Disorders of Vasopressin Flashcards
What neurones are present in the hypothalamus and the posterior pituitary gland?
Hypothalamic magnocellular neurons
What do hypothalamic magnocellular neurons contain?
AVP or oxytocin
Describe hypothalamic magnocellular neurons?
Long, originate in supraoptic and paraventricular neurons
What is the main physiological action of vasopression/ADH?
Stimulation of water reabsorption in the renal collecting duct (concentrating urine)
Where does vasopressin act?
the V2 receptor in the kidney
also the V1 receptor
What is the secondary action of vasopressin?
- vasoconstriction via the V1 receptor
- stimulates the release of ACTH from the anterior pituitary gland
How does vasopressin concentrate urine?
- binds to the V2 receptor on the basolateral membrane
- encourages the movement of water from the apical membrane to the basolateral membrane (into the blood) via aquaporin-2 and aquaporin-3
How does the posterior pituitary gland look in MRIs?
shows as a bright spot, not visualised in all healthy individuals
What is the stimuli for AVP release?
- Response to dehydration
- Increase in plasma osmolality sensed by osmoreceptors
- Osmoreceptors are special sensory receptors in the hypothalamus
How do osmoreceptors regulate vasopressin?
- increase in extracellular Na+
- water moves out of osmoreceptor
- osmoreceptor shrinks
- increased osmoreceptor firing
- AVP release from the hypothalamic neurons
What is the physiological response to water deprivation?
- increased plasma osmolarity
- stimulation of osmoreceptors
- thirst
- release of AVP
- increased water reabsorption from renal collecting ducts
- reduced urine volume, increased urine osmolarity
- reduction in plasma osmolarity
What are the symptoms of vasopressin insufficency?
- polyuria
- nocturia
- thirst (often extreme)
- polydipsia
What is the difference between diabetes mellitus and vasopressin insufficency?
In diabetes mellitus, the symptoms are caused by osmotic diuresis.
In vasopressin insufficency, the symptoms are caused due to a problem with AVP
What are the two different types of VI?
- vasopressin deficiecny (cranial diabetes insipidus)
- vasopressin resistance (nephrogenic diabetes insipidus)
Describe vasopressin deficiency
A problem with the hypothalamus and/or the posterior pituitary - unable to make AVP
Describe vasopressin resistance
- Normal AVP production (normal hypothalamus and posterior pituitary)
- Abnormal kidney collecting duct (unable to respond)
What are the possible causes of vasopressin deficiency?
Acquired (more common)
* Traumatic brain injury
* Pituitary surgery
* Pituitary tumours
* Metastasis to the pituitary gland eg breast
* Granulomatous infiltration of pituitary stalk eg TB, sarcoidosis
* Autoimmune
Congenital
What are the possible causes of vasopressin resistance?
Much less common than vasopressin deficiency
Congenital
- rare (e.g. mutation in gene encoding V2 receptor, aquaporin 2 type water channel)
Acquired
- Drugs (e.g. lithium)
What is the presentation of vasopressin insufficency
Urine - very dilute (hypo-osmolar) - large volumes Plasma - increased concentration (hyper-osmolar) - increases sodium (hypernatraemia) - NORMAL GLUCOSE
Can vasopressin insuffieceny cause death?
Only if there is not a constant access to water, as it will lead to dehydration and death.
What is psychogenic polydipsia?
Problem caused by overconsumption of water leading to large volumes of dilute urine
How does psychogenic polydipsia present?
same as diabetes insipidus - nocturia - polyuria - polydipsia (BUT no problem with AVP)
What causes the symptoms of psychogenic polydipsia?
- increased drinking (polydipsia)
- plasma osmolarity falls
- less AVP is secreted by the posterior pituitary
- large volumes of dilute (hypotonic) urine
- plasma osmolarity returns to normal
How to distinguish between vasopressin insufficency and psychogenic polydipsia?
A water deprivation test
What is involved in a water deprivation test?
no access to any drink over time, measure: - urine volumes - urine concentration - plasma concentration weigh regularly, if lose more than 3% of body weight (significant dehydration) stop.
How to differentiate between vasopressin insufficency and psychogenic polydipsia based on the results of the water deprivation test?
Psychogenic polydipsia:
* urine osmolarity increases are time progresses, but not to the same extent as normal
Diabetes Insipidus:
* no change in urine osmolarity over time (as problem with AVP)
How to distinguish between vasopressin deficiecny and vasopressin resistance during a water deprivation test?
- give ddAVP (similar to AVP)
if AVP-D:
will respond to ddAVP, urine will concentrate as collecting duct is fine
if AVP-R:
no response, and no change to urine concentration as collecting duct is resistant to AVP.
What is the approximate plasma osmolarity with vasopressin insufficency?
> 290 mOsm/kg
What is the approximate plasma osmolarity with psychogenic polydipsia?
<270 mOsm/kg
What is the treatment of vasopressin deficiency?
- replace AVP with desmopressin
- selective for V2 receptor (V1 would be unhelpful)
- available either in tablets or intranasal
Hospital neglect and diabetes insipidus?
- desmopressin nasal spray is often disregarded upon admission
- fluid restriction which may sometimes be necessary is dangerous and can cause death in patients with VI
What is the treatment for vasopressin resistance?
Difficult to treat successfully but luckily very rare
What is the Syndrome of Inappropriate Anti-Diuretic Hormone (SIADH)?
The presence of too much AVP
How does SIADH present?
- reduced urine output
- water retention
- high urine osmolarity
- low plasma osmolarity
- dilutional hyponatraemia
What are the causes of SIADH?
CNS - head injury - stroke - tumour Pulmonary disease - pneumonia - bronchiectasis Malignancy - small cell lung cancer Drug related - Carbamazepine - SSRIs Idiopathic
What is the management plan for SIADH?
- fluid restriction
- can use vasopressin antagonist (vaptan) that binds to V2 receptors in the kidney
(£££)
What was vasopressin insufficency formerly known as?
Diabetes insipidus
What is desmopressin?
Modified, non-biodegradable version of vasopressin to counteract its short half life
