Neurohypophysial disorders Flashcards
Name the two main nuclei within which neurones of the neurohypophysis have their cell bodies.
Paraventricular Nucleus
Supraoptic Nucleus
What two hormones are produced by the neurohypophysis?
Vasopressin
Oxytocin
What is the principal action of vasopressin and how does it carry out this action?
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
State some other actions of vasopressin.
Vasoconstriction
Corticotrophin release
Factor VIII and von Willebrand factor synthesis
Central effects
What are the main actions of oxytocin?
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
What are the consequences of a lack of the neurohypophysial hormones?
Lack of Oxytocin – not clinically significant
Lack of Vasopressin – Diabetes Insipidus
What are the two forms of diabetes insipidus?
Central (cranial) and Nephrogenic Diabetes Insipidus
What can cause central diabetes insipidus?
Damage to neurohypophysial system (injury, surgery, cerebral thrombosis, tumours (Craniopharyngioma), granulomatous infiltration)
Idiopathic
Familial (rare)
What can cause nephrogenic diabetes insipidus?
Familial (rare)
Drugs e.g. lithium, dimethyl chlortetracycline (DMCT)
State some signs and symptoms of diabetes insipidus.
Polyuria Polydipsia Hypo-osmolar urine Dehydration Possible disruption of sleep Possible electrolyte imbalance
State another cause of polydipsia that isn’t diabetes.
Psychogenic polydipsia
This is a central disturbance that increases the drive to drink
Unknown aetiology, but may be due to anti-cholinergic nature of psychiatric medication (causes ‘dry mouth’)
What test can be used to distinguish between normal, psychogenic polydipsia, central DI and nephrogenic DI? Describe the results you would expect.
Fluid deprivation test
(Patient’s with psychogenic polydipsia have lower blood osmolality from beginning)
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)
Why is the urine osmolality of someone with psychogenic polydipsia lower (in the fluid deprivation test) than a normal subject?
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
Describe the normal change in urine osmolality as plasma osmolality increases.
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
Describe changes in plasma vasopressin following administration of hypertonic saline in a normal subject, psychogenic polydipsia, central DI and nephrogenic DI.
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
What is SIADH?
Syndrome of Inappropriate ADH = when the plasma vasopressin concentration is inappropriate for the existing plasma osmolality
State some signs of SIADH.
Decreased urine volume
Increased urine osmolality
What is the main consequence of SIADH?
Hyponatraemia
At relatively mild hyponatraemia = generalized weakness, poor mental function, nausea
Severe hyponatraemia = confusion, coma, death
State some causes of SIADH.
Tumours, especially small cell carcinoma in lungs (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 - Carbamzepine, SSRI (selective serotonin re-uptake inhibitor)
Idiopathic
How is SIADH treated?
Fluid Restriction (First treatment)
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
What is the name given to exogenous vasopressin?
Argipressin
State the pharmacological actions of argipressin.
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
Where are V1 and V2 receptors found?
V1 Vascular smooth muscle Non-vascular smooth muscle Anterior pituitary Liver Platelets CNS
V2
Kidney
Collecting duct
State two selective peptidergic vasopressin selective agonists.
V1 – Terlipressin
V2 - Desmopressin
Compare the effects of argipressin and desmopressin.
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
State some clinical uses of Desmopressin.
Treatment of diabetes insipidus
Treatment of nocturnal eneuresis
Haemophilia (need V2 stimulation)
NOTE: it is taken orally or nasally
State some unwanted effects of Desmopressin.
Nausea
Headaches
Abdominal pain
Fluid retention and hyponatraemia
State one treatment used for nephrogenic diabetes insipidus and its possible mechanism of action.
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
What are vaptans?
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
State some drugs that increase or decrease vasopressin secretion.
Increase vasopressin secretion = nicotine
Decrease vasopressin secretion = alcohol + glucocorticoids
Endothelial cells
