Vasopressin disorders final Flashcards
What is the posterior pituitary anatomically continuous with?
Hypothalamus
What neurons are found in the hypothalamus
Parvocellular that terminate at median eminence ( anterior pit) Magnocellular neurons ( long) that travel into the pit stalk and into the posterior pit
what do you magnocellular neurons originate and what do they contain
Superoptic ( AVP)
Oxytocin ( paraventricular)
How is the posterior pit regulated
Hypothalamic secretory neurons make AVP ( superoptic) and oxytocin ( paraventricular . Excitation of these neurons releases these into the post pit
What is the function of Vasopressin or ADH
1) stimulation of water reabsorption in renal collecting duct via V2 receptor in kidney. This concentrates the urine
2) Vasoconstrictor via V1 receptor. it stimulated ACTH release from anterior pit
How does vasopressin concentrate urine?
AVP binds to V2 receptors which cause intracellular signalling cascade. This causes aquaporins to bind to cell membrane on the apical membrane ( tubular side). Water reabsorbed through aquaporin II and leaves to basolateral side ( plasma side) through Aquaporin III . See image in notes
How is the posterior pit visualised on an MRI
Post pit is seen as a bright spot on MRI. Though not present in all healthy individuals so expect variation
What are the two stimuli for vasopressin release ( aka what things increase vasopressin release)
1) osmotic –> increase in plasma osmolarity ( increase in concentration of plasma ) sensed by osmoreceptors
2) Non osmotic –> decrease in atrial pressure sensed by atrial stretch receptors
Where are osmoreceptors found
organum vasculosum and subfornical organ ( both nuclei are found around the 3rd ventricle aka circumventricular). Both have no blood brain barrier and are highly vascularised so neurons in them can respond to changes in systemic circulation . The neurons here project into the supraoptic nucleus where vasopressinergic neuros are found
How do osmoreceptors regulate vasopressin
When there is an increase in extracellular Na+ . H2O moves out the osmoreceptor by osmosis causing it to shrink. When it shrinks there is increased osmoreceptor firing –> more AVP release
See how osmotic stimulation causes vasopressin release
How does non osmotic stimulation affect vasopressin release?
1) If Atrial stretch receptors detect increase pressure right atrium
2) Vasopressin release is inhibited via afferent vagus nerves to hypothalamus
Note remember vasopressin is a vasoconstrictor so it would increase pressure
3) Reduction in circulating volume
Where are stretch receptors found
Right atrium
what happens to vasopressin release during a haemorrhage
Less stretch of atrial stretch receptors leasing to less inhibition of vasopressin
Why is vasopressin released following a haemorrhage ( ie reduction in circulating blood volume)
1) Increases water absorption in kidney via V2 receptors ( allows some restoration of circulating volume)
2) Vasoconstriction via V1 receptors ( not renin - aldosterone system will also help this)
What is the physiological response to water deprivation
1) increased plasma osmolality
2) Stimulation of osmoreceptors –> thirst and increased AVP rate
3) Increased AVP –> increased water reabsorption from renal collecting ducts
4) reduced urine volume , increase in urine osmolality
5) reduction in plasma osmolality
symptoms of diabetes insipidus
Polyuria + hypo- osmolar ( dilute) urine
Nocturia
Extreme thirst ( Polydipsia) Plasma: increase conc ( hyper-osmolar) as patient becomes dehydrated increased sodium ( hypernatremia)
REMEMBER GLUCOSE is normal ( only high in Diabetes mellitus)
How are the symptoms of diabetes insipidus different to diabetes mellitus
In DM ( hyperglycaemia) symptoms caused due to osmotic diuresis
In DI symptoms due to problem with arginine vasopressin
REMEMBER DM IS MORE COMMON THAN DI
what are the 2 types of diabetes insipidus
Cranial / central ( VASOPRESSIN INSUFFICIENCY )
( More common than nepherogenic)
Nepherogenic ( VASOPRESSIN RESISTANCE)
What is cranial diabetes insipidus caused by
Problem with post pituitary or hypothalamus –> unable to make AVP , VASOPRESSIN INSUFFICEINCY
What is Nephrogenic DI caused by
Can make AVP ( normal post pit + hypothalamus ) but kidney ( collecting duct ) unable to respond to it ( VASOPRESSIN RESISTANCE)
Causes of Cranial Diabetes Insipidus
1) Congenital ( rare)
2) Acquired –> trauma to brain , pit surgery / tumours . metastasis to pit gland (ie from breast cancer) , granulomatous infiltration of pit stalk (ie TB , Sarcoidosis) , autoimmune
Causes of nephrogenic DI
1) Congenital ( rare) –> mutation of gene encoding V2 receptor ( aquaporin 2 water channel)
2) Drugs ( lithium)
What causes symptoms of DI/ Why does DI cause death
BONUS: and what happens if the patients has no water
1) Problem in AVP ( not enough CDI / not responding NDI)
2) Impaired conc of urine in renal collecting duct
3) Large volumes or dilute urine
4) Increase in plasma conc + Na+
5) stimulation of osmoreceptors
6) Thirst
7) body maintains circuiting blood volume as long as patient has access to water
if no water leads to dehydration and death
What is psychogenic polydipsia
patient drinks all the time so passes large volumes of dilute urine
similar presentation to DI :
- Polydipsia , polyuria , Nocturia
Remember unlike DI not problem with AVP
What are the symptoms of psychogenic polydipsia and why do they occur
- Polydipsia , polyuria , Nocturia
1) increased drinking
2) fall in plasma osmolality
3) Less AVP secreted by post pit
4) large volumes of dilute urine
5) plasma osmolality returns to normal
How do we test between DI and Psychogenic polydipsia
Water deprivation test
1) No access to fluids
2) measure : Urine volume , urine osmolality , plasma osmolality over time
3) Weigh regularly –> stop test if >3% body weight loss ( sign of dehydration )
after few hours of water deprivation:
Normal –> urine osmolality high
Psychogenic –> medium
DI – >low
How to distinguish between cranial and nephrogenic DI
1) give ddAVP ( works like AVP)
2) Measure urine osmolality
cranial –> urine concentrates in response to ddAVP
nephro –> no increase in urine osmolality as kidney’s can’t respond
How does plasma osmolality compare btwn Di and Psyco Polydipsia
normal is 280 mOSM/Kg H2o
DI –> above range
PP–> below range
Treatment of cranial DI
Replace AVP using demopressin
can take tablets / intranasal
Treatment must be selective for V2 receptor ( V1 receptor activation unhelpful)
Treatment of nephrogenic DI
Difficult to treat as v rare.
Thiazide diuretics is bendofluazide
What is SIADH ( syndrome of inappropriate ADH) and symptoms
Too much AVP causes reduced urine output , water retention , high urine osmolality , low plasma osmolality , dilutional hyponatraemia
Causes of SIADH
1) CNS –> head injury , stroke , tumour
2) Pulmonary disease –> pneumonia , bronchiectasis
3) Malignancy –> lung cancer
4) Drug related –> Carbamazepine , serotonin reuptake inhibitors (SSSRIs)
5) Idiopathic
Management of SIADH
Fluid restriction in hospital
can use vasopressin antagonist ( vaptan) that binds to V2 receptors in kidney but v expensive
