pituitary Flashcards
SIADH: recall the pathophysiology of syndrome of inappropriate antidiuretic hormone (SIADH), list the principle causes, recall the clinical features and explain treatment options
what 2 hormones does neurohypophysis (posterior pituitary gland) produce
oxytocin, vasopressin (ADH)
what does the posterior pituitary gland show as on MRI; location and relevance of optic chiasma
bright spot on pituitary (hangs down by stalk; dopamine comes down to inhibit prolactin secretion); optic chiasma runs along top of pituitary gland with little gap in between
hypothalamo-neurohypophysial system
derived from neural tissue; paraventricular and supraoptic nuclei in hypothalamus project through median eminence into posterior pituitary (paraventricular nuclei also project to other parts of CNS) -> release of vasopressin and/or oxytocin
principle effect of vasopressin and how this is achieved (receptor)
anti-diuretic so increases water reabsorption from renal cortical and medullary collecting ducts via V2 receptors, reducing urine production
how does vasopressin cause AQP2 channels to be inserted into apical membrane of collecting duct
binds to V2 receptor on basolateral membrane -> activates G-protein -> adenyl cyclase converts ATP to cAMP -> activates PKA and other intracellular mediators -> AQP2 synthesised -> aggraphores migrate to apical membrane
how is water absorbed from tubule lumen to plasma
enters apical membrane through AQP2 -> enters plasma via basolateral membrane through AQP3 and AQP4
how is vasopressin release regulated
in organum vasculosum, osmoreceptors (neurones) present which project to hypothalamic paraventricular and supraoptic nuclei
how do osmoreceptors work to release vasopressin
very sensitive to changes in EC osmolality, so increase in EC Na+ means water diffuses out of osmoreceptor, so it shrinks, becoming irritable and increasing osmoreceptor firing and causing vasopressin to be released from paraventricular and supraoptic nuclei in hypothalamus
normal response to water deprivation
increased serum osmolality -> stimulation of osmoreceptors -> thirst and increased vasopressin released -> increased water reabsorption from renal collecting ducts -> reduced serum osmolality and reduced urine volume, increasing urine osmolality
definition of syndrome of inappropriate ADH (SIADH)
plasma vasopressin concentration is inappropriately high for existing plasma osmolality
how does increased vasopressin cause hyponatraemia but with euvolaemia
increased vasopressin -> increased H2O reabsorption from renal collecting ducts -> expansion of ECF volume -> direct hyponatraemia or atrial nariuretic peptide (ANP) released from right atrium -> natriuresis -> hyponatraemia and euvolaemia (normal blood plasma volume)
2 signs of SIADH
raised urine osmolality with decreased urine volume (initially); decreased p[Na+] (hyponatraemia), mainly due to increased water reabsorption
symptoms of SIADH: p[Na+] < 120mM; p[Na+] < 110mM
can be symptomless; p[Na+] < 120mM: generalised weakness, poor mental function, nausea; p[Na+] < 110mM: confusion leading to coma and death
5 causes of SIADH: normally head or lung pathology
CNS, pulmonary disease, malignancy, drug-related, idiopathic
4 SIADH CNS causes
SAH, stroke, tumour, TBI
2 SIADH pulmonary disease causes
pneumonia, bronchiectasis
SIADH malignancy cause
lung (small cell)
2 SIADH drug-related causes
carbamazepine (epilepsy), SSRI (low mood)
general treatment for SIADH
appropriate e.g. surgery for tumour
treatment for SIADH: what is done a) immediately and b) longer-term, to reduce immediate concern of hyponatraemia
immediately: fluid restriction; longer-term: use drugs which prevent vasopressin action in kidneys
what drugs are used to treat SIADH in the longer-term
demeclocyline to induce nephrogenic diabetes insipidus to reduce renal water reabsorption; V2 receptor antagonists to inhibit action of ADH
example of non-competitive V2 receptor antagonists
vaptans
how do V2 receptor antagonists
inhibit AQP2 synthesis and transport to collecting duct apical membrane, preventing water reabsorption, but promote aquaresis
what is aquaresis and compare with diuresis
solute-sparing renal excretion of water (just excreting water not salts), preventing loss of more Na+ as already hyponatraemic; contrast with diuretics (diuresis) which produce simultaneous electrolyte loss as well as water loss
features of SIADH V2 receptor antagonists in UK
licensed in UK for treatment of hyponataemia associated with SIADH; very expensive