Neurohypophysial disorders

Question 1

What are magnocellular neurones?

Answer 1

Neurones that project into the neurohypophysis and have herring bodies

Question 2

What are the 2 neurohypophysial hormones?

Answer 2

Oxytocin and vasopressin

Question 3

What does vasopressin do?

Answer 3

It is an anti-diuretic and it acts by increasing water reabsorption

Question 4

How does vasopressin act? (summary)

Answer 4

By increasing water reabsorption from the renal cortical and medullary collecting ducts via V2 receptors

Question 5

What is the detailed action of VP?

Answer 5

1. VP binds to V2 receptors which are Gs receptors
2. Aquaporin 2 molecules are created which move to the apical membrane in aggraphores
3. The AQA2 insert in the apical membrane to allow water reabsorption

Question 6

Where are osmoreceptor neurones located? What’s special about this place

Answer 6

In the organum vasculosum which has no blood brain barrier

Question 7

What is the homeostatic response of osmoreceptors when blood osmolarity goes up?

Answer 7

Water moves out of osmoreceptor cells and the osmoreceptors shrink which triggers them to send more signals to the hypothalamus to release VP and also stimulates thirst. This increases water reabsorption from renal collecting ducts, reduction in blood plasma osmolarity and reduced urine volume but a higher urine osmolarity

Question 8

What are the two types of diabetes insipidus?

Answer 8

Cranial/Central and Nephrogenic

Question 9

How can cranial DI be acquired? (More common than congenital)

Answer 9

Traumatic brain injury
Pituitary surgery
Pituitary tumours, craniopharyngioma
Metastasis to pituitary gland
Granulomatous infiltration of median eminance

Question 10

How can you aquire a nephrogenic DI?

Answer 10

Drug use eg lithium

Question 11

What are examples of mutations that can cause congenital nephrogenic DI?

Answer 11

Mutation in gene encoding V2 receptor

AQA2 type water channels

Question 12

What is the fundamental cause of diabetes insipidus?

Answer 12

Insufficient ADH/Vasopressin

Question 13

What are signs and symptoms of DI?

Answer 13

Polyuria
Hypo-osmolar urine
Polydipsia
Dehydration
Disruption to sleep and fatigue

Question 14

What is psychogenic polydipsia?

Answer 14

Excess fluid intake and polyuria but VP secretion ability preserved

Question 15

What is a possible aetiology of psychogenic polydipsia?

Answer 15

Anti-cholinergic effects of medication stimulating a ‘dry mouth’ effect

Question 16

What type of people frequently show signs of psychogenic polydipsia?

Answer 16

Psychiatric patients and in-patients told to ‘drink plenty’ by healthcare professionals

Question 17

What is the plasma osmolarity difference in people with DI and PP?

Answer 17

People with DI will have a HIGH plasma osmolarity but people with PP will have a LOW plasma osmolarity even though they both drink a lot- due to differences in VP

Question 18

How is the water deprivation test done?

Answer 18

No water given to patient. A cannular inserted to take regular readings, and patient’s weight is taken regularly to make sure they don’t become too dehydrated

Question 19

What is DDAVP?

Answer 19

Synthetic AVP that differentiates between cranial and central readings - used in water deprivation tests and to treat DI

Question 20

Why are the results of PP very similar to normal levels in a water deprivation test?

Answer 20

It is mostly psychogenic! PP is slightly lower because polydipsia has ‘washed away’ the concentration gradient in the medulla slightly

Question 21

What are biochemical features of DI?

Answer 21

Hypernatraemia, raised urea, increased plasma osmolarity, hypoosmolar urine

Question 22

What are biochemical features of PP?

Answer 22

Mild hyponatraemia, low plasma osmolarity and hypoosmolar urine

Question 23

What is the treatment for cranial diabetes insipidus?

Answer 23

Only want to target V2 kidney receptors so use selective VP receptor agonists

• V1 Terlipressin
• V2 Desmopressin (DDAVP)

Question 24

How can DDVAP be administered?

Answer 24

Nasal spray, orally or subcutaneous

Question 25

What does DDVAP do?

Answer 25

Reduce urine conc and volume in cranial DI however patients must be told to NOT CONTINUE drinking large volumes of water

Question 26

What is the treatment for nephrogenic DI?

Answer 26

Thazides eg bendroglumethazide which inhibits the Na+/Cl- transport in DCT in kidneys therefore promotes diuresis. This leads to volume depletion and an increase in Na+ reabsorption in PCT. This increases water reabsorption in PCT and reduces urine volume.

Question 27

Why is nephrogenic DI hard to treat

Answer 27

Problem lies in kidneys, not the hormone itself

Question 28

What is SIADH

Answer 28

Syndrome of inappropriate ADH is where there is an excessively high ADH , natriuresis and eurolaemia

Question 29

What are the signs of SIADH

Answer 29

Small volumes of conc urine, hyponatraemia

Question 30

What are the symptoms of SIADH

Answer 30

Can be symptomless, but can also if hyponatraemia <120mM show weak, poor mental function and nausea or <110mM can lead to coma or death

Question 31

What can be the causes of SIADH

Answer 31

Primary brain injury – e.g. meningitis. subarachnoid haemorrhage (SAH)
Malignancy – e.g. small-cell lung cancer
Drugs – e.g. carbamazepine, SSRIs, amitriptyline
Infectious – e.g. atypical pneumonia, cerebral abscess
Hypothyroidism

Question 32

What are treatment plans for SIADH

Answer 32

Remove tumour
Fluid restriction - immediate
Demeclocyline - long term which induces nephrogenic DI by reducing renal water absorption to prevent VP action in the kidneys
VAPTANS which are non competitive V2 receptor antagonists that inhiit AQA2 synsthesis and transport and causes aquaresis - solute sparing renal excretion of water but are very expensive