Neurohypophysial disorders

Question 1

What does the posterior pituitary look like on an MRI?

Answer 1

It looks like a bright spot on the pituitary MRI

Question 2

What are the two nuclei involved with the neurohypophysis? Including in the secretion of VP

Answer 2

Supraoptic nucleus

Paraventricular nucleus

Question 3

What are the main two hormones involved in the neurohypophysis?

Answer 3

Vasopressin (ADH)

Oxytocin

Question 4

What is the principle effect of vasopressin?

Answer 4

It acts as an antidiuretic increases water absorption from renal cortical and medullary collecting ducts via V2 receptors.

V1a - vasoconstrictor activity
V1b - corticotrophin (ACTH) release
V2 - also Factor VIII and von Willebrand factor secretion

Question 5

What is function of oxytocin?

Answer 5

Constriction of myometrium at parturition
Milk ejection reflex
Central effects
Acts on oxytocin receptors

Question 6

What measures the osmolality of the blood so that vasopressin can be stimulated to be released?

Answer 6

Osmoreceptors located in the organum vasculosum project to the PVN and SON

Question 7

How do osmoreceptors cause the release of vasopressin?

Answer 7

When there is low water content in the blood there is a greater concentration of Na+ (extracellular Na+ is higher). As a result water flows out the cell by osmosis causing the osmoreceptor to shrink. This change in the shape causes increased osmoreceptor firing causing VP release from hypothalamic PVN and SON.

Question 8

What is the main factor for water deprivation?

Answer 8

Serum osmolality

Question 9

What are the types of diabetes insipidus?

Answer 9

Cranial/Central - Absence or lack of circulating vasopressin. Most common diabetes insipidus
Nephrogenic - End-organ (kidneys) resistance to vasopressin

Question 10

What are the causes of cranial diabetes insipidus?

Answer 10

Damage to neurohypophysial system - Traumatic brain injury, pituitary surgery, pituitary tumours, craniopharyngioma, metastasis to the pituitary gland e.g Breast, granulomatous infiltration of median eminence e.g TB, sarcoidosis
Congenital is rare

Question 11

What are the causes of nephrogenic diabetes insipidus?

Answer 11

Congential - rare (mutation in V2 receptor or in aquaporin type 2)
Acquired - Drugs (lithium - used to treat bipolar disorder)

Question 12

Signs and symptoms of diabetes insipidus?

Answer 12

Polyuria, hypo-osmolar (dilute urine), polydipsia, nocturea, dehydration - can lead to death

Question 13

Describe the mechanism of diabetes insipidus

Answer 13

See diagram on slides

Question 14

What is psychogenic polydipsia?

Answer 14

Most frequently seen in psychiatric patients - Excess fluid intake and urine output but ability to secrete VP is preserved.
See notes

Question 15

How to differentiate between diabetes insipidus and polydipsia? And cental vs nephrogenic

Answer 15

The normal range for plasma osmolality is 270 to 290 mOsm/kg H2O. Diabetes insipidus patients may have a higher plasma osmolality whereas psychogenic polydipia patient have a lower plasma osmolality
Injection of synthetic VP and see the changes.
Water deprivation test - see notes

Question 16

What are the biochemical features of those with diabetes insipidus and psychogenic polydipsia?

Answer 16

Diabetes insipidus - [Hypernatraemia, raised urea, increased plasma osmolality] these features are all due to dehydration. Hypo-osmolar urine
Psychogenic polydipsia - Mild hyponatraemia - excess plasma osmolality, hypo-osmolar urine

Question 17

What can be used to treat cranial diabetes insipidus?

Answer 17

Desmopressin - specific for V2 receptor in the kidneys (replaces VP). Doesn’t bind to V1 receptors which cause vasoconstriction. Terlipressin is used for GI bleeds because it causes vasocontriction.

Question 18

How can you administer desmopressin?

Answer 18

Nasally (normal way), orally and as an injection.

Need to tell patients not to continue drinking large amounts of fluids, risks of hyponatraemia.

Question 19

What can be used to treat nephrogenic diabetes insipidus?

Answer 19

Thiazide diruetics - not clear how it works.

bendroflumethiazide

Question 20

Define SIADH

Answer 20

The plasma VP concentration is inappropriately high for the existing plasma osmolality

Question 21

Describe the effects and mechanisms of increased VP

Answer 21

See diagram
euvolaemia - surprising. Stretch in heart due to increase water causing the release of an atrial natriuetic peptide (ANP) from the right atrium. This causes natriuresis in the urine.
Hyponatraemia - due to lots of water being retained

Question 22

What are the clinical features of SIADH?

Answer 22

Raised urine osmolality, decreased urine volume (initially)
Hyponatreaemia
Opposite of diabetes insipidus

Question 23

What are the symptoms of SIADH?

Answer 23

Can be symptomless
If p[Na+] < 120mM: generalised weakness, poor mental function, nausea = this just adds to the hyponatreamia because you losing sodium in the vomit
If p[Na+] <110mM: confusion, coma, death

Question 24

What are the causes of SIADH?

Answer 24

CNS
Pulmonary disease
Malignancy
Drug related

See notes for specific causes

Question 25

What is the treatment for SIADH?

Answer 25

Treat the underlying cause (e.g surgery for tumour)
Manage the anything that causes immediate concern. (hyponatraemia) - fluid restriction
Longer term: Use drugs that prevent action of VP at the kidneys - inducing nephrogenic DI by reducing renal water reabsorption with demeclocyline
Inhibit the action of ADH - V2 receptor antgonist

Question 26

What are Vaptans?

Answer 26

See notes