Neurohypophysial Disorders

Question 1

Name the two main nuclei within which neurones of the neurohypophysis have their cell bodies. State the types of neurones for each

Answer 1

Paraventricular Nucleus - Parvocellular and Magnocellular

Supraoptic Nucleus - just Magnocellular

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 binds to V2 receptors in the renal cortical and medullary collecting ducts.
It stimulates the synthesis and assembly of aquaporin 2 (via Gs protein coupled receptor pathway), which then increases water reabsorption and has an antidiuretic effect => increased urine osmolality, reduced serum osmolality

Question 4

State some other actions of vasopressin

Answer 4

• Vasoconstriction
• Corticotrophin release
• Factor VIII and von Willebrand factor synthesis

Question 5

Describe how vasopressin release is regulated

Answer 5

Osmoreceptors shrink in response to and increase in extracellular osmolality (increased Na+) => increased osmoreceptor firing => increased VP release

Question 6

Where are osmoreceptors found within the brain?

Answer 6

Organum vasculosum of the lamina terminalis

Question 7

What are the two types of Diabetes Insipidus, and characterise the two?

Answer 7

Cranial (or central) = Absence or lack of circulating vasopressin

Nephrogenic = Kidneys resistant to vasopressin

Question 8

Cranial DI is mainly as a result of damage to the neurohypophysial system. List possible causes for such damage.

Answer 8

• Traumatic brain injury
• Pituitary surgery
• Pituitary tumours, craniopharyngioma
• Metastasis to the pituitary gland eg breast
• Granulomatous infiltration of median eminence eg TB, sarcoidosis
• Congenital (rare)

Question 9

What can cause nephrogenic diabetes?

Answer 9

• Congenital (e.g. V2 receptor/ AQP2 channel gene mutation)

- Acquired due to drugs (e.g. lithium)

Question 10

What are the signs and symptoms of diabetes insipidus?

Answer 10

Polyuria 
Polydipsia 
Hypo-osmolar urine 
Dehydration 
Possible disruption of sleep

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 (VP secretion and response is normal)

Question 12

What is the approximate plasma osmolality for DI and PP?

Answer 12

DI = 290 mOsm/kg H2O
PP = 270 mOsm/kg H2O

Normal (hydrated) range = 280

Question 13

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

Answer 13

FLUID DEPRIVATION TEST

• Normal and psychogenic polydipsia = rise in urine osmolality
• Central and nephrogenic diabetes insipidus will show little or no change in urine osmolality
• After fluid deprivation with administration of DDAVP (Desmopressin), only Central diabetes insipidus will show a rise in urine osmolality

Question 14

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

Answer 14

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 15

List the biochemical features of diabetes insipidus

Answer 15

• Hypernatraemia
• Raised urea
• Increased plasma osmolality
• Dilute (hypo-osmolar) urine (i.e. low urine osmolality)

Question 16

List the biochemical features of psychogenic polydipsia

Answer 16

• Mild hyponatraemia
• Low plasma osmolality
• Dilute (hypo-osmolar) urine (i.e. low urine osmolality)

Question 17

State two selective vasopressin receptor peptidergic agonists

Answer 17

V1 –TERLIPRESSIN

V2 – DESMOPRESSIN (DDAVP)

Question 18

Why is exogenous vasopressin NOT used in the treatment of cranial DI?

Answer 18

Exogenous vasopressin would activate all receptors (V1a, V1b and V2) affecting other tissues/organs (e.g. vasculature, liver)

Question 19

How may cranial DI be treated?

Answer 19

• Administration (nasally, orally or subcutaneous) of desmopressin
• Note that the patient must be told NOT to continue drinking large amounts of fluid for risk of hyponatraemia

Question 20

How may nephrogenic DI be treated?

Answer 20

Thiazides (e.g. bendroflumethiazide)

Question 21

Describe the possible mechanism for thiazides in the treatment of nephrogenic DI?

Answer 21

• Inhibits Na+/Cl- transport in distal convoluted tubule and so sodium reabsorption (diuretic effect)
• Compensatory increase in Na+ reabsorption from the proximal tubule (plus small decrease in GFR)
• Increased proximal water reabsorption
• Decreased fluid reaches collecting duct
• Reduced urine volume

Question 22

Define Syndrome of Inappropriate ADH

Answer 22

Plasma vasopressin concentration is inappropriately high for the existing plasma osmolality

Question 23

What are the effects of inappropriately increased vasopressin?

Answer 23

• Increased water reabsorption => raised urine osmolality
• Expansion of ECF volume (=>hyponatraemia)
• Release of atrial natriuretic peptide from right atrium => natriuresis => hyponatraemia + euvolaemia

Question 24

List some symptoms of SIADH

Answer 24

• Can be symptomless

If p[Na+] <120 mM => generalised weakness, poor mental function, nausea

If p[Na+] <110 mM => CONFUSION leading to COMA and ultimately DEATH

Question 25

List potential causes of SIADH

Answer 25

CNS: e.g. Sub-arachnoid Haemorrhage, stroke, tumour

Pulmonary disease: e.g.
Pneumonia, bronchiectasis

Malignancy: Lung cancer (small cell)

Drug-related: e.g. Carbamazepine, Selective Serotonin Re-uptake Inhibitors

Idiopathic

Question 26

What is the treatment for SIADH?

Answer 26

To reduce the immediate concern of hyponatraemia:

• Fluid restriction (immediate)
• Drugs to inhibit action of ADH and induce nephrogenic DI (e.g. demeclocyline, V2 receptor antagonists)

Question 27

What are Vaptans?

Answer 27

Non-competitive V2 receptor antagonists.

Cause solute-sparing renal excretion of water (i.e. no simultaneous electrolyte loss)