Endo 3: Neurohypophysial Disorders Flashcards
describe how posterior pituitary would be describe on pituitary MRI
- bright spot
What is the principal effect of vasopressin?
Vasopressin =
- anti diuretic
- increases water reabsorption from renal cortical + medullary collecting ducts (via V2 receptors)
What is vasopressin also known as?
- ADH
How is vasopressin release regulated?
- regulated via osmoreceptors
Describe the process of VP release.
starting from the stimulus
Stimulus = increase in EC Na+ conc
- detected by osmoreceptor
- increase in water outflow from osmoreceptors
- osmoreceptor shrinks
- causes increased osmoreceptor firing
- causes release from hypothalamic PVN + SON neurons
Describe the normal response to water deprivation.
- water deprivation
- causes increase serum osmolality
- stimulates osmoreceptors
- causes sensation of thirst - then causes increase in VP release
- which increases water reabsorption from renal Collecting ducts
- results in REDUCED URINE VOLUME + INCREASE URINE OSMOLALITY
- and also REDUCTION IN SERUM OSMOLALITY
Describe the aetiology of cranial diabetes insipidus.
- Damage to neurohypophysial system
(injury to neurohypophysis, surgery, cerebral thrombosis) - idiopathic
- familial
NOTE: usually acquired
Describe the aetiology of nephrogenic diabetes insipidus.
- congenital = rare
- usually acquired
( e.g drugs - lithium)
–> bipolar disorder medication
What are signs and symptoms of diabetes insipidus
- polyuria (large volumes)
- hypo-osmolar urine (dilute)
- polydipsia (thirst + inc. drinking)
- dehydration
Describe the onset of diabetes inspidus
- inadequate production of VP
- large vol of dilute urine produced
- causes increase in plasma osmolality
- causes reduction in EC fluid volume
- leads to polydipsia (thirst)
- re-expansion of EC fluid volume
Note: if no access to water –> causes dehydration + death
State a difference between Diabetes Insipidus and psychogenic polydipsia.
UNLIKE Diabetes Insipidus:
- ability to secrete VP in response to osmotic stimuli = preserved
Describe the onset of psychogenic polydipsia
- there is central disturbance
- increases drive to drink
- leads to fall in plasma osmolarity
- so VP is inhibited
- and you produce large vol of urine
- this increase in urine excretion –> reduces ECFV + increases plasma osmolarity
What are biochemical features of DI ?
- hypernatraemia
- raised urea
- increased plasma osmolarity
- dilute urine
What are biochemical features of Psychogenic polydipsia ?
- mild hyponatraemia
- low plasma osmolarity
- dilute urine
List methods of administrating desmopressin
- nasally
- orally
- SC
What is the effect of Desmopressin (DDAVP) on person with CENTRAL DI?
effect:
- allows concentration of urine
- (because their VP receptors are working properly + can be stimulated by DDAVP
What is the effect of DDAVP on a person with NEPHROGENIC DI ?
- no effect
- no response
Give a main method of treatment of nephrogenic diabetes insipidus.
- thiazides
e. g bendroflumethiazide
Explain the mechanism of thiazides as a method of treating nephrogenic DI.
EXTRA STUDY
mechanism - thiazide:
- inhibits Na+/Cl- transport in DCT
- causes volume depletion
- causes compensatory increase in Na+ reabsorption from PCT
- which increases proximal water reabsorption
- decreased fluid reaches CD
- causes reduced urine volume
e.g bendroflumethiazide
Define Syndrome of Inappropriate ADH (SIADH)
SIADH
- the plasma vasopressin concentration = inappropriately high for the existing plasma osmolality .
Describe the mechanism of SIADH
- excess Vasopressin in plasma
- causes increase in water reabsorption form renal collectiong ducts
- which causes an increase in ECF volume
- and leads to HYPONATRAEMIA
- and ANP (atrial natriuretic peptide) = produce from the right atrium
which causes natriuresis - which also causes hypo natraemia
- as well as euvolaemia.
What are some signs of SIADH?
- raised urine osmolality
- decreased urine volume
- decreased p{na+] (HYPONATRAEMIA)
due to increased water reabsorption.
What are some symptoms of SIADH?
- SIADH can be symptomless
- if p[na+] < 120 mM
- -> causes generalized weakness, poor mental function, nausea
- if p[na+] <110 mM
- -> causes CONFUSION
- leading to coma –> death
What are some causes of SIADH?
- CNS (stroke, SAH, tumor)
- PULMONARY DISEASE (pneumonia, bronchiectasis)
- MALIGNANCY (lung - small cell)
- DRUG RELATED (carbamazepine, SSRI)
- IDIOPATHIC
What are some treatments of SIADH?
- e.g surgery for tumor
if hyponatraemia:
- immediate = fluid restriction
- long term = drugs to prevent VP action in kidneys (e.g DMCT, V2 receptor antagonists- inhibits action of ADH)
What is VAPTANS?
VAPTANS:
- Non competitive V2 receptor antagonists
How do VAPTANS work?
What is its effect?
VAPTANS:
- inhibits AQP2 synthesis + transport
- prevents renal water resorption
- causes aquaresis
- used for treatment of hyponatraemia associated with SIADH
What are osmorecptors
- they project to the PVN + SON
Where are osmoreceptors located in ?
the organum vasculosum
what is diabetes insipidus?
- ADH problem
- large volumes of insipid urine
Whats the ranger or normal plasma osmolality?
how does this differ in diabetes insipidus patients?
how does this differ in psychogenic polydipsia patients?
270-290 mOsm/kg H2O
DI: higher than 290
Psychogenic polydipsia: Lower than 270
give central DI patients high dose of vasopressin –>
responds well to DDAVP
What is DDAVP?
- synthetic AVP
- vasopressin receptor peptidergic agonists
- desmopressin
how does desmopressin work?
- nasally/ orally/ SC administrated
–> causes reduction in urine value + conc in CRANIAL DI only
What should you warn patients who have started on desmopressin?
- tell patient starting this NOT to continue drinking large amounts of fluid
- -> due risk of hyponatraemia
give 3 actions of vasopressin
and the respective receptors for each action.
- antidiuretic effect –> inserts AQP2 (V2 receptors)
- Vasoconstrictor activity (V1a)
- ACTH release (V1b)
what are 2 conditions vasopressin agonist is used for?
- cranial DI (desmopressin)
- Oesophageal varices (terlipressin)
