Neurohypophysial disorders

Question 1

Neurohypophysis produce which 2 hormones

Difference in mechanism between adenohypophyis and neurohypophysis

Where does vasopressin act?

Answer 1

Vasopressin and Oxytocin

Adenohypophysis: neurosecretion occurs at ME.
Neurohypophysis: Neurosecretion occurs directly into post p.g

Renal cortical and medullary collecting ducts

Question 2

What are the principal actions of vasopressin?

Answer 2

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

Question 3

What are the other actions of vasopressin?

Osmoreceptors located where
What happens when low water

Answer 3

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

Organum Vasculosum– project to hypothalamic PVN and SON

Osmoreceptor shrinks
Increased osmoreceptor firing
VP released from hypothalamic PVN and SON neurones

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 cranial diabetes insipidus caused?

Answer 8

Damage to the neurohypophysial system:
Injury
Surgery-out
Metastasis to the pituitary gland– e.g breast
Pit Tumours, craniopharngioma
Granulomatous infiltration of median eminence e.g TB

Congenital (rare)

Question 9

How is nephrogenic DI caused?

Answer 9

Familial (rare)– mutation in gene encoding V2 receptor, aquaporin 2 type water channel
Drugs e.g lithium

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

What is psychogenic polydipsia?

Answer 12

Central disturbance that increases the drive to drink
Excess fluid intake (polydipsia) and excess urine output (polyuria) BUT unlike DI, ability to secrete vasopressin in response to osmotic stimuli is preserved.

Question 13

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

Answer 13

Fluid deprivation test

Desmopressin (DDAVP)– analogue of VP

Question 14

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 14

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 15

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

Answer 15

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

Question 16

Diabetes insipidus biochemical features
Salt
Urea
Plasma osmolality
Urine

Answer 16

Hypernatraemia
Raised urea
Increased plasma osmolality
Dilute- hypo osmolar urine- low urine osmolality

Question 17

Psychogenic polydipsia biochemical features
Salt
Osmolality
Urine

Answer 17

Mild hyponatraemia -excess water intake
Low plasma osmolality
Dilute (hypo-osmolar) urine i.e low urine osmolality

Question 18

What is the syndrome of inappropriate ADH (SIADH)?

Answer 18

The plasma vasopressin concentration is inappropriately for the existing plasma osmolarity

Question 19

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

Function of Atrial Natriuretic Peptide ANP

Answer 19

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

Expansion of ECF volume by increasing sodium excretion

Question 20

What are the signs of SIADH?

Answer 20

Raised urine osmolarity
Decreased urine volume
Hyponatremia

Question 21

What are the symptoms of SIADH?

Answer 21

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 22

What are the causes of SIADH?

Answer 22

CNS
-SAH, stroke, tumour, TBI
Pulmonary disease
-Pneumonia, bronchiectasis
Malignancy
-Lung (small cell)
Drug related
-carbamazepine, SSRI
Idiopathic

Question 23

What is the treatment of SIADH?

Answer 23

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 Demeclocyline-induce nephrogenic DI

Question 24

What two receptors does vasopressin act on?

Answer 24

V1 and V2

Question 25

Where are V1 receptors?

Where are V2

Answer 25

V1
Vascular smooth muscle
Non-vascular smooth muscle
Anterior pituitary
Liver
Platelets 
CNS

V2

• Kidney
• Endothelial

Question 26

What are effects of V1 receptors?

Answer 26

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

Question 27

What are Terlipressin and desmopressin?

Answer 27

Selective vasopressin receptor peptidergic agonists

Question 28

What is Terlipressin?

Answer 28

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

Question 29

What is desmopressin used to treat?

Administered

Risk

Answer 29

Cranial diabetes insipidus
Reduction in urine volume

Nasally, orally, SC

Must tell patients to NOT to continue drinking large amounts of water– risk of hyponatraemia

Question 30

What is nephrogenic diabetes insipidus treated with?

Answer 30

Thiazides e.g. bendroflumethiazide

Question 31

What is the mechanism of action of thiazides?

Answer 31

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 32

What are vaptans?

Answer 32

Non-competitive v2 receptor antagonists

Question 33

Action of vaptans

Treat

Disadvantage

Answer 33

Inhibit aquaporin 2 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

Treat:
Hyponatraemia associated with SIADH

Expensive

Question 34

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

Answer 34

Diabetes insipidus

Question 35

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

Answer 35

Psychogenic polydipsia