Neurohypophysial disorders Flashcards
How can the posterior pituitary be identified?
Bright spot at back of pituitary on MRI.
Why is the posterior pituitary sometimes called the neurohypophosis?
It is derived from neural cells rather than glandular cells.
Label diagram of hypothalamo-neurophypophysial system.
What are the primary secretions of the posterior pituitary?
vasopressin and oxytocin.
What is the principal effect of vasopressin?
Anti-diuretic: increase water reabsorption from renal cortical and medullary collecting ducts via V2 receptors.
Label diagram outlining action of vasopressin at collecting duct.
How do osmoreceptors aid plasma H2O regulation?
Osomoreceptors near hypothalamus. Project into PVN and SON which secrete vasopressin.
Outline how osmoreceptors might regulate plasma H2O.
Increase in plasma Na+ leads to H2O osmosing out of osmoreceptors. Osmoreceptor shrinks –> increased firing rates –> increased VP release from PVN and SON neurons in hypothalamus.
Outline the normal response to water deprivation.
What 2 ways can vasopressin relate to diabetes insipidus?
Absence/lack of circulating vasopressin = central diabetes insipidus.
Organ resistance (kidneys) resistance to vasopressin = nephrogenic diabetes insipidus.
What can cause central diabetes insipidus?
Traumatic brain injury
pituitary surgery
pituitary tumours (craniopharyngioma)
metastasis to pituitary gland
granulomatous infiltration of median eminence.
drugs - e.g. lithium.
congenital (rare)
What can cause congenital diabetes insipidus?
e.g. mutation in gene encoding V2 receptor/ aquaporin 2 type water channel.
List the signs and symptoms of diabetes insipidus.
Polyuria
Very dilute urine
Thirst (polydipsia)
Dehydration
Sleep disruption associated with polyuria and polydipsia.
Outline the pathology of diabetes insipidus. How might it lead to death?
Failure to drink in response to polydipsia.
Why is psychogenic polydipsia most frequently seein in psychiatric patients?
May reflect anti-cholinergic effects of medication creating a dry mouth sensation.
Patients being told to drink plenty by healthcare professionals.
Outline the main features of psychogenic polydipsia.
Polydipsia + polyuria, but vasopressin system is functional, though not secreted due to high H2O intake.
How can diabetes insipidus and psychogenic polydipsia be distingiushed?
DI = high plasma osmolality (>290 mOsm/kg H2O)
PP = low plasma osmolality (<270)
How can DI and PP be distinguished with a fluid deprivation test (diagram)?
PP - increased urine osmolality.
DI - no change in urine osmolality.
How can central and nephrogenic DI be distinguished with a fluid deprivation test?
DDAVP administration - VP analogue.
Leads to increased urine osmolality in central DI, nephrogenic DI stays low.
List some biochemical features of DI.
Hypernetraemia.
Raised urea.
Increased plama osmolality.
Low urine osmolality.
List some biochemical features of psychogenic polydipsia.
Mild hyponatraemia (due to excess water intake)
Low plasma osmolality.
Low urine osmolality.
Why must vasopressin receptor peptidergic agonists be selective.
We have V1 and V2 receptors - activating V1 receptors would have effects in unwanted systems e.g. vascular smooth muscle, liver, platelets etc.
Drug must be specific for V2 receptors.
Name a V1 and V2 vasopressin receptor peptidergic agonist.
V1 - terlipressin.
V2 - desmopressin (DDAVP).
How can desmopressin be administered?
Nasally
Orally
Subcutaneous injection
What effect does desmpressin have on central DI patients? What concern does this crease?
reduction in urine volume and concentration - patient must be told to sotp drinking large amounts to avoid hyponatraemia.
How can nephrogenic DI be treated?
Thiazides, e.g. bendroflumethiazide.
Outline the mechanism of action of thiazides.
–Inhibits Na+/Cl-transport in distal convoluted tubule(→diuretic effect)
–Volume depletion
–Compensatory increase in Na+ reabsorption from the proximal tubule (plus small decrease in GFR, etc.)
–Increased proximal water reabsorption
–Decreased fluid reaches collecting duct
–Reduced urine volume
What is syndrome of inappropriate ADH (SIADH)?
Plasma vasopressin concentration is inappropriately high for plasma osmolality.
Outline the pathology of SIADH (diagram).
Re
List the signs and symptoms of SIADH.
signs:
raised urine osmolality, reduced urine volume.
hyponatraemia.
symptoms (if any):
p[Na+]<120mM –> generalised weakness, poor mental function, nausea.
p[Na+]<110 mM –> confusion leading to coma and death.
List potential causes of SIADH.
CNS - sub-arachnoid haemorrhage, stroke, tumour, TBI
Pulmonary idsease - pneumonia, bronchiectasis.
Malignancy - lung
Drug-related - carbamazepine, selective serotonin reuptake inhibitors (SSRI)
Can be idiopathic.
How is SIADH treated?
long term - surgery
immediate concern - fluid restriction, use drugs that reduce VP action in kidneys e.g. demeclocyline.
What are Vaptans?
non-competitve V2 receptor antagonists.
Inhibit AQP2 syn. and transport, preventing renal H2O reabsorption.
Aquaresis - solute sparing H2O renal excretion.
