Disorders Of Vasopressin Flashcards
Where does vasopressin come from?
Vasopressin = antidiuretic hormone =AVP
Comes from posterior pituitary, magnocellular neurones
What is the posterior pituitary like?
Anatomically continuous with the hypothalamus
Neural tissue. No blood system
Hypothalamic magnocellular neuroma contain AVP or oxytocin
Neurones are long and originate in supraoptic and paraventricular hypothalamic nuclei
Nuclei -> stalk -> posterior pituitary
What is the action and mechanism of action of vasopressin?
Anti diuretic hormone :. Stops you peeing/concentrates the urine
It does this by stimulating water reabsorbtion in the renal collecting duct
It acts to reabsorb water via the V2 receptor in the kidney
also acts as a vasoconstrictor via the V1 receptor. Acts via a G protein coupled receptor to cause aquaporin 2 channels to bind to the apical membrane (near the urine). This means more water is absorbed.
And stimulates ACTH release from the anterior pituitary
How can the posterior pituitary be viewed radiologically?
MRI
Appears as a bright spot
But not necessarily seeing in all healthy individuals
The optic chias can be seen at the top, then the pituitary stalk (infundibulum). And then the posterior pituitary. (Anterior is much larger)
What are the stimuli for vasopressin release?
Osmotic:
Rise in plasma osmolality (concentration - so more ions) sensed by osmoreceptors
Non-osmotic:
Decrease in atrial pressure sensed by atrial stretch receptors
What is osmolality?
Basically concentration
Higher osmolality means more concentrated, so less water and more ions
How, specifically, does osmotic stimulation of vasopressin release work?
Stimuli is an increase in plasma osmolality
Detected by the organum vasculosum and subfornical organ. These are both nuclei that sit around the 3rd ventricle
There is no blood brain barrier here so the neurones can respond directly to changes in osmolality in the systemic circulation
Organum vasculosum and subfornical organ are highly vascularised
Their brutes project into the supraoptic nucleus, the site of vasopressinergic neurones
How do osmoreceptors work and regulate vasopressin release?
The osmoreceptors are in direct contact with plasma.
If there is an increase in extra cellular (so plasma) concentration (osmolality increases), water flows out of the receptor
This causes it to shrink and change shape
This leads to osmoreceptor firing
Leading to vasopressin release from hypothalamic neurones
How do atrial stretch receptors work and regulate vasopressin release?
Atrial stretch receptors detect pressure in the right atrium
Vagal afferents to the hypothalamus inhibit vasopressin release
Reduction in circulating volume (eg. After haemorrhage) means LESS stretch receptor firing so LESS INHIBITION of vasopressin release
Vasopressin release increases following haemorrhage to restore some of the blood volume and blood pressure. Increases water reabsorbtion through V2, and vasoconstricts through V1
The renin-angiotensin system will also be important, sensed by juxtaglomerular appratus
What is the physiological response to water deprivation?
Increased plasma osmolality (due to less water intake) ->
Stimulation of osmoreceptors ->
Thirst AND
Increased AVP release ->
Increased water absorption from renal collecting ducts ->
Reduced urine volume, increased urine osmolality (more concentrated/yellow) ->
Reduction in plasma osmolality
What is diabetes insipidus?
Hyper glycaemia
But unlike mellitis, which is due to insulin problems, insipidus is due to problems with arginine vasopressin
It is way less common than diabetes mellitus
In mellitus excessive peeing is due to osmotic diuresis (lots of glucose in blood, not all can be reabsorbed in the kidney so is left in urine. Higher conc of urine means more water is drawn into pee, so more volume of pee)
In insipidus, excessive peeing is due to problems with vasopressin (none produced or resistance)
What are the symptoms and presentation of diabetes insipidus?
Polyuria
Nocturia
Polydipsia
Urine:
Very dilute (hypo osmolar)
Large volumes
Plasma:
Increased concentration (hyper osmolar) as patient becomes dehydrated
Increased sodium (hyper natraemia)
GLUCOSE IS NORMAL
These symptoms may be kept under control though if they are drinking enough water to compensate
What are the two types of diabetes insipidus?
Cranial:
Problem with hypothalamus and/or posterior pituitary
Unabated to make AVP
CRANIAL= VASOPRESSIN DEFICIENCY
Nephrogenic:
Can make Vasopressin (ie. hypothalamus and PP are normal)
V2 receptors on kidney collecting duct are unable to respond to it
NEOHROGENIC= VASOPRESSIN RESISTANCE
What are some causes of cranial diabetes insipidus?
