Disorders of Vasopressin Flashcards
Describe the structure of post pit magnocellular neurones?
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/ADH?
- refer to previous cc for how ADH does this
stimulation of water reabsorption in the RENAL COLLECTING DUCT
This concentrates urine
Acts through the V2 receptor in the kidney
Also a vasoconstrictor (via V1 receptor)
Stimulates ACTH release from anterior pituitary
How does pituitary look on MRI?
Posterior pituitary ‘bright spot’ on MRI
Not visualised in all healthy individuals, so absence may be normal variant
Describe the osmotic stimuli for vasopressin release?
Rise in plasma osmolality sensed by osmoreceptors
Describe the non- osmotic stimuli for vasopressin release?
Decrease in atrial pressure sensed by atrial stretch receptors
Which nuclei sit around the 3rd ventricle and stimulate vasopressin release?
organum vasculosum and subfornical organ
How do osmoreceptors regulate vasopressin
increase in sodium, increase osmolality down gradient out of receptor, shape changes of osmoreceptor triggering receptor firing which stimulates vasopressin release from hypothalamus
What do atrial stretch receptors do?
Detect pressure in right atrium
and
inhibit vasopressin release via vagal afferents to hypothalamus
Descrive atrial stretch receptors involved with haemorrhage?
/
Why is vasopressin reeased following a haemorrage?
in response to reduction in circulating volume
Vasopressin release results in increased water reabsorption in the kidney (some restoration of circulating volume) V2 receptors
vasoconstriction via V1 receptors
(NB renin-aldo system will also be important, sensed by JG apparatus)
Physiological response to water deprivation? (6)
- > Plasma osmolality increases
- > Stimulate osmoreceptors
-> Causes:
Thirst + Increased AVP release
- > Increased water reabsorption from renal collecting ducts
- > decrease urine volume + increase urine osmolality
==> reduction in plasma osmolality
What are clinical symptoms of diabetes insipidus?
Polyuria
Nocturia
Thirst – often extreme
Polydispia
Although the symptoms are same as Diabetes Mellitus, what makes Diabetes Insipidus different?
In diabetes mellitus (hyperglycaemia), these symptoms are due to osmotic diuresis
In diabetes insipidus, these symptoms are due to a problem with arginine vasopressin
- Diabetes M is more common
What is cranial /central diabetes inspidus?
Problem with hypothalamus &/or posterior pituitary
Unable to make arginine vasopressin
‘VASOPRESSIN INSUFFICIENCY’
What is nephrogenic diabetes inspidus?
Can make arginine vasopressin (normal hypothalamus & posterior pituitary)
Kidney (collecting duct) unable to respond to it
‘VASOPRESSIN RESISTANCE
What are the causes of cranial diabetes insipidus?
Acquired causes:
- Traumatic brain injury
- Pituitary surgery
- Pituitary tumours
- Metastasis to the pituitary gland eg breast
- Granulomatous infiltration of pituitary stalk eg TB, sarcoidosis
- Autoimmune
Or congenital although very rare
What are the causes of nephrogenic diabetes inspidus?
less common than cranial
- Congenital:
rare (e.g. mutation in gene encoding V2 receptor, aquaporin 2 type water channel)
- Acquired:
Drugs (e.g. lithium)
Urine trends in diabetes I?
Very dilute (hypo osmolar) large volumes of urine
Plasma trends seen in Diabetes I?
Hyper-osmolar so increased concentration due to dehydration
Increased Na = hypernatraemia
Normal glucose!
Why do DI patients have their symptoms?
->ARGININE VASOPRESSIN PROBLEM Not enough (CDI) Not responding (NDI)
- > imapired concentrations of urine in renal collecting duct
- > large volumes of dulite urine
- increase in plasma osmlality including Na
- > stimulation of osmoreceptors
- > thirst
- > drink water - maintain circulating volume
Why can DI be a cause of death?
If there is no access to water to maintain circulating volume due to dehydration
What is psychogenic polydipsia?
Unlike DI - no problem with arginine vasopressin
problem is px drinks all the time = large volumes of dilute urine
- Has similar presentation as DI
- can be in mental health px
How do we distinguish between diabetes insipidus & psychogenic polydipsia?
Water deprivation test :
No access to anything to drink Over time, measure - Urine volumes - Urine concentration (osmolality) - Plasma concentration through blood sample ( osmolality )
What indicator as a part of the water deprivation test marks DI?
Weigh regularly : stop test if lose >3% body weight (a marker of significant dehydration which can occur in diabetes insipidus)
What do you expect to see in a px with DI during a water deprivation test?
progressive increase in plasma osmolality
How do we distinguish between cranial & nephrogenic diabetes insipidus?
Give ddAVP
will work like vasopressive
Cranial : urine will concentrate
Nephrogenic : no incease in urine osmality so nothing happens
Plasma osmolality in DI vs psychogenic polydipsia?
290 DI
270 PSYCHOGENIC POLYDIPSIA
normal range is around 280
treatment of CDI?
Cranial DI:
Replace vasopressin
= Desmopressin
Selective for V2 receptor
Tablets OR Intranasal
Treatment of NDI?
Thiazide diuretics eg bendofluazide
Mechanism unclear
What is SIADH?
Syndrome of Inappropriate Anti-Diuretic Hormone
Too much Arginine vasopressin:
Reduced urine output
Water retention
High urine osmolality
Low plasma osmolality
Dilutional hyponatraemia
What are the causes of SIADH?
CNS:
Head injury, stroke, tumour,
Pulmonary disease:
Pneumonia, bronchiectasis
Malignancy: Lung cancer (small cell)
Drug-related:
Carbamazepine, Serotonin Reuptake Inhibitors (SSSRIs)
Idiopathic
How to manage SIADH?
Long hospital stays - need to get hyponatraemia back to normal
Fluid restriction
Can use a vasopressin antagonist (vaptan) – binds to the V2 receptors in the kidney (£)
