disorders of vasipressin Flashcards
how does anterior pituitary communicate with hypothalamus structurally?
not anatomically continuous, hormones sent through hypothalamic- pituitary portal system
how does hypothalamus communicate with posterior pituitary?
they are anatomically continuous
long neurons originate in supraoptic and paraventricular hypothalamic nuclei, go through stalk and terminate in posterior pit
other name for arginine vasioressin
anti diuretic hormone
Main physiological action of vasopressin
stimulation of water reabsorption in the renal collecting duct when dehydrated
does vasopressin make urine more or less concentrated?
more
what receptor does vasopressin mainly bind to in which organ?
V2 receptor in kidney
what other functions does vasopressin have?
responce to stress:
vasoconstriciton by binding to V1 receptor
stimulates ACTH release from anterior pituitary
describe mechanism of water reabsorption stimulated by avp in renal tubule cell (also see slide 5 image)
1) avp binds to V2 receptor in basolateral membrane
2) g protein links to V2 receptor and activates adenylate cyclase
3)- activates cAMP - activates protein kinase A-> leads to aquaporins binding on both apical and basolateral membranes
what does posterior pit look like on MRI?
bright spot (little white - comma shaped lol) look at image ipad
what is the stimulus for AVP release?
increase in plasma osmolarity (happens when ur dehydrated) sensed by osmoreceptors
what are osmoreceptors and where?
special sensory receptors in hypothalamus
How do osmoreceptors communicate the need for AVP to hypothalamus?
when increased osmolarity in blood, osmoreceptor cells loose water, they shrink
the shrinking leads to increased osmoreceptor firing to hypothalamus leading to AVP release
what is the end goal of the body in its physiological responce to water deprivaion?
reducing the plasma osmolarity so that you dont get even more dehydrated by your cells losing fluids in your blood
problem in what areas can cause AVP deficiency? (AVP-D)
hypothalamus or posterior pituitary
what is the old name for AVP-D
Cranial (central) diabetes insipidus
what is the pathology in AVP-R
KIDNEY is unable to respond to AVP but hypothalamus and posterior pituitary are wokring fine
what is the other name for arginine vassopressin resistance
nephrogenic diabetes insipidus
why do we not call them diabetes insipidus any more
huge confusion in doctors with diabetes melitus and ppl have died
what happens to urine volume and concentration during AVP defeciency and resistance ?
increased volume and decreased osmolarity (more dilute)
what happens to plasma osmolarity during AVP - D and R ?
increases
what do we feel as a response in increased plasma osmolarity and how is it detected?
the response is thirst and the detection method is stimulation of osmoreceptors
can avp resistant/ deficient patients be ok without medication?
yes as long as they have access to water
what happens if AVP resistant/ deficient patients don’t have access to water?
it can lead to dehydration and death
what are the sympotms of AVP- and R
Polyuria
Nocturia
Thirst – often extreme
Polydipsia
what is the most common diagnosis for the symptoms of polyuria, nocturia, thirst (often extreme) and polydipsia and what causes them? what is alternative diagnosis
diabetes melitus due to osmotic diuresis
alt: AVP - D OR R
HOW to distinguish between diabetes melitus and AVP - D R
in avp r and d
in blood
glucose normal
hypernatraemia
hyperosmolar blood
and
very dilute urine
large volumes
is congenital or acquired AVP-D more common?
acquired
what are some acquired causes of AVP-D
Traumatic brain injury
Pituitary surgery
Pituitary tumours
Metastasis to the pituitary gland eg breast
Granulomatous infiltration of pituitary stalk eg TB, sarcoidosis
Autoimmune
is AVP resistance or deficiency more common?
AVP deficiency
is congenital AVP resistance common? what is the cause
no, : mutation in gene encoding V2 receptor (aquaporin 2 type water channel)
example of acquired cause of AVP R
drugs : lithium (lithium carbonate taken for manic depression and mental stuff )
what is a differential diagnosis other than diabetes melitus and AVP -D or R for polydipsia, polyuria and nocturia?
psychogenic polydipsia
what happens in psychogenic polydipsia?
no problem with arginine vasopressin
problem is patient drinks too much water because they think they have some issue/ think they need to and they pass large volumes of dilute urine
explain exact mechanism (with avp) of how drinking too much water makes you pee large volumes of dilute urine
1) increased drinking 2) plasma osmolarity decreases 3) less AVP released 4) more volume of dilute urine excreted 5) plasma osmolarity back to normal
what is done to distinguish between AVP def resistance and psychogenic polydipsia?
water deprivation test,
1) no access to anything to drink
2) measure:
-urine osmolarity
-urine volumes
-plasma osmolarity
-weight regularly
3) over 8 hours
(see ipad for graphs)- urine osmolarity over time increases for normal, increases but LESS than normal for psychogenic bc some concentrating ability lost
for defeciencies osmolarity remains super low
what is a marker that should interupt the test?
if loss of > 3% of body weight its a sign of significant dehydration which can occure in AVP resistance/ deficiency
what is done to distinguish between avp d and r?
desmopressin is given which will act as AVP. In deficiency there will be a change (increase in urine osmolarity over few hours whereas there will be no change in avp r as the kidneys cant respond.
what is the treatment for AVP-d
-need to replace vasopressin
-give desmopressin
why is chemically prepared: desmopressin given as medication to avp d instead of arginine vasopressin?
1) desmopressin is selective to V2 receptor (doesnt act on V1 receptor, this would aimlessly raise BP)
2) chemically prepared is not biodegradable so it lasts way more: whole day
different preparaitons of desmopressin
tablets
intranasal
AVP resistance treatment
thankfully its very rare bc its difficult to treat successfully
what is syndrome of inappropriate Anti-Diuretic Hormone? (SIADH)
too much AVP
What are the symptoms of SIADH
REDUCED URINE OUTPUT: water retention
increased urine osmolarity
reduced plasma osmolarity
dilutional hyponatraemia
what is dilutional hyponatraemia
when you get confused because of too much water/ little sodium in the brain
categories of causes of SIADH
CNS related,
lung related
drug related
idiopathic (we don’t know why)
CNS causes of SIADH
head injury
stroke
tumour
lung related causes of SIADH
PNEUMONIA,
BRONHIECTASIS,
small cell lung cancer (cells retain a lot if water in this condition)
why are lungs so relevant:
(in general sometimes lung cells release adh ans hang on to water, maybe evolutionary for when you are septic to have water but now we have antibiotics so its actually more harm than good)
drug related causes od SIADH
Carbamazepine, Serotonin Reuptake Inhibitors (SSSRIs)
what does SIADH commonly lead toin hospital ?
common to cause a prolonged hospital stay
how do you treat SIADH ?
restrict fluids
can use a vasopressin receptor antagonist (vaptan) binds to v2 receptor in kidney (very expensive) (also not good long term solution)
what should you be careful with in SIADH patients when in hospital?
how many fluids you give them, in normal patients for sepsis for ex ud give so many fluids in these patients sodium conc in blood drops and theres confusion
