Neurohypophysial Disorders Flashcards

1
Q

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

A

Paraventricular Nucleus

Supraoptic Nucleus

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2
Q

What two hormones are produced by the neurohypophysis?

A

Vasopressin

Oxytocin

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3
Q

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

A

Vasopressin’s main action is on the V2 receptors in the renal cortical and medullary collecting ducts
It stimulates the synthesis and assembly of aquaporin 2, which then increases water reabsorption and has an antidiuretic effect

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4
Q

State some other actions of vasopressin.

A

Vasoconstriction
Corticotrophin release
Factor VIII and von Willebrand factor
Central effects

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5
Q

What are the main actions of oxytocin?

A

It is a contractile molecule that binds to oxytocin receptors
It causes contraction of the myometrium during parturition and is involved in milk ejection
It also has central effects

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6
Q

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

A

Lack of Oxytocin – not clinically significant

Lack of Vasopressin – Diabetes Insipidus

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7
Q

What are the two forms of diabetes insipidus?

A

Central (cranial) and Nephrogenic Diabetes Insipidus

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8
Q

What can cause central diabetes insipidus?

A

Damage to neurohypophysial system (injury, surgery, cerebral thrombosis, tumours, granulomatous infiltration)
Idiopathic
Familial (rare)

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9
Q

What can cause nephrogenic diabetes insipidus?

A

Familial (rare)

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

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10
Q

State some signs and symptoms of diabetes insipidus.

A
Polyuria 
Polydipsia 
Hypo-osmolar urine  
Dehydration 
Possible disruption of sleep  
Possible electrolyte imbalance
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11
Q

State another cause of polydipsia that isn’t diabetes.

A

Psychogenic polydipsia

This is a central disturbance that increases the drive to drink

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12
Q

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

A

Fluid deprivation test
 Normals and psychogenic polydipsia will show a rise in urine osmolality
 Central and nephrogenic diabetes insipidus will show little or no change in urine osmolality
Fluid deprivation with administration of DDAVP (Desmopressin)
 Central diabetes insipidus will show a rise in urine osmolality
 Nephrogenic DI will still have a low urine osmolality (because of end-organ resistance)

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13
Q

Why is the urine osmolality of someone with psychogenic polydipsia lower (in the fluid deprivation test) than a normal subject?

A

Over time, the constant passage of large volumes of water through the kidneys will wash out the osmotic gradient that is necessary for AVP to exert its diuretic effect

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14
Q

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

A

Normally, urine osmolality will increase as plasma osmolality increases (in a graph of urine osmolality against plasma osmolality it will show a sigmoid shape)
In DI, there is little change in urine osmolality as plasma osmolality increases

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15
Q

Describe changes in plasma vasopressin following administration of hypertonic saline in a normal subject, psychogenic polydipsia, central DI and nephrogenic DI.

A

Hypertonic saline will increase the plasma osmolality and hence will increase the vasopressin secretion in patients that have the capacity to produce vasopressin (normal, psychogenic polydipsia and nephrogenic DI)
Patients with central DI can’t produce vasopressin at all so the hypertonic saline will show no change in plasma vasopressin

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16
Q

What is SIADH?

A

Syndrome of Inappropriate ADH = when the plasma vasopressin concentration is inappropriate for the existing plasma osmolality

17
Q

State some signs of SIADH.

A

Decreased urine volume Increased urine osmolality

18
Q

What is the main consequence of SIADH?

A

HYPONATRAEMIA

19
Q

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

A

At relatively mild hyponatraemia = generalized weakness, poor mental function, nausea
Severe hyponatraemia = confusion, coma, death

20
Q

State some causes of SIADH.

A

Tumours (ectopic secretion)
Neurohypophysial malfunction (e.g. meningitis, cerebrovascular disease)
Thoracic disease (e.g. pneumonia)
Endocrine disease (e.g. Addison’s)
Physiological – it can happen under normal circumstances where AVP is release is stimulated by non-osmotic stimuli (e.g. hypovolaemia, pain, surgery)
Drugs
Idiopathic

21
Q

How is SIADH treated?

A

Fluid Restriction
Provide appropriate treatment when the cause is identified (e.g. surgery for a tumour)
NOTE: if someone is hyponatraemic you need to deal with that as soon as possible – e.g. use drugs that prevent vasopressin action in the kidneys

22
Q

What is the name given to exogenous vasopressin?

A

Argipressin

23
Q

Where are V1 and V2 receptors found?

A
V1
 Vascular smooth muscle 
 Non-vascular smooth muscle 
 Anterior pituitary
 Liver 
 Platelets 
CNS
V2
 Kidney
 Endothelial cells
24
Q

State the pharmacological actions of argipressin.

A

NATRIURESIS – this is one of the unexplained side-effects of having a large amount of vasopressin – it is V2 mediated and only happens when given at high doses
PRESSOR ACTION – V1 mediated vasoconstriction – the coronary vessels are particularly sensitive to vasopressin (this can cause cardiac ischaemia and angina attacks)
Contraction of vascular smooth muscle
Increased ACTH secretion
Increased factor VIII and vWF production

25
Q

State two selective peptidergic vasopressin selective agonists.

A

V1 – Terlipressin

V2 - Desmopressin

26
Q

Compare the effects of argipressin and desmopressin.

A

Argipressin acts on V1 and V2
Argipressin is more effective in causing vasoconstriction via V1 receptors Desmopressin is more effective in the kidneys in causing water reabsorption via V2 receptors

27
Q

State some clinical uses of Desmopressin.

A

Treatment of diabetes insipidus
Treatment of nocturnal eneuresis
Haemophilia (need V2 stimulation)
NOTE: it is taken orally or nasally

28
Q

State some unwanted effects of Desmopressin.

A

Nausea
Headaches
Abdominal pain
Fluid retention and hyponatraemia

29
Q

State two peptidergic V1 receptor agonists and their uses.

A

Terlipressin – used to treat oesophageal varices (it causes vasoconstriction)
Felypressin – injected by dentists along with local anaesthetic (the vasoconstriction keeps the local anaesthetic at the site of injection for longer thus prolonging the action of the local anaesthetic)

30
Q

State one treatment used for nephrogenic diabetes insipidus and its possible mechanism of action.

A

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

31
Q

What are vaptans?

A

Non-peptide vasopressin receptor antagonists
Tolvaptan = V2 receptor antagonist
It is used to treat hyponatraemia associated with SIADH and may be useful in treating congestive heart failure

32
Q

State some drugs that increase or decrease vasopressin secretion.

A

Increase vasopressin secretion = nicotine

Decrease vasopressin secretion = alcohol + glucocorticoids