🧪Endocrinology🧪 - Disorders of Vasopressin Flashcards
What is the pathway of AVP release?
Supraoptic hypothalamic nuclei -> pituitary stalk -> posterior pituitary
Originates in magnocellular neurones
What is the other name for arginine vasopressin (AVP)?
Anti-diuretic hormone (ADH)
What is diuresis?
The production of urine
What is the main physiological action of AVP?
Stimulation of water reabsorption in the renal collecting duct, via V2 receptors
Concentrates urine, increases blood volume
What are 2 physiological effects of AVP, other than stimulating water reabsorption?
Acts as a vasoconstrictor, via the V1 receptor
Stimulates ACTH release from anterior pituitary (much smaller impact than CRH obviously)
Describe the chemical cascade after AVP binds to its target
AVP binds to g-protein coupled v2 receptor
Causes adenylate cyclase to form cAMP
cAMP then forms protein kinase A
Protein kinase A interacts with vesicles containing aquaporin-2
Aquaporin-2 channels insert into the apical membrane, leading to water movement into the cell
What receptors are responsible for the release of AVP?
Osmoreceptors
What triggers osmoreceptors?
Increase in plasma osmolality is sensed
Where are osmoreceptors located?
The hypothalamus
How do osmoreceptors regulate AVP release?
What is the normal physiological response to water deprivation?
What are the 2 types of conditions relating to the inefficacy of AVP?
Arginine vasopressin deficiency (AVP-D)
Arginine vasopressin resistance (AVP-R)
Outline AVP-D
Cranial (central) diabetes insipidus
Problem with the hypothalamus and/or posterior pituitary
Inability to properly produce AVP
Outline AVP-R
Nephrogenic diabetes insipidus
AVP production is fine
Kidney (collecting duct) unable to respond
Is insensitivity to AVP
How does AVP deficiency/resistance present?
How can AVP deficiency lead to death?
Restricted access to water leads to rapid dehydration and death
What is the clinical presentation of AVP deficiency/resistance?(4)
Polyuria
Nocturia
Thirst - often extreme
Polydipsia
A patient presents with polyuria, nocturia and polydipsia, what is the most common cause?
Diabetes MELLITUS
Why is diabetes mellitus always considered first, before a problem with vasopressin?
Because the symptoms present the same/very similarly upon first presentation, and diabetes mellitus is much more common
What is the most common cause of AVP deficiency, and how may it arise?
Acquired
Traumatic brain injury
Pituitary surgery
Pituitary tumours
Inflammation of pituitary stalk (e.g. TB)
Autoimmune damage
Congenital is rare
What are the causes of AVP resistance?
Much less common than AVP deficiency
Acquired - via drugs (e.g. lihtium)
Congenital - rare (mutation in gene encoding for V2 receptor)
What would the urine of someone with AVP issues be like?
Very dilute - hypo-osmolar
Large volume
What would the blood plasma of someone with diabetes insipidus look like, and how could it be distinguished from diabetes mellitus?
Increased concentration (hyperosmolar)
Hypernatraemia
Normal glucose (used to distinguish from DM)
What condition other than diabetes mellitus can mimic AVP deficiency?
Psychogenic polydipsia
What is psychogenic polydipsia?
A patient drinks vast amounts of water, so passes huge volumes of urine, and this can lead to low plasma osmolality, and hyponatraemia
Entirely psychological
How might someone with psychogenic polydipsia present?
Polydipsia
Polyuria
Nocturia
How do the symptoms arise in psychogenic polydipsia?
Increased water intake leads to increased blood volume and filtration in kidneys
Plasma osmolality falls, including sodium levels
Less AVP secreted by posterior pituitary, to discourage water reabsorption and so increase urine volume
Large volumes of dilute, hypotonic urine
Plasma osmolality returns to normal
How is AVP deficiency distinguished from psychogenic polydipsia?
Water deprivation test
No access to any fluid intake
Over time measures of:
-Urine volumes
-Urine osmolality
-Plasma osmolality
What must also be carefully monitored during the water deprivation test?
Body weight
Test should be stopped if more than 3% of body weight is lost - a marker of significant dehydration
What will the results of the water deprivation test look like for psychogenic polydipsia and AVP deficiency?
Why does psychogenic polydipsia show a lower level of water reabsorption than the normal person during the water deprivation test?
(Depends on severity and duration of the condition) over time the kidney loses ability to concentrate urine as effectively, so less water reabsorption
Urine concentration will eventually match that of “normal” graph, but takes more time
How do we distinguish between AVP deficiency and AVP resistance?
Give desmopressin
AVP deficiency will give a positive response
AVP resistance will give no response as kidneys cant respond
How is AVP-deficiency treated?
Replaced vasopressin
Desmopressin commonly used
Selective for V2 receptor
Comes in tablet and intranasal forms, recently more push towards the tablet form
How is AVP-resistance treated?
Very difficult to treat successfully, luckily is very rare
Symptom management - low sodium diet and adequate hydration
What is Syndrome of Inappropriate Anti-Diuretic Hormone (SIADH)?
Too much arginine vasopressinsecretion
Leads to reduced urine output and urine retention
What are the physiological changes brought on by SIADH?
High urine osmolality
Low plasma osmolality
Low plasma sodium (dilute)
What are some causes of SIADH?
CNS - head injury, stroke tumour
Lung infections - pneumonia
Malignancy - Lung cancer (small cell)
Drug related - anti-epileptics, anti-depressants
Idiopathic
How is SIADH managed?
Fluid restriction
Can use a vasopressin receptor antagonist (vaptan) - binds to the V2 receptors in the kidney, preventing activation - very expensive
