Neurohypophyseal disorders Flashcards
Principle actions of AVP
acts on collecting duct cells
stimulates synthesis of AQP2
caused increased water reabsorption - anti-diuretic effect
acts on V2 receptors
vasoconstrictor activities on V1a
ACTH release V1b
Factor VIII and VWF V2
Principle actions of oxytocin
milk ejection
contraction of the myometrium at parturition
Lack of oxytocin and AVP
oxytocin - not too bad. partuition and milk ejection are reduced/ replaced by other means
AVP - Diabetes insipidus
forms of diabetes insipidus
central/cranial - absence or lack of circulating VP
Nephrogenic (rare) - kidneys resistant to VP
Causes of central/cranial DI
rare: familial - receptor gene mutations (V2R/ AQP2)
Acquired: damage to neurohypophyseal system
- damage to neurohypophysis
- traumatic brain surgery
- pituitary metastasis
- cerebral thrombosis
- tumours (intrasellar and suprasellar)
- granulomatous infiltration of medical eminence e.g. TB or sarcoidosis
Idiopathic
Causes of nephrogenic DI
rare: familial- receptor gene mutations (V2R/ AQP2)
drugs: lithium, DMCT
Signs and symptoms of DI
polyuria hypoosmolar / dilute urine polydipsia nocturia dehydration if fluid intake isn't maintained possible electrolyte imbalance
Explain the pathophysiology of DI
decreased/ poor response to VP –>
less water reabsorbed/ more dilute urine produced –>
increase in plasma osmolarity –>
decreased in extracellular fluid volume –>
NORMALLY osmoreceptors detects this and trigger VP release and cause polydipsia –> extracellular fluid volume rises again
in DI –> dehydrated if they can’t access water and will die
Normal range for plasma osmolarity
DI
psychogenic polydipsia
Normal: 270-290
DI: 290+
PP: <270
Cause of psychogenic polydipsia
central disturbance –> polydipsia –>decreased osmolarity –> polyuria –>reduction of extracellular fluid volume –> polydipsia
How to distinguish between PP, central DI and nephrogenic DI
First: fluid deprivation test. Normal people can concentrate their urine so urine osmolarity rises. In PP, the VP system is working fine so urine osmolarity also rises. DI –> urine osmolarity remains low
give DDAVP (desmopressin)
Central DI –> will be able to concentrate their urine (urine osmolarity increases) because they lack VP but their VP receptors are fine
Nephrogenic DI –> urine osmolarity remains low. (have VP anyway)
Stimulation with hypertonic saline IV: normal, PP, cranial and nephrogenic DI
normal, PP and nephrogenic DI all show a rapid increase in VP release ( in response to the increase in plasma osmolarity)
In central DI, there is no change in VP
Treatment for DI (C and N)
Cranial – give DDAVP (nasal, oral, SC)
Nephrogenic – thiazide diuretics
Psychogenic polydipsia is often caused by…
anti-cholinergic meds
Define SIADH
plasma VP/ADH concentration is inappropriate for the plasma osmolarity
Causes of SIADH
- tumour (ectopic secretion)
- neurohypophyseal malfunction (meningitis, cerebrovascular disease)
- Endocrine disease e.g. Addison’s
- drug related e.g. SSRI, carbamazepine, chlopropamide
- Thoracic disease e.g. pneumonia, bronchiectasis
- idiopathic
- small cell carcinoma (lung)
Clinical features of SIADH
increased urine osmolarity
decreased urine volume initially
hyponatraemia – main consequence
Symptoms of SIADH
can be asymptomatic when Na < 120mM: • Generalised weakness • Poor mental function • Nausea
When Na+ concentration falls <110 mM you get:
• CONFUSION
• COMA
• DEATH
Treatment of SIADH
Treat cause e.g. surgery for tumour If hyponatraemic, immediate: - fluid restriction LT: - drugs that prevent VP action in the kidneys e.g. lithium, DMCT, V2 receptor antagonists (vaptans)
Possible mechanism of action of thiazides for nephrogenic DI
- inhibits Na/Cl transport in DCT –> diuretic effect
- volume depletion
- compensatory increase in Na reabsorption in PCT
- increased proximal water reabsorption
- decreased fluid reaching collecting duct
- lower volume of urine produced
