1B disorders of vasopressin Flashcards
How does the posterior pituitary work?
- It’s anatomically continuous with the hypothalamus
- Hypothalamic magnocellular neurons containing AVP or oxytocin
- Long, originate in supraoptic and paraventricular hypothalamic nuclei
- Nuclei → stalk → posterior pituitary
What is the physiological action of vasopressin aka ADH?
- Stimulation of water reabsorption in renal collecting duct which concentrates urine- acts through V2 receptor in the kidney
- Also a vasoconstrictor via V1 receptor
- Stimulates ACTH release from anterior pituitary
How does the posterior pituitary come up on MRI?
- As a bright spot
- Not visualised in all healthy individuals, so absence may be normal variant
What are the 2 triggers for vasopressin release?
- osmotic: rise in plasma osmolality (conc) sensed by osmoreceptors
- non-osmotic
What nuclei sense plasma osmolality and how are they adapted for their job?
- Organum vasculosum and subfornical organ- both sit around 3rd ventricle (circumventricular)
- Neurons project to supraoptic nucleus- site of vasopressinergic neurons
- No BBB- so neurons can respond to changes in the systemic circulation
- Highly vascularised
How do osmoreceptors regulate vasopressin?
- Increase in plasma osmolality (e.g. increase in extracellular Na+ in diagram)
- Via osmosis, water flows out of osmoreceptor
- Osmoreceptor changes shape and shrinks
- Increases osmoreceptor firing
- AVP release from hypothalamic neurons
How does a non-osmotic trigger for vasopressin release work?
- Decrease in atrial pressure sensed by atrial stretch receptors in right atrium
- Stretch receptors usually inhibit vasopressin release via vagal afferents to hypothalamus
- Reduction in circulating volume e.g. haemorrhage means less stretch of these atrial receptors, so less inhibition of vasopressin
What does the release of vasopressin help do?
- Vasopressin release results in increased water reabsorption in the kidney (some restoration of circulating volume) via V2 receptors
- Vasoconstriction via V1 receptors (renin-aldo system will also be important, sensed by JG apparatus)
What is the physiological response to water deprivation?
1) Increased plasma osmolality
2) stimulation of osmoreceptors, leading to thirst
3) increased AVP release
4) increased water reabsorption from renal collecting ducts
5) reduced urine volume, increase in urine osmolality
6) reduction in plasma osmolality
What are the symptoms of Arginine Vasopressin Deficiency/Resistance?
- Polyuria
- Nocturia
- Polydipsia (thirst- often extreme)
What happens to urine in AVP-D/R?
Very dilute (hypoosmolar) and large volumes
What happens to plasma in AVP-D/R?
Increased concentration (hyperosmolar) as patient becomes dehydrated, increased sodium (hypernatraemia), glucose is normal
Why do patients with AVP-D/R have polydipsia, polyuria and nocturia?
1) Arginine vasopressin problem- either not enough (CDI) or not responding (NDI)
2) Impaired conc of urine in renal collecting duct
3) large volumes of dilute (hypotonic) urine
4) Increase in plasma osmolality and sodium
5) Stimulation of osmoreceptors
6) Thirst- polydipsia
7) Maintains circulating volume as long as patient has access to water
When does AVP-D/R lead to death?
When there is no access water, the patient dehydrates and dies.
Why are symptoms different in diabetes mellitus (hyperglycaemia) vs insipidus (AVP disorders)?
In mellitus (hyperglycaemia), the symptoms arise due to osmotic diuresis.
In insipidus, these symptoms are due to problems with arginine vasopressin.
Which is more common out of diabetes mellitus and diabetes insipidus for these symptoms?
Diabetes mellitus is much more common.
- If you see a patient with these symptoms, check their blood sugar first because of this
- Preventing a patient with insipidus from drinking or not giving fluids if unable to drink can cause death
What are the two types of diabetes insipidus?
- Cranial (central) diabetes insipidus/ AVP-D
- Nephrogenic diabetes insipidus/ AVP-R
What is AVP-D?
- Problem with hypothalamus and/or posterior pituitary
- Unable to make arginine vasopressin
therefore vasopressin insufficiency
What are the two causes of AVP-D?
- Acquired (common)
- Congenital (rare)
What are examples of acquired causes of AVP-D?
- Traumatic brain injury
- Pituitary surgery
- Pituitary tumours
- Metastasis to the pituitary gland e.g. breast
- Granulomatous infiltration of pituitary stalk e.g. TB, sarcoidosis
- Autoimmune
What is the treatment for AVP-D?
- Want to replace vasopressin with something selective for V2 receptor (V1 receptor activation would be unhelpful)
- Desmopressin
- Different preparations- tablets or intranasal
What is AVP-R?
- Can make arginine vasopressin (normal hypothalamus and posterior pituitary)
- Kidney (collecting duct) unable to respond to it
therefore vasopressin resistance
What are the causes of AVP-R?
- Much less common than cranial diabetes insipidus
- Acquired- drugs e.g. lithium
- Congenital- rare- e.g. mutation in gene encoding V2 receptor, aquaporin 2 type water channel
What is the treatment for AVP-R?
- Very rare disease: difficult to treat successfully
- Thiazide diuretics e.g. bendofluazide works
- Paradoxical: mechanisms unclear
