Neurohypophysial Disorders

Question 1

Name the 2 main nuclei within which neurones of the neurohypophysis have their cell bodies.

Answer 1

Paraventricular Nucleus

Supraoptic Nucleus

Question 2

What 2 hormones are produced by the neurohypophysis?

Answer 2

Vasopressin

Oxytocin

Question 3

What is the principal action of vasopressin and how does it carry out this action?

Answer 3

Antidiuretic: increased water reabsorption from renal cortical + medullary collecting ducts via V2 receptors.
Stimulates synthesis of AQP 2, which is inserted into the apical membrane

Question 4

State 5 other actions of vasopressin.

Answer 4

Vasoconstriction  
Corticotrophin release 
Factor VIII + von Willebrand factor 
Central effects
Stimulates thirst

Question 5

What are the main actions of oxytocin?

Answer 5

Contractile molecule that binds to oxytocin receptors
Causes contraction of the myometrium during parturition + is involved in milk ejection
It also has central effects

Question 6

What are the consequences of a lack of the neurohypophysial hormones?

Answer 6

Lack of Oxytocin: not clinically significant

Lack of Vasopressin: Diabetes Insipidus

Question 7

What are the 2 forms of diabetes insipidus?

Answer 7

Central (cranial): absence/ lack of circulating ADH

Nephrogenic: end-organ (kidneys) resistance to vasopressin

Question 8

What can cause central diabetes insipidus?

Answer 8

Damage to neurohypophysial system (brain injury, pituitary surgery, metastasis to pituitary, pituitary tumours, granulomatous infiltration)
Familial (rare)

Question 9

What can cause nephrogenic diabetes insipidus?

Answer 9

Familial (rare)

Drugs e.g. lithium, dimethyl chlortetracycline (DMCT)

Question 10

State 5 signs and symptoms of diabetes insipidus.

Answer 10

Polyuria 
Polydipsia 
Hypo-osmolar urine  
Dehydration 
Possible disruption of sleep

Question 11

State a cause of polydipsia that isn’t DM or DI

Answer 11

Psychogenic polydipsia
=a central disturbance that increases the drive to drink.
Frequently seen in psychiatric patients

Question 12

What test can be used to distinguish between normal, psychogenic polydipsia, central DI and nephrogenic DI? Describe the results you would expect.

Answer 12

Fluid deprivation test
Normals + PP: Increase in urine osmolality
DI: little or no change in urine osmolality
Fluid deprivation with administration of DDAVP (Desmopressin)
CDI: Increase in urine osmolality
NDI: still have a low urine osmolality (end-organ resistance)

Question 13

Describe plasma osmolality of someone with psychogenic polydipsia + someone with DI

Answer 13

PP: Plasma osmolarity lower than usual (as diluting plasma)
DI: Plasma osmolarity higher than usual (as passing out huge volumes of dilute urine)

Question 14

Describe the normal change in urine osmolality as plasma osmolality increases.

Answer 14

Urine osmolality will increase as plasma osmolality increases (sigmoid shape graph)
In DI, there is little change in urine osmolality as plasma osmolality increases

Question 15

What is SIADH?

Answer 15

Syndrome of Inappropriate ADH = plasma vasopressin concentration is inappropriately high for the existing plasma osmolality

Question 16

State 3 signs of SIADH.

Answer 16

Decreased urine volume
Increased urine osmolality
Hyponatraemia (due to increased water reabsorption)

Question 17

State some symptoms of SIADH that are caused by the hyponatraemia.

Answer 17

May be symptomless
Mild hyponatraemia = generalised weakness, poor mental function, nausea
Severe hyponatraemia = confusion, coma, death

Question 18

State 5 causes of SIADH.

Answer 18

CNS (Stroke, Tumours)
Pulmonary disease (pneumonia) 
Malignancy (lung)
Drugs e.g. Carbamezipine
Idiopathic

Question 19

How is SIADH treated?

Answer 19

Appropriate treatment (e.g. surgery for tumour)
Fluid Restriction
Longer term: use drugs which prevent ADH action in kidneys

Question 20

Which receptors do we want to target in treatment of CDI?

Answer 20

V2 receptors

Question 21

Where are V1 and V2 receptors found?

Answer 21

V1: Vascular + non-vascular smooth muscle, Anterior pituitary, Liver, Platelets, CNS
V2: Kidney + Endothelial cells

Question 22

Describe the administration, effects and precautions of Desmopressin in treatment of CDI

Answer 22

Admin: Nasally, Orally, SC
Effects: Reduces urine volume + increases concentration
Care: Stop drinking large amounts of fluid (risk of hyponatraemia)

Question 23

State 2 selective peptidergic vasopressin selective agonists.

Answer 23

V1: Terlipressin
V2: Desmopressin (DDAVP)

Question 24

State a treatment used for NDI and its possible mechanism of action.

Answer 24

Thiazide Diuretics (e.g. bendroflumethiazide)
Inhibits the Na+/Cl- pump in the DCT leading to a diuretic effect
This leads to volume depletion resulting in a compensatory increase in Na+ reabsorption from the PCT
This increases proximal water reabsorption so less water reaches the collecting duct
Ultimately leads to reduced urine volume

Question 25

What are vaptans?

Answer 25

Non-competitive V2 receptor antagonists
Inhibit AQP2 synthesis + transport to CD, preventing water reabsorption
Allows Aquaresis (solute sparing renal excretion)
Used to treat hyponatraemia associated with SIADH

Question 26

What regulates release of vasopressin?

Answer 26

Osmoreceptors in organum vasculosum senses changes in plasma osmolarity
If osmolarity increases, water flows out of osmoreceptor + it shrinks.
Increases osmoreceptor firing, triggering release of vasopressin from hypothalamic PVN + SON neurones

Question 27

What will result if someone with DI has no access to water?

Answer 27

Dehydration

Death

Question 28

What is closely monitored during a fluid deprivation test? Why?

Answer 28

Body weight

If a patient loses 3% of their weight, stop as this is a clinical marker of dehydration

Question 29

Describe 4 biochemical features of diabetes insipidus

Answer 29

Hypernatraemia
Raised urea
Increased plasma osmolarity
Hypo-osmolar urine

Question 30

Describe 4 biochemical features of psychogenic polydipsia

Answer 30

Mild hyponatramia (excess water intake)
Low plasma osmolarity
Hypo-osmolar urine