3.3 - Disorders of vasopressin Flashcards
How does the posterior pituitary gland work?
- anatomically continuous with hypothalamus
- hypothalamic magnocellular neurons containing arginine vasopressin (AVP) or oxytocin
- neurons are long, originate in supraoptic and paraventricular hypothalamic nuclei
- nuclei –> stalk –> posterior pituitary
What is diuresis?
Production of urine
What is the physiological action of vasopressin (ADH)? (3)
- stimulation of water reabsorption in renal collecting duct - acts through V2 receptor
- also a vasoconstrictor via V1 receptor
- stimulates ACTH release from anterior pituitary
How does AVP concentrate urine?
- AVP from pituitary enters bloodstream and binds to V2 receptor on kidney tubule cell
- cascade
- aquaporin-2 inserted into apical membrane of kidney tubule cell
- water enters the kidney tubule cell from the tubular lumen
- water leaves the kidney tubule into the blood via aquaporin-3
How does the posterior pituitary come up on MRI?
- as a bright spot
- not visualised in all healthy individuals, so absence may be normal
What is the stimuli for vasopressin release?
- increase in plasma osmolality (concentration) sensed by osmoreceptors
- osmoreceptors are special sensory receptors in the hypothalamus
How do osmoreceptors regulate vasopressin?
- increase in plasma osmolality (e.g. increase in extracellular Na+, due to dehydration)
- water moves out of the osmoreceptor via osmosis
- osmoreceptor shrinks
- stimulates increased osmoreceptor firing
- AVP release from hypothalamic neurons
What is the physiological response to water deprivation?
- increased plasma osmolality
- stimulation of osmoreceptors
- leads to increased thirst AND increased AVP release
- increased AVP release leads to increased water reabsorption from renal collecting ducts
- reduced urine volume, increase in urine osmolality
- reduction in plasma osmolality as more water reabsorbed
What is arginine vasopressin deficiency (AVP-D)?
- previously known as cranial (central) diabetes insipidus
- problem with hypothalamus and/or posterior pituitary
- unable to make AVP
What is arginine vasopressin resistance (AVP-R)?
- previously known as nephrogenic diabetes insipidus
- can make AVP (normal hypothalamus and posterior pituitary)
- kidney (collecting duct) unable to respond to AVP (e.g. damaged receptors)
Why do the symptoms of AVP deficiency/resistance occur?
- AVP problem - deficiency/resistance
- impaired concentration of urine in renal collecting duct
- large volumes of dilute (hypotonic) urine
- increase in plasma osmolality (and sodium)
- stimulation of osmoreceptors
- thirst - polydipsia
- maintains circulating volume as long as patient has access to water
How can AVP deficiency/resistance lead to death?
When there is no access to water, the patient dehydrates and dies (since water cannot be reabsorbed from urine therefore rely on drinking water)
Why have we moved away from using the term diabetes insipidus?
- diabetes insipidus is not the same as diabetes mellitus
- preventing a patient with DI from drinking / not giving fluids if unable to drink can cause death
- moved away from DI due to this reason
- AVP deficiency = cranial DI
- AVP resistance = nephrogenic DI
What are the symptoms of AVP deficiency/resistance? (3)
- polyuria
- nocturia
- polydipsia - extreme thirst
Why do the symptoms occur differently in diabetes mellitus vs AVP deficiency/resistance?
- in DM (hyperglycaemia), these symptoms are due to osmotic diuresis (high glucose conc in urine = large volumes)
- in AVP deficiency/resistance, these symptoms are due to a problem with AVP
Which is more common out of diabetes mellitus vs insipidus for these symptoms?
- diabetes mellitus
- if you see someone with these symptoms, check their BGC first
What are the two types of causes of AVP deficiency?
- acquired (more common)
- congenital (rare)
What are examples of acquired causes of AVP deficiency? (6)
- traumatic brain injury
- pituitary surgery
- pituitary tumours
- metastasis to pituitary gland e.g. breast
- granulomatous infiltration of pituitary stalk e.g. TB, sarcoidosis
- autoimmune
What are the causes of AVP resistance?
- much less common than AVP-deficiency
- congenital - rare e.g. mutation in gene encoding V2 receptor, aquaporin-2 type water channel
- acquired - drugs e.g. lithium
What happens to urine in AVP deficiency / resistance?
- very dilute (hypo-osmolar)
- large volumes
What happens to plasma in AVP deficiency / resistance?
- increased concentration (hyper-osmolar) as patient becomes dehydrated and cannot reabsorb water
- increased sodium (hypernatraemia)
- glucose normal - always check this in a patient with these symptoms
What is psychogenic polydipsia?
- similar presentation to AVP-deficiency/resistance
- polydipsia, polyuria and nocturia
- no problem with AVP
- problem is that patient drinks all the time, so passes large volumes of dilute urine
How does increased drinking lead to the symptoms of psychogenic polydipsia?
- increased drinking (polydipsia)
- plasma osmolality and sodium falls
- less AVP secreted by posterior pituitary
- large volumes of dilute (hypotonic) urine
- plasma osmolality returns to normal
How do we distinguish between AVP deficiency/resistance and psychogenic polydipsia?
- water deprivation test - no access to anything to drink
- over time, measure urine volumes, urine concentration (osmolality) and plasma concentration (osmolality)
- weigh regularly - stop test if patient loses >3% body weight (marker of significant dehydration which can occur with AVP-D/R)
What do the graphs of urine osmolality against hours of water deprivation for
normal vs psychogenic polydipsia vs AVP-deficiency/resistance look like?
- normal = increases and levels off at highest
- psychogenic polydipsia = lower than normal
- AVP deficiency/resistance = flat line from start
How do we distinguish between AVP-deficiency and resistance?
- give desmopressin (ddAVP) during water deprivation test - works like AVP
- AVP deficiency - response to desmopressin, urine osmolality increases
- AVP resistance - no increase in urine osmolality as kidneys cannot respond
How do we treat AVP deficiency?
- want to replace vasopressin with something selective for V2 receptor (V1 activation would be unhelpful) and a longer half life
- desmopressin
- different preparations - tablets and intranasal (preferred as tablet requires high doses)
How is AVP resistance treated?
- very rare disease - difficult to treat
- thiazide diuretics e.g. bendofluazide work
What is syndrome of inappropriate anti-diuretic hormone (SIADH)? (6)
- too much AVP
- reduced urine output
- water retention
- high urine osmolality
- low plasma osmolality
- dilutional hyponatraemia - makes you feel confused
What are the causes of SIADH? (5)
- CNS - head injury, stroke, tumour
- pulmonary disease (lung cells release ADH) - pneumonia, bronchiectasis
- malignancy - lung cancer (small cell)
- drug-related - carbamazepine, SSRIs
- idiopathic (we do not know)
How is SIADH managed?
- common cause of prolonged hospital stay
- fluid restrict
- can use a vasopressin antagonist (vaptan) - binds to V2 receptors in kidney, very expensive
