What is the hypothalamo-neurohypophysial system?
What are the effects of vasopressin?
Anti-diuretic -> acts on renal cortical and medullary collecting ducts via V2 receptors
What is the mechanism of action of VP on the collecting duct cell to cause AQP2, 3 and 4 insertion?
Where is VP release regulated?
Osmoreceptors are located in the Organum vasculosum -> projecting to hypothalamic PVN (paraventricular nucleus) and SON (supraoptic nucleus)
How do the osmoreceptors react to changes in osmolality?
Osmoreceptors are very sensitive to changes in EC osmolarity, so if increase in EC Na, osmoreceptor shrinks stimulating osmoreceptor firing, causing release from hypothalamic PVN and SON
What is the normal response to water deprivation?
Retaining water at the kidneys means that urine volume decreases and serum osmolality is maintained
What are the 2 forms of diabetes insipidus?
Absence/lack of circulating VP (cranial/central) OR end-organ (kidneys) resistance to VP (nephrogenic)
How is cranial diabetes insipidus caused and what are the 2 types?
Acquired: Damage to neurohypophysial system due to traumatic brain injury, pit surgery, pit tumours, craniopharyngiomas, metastasis to pit gland, granulomatous infiltration of median eminence (TB, sarcoidosis). Congenital (rare)
How is nephrogenic diabetes insipidus caused?
Congenital (rare -> mutation in gene encoding V2 receptor, AQP2) OR acquired (drugs -> lithium: used for bipolar disorder but can cause primary hypoparathyroidism as well)
What are the signs and symptoms of DI?
How does the DI thirst loop differ if no water is given?
What is psychogenic polydipsia?
Seen in psych patients due to 'dry mouth' -> could be in patients told to drink plenty; leading to polydipsia and polyuria without DI as VP secretion is preserved
How does the cycle of osmolarity work in psychogenic polydipsia?
How does the plasma osmolarity differ between DI, normal and psychogenic polydypsia?
NB: don't worry about the actual numbers
How does the urine osmolarity differ between DI, normal and psychogenic polydipsia during a water deprivation test?
First part of test is to differentiate between psychogenic polydipsia and DI -> measure concentration and volume of urime made and osmolality of circulating blood (also weigh them frequently) Second part is to differentiate between nephrogenic and cranial DI with a synthetic VP analogue (central is due to not enough VP so giving them VP improves their function but nephrogenic can't respond to VP so isn't going to help the patient)
What are the biochemical features of DI?
Hypernatraemia, raised urea, increased plasma osmolarity, hypo-osmolar urine (dilute)
What are the biochemical features of psychogenic polydipsia?
Mild hyponatraemia (excess water intake), low plasma osmolality, Hypo-osmolar urine (dilute)
What examples of selective VP receptor peptidergic agonists exist for V1 and V2?
V1 - terlipressin, V2 - desmopressin (DDAVP)
What is desmopressin - administration, use and care?
Admin - nasally, orally, SC; Use - reduction in urine volume and concentration in cranial DI; Care - tell patient to NOT drink large amounts of fluid, risk of hyponatraemia
How do you treat nephrogenic diabetes insipidus and what is the mechanism?
Thiazides (bendroflumethiazide) -> Inhibits Na/Cl transport in DCT, volume depletion, compensatory increase in Na reabsorption from PCT, increase proximal water reabsorption, decreased fluid reaching collecting duct, reduced urine volume
What is SIADH?
Syndrome of inappropriate ADH -> plasma VP concentration is inappropriately high for existing plasma osmolality
What happens when VP is increased (hyponatraemia and euvolaemia)?
Euvolemic means have normal circulating volume
What are the signs of SIADH?
Raised urine osmolality, decreased urine volume, hyponatraemia due to increased water reabsorption
What are the symptoms of SIADH?
Can be symptomless, but if p[Na] < 120mM: generalised weakness, poor mental function, nausea and if p[Na] <110mM, confusion leading to coma and ultimately DEATH
What are the causes of SIADH?
What is the treatment for SIADH?
Appropriate -> surgery for tumour; reducing immediate concern -> fluid restriction (immediate) and then use drugs preventing VP action in kidneys (long-term), inducing nephrogenic DI (reducing renal water reabsorption (demeclocyline - V2 receptor antagonists)
What are vaptans?
V2 receptor antagonists (Non-competitive) -> very expensive and licensed in UK to treat hyponatraemia associated with SIADH
How do vaptans function?
Inhibit AQP2 synthesis and transport to collecting duct apical membrane preventing renal water reabsorption
What is aquaresis?
Solute sparing renal excretion of water, contrasting with diuretics which produce simultaneous electrolyte loss
Which hormones are secreted from the thyroid gland?
T4 and T3