pituitary

Question 1

what 2 hormones does neurohypophysis (posterior pituitary gland) produce

Answer 1

oxytocin, vasopressin (ADH)

Question 2

what does the posterior pituitary gland show as on MRI; location and relevance of optic chiasma

Answer 2

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

Question 3

hypothalamo-neurohypophysial system

Answer 3

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

Question 4

principle effect of vasopressin and how this is achieved (receptor)

Answer 4

anti-diuretic so increases water reabsorption from renal cortical and medullary collecting ducts via V2 receptors, reducing urine production

Question 5

how does vasopressin cause AQP2 channels to be inserted into apical membrane of collecting duct

Answer 5

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

Question 6

how is water absorbed from tubule lumen to plasma

Answer 6

enters apical membrane through AQP2 -> enters plasma via basolateral membrane through AQP3 and AQP4

Question 7

how is vasopressin release regulated

Answer 7

in organum vasculosum, osmoreceptors (neurones) present which project to hypothalamic paraventricular and supraoptic nuclei

Question 8

how do osmoreceptors work to release vasopressin

Answer 8

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

Question 9

normal response to water deprivation

Answer 9

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

Question 10

definition of syndrome of inappropriate ADH (SIADH)

Answer 10

plasma vasopressin concentration is inappropriately high for existing plasma osmolality

Question 11

how does increased vasopressin cause hyponatraemia but with euvolaemia

Answer 11

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)

Question 12

2 signs of SIADH

Answer 12

raised urine osmolality with decreased urine volume (initially); decreased p[Na+] (hyponatraemia), mainly due to increased water reabsorption

Question 13

symptoms of SIADH: p[Na+] < 120mM; p[Na+] < 110mM

Answer 13

can be symptomless; p[Na+] < 120mM: generalised weakness, poor mental function, nausea; p[Na+] < 110mM: confusion leading to coma and death

Question 14

5 causes of SIADH: normally head or lung pathology

Answer 14

CNS, pulmonary disease, malignancy, drug-related, idiopathic

Question 15

4 SIADH CNS causes

Answer 15

SAH, stroke, tumour, TBI

Question 16

2 SIADH pulmonary disease causes

Answer 16

pneumonia, bronchiectasis

Question 17

SIADH malignancy cause

Answer 17

lung (small cell)

Question 18

2 SIADH drug-related causes

Answer 18

carbamazepine (epilepsy), SSRI (low mood)

Question 19

general treatment for SIADH

Answer 19

appropriate e.g. surgery for tumour

Question 20

treatment for SIADH: what is done a) immediately and b) longer-term, to reduce immediate concern of hyponatraemia

Answer 20

immediately: fluid restriction; longer-term: use drugs which prevent vasopressin action in kidneys

Question 21

what drugs are used to treat SIADH in the longer-term

Answer 21

demeclocyline to induce nephrogenic diabetes insipidus to reduce renal water reabsorption; V2 receptor antagonists to inhibit action of ADH

Question 22

example of non-competitive V2 receptor antagonists

Answer 22

vaptans

Question 23

how do V2 receptor antagonists

Answer 23

inhibit AQP2 synthesis and transport to collecting duct apical membrane, preventing water reabsorption, but promote aquaresis

Question 24

what is aquaresis and compare with diuresis

Answer 24

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

Question 25

features of SIADH V2 receptor antagonists in UK

Answer 25

licensed in UK for treatment of hyponataemia associated with SIADH; very expensive