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
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, granulomatous infiltration)
Idiopathic
Familial (rare)

Question 9

What can cause nephrogenic diabetes insipidus?

Answer 9

Familial (rare)

Drugs e.g. lithium

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

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
 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

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

Answer 13

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 14

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

Answer 14

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 15

What is SIADH?

Answer 15

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

Question 16

State some signs of SIADH.

Answer 16

Decreased urine volume Increased urine osmolality

Question 17

What is the main consequence of SIADH?

Answer 17

HYPONATRAEMIA

Question 18

State some symptoms of SIADH that are caused by the hyponatraemia.

Answer 18

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 (ectopic secretion)
Neurohypophysial malfunction (e.g. meningitis, cerebrovascular disease)
Respiratory- small cell lung cancer and pneumonia
Drugs- SSRIs and carbamazepine

Question 20

How is SIADH treated?

Answer 20

Fluid Restriction
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

Where are V1 and V2 receptors found?

Answer 22

V1
 Vascular smooth muscle 
 Non-vascular smooth muscle 
 Anterior pituitary
 Liver 
 Platelets 
CNS
V2
 Kidney
 Endothelial cells

Question 23

State the pharmacological actions of argipressin.

Answer 23

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 24

Compare the effects of argipressin and desmopressin.

Answer 24

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 25

State some unwanted effects of Desmopressin.

Answer 25

Nausea
Headaches
Abdominal pain
Fluid retention and hyponatraemia

Question 26

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

Answer 26

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 27

What are vaptans?

Answer 27

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 28

State some drugs that increase or decrease vasopressin secretion.

Answer 28

Increase vasopressin secretion = nicotine

Decrease vasopressin secretion = alcohol + glucocorticoids