Neurohypophysial disorders

Question 1

Name the two main nuclei within which neurones of the neurohypophysis have their cell bodies.

Answer 1

Paraventricular Nucleus

Supraoptic Nucleus

Question 2

What two hormones are produced by the neurohypophysis?

Answer 2

Vasopressin

Oxytocin

Question 3

What is the principal action of vasopressin and how does it carry out this action?

Answer 3

Vasopressin’s main action is on the V2 receptors in the renal cortical and medullary collecting ducts
It stimulates the synthesis and assembly of aquaporin 2, which then increases water reabsorption and has an antidiuretic effect

Question 4

State some other actions of vasopressin.

Answer 4

Vasoconstriction
Corticotrophin release
Factor VIII and von Willebrand factor synthesis
Central effects

Question 5

What are the main actions of oxytocin?

Answer 5

It is a contractile molecule that binds to oxytocin receptors
It causes contraction of the myometrium during parturition and is involved in milk ejection
It also has central effects

Question 6

What are the consequences of a lack of the neurohypophysial hormones?

Answer 6

Lack of Oxytocin – not clinically significant

Lack of Vasopressin – Diabetes Insipidus

Question 7

What are the two forms of diabetes insipidus?

Answer 7

Central (cranial) and Nephrogenic Diabetes Insipidus

Question 8

What can cause central diabetes insipidus?

Answer 8

Damage to neurohypophysial system (injury, surgery, cerebral thrombosis, tumours (Craniopharyngioma), granulomatous infiltration)
Idiopathic
Familial (rare)

Question 9

What can cause nephrogenic diabetes insipidus?

Answer 9

Familial (rare)

Drugs e.g. lithium, dimethyl chlortetracycline (DMCT)

Question 10

State some signs and symptoms of diabetes insipidus.

Answer 10

Polyuria 
Polydipsia 
Hypo-osmolar urine 
Dehydration 
Possible disruption of sleep 
Possible electrolyte imbalance

Question 11

State another cause of polydipsia that isn’t diabetes.

Answer 11

Psychogenic polydipsia
This is a central disturbance that increases the drive to drink
Unknown aetiology, but may be due to anti-cholinergic nature of psychiatric medication (causes ‘dry mouth’)

Question 12

What test can be used to distinguish between normal, psychogenic polydipsia, central DI and nephrogenic DI? Describe the results you would expect.

Answer 12

Fluid deprivation test
(Patient’s with psychogenic polydipsia have lower blood osmolality from beginning)

Normals and psychogenic polydipsia will show a rise in urine osmolality
Central and nephrogenic diabetes insipidus will show little or no change in urine osmolality

Fluid deprivation with administration of DDAVP (Desmopressin)
Central diabetes insipidus will show a rise in urine osmolality
Nephrogenic DI will still have a low urine osmolality (because of end-organ resistance)

Question 13

Why is the urine osmolality of someone with psychogenic polydipsia lower (in the fluid deprivation test) than a normal subject?

Answer 13

Over time, the constant passage of large volumes of water through the kidneys will wash out the osmotic gradient that is necessary for AVP to exert its diuretic effect

Question 14

Describe the normal change in urine osmolality as plasma osmolality increases.

Answer 14

Normally, urine osmolality will increase as plasma osmolality increases (in a graph of urine osmolality against plasma osmolality it will show a sigmoid shape)
In DI, there is little change in urine osmolality as plasma osmolality increases

Question 15

Describe changes in plasma vasopressin following administration of hypertonic saline in a normal subject, psychogenic polydipsia, central DI and nephrogenic DI.

Answer 15

Hypertonic saline will increase the plasma osmolality and hence will increase the vasopressin secretion in patients that have the capacity to produce vasopressin (normal, psychogenic polydipsia and nephrogenic DI)

Patients with central DI can’t produce vasopressin at all so the hypertonic saline will show no change in plasma vasopressin

Question 16

What is SIADH?

Answer 16

Syndrome of Inappropriate ADH = when the plasma vasopressin concentration is inappropriate for the existing plasma osmolality

Question 17

State some signs of SIADH.

Answer 17

Decreased urine volume

Increased urine osmolality

Question 18

What is the main consequence of SIADH?

Answer 18

Hyponatraemia
At relatively mild hyponatraemia = generalized weakness, poor mental function, nausea
Severe hyponatraemia = confusion, coma, death

Question 19

State some causes of SIADH.

Answer 19

Tumours, especially small cell carcinoma in lungs (ectopic secretion)
Neurohypophysial malfunction (e.g. meningitis, cerebrovascular disease)
Thoracic disease (e.g. pneumonia)
Endocrine disease (e.g. Addison’s)
Physiological – it can happen under normal circumstances where AVP is release is stimulated by non-osmotic stimuli (e.g. hypovolaemia, pain, surgery)
Drugs - Carbamzepine, SSRI (selective serotonin re-uptake inhibitor)
Idiopathic

Question 20

How is SIADH treated?

Answer 20

Fluid Restriction (First treatment)
Provide appropriate treatment when the cause is identified (e.g. surgery for a tumour)
NOTE: if someone is hyponatraemic you need to deal with that as soon as possible – e.g. use drugs that prevent vasopressin action in the kidneys

Question 21

What is the name given to exogenous vasopressin?

Answer 21

Argipressin

Question 22

State the pharmacological actions of argipressin.

Answer 22

NATRIURESIS – this is one of the unexplained side-effects of having a large amount of vasopressin – it is V2 mediated and only happens when given at high doses
PRESSOR ACTION – V1 mediated vasoconstriction – the coronary vessels are particularly sensitive to vasopressin (this can cause cardiac ischaemia and angina attacks)
Contraction of vascular smooth muscle
Increased ACTH secretion
Increased factor VIII and vWF production

Question 23

Where are V1 and V2 receptors found?

Answer 23

V1 
Vascular smooth muscle 
Non-vascular smooth muscle 
Anterior pituitary 
Liver 
Platelets 
CNS 

V2
Kidney
Collecting duct

Question 24

State two selective peptidergic vasopressin selective agonists.

Answer 24

V1 – Terlipressin

V2 - Desmopressin

Question 25

Compare the effects of argipressin and desmopressin.

Answer 25

Argipressin acts on V1 and V2
Argipressin is more effective in causing vasoconstriction via V1 receptors Desmopressin is more effective in the kidneys in causing water reabsorption via V2 receptors

Question 26

State some clinical uses of Desmopressin.

Answer 26

Treatment of diabetes insipidus
Treatment of nocturnal eneuresis
Haemophilia (need V2 stimulation)
NOTE: it is taken orally or nasally

Question 27

State some unwanted effects of Desmopressin.

Answer 27

Nausea
Headaches
Abdominal pain
Fluid retention and hyponatraemia

Question 28

State one treatment used for nephrogenic diabetes insipidus and its possible mechanism of action.

Answer 28

Thiazide Diuretics (e.g. bendroflumethiazide)
This inhibits the Na+/Cl- pump in the DCT leading to a diuretic effect
This leads to volume depletion resulting in a compensatory increase inNa+ reabsorption from the PCT
This increases proximal water reabsorption so less water reaches the collecting duct
This ultimately leads to reduced urine volume

Question 29

What are vaptans?

Answer 29

Non-peptide vasopressin receptor antagonists
Tolvaptan = V2 receptor antagonist
It is used to treat hyponatraemia associated with SIADH and may be useful in treating congestive heart failure

Question 30

State some drugs that increase or decrease vasopressin secretion.

Answer 30

Increase vasopressin secretion = nicotine
Decrease vasopressin secretion = alcohol + glucocorticoids
Endothelial cells