 2 synthesis and migration to collecting duct apical membrane, preventing renal water reabsorption

VAPTANS cause patients to excrete just water (aquaresis), preventing electrolyte loss however there is currently limited use because they are so expensive