Neurohypophysial disorders

Question 1

Where does vasopressin act?

Answer 1

Renal cortical and medullary collecting ducts

Question 2

What are the principal actions of vasopressin?

Answer 2

Stimulates synthesis and assembly of aquaporin 2
Increased water transport
Increased water reabsorption- antidiuretic
Acts on V2 receptors

Question 3

What are the other actions of vasopressin?

Answer 3

Vasoconstrictor activity- V1a
Corticotrophin release- V1b
Factor VIII and Von Willebrand factor release- V2
Central effects

Question 4

What is the action of oxytocin?

Answer 4

Constriction of myometrium at parturition

Milk ejection reflex

Question 5

What happens if you lack oxytocin?

Answer 5

Nothing serious- effect is induced by something else

Question 6

What happens if you lack vasopressin?

Answer 6

Diabetes insipidus

Question 7

What are the two forms of diabetes insipidus?

Answer 7

Central (cranial)- Absence or lack of circulating vasopressin
Nephrogenic- Kidney resistance to vasopressin

Question 8

How is central diabetes insipidus caused?

Answer 8

Damage to the neurohypophysial system:
Injury
Surgery
Cerebral thrombosis
Tumours
Granulomatous infiltration of median eminence

Idiopathic
Familial (rare)

Question 9

How is nephrogenic DI caused?

Answer 9

Familial (rare)

Drugs

Question 10

What are the signs and symptoms of diabetes insipidus?

Answer 10

Large volumes of urine- polyuria
Very dilute urine- hypo-osmolar
Thirst and increased drinking- polydipsia
Dehydration
Disruption of sleep
Electrolyte imbalance

Question 11

What is the cycle in diabetes insipidus?

Answer 11

If you are unable to make vasopressin, you can’t reabsorb water so this leads to an increase in urine excretion and a reduction in extracellular fluid volume. This will lead to an increase in plasma osmolarity so that will lead to osmoreceptors triggering vasopressin release and it will trigger thirst, this will lead to drinking, decrease in plasma osmolarity and expansion of extracellular fluid volume

Question 12

If a patient has a plasma osmolarity above 290mOsm.kg H2O^-1, what do they have?

Answer 12

Diabetes insipidus

Question 13

If a patient has a plasma osmolarity below 270 mOsm.kg H2O^-1, what do they have?

Answer 13

Polydipsia

Question 14

What is psychogenic polydipsia?

Answer 14

Central disturbance that increases the drive to drink

Question 15

What two tests do you use to distinguish between polydipsia, central and nephrogenic diabetes insipidus?

Answer 15

Fluid deprivation test

Desmopressin (DDAVP)

Question 16

What results in terms of urine osmolarity will you see in a fluid deprivation test of a normal person, someone with polydipsia and people with central and nephrogenic DI?

Answer 16

In a normal person, fluid deprivation will stimulate vasopressin system and they will release AVP and concentrate the urine so urine osmolarity increases and plasma osmolarity will remain normal
In polydipsia, vasopressin works fine so response is same as normal
In central/nephrogenic DI, there will be little or no change in urine osmolarity as vasopressin system doesn’t work

Question 17

What results in terms of urine osmolarity would you see when DDAVP is administered to all patients?

Answer 17

Urine osmolarity will increase in normal, polydipsia and central DI but not nephrogenic because their receptors don’t respond to vasopressin anyway

Question 18

How can you quickly check if a patient can release vasopressin without waiting for them to become dehydrated?

Answer 18

IV saline stimulation

Question 19

How does IV saline stimulation work?

Answer 19

IV saline quickly increases plasma osmolarity and stimulates AVP release. Normals, polydipsics and nephrogenics will show a rapid increase in plasma AVP which can be measured but central will show no change

Question 20

What is the syndrome of inappropriate ADH (SIADH)?

Answer 20

The plasma vasopressin concentration is inappropriate for the existing plasma osmolarity

Question 21

In SIADH, what happens due to the increase in water reabsorption?

Answer 21

You start to dilute the ions in plasma and you become hyponatraemic and there is a decrease in urine volume

Question 22

What are the signs of SIADH?

Answer 22

Raised urine osmolarity
Decreased urine volume
Hyponatremia

Question 23

What are the symptoms of SIADH?

Answer 23

Can be asymptomatic
When Na concentration falls below 120mM:
Generalised weakness
Poor mental function
Nausea
When Na concentration falls below 110mM:
Confusion
Coma
Death

Question 24

What are the causes of SIADH?

Answer 24

Tumours
Neurohypophysial malfunction
Thoracic disease (pneumonia)
Endocrine disease (Addison's)
Physiological- under normal conditions (hypovolaemia, pain and surgery)
Drugs
Idiopathic

Question 25

What is the treatment of SIADH?

Answer 25

Surgery- for tumours If hyponatraemic, this needs to be dealt with immediately- Fluid restriction Longer term- Use drugs that prevent vasopressin action in the kidneys (lithium, dimethyl chloritetracyline (DMCT))

Question 26

What two receptors does vasopressin act on?

Answer 26

V1 and V2

Question 27

Where are V1 receptors?

Answer 27

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

Question 28

What are effects of V1 receptors?

Answer 28

Vasoconstriction due to contraction of vascular smooth muscle Affect the intestines by acting on non-vascular smooth muscle

Question 29

What are Terlipressin and desmopressin?

Answer 29

Selective vasopressin receptor peptidergic agonists

Question 30

What is Terlipressin?

Answer 30

Analogue of vasopressin but only has effects on V1 (Desmopressin only has effects on V2)

Question 31

In terms of effectiveness, how does desmopressin compare to argipressin in the vasculature and kidneys?

Answer 31

IN vasculature, desmopressin < argipressin | In kidneys, desmopressin > argipressin

Question 32

What is desmopressin used to treat?

Answer 32

Cranial diabetes insipidus Nocturnal enuresis (bedwetting) Haemophilia

Question 33

What are unwanted effects of desmopressin?

Answer 33

Fluid retention and hyponatraemia Abdominal pain Headaches Nausea

Question 34

What does peptidergic mean?

Answer 34

Nerve cells or fibres that use small peptide molecules as their neurotransmitters

Question 35

What is terlipressin, the V1 peptidergic agonist, used to treat?

Answer 35

Oesophageal varices (causes vasoconstriction)

Question 36

What is felypressin used for?

Answer 36

It is added to anaesthetics that dentists use to prolong their action (and other local anaesthetics). IT causes vasoconstriction so will keep local anaesthetic in area for longer

Question 37

What is nephrogenic diabetes insipidus treated with?

Answer 37

Thiazides e.g. bendroflumethiazide  

Question 38

What is the mechanism of action of thiazides?

Answer 38

Inhibits Na+/Cl- transport in distal convoluted tubule- this leads to a diuretic effect Volume depletion leads to compensatory increase in sodium reabsorption at PCT Increased proximal water reabsorption so decreased amount of water reaches DCT so reduced urine volume

Question 39

What are vaptans?

Answer 39

Non-peptide vasopressin analogues

Question 40

What is tolvaptan and what is it used to treat?

Answer 40

V2 receptor antagonist and hyponatraemia associated with SIADH

Question 41

What drug increases vasopressin secretion?

Answer 41

Nicotine

Question 42

What drugs decrease vasopressin secretion?

Answer 42

Alcohol | Glucocorticoids