Neurohypophysial Disorders

Question 1

What does vasopressin do?

Answer 1

Anti-diuretic = against increase in urine production

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.

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 2

What is the pathway for vasopressin release?

Answer 2

Water deprivation -> 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 3

What are the two types of diabetes insipidus?

Answer 3

Cranial/central - not making enough VP.
- Acquired - more common:
Traumatic brain injury. Pituitary surgery. Pituitary tumours, craniopharyngioma. Metastasis to pituitary gland.
Granulomatous infiltration of median eminence (e.g. TB).
- Congenital–rare.

Nephrogenic - 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 4

What are the signs and symptoms of DI?

Answer 4

• Polyuria - increase in volume of urine and frequency
• Very dilute urine (hypo-osmolar urine).
• Polydipsia –thirst and increased drinking.
• Dehydration.
• Disruption to sleep and fatigue.

Question 5

What is psychogenic polydypsia? What’s the difference between DI and PP?

Answer 5

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.
• 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 6

How can you distinguish between DI and PP?

Answer 6

Water Deprivation Test:

DDAVP is synthetic AVP – differentiates cranial and central.

A cannula is inserted to take regular readings.

PP osmolality is very similar to normal as it’s mostly psychogenic - slightly lower because the polydipsia has ‘washed away’ the concentration gradient in the medulla slightly

Central DI osmolality lower (DDAVP fixes problem - can concentrate urine) and nephrogenic osmolality very low (kidneys can’t respond to DDAVP) - water not reabsorbed, urine not concentrated

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 7

What is the treatment for cranial DI?

Answer 7

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) - could lead to hyponatraemia.

Question 8

What is the treatment for nephrogenic DI?

Answer 8

Thiazides – e.g. Bendroflumethiazide.

Possible mechanism:
- 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 9

What is SIADH?

Answer 9

plasma vasopressin concentration is inappropriately high for the existing plasma osmolarity

Natriuresis – excretion of sodium in the urine

Euvolaemia – the state of normal body fluid volume

Question 10

What are the signs and symptoms of SIADH?

Answer 10

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

Question 11

What are the causes of SIADH?

Answer 11

Causes can include:

• CNS – SAH, stroke, tumour, TBI.
• Pulmonary disease – pneumonia, bronchiectasis.
• Malignancy – lung (small cell).
• Drug-related – carbamazepine, SSRI.
• Idiopathic.

Question 12

What is the treatment for SIADH?

Answer 12

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)

VAPTANS – Non-competitive V2-receptor Antagonists.

• These inhibit AQA2 synthesis and transport (to apical membrane).
• Aquaresis – solute-sparing renal excretion of water (in contrast to diuretics which lose equal amounts of electrolytes).
• These are VERY expensive though