Neurohypophysial disorders

Question 1

What are magnocellular neurones?

Answer 1

neurones that project into the neurohypophysis (with herring bodies)

Question 2

What distinguishes anterior and posterior pituitary on and MRI?

Answer 2

Posterior pituitary is bright white on MRI

Question 3

How does vasopressin work?

Answer 3

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

Osmoreceptor neurones are located in the Organum Vasculosum (has NO BBB). These neurones then project their axons into the hypothalamic paraventricular and supraoptic nuclei.
When blood osmolarity goes up, water moves out of osmoreceptor cells and the osmoreceptors shrink which triggers them to send more signals to the hypothalamus to release VP.

Question 4

What happens if a normal person is water deprived?

Answer 4

Increased blood plasma osmolarity -> stimulation of osmoreceptors (thirst) -> increased VP release -> increased water reabsorption from renal collecting ducts -> reduction in blood plasma osmolarity & reduced urine volume (but higher urine osmolarity).

Question 5

What are the two types of diabetes insipidus?

Answer 5

cranial (central)

nephrogenic

Question 6

What are some causes of acquired and congenital central DI?

Answer 6

• Traumatic brain injury.
• Pituitary surgery.
• Pituitary tumours, craniopharyngioma.
• Metastasis to pituitary gland.
• Granulomatous infiltration of median eminence (e.g. TB).

CONGENITAL IS RARE

Question 7

What are some causes of acquired and congenital nephrogenic DI?

Answer 7

The target organ (kidneys) have resistance.

• Acquired – drugs (e.g. lithium)
• Congenital – RARE (e.g. mutation in gene encoding V2 receptor, AQA2 type water channels).

Question 8

What are the signs and symptoms of diabetes insipidus?

Answer 8

• polyuria (high volume and frequency)
• polydipsia
• nocturia
• dehydration
• fatigue
• very dilute urine (hypoosmoloar)

Question 9

What is psychogenic polydipsia?

Answer 9

Excess fluid intake (polydipsia) and polyuria but VP secretion ability preserved.

• Frequently seen in psychiatric patients with possible aetiology being anti-cholinergic effects of medication stimulating a “dry-mouth” effect.
• May also be seen in in-patients told to “drink plenty” by healthcare professionals.

Question 10

Compare the plasma osmolarity of people with DI and PP

Answer 10

DI people will have a high plasma osmolarity and PP people will have a low osmolarity (even though they both drink a lot of water – difference lies in differences in VP).

Question 11

How is DI and psychogenic polydipsia diagnosed?

Answer 11

water deprivation test

• normal people will have very high urine osmolality
• those with PP will have high but slightly lower than normal as constant drinking reduces gradient in medulla
• DI will have low
• To differentiate cranial and nephrogenic give DDAVP which is synthetic AVP and cranial will have a regular response to dehydration

Question 12

What things are important to watch during water deprivation test?

Answer 12

• Take regular weight to ensure patients don’t over dehydrate (SHOULDN’T GO LESS THAN 2% OF THEIR BODY WEIGHT)

Question 13

Biochemical features of DI and PP

Answer 13

Diabetes Insipidus:
- Hypernatraemia (high blood sodium), raised urea, increased plasma osmolarity, hypo-osmolar urine

Psychogenic Polydipsia:
- Mild hyponatraemia, low plasma osmolarity, hypo-osmolar urine

Question 14

What is important when giving DI treatment?

Answer 14

Remember that all vasopressin receptors will be activated – we want to target just the V2 kidney receptors.

• To treat cranial DI, we use selective VP receptor agonists:
  V1 – Terlipressin
  V2 – Desmopressin
  (DDAVP)

Question 15

Cranial diabetes insipidus treatment

Answer 15

Desmopressin (DDAVP)

• Can be administered as; nasal spray, orally or SC (sub-cutaneous)
• DDAVP will reduce the urine concentration and volume in cranial DI.
• The patient must be told to not continue drinking large volumes of water (which they usually do or it could lead to hyponatraemia

Question 16

Nephrogenic diabetes insipidus treatment

Answer 16

Thiazides – e.g. Bendroflumethiazide

• Inhibits the Na+/Cl- transport in DCT in kidneys (promotes dieresis) -> volume depletion -> increase in Na+ reabsorption in PCT -> increase water reabsorption in PCT -> reduced urine volume

This is the only drug we have (thiazides) and it’s not very effective but it is very hard to treat (as the problem lies in the kidneys, not in the hormone itself).

Question 17

What is SIADH?

Answer 17

Excessively high ADH

Question 18

What is natriuresis and euvolaemia?

Answer 18

Natriuresis – excretion of sodium in the urine.

Euvolaemia – the state of normal body fluid volume.

Question 19

Describe the pathway that occurs in SIADH

Answer 19

high VP -> more water reabsorption -> expansion of ECF volume -> hyponatraemia and ANP release -> ANP leads to natriuresis -> more hyponatraemia and euvolaemia

Question 20

What are the signs and symptoms of SIADH?

Answer 20

• small volumes of concentrated urine
• hyponatraemia.
• if hyponatraemic (<120mM) then weak, poor mental function and nausea or (<110mM) then coma and death

Question 21

Causes of SIADH?

Answer 21

CNS – SAH, stroke, tumour, TBI.

Pulmonary disease – pneumonia, bronchiectasis.

Malignancy – lung (small cell).

Drug-related – carbamazepine, SSRI.

Idiopathic.

Question 22

Treatment for SIADH

Answer 22

• Appropriate treatment – i.e. remove the tumour.
• To reduce immediate concern (i.e. hyponatraemia):
  Immediate – fluid restriction – thus won’t have water to reabsorb in the nephron
  Long-term – demeclocyline – induce nephrogenic DI – reduce renal water reabsorption. These prevent VP action in the kidneys.

Question 23

What are Vaptans?

Answer 23

Non-competitive V2-receptor Antagonists

• These inhibit AQA2 synthesis and transport (to apical membrane).
• This is aquaresis – solute-sparing renal excretion of water (in contrast to diuretics which lose equal amounts of electrolytes).

These are very expensive though.