Neurohypophysial Disorders

Question 1

what are magnocellular neurones?

Answer 1

neurones that project into the neurohypophysis with herring bodies

come from the paraventricular nucleus of the hypothalamus

Question 2

the 2 neurohypophysis hormones

Answer 2

• oxytocin

- vasopressin (ADH)

Question 3

what receptors does VP bind to?

Answer 3

V2 receptors in the renal cortical and medullary collecting ducts

Question 4

the pathway of VP action

Answer 4

1) VP binds to V2 receptor
2) G protein activates the conversion of ATP to cAMP
3) PKA is activated
4) mediators lead to the synthesis of AQP2
5) AQP2 move towards the apical membrane in aggraphores
6) APQ2 insertion leads waster in from the lumen
(APQ 3 and 4 let it into the circulation)

Question 5

what is the response to water deprivation?

Answer 5

• increased plasma osmolarity
• stimulation of osmoreceptors (thirst)
• increased VP release
• increased water reabsorption from renal collecting ducts
• reduction in plasma osmolarity
• reduce urine volume, increase in urine osmolarity

Question 6

what are the two forms of Diabetes Insipidus (DI)?

Answer 6

• cranial/ central

- nephrogenic

Question 7

difference between cranial/central and nephrogenic DI

Answer 7

Cranial DI is not making enough VP

nephrogenic DI is the target organ being resistant to VP

Question 8

acquired cranial DI

Answer 8

more common 
due to:
- traumatic brain injury 
- pit. surgery 
- pit. tumours, craniopharygioma
- metastases to pit. gland
- granulotamous infiltration of median eminence e.g. TB

congenital cranial DI is rare

Question 9

causes of acquired and congenital nephrogenic DI

Answer 9

acquired- drugs e.g. lithium

congenital- rare, due to mutation in V2 receptor encoding gene, AQP2 channel gene

Question 10

signs and symptoms of DI

Answer 10

• polyuria (urine volume increases)
• very dilute urine (hypo-osmolar
• polydipsia
• dehydration
• sleep distruption, fatigue e

Question 11

what is psychogenic polydipsia?

Answer 11

excess fluid intake causing polyuria but there is nothing wrong with VP system

Question 12

where is psychogenic polydipsia seen?

Answer 12

in psychiatric patients, possibly due to the anti-cholinergic effects of medication causing a “dry mouth” effect

also seen in those that drink plenty of water when instructed to by health professionals

Question 13

what is the difference between those with DI and those with PP?

Answer 13

DI patients have a high plasma osmolarity while PP patients have a low plasma osmolarity despite the same intake of water

Question 14

what is the normal range of plasma osmolarity?

Answer 14

270-290 mOsm/kg H2O

<270 –> psychogenic polydipsia

> 290 –> diabetes insipidus

Question 15

what are the biochemical features of DI?

Answer 15

• hypernatraemia
• raised urea
• increased plasma osmolarity
• hypo-osmolar urine

Question 16

biochemical features of primary polydipsia?

Answer 16

• mild hyponatraemia
• low plasma osmolarity
• hypo-osmolar urine

Question 17

what needs to be taken into consideration in the treatment of DI?

Answer 17

as all vasopressin receptors will be activated, they need to be specific to kidney receptors

Question 18

treatment of cranial DI

Answer 18

V1- terlipressin
V2- desmopressin (DDVAP0

DDVAP is a synthetic AVP

Question 19

what is DDVAP used for?

Answer 19

for cranial DI (as the kidneys are still sensitive, therefore not used in nephrogenic)

administered as nasal spray, orally or sub-cutaneous
- reduces urine concentration and volume

Question 20

what must be told to a patient if they are told to take DDAVP?

Answer 20

they should not continue drinking large volumes of water as this could lead to hyponatraemia

Question 21

what is the treatment of nephrogenic DI?

Answer 21

thiazides e.g. bendroflumethiazide (diuretic)

- causes mild hypovolaemia and therefore encourages salt and water reuptake in the PCT

Question 22

mechanism of thiazides for nephrogenic DI

Answer 22

inhibition of Na+/Cl- transport in the DCT in kidneys
this promotes diuresis 
volume depletion 
increase in Na+ reabsorption in PCT
increase water reabsorption 
reduce urine volume

Question 23

what is SIADH?

Answer 23

Syndrome of Inappropriate ADH

excessively high ADH

Question 24

what is natriuresis and euvolaemia?

Answer 24

natriuresis- excretion of sodium in the urine (consequence of SIADH)

euvolaemia- state of normal body fluid volume

Question 25

signs and symptoms of SIADH

Answer 25

Small volumes of concentrated urine,

hyponatraemia (leads to poor nerve conduction–> confusion and unsteadiness)

can be symptomless

Question 26

what are the different symptoms seen with different hyponatraemia levels?

Answer 26

<120mM- weakness, poor mental function and nausea

<110mM- coma and death

Question 27

causes of SIADH

Answer 27

• CNS: SAH, stroke, tumour, traumatic brain injury
• pulmonary disease: pneumonia, bronchiectasis
• malignancy: small cell lung cancer
• drug-induced: carbamazepine, SSRI
• idiopathic

Question 28

what are the SIADH treatment options?

Answer 28

1) remove the tumour
2) reduce immediate concern e.g. hyponatraemia
- fluid restriction
3) VAPTANS (v2 receptor antagonists–> prevent AQ2 synthesis)

Question 29

long term treatment of SIADH

Answer 29

demeclocycline
induces nephrogenic DI, reduce renal water reabsorption
prevent VP action in the kidneys

Question 30

what are VAPTANS?

Answer 30

non-competitive V2 receptor antagonists

• inhibits AQP2 synthesis and transport to the apical membrane
• causes aquaresis (solute sparing excretion of water; electrolytes are not lost)
• however very expensive

Question 31

how is desmopressin administered?

Answer 31

as a nasal spray usually

Question 32

what type of DI does desmopressin respond to best?

Answer 32

cranial DI

nephrogenic DI patients dont respond to DDAVP as they do not recognise it