Neurohypophysial disorders

Question 1

What are the effects of vasopressin

Answer 1

Anti-diuretic - increase water reabsorption form renal cortical and medullary collecting ducts via V2 receptors

Question 2

What is the mechanism of vasopressin action

Answer 2

1. vasopressin binds to V2
2. G-protein action activates adenyl cyclase
3. ATP turns into cyclic AMP
   4 protein kinase A activated
4. synthesis of aquaporin molecules (AQP2)
5. aggraphores move to the apical membrane
6. insertion of aquaporins onto the membrane
7. Water moves through down its concentration gradient
8. AQP 3 and 4 are less sensitive to vasopressin but attach to the basolateral (serosal) membrane

Question 3

How is vasopressin release regulated

Answer 3

Osmoreceptors located in the organum vasculosum project to the hypothalamic

1. Increase in extracellular NA+
2. Osmoreceptor shrinks as water diffuses out
3. Increased osmoreceptor firing rate
4. Vasopressin released

Question 4

What is the normal response to water deprivation

Answer 4

1. Increased serum osmolality
2. stimulation of osmoreceptors (thirst)
3. increased vasopressin released
4. increased water reabsorption from renal collecting ducts
5. Reduced urine volume, increase in urine osmolality and reduction in serum osmolality

Question 5

What is the consequence of a lack of vasopressin

Answer 5

Diabetes insipidus

Question 6

What is syndrome of inappropriate ADH

Answer 6

Too much vasopressin.g. tumours absorb water

Question 7

What are the two type of diabetes insipidus

Answer 7

Central/ cranial and nephrogenic

Question 8

What is central/cranial DI

Answer 8

Lack of vasopressin

Question 9

What is nephrogenic DI

Answer 9

Kidneys are resistant to vasopressin

Question 10

What are the symptoms of DI

Answer 10

polydipsia (increased thirst)
polyuria (large urine volume)
Dilute urine (hypo-osmolar)
Dehydration
Possible disruption to sleep with associated problems

Question 11

What is the aetiology of cranial diabetes insipidus

Answer 11

Acquired
Damage to neurohyophysial system
Traumatic brain injury
Pituitary surgery
Pituitary tumours, craniopharyngioma
Metastasis to the pituitary gland e.g. breast
Granulomatous infiltration of media eminence e.g. TB , sarcoidosis

Congenital is rare

Question 12

What is the aetiology of nephrogenic DI

Answer 12

Acquired
Drugs e.g. lithium

Congenital - rare
Mutation in gene encoding V2 receptor, AQP2

Question 13

What is psychogenic polydipsia

Answer 13

Seen in psychiatric patients
Polydipsia and polyuria but ability to secrete vasopressin in response to osmotic stimuli is preserved
May be due to dry mouth side effects of anti-cholinergic agents or patients told to drink a lot

Question 14

What are the biochemical features of DI

Answer 14

Hypernatraemia
Raised urea
Increased plasma osmolality
Dilute (hypo-osmolar) urine

Question 15

What are the biochemical features of psychogenic polydipsia

Answer 15

Mild hyponatraemia – excess water intake
Low plasma osmolality
Dilute (hypo-osmolar) urine - ie low urine osmolality

Question 16

Where is V1 found

Answer 16

Vascular smooth muscle
Non-vascular smooth muscle
Anterior pituitary
Liver 
Platelets
CNS

Question 17

Where is V2 found

Answer 17

Kidney

Endothelial cells

Question 18

Give examples of selective vasopressin receptors peptidergic agonsists

Answer 18

V1 - Terlipressin

V2 - Desmopressin (DDAVP)

Question 19

Describe desmopressin (administration, effect and care)

Answer 19

Nasal, oral administration
Reduction in urine volume and concentration for cranial DI
Tell patient not to continue dirking large amounts of fluid (may lead to hyponatraemia)

Question 20

What is used to treat nephrogenic diabetes insipidus

Answer 20

Thiazides e.g. bendroflumethiazide

Question 21

What is the possible mechanism for thiazide action

Answer 21

1. Inhibits Na+/Cl- transport in distal convoluted tubule (→ diuretic effect)
2. Volume depletion
3. Compensatory increase in Na+ reabsorption from the proximal tubule (plus small decrease in GFR, etc.)
4. Increased proximal water reabsorption
5. Decreased fluid reaches collecting duct
6. Reduced urine volume

Question 22

What is a syndrome of inappropriate ADH

Answer 22

Plasma vasopressin concentration is inappropriately high for the existing plasma osmolality

Question 23

How does a syndrome of inappropriate ADH lead to hyponatraemia

Answer 23

1. Increased vasopressin
2. Increased water reabsorption form Renal collecting ducts
3. Expansion of ECF volume
4. Atrial natriuretic peptide from right atrium -> natriuresis
5. Euvolaemia and hyponatraemia

Question 24

What are the signs or a syndrome of inappropriate ADH

Answer 24

Raised urine osmolality, decreased urine volume (initially)

Decreased p[Na+] (HYPONATRAEMIA) mainly due to increased water reabsorption

Question 25

What are the symptoms of a syndrome of inappropriate ADH

Answer 25

May be symptomless
If p[Na+] <120 mM: generalised weakness, poor mental function, nausea
If p[Na+] <110 mM: confusion leading to coma and ultimately death

Question 26

What are the causes of a syndrome of inappropriate ADH

Answer 26

CNS (SAH, stroke tumour,TBI)

Pulmonary disease (pneumonia, bronchiecstasis)

Malignancy
(Small cell lung)

Drug related (carbamazepine, SSRI)

Idiopathic

Question 27

What is the treatment for a syndrome of inappropriate ADH

Answer 27

Reduce immediate concern e.g. hyponatraemia
Immediate: fluid restriction
Long term: use drugs which prevent vasopressin action in the kidneys
e.g. induce nephrogenic DI via demeclocyline
Inhibit action of ADH via V2 receptor antagonists

Question 28

What is Vaptains

Answer 28

Non-Competitive V2 receptor antagonists
Inhibit AQP2 synthesis and transport to collecting duct apical membrane, preventing renal water reabsorption
Aquaresis – solute-sparing renal excretion of water, contrast with diuretics (diuresis) which produce simultaneous electrolyte loss
Licensed in the UK for treatment of hyponatraemia associated with SIADH
Very expensive – limits their current use