neurohypophysial disorders Flashcards
summarise the neurohypophysial system
the paraventricular nucleus and the supraoptic nucleus are in the hypothalamus
the neurons from these project through the stalk into the posterior pituitary
oxytocin and vasopressin are released from these neurons
what is the principle effect of vasopressin
Anti-diuretic hormone - increases water reabsorption from renal cortical and medullary collecting ducts by binding to V2 receptors and reduce urine production
define diuresis
increase in urine production and loss of electrolytes
what are the posterior pituitary hormones *
oxytocin and vasopressin
describe the how vasopressin causes water reabsorption
VP binds to V2 receptors
causes an intracellular signalling cascade
stimulate AC
elevate cAMP
activate PKA
which results in the synthesis of aquaporin 2
the aggraphores migrate towards the apical membrane
AQP2 inserts into the wall
provides a water channel and allow water down the osmotic gradient into the collecting duct cell
water then continues down the conc grad into the plasm through AQP 3 and 4
where are the osmoreceptors and what are they near
organum vasculosum, near the hypothalamus
the neurons project to the paraventricular nucleus and supraoptic nucleus which release VP
describe how osmoreceptors are involved in VP release
they are v sensitive to changes in EC osmolarity
if there is an increase in EC Na conc - ie osmolarity of the blood
this causes water to leave the osmoreceptor down the osmotic gradient
the osmoreceptor then shrinks - this irritates the osmoreceptor and causes increased osmoreceptor firing
this results in VP release for the hypothalamic PVN and SON neurons that are in the hypothalamus
describe the normal response to water deprivation
increased plasma osmolarity
this stimulates osmoreceptors (induces thirst)
increase VP release
increase water reabsorption from the renal collecting ducts - body retain as much as impossible
therefore the serum osmolarity is reduced and there is reduced urine vol, increase in urine osmolarity
what is the problem with diabetes insipidus *
cant absorb water properly = dehydration
what are the 2 subtypes of DI *
cranial/central (CNS) - absence or lack of circulating VP - problem with VP production
nephrogenic - end organs (kidneys) are resistant to VP - the intracellular cascade is abnormal, kidney cant respond to VP
what is the cause of cranial DI *
acquired more common than congenital
damage to the neurohypophysial system - mess with the pituitary of the stalk
traumatic brain injury
pit surgery - transiently
pituitary tumours eg craniopharyngioma (tumour derived from pit embryonic tissue)
metastasis to the pituitary gland eg breast
granulomatous infiltration of median eminence eg TB, sarcoidosis, hypophysitis - if inflamed the VP cant get into the posterior pit - VP travel down stalk from hypothalamus
what is the cause of nephrogenic DI *
congenital - mutation anywhere in the cascade eg mutation in gene encoding V2 receptor, AQP2 type water channel.
acquired - drug eg lithium - toxicity/long term lithium can also cause primary hypoparathyroidism
high Ca
signs and symptoms of DI *
polyuria (cant absorb the water
very dilute urine - hypo-osmolar
polydipsia and thirst - to replace the lost water
because large vol
dehydration and death if the fluid intake is not maintained because a large volume of fluid is lost in the urine.
possible disruption to sleep - getting up in the night to pass urine
what is the osmolarity of urine for people with DM and why
hyperosmolar - there is a lot of glucose in the urine
describe the process of fluid control in DI *
there is inadequate production of or response to ADH
therefore large vol of dilute (hypotonic) urine is produced (no water reabsorbed)
become dehydrated so there is an increase in the plasma osmolarity and Na and a reduction in EC fluid vol
this causes thirst - polydipsia - have to drink all the time to stay alive
EC fluid vol expands as you drink more
what happens in DI when you have no access to water *
you have the reduction in EC vol, increase in plasma os and Na
you cant maintain plasma osmolarity by large intake of water -> dehydration and death
why would you have no access to water
stroke
post-op so under general anaesthetic (GA)
describe the overall concept of psychogenic/primary polydipsia *
they have excess fluid intake - polydipsia and therefore pass a lot of hypotonic urine - natural process
ability to produce VP in response to osmotic stimuli is preserved.
what kind of people get psychogenic polydipsia *
psychiatric patients
people told to drink plenty
aetiology of psychogenic/primary polydipsia *
unclear
may be because of anti-cholinergic effects of medication in psychiatric patients - dry mouth so drink more
describe the pathway of psychogenic polydipsia *
increased drinking
expansion of EC fluid vol, reduce in plasma osmolarity
therefore less VP secreted by posterior pituitary gland
therefore large vol of hypotonic urine is produced
EC vol returns to normal
what is the difference in the plasma osmolarity of someone with DI and someone with psychogenic polydipsia *
plasma osmolarity high in DI because intake cant keep up with the water leaving as urine
polydipsia - plasma osmolarity is lower - plasma is diluted by the excess intake of water
what is the process of a water stress test *
place the person in a room with no water and measure the conc of the urine, vol of urine and plasma osmolarity
it is used to test for DI and psychogenic polydipsia
measure body weight every hour, if lose 3% weight - stop experiment it shows clinical dehydration and is dangerous. also shows it is DI, because the person cant conc urine even when there is no fluid intake so are losing a lot of fluid
describe what the normal response should be to a water stress test when fluid deprived and when you have DDAVP administration (analogue of VP) *
urine osmolarity increases when fluid deprived - VP produced and reabsorb more water from the urine - produce little/no urine - maintain plasma osmolarity
when DDAVP is added - there is no further change to urine osmolarity as VP was already present and worked