Aquired (more common): Traumatic brain injury Pituitary surgery Pituitary tumour Metastasis Granulomatous infiltration of stalk (such as in TB or sarcoidosis). Causes thickening of stalk, visible on MRI Autoimmune
Congenital:
Rare
What are some causes of nephrogenic diabetes insipidus?
(Much less common than cranial)
Acquired:
Drugs (eg. Lithium)
Congenital:
Rare
Eg. Mutation in gene encoding V2 receptor, aquaporin 2 type water channel
Why do the symptoms of diabetes insipidus occur?
Not enough/ not responding to AVP->
Impaired concentration of urine in renal collecting duct ->
Large volumes of dilute urine ->
Increase in plasma osmolality ->
Stimulation of osmoreceptors ->
Thirst - polydipsia ->
Maintains circulating volume as long as patient has access to water
If the patient doesn’t doesn’t have access to water ->
Dehydration and death
What is psychogenic polydipsia?
Has similar presentation to diabetes insipidus
Polyuria
Polydipsia
Nocturia
But unlike diabetes insipidus, there is no problem with AVP
Problem is they just drunk way too much water for whatever reason. So pee all the time
May be a side effect of some psychiatric drug’s
In diabetes insipidus plasma osmolality is high. In psychogenic polydipsia plasma osmolality is low
What is the mechanism of psychogenic polydipsia?
Patient drinks a lot (polydipsia) ->
Plasma osmolality falls ->
Less osmoreceptor firing ->
Less vasopressin secretion by posterior pituitary ->
Less water reabsorbed from the urine ->
Large volumes of dilute urine ->
So plasma osmolality returns to normal
What test is done to distinguish between diabetes insipidus and psychogenic polydipsia?
Water deprivation test:
No access to anything to drink
Measure urine volume, urine concentration and plasma concentration over time
You also have to look out for weight. A >3% loss of body weight is a trigger to stop the test as these people will have insipidus, and this is a marker of significant dehydration which is dangerous
Normal results:
As time increases without water, urine osmolality increases as more water is retained in the body
Psychogenic polydipsia:
As time without water increases, urine osmolality increases but not as much as normal. This is because AVP reabsorbs some water but there is still excess water in the body
Diabetes insipidus:
No increase in urine osmolality as the body is unable to use AVP, so no water is reabsorbed and it is all peed out. They can’t concentrate their urine. Even if they don’t drink they still pee loads this leads to dehydration
What test is done to distinguish between cranial and nephrogenic diabetes insipidus, and what are the results of this?
Give ddAVP
This is synthetic AVP
But it only acts on V2 receptors. So no vasoconstriction as this could be dangerous
It induces the same effects as vasopressin
Cranial response:
Can’t make vasopressin
But responds, so water is reabsorbed and urine osmolality (concentration) increases
Nephrogenic response:
Resistance to vasopressin
ddAVP still cannot bind to V2 receptors in kidney collecting ducts. So no water reabsorbtion. Urine remains dilute (low osmolality). Plasma osmolality remains high
How is cranial diabetes insipidus treated?
Desmopressin - vasopressin replacement
Selective for V2 receptor. V1 (vasoconstriction) would be unhelpful
Comes in tablet and nasal spray form
Patients on desmopressin must be allowed this and must be given access to water, or they could die. This happens sometimes as insipidus is not very well known so people assume mellitus and people don’t get the treatment they need
How is nephrogenic diabetes insipidus treated?
Much rarer
Much harder to treat
Thiazide diuretics used.
Eg. Bendofluazide
No one knows why this works
It is paradoxical
What is syndrome of inappropriate ADH (SIADH)?
Too much AVP->
Water retention and reduced urine output
High urine osmolality
Low plasma osmolality
Dilutional hyponatremia (very low sodium makes you feel unwell)
Commonly idiopathic
What are causes of SIADH?
CNS:
Head injury
Stroke
Tumour
Pulmonary disease:
Pneumonia
Bronchiectasis
Malignancy:
Lung cancer
Drug related:
Carbamazepine
SSRIs
Idiopathic
How is SIADH managed?
It is often a cause of prolonged hospital stay
Fluid restriction
You can use a vasopressin antagonist (vaptan) - but this is reallllly pricey so never done
