Theme 1: The Endocrine System

203: Theme 1: The Endocrine System 10. Thirst and Fluid Balance Physiology of Thirst and Fluid Balance • Where are osmoreceptors in the brain located? anterior wall of 3rd ventricle • How do these osmoreceptors impact thirst and fluid balance? volume of cells is altered by transmembrane flux of water → initiates neural impulses → hypothalamus synthesises ADH, cerebral cortex registers thirst • Where in the hypothalamus is vasopressin synthesised? paraventricular + supraoptic nuclei → secretory granules travel to and are released from posterior PG • How does ADH increase water intake by the kidneys? o binds to V2 receptors on collecting ducts o expression of aquaporin-2 channels on surface Pathophysiology of Diabetes Insipidus • Cranial Diabetes Insipidus o common causes ▪ idiopathic ▪ genetic ▪ secondary e.g. surgery/trauma o rare causes ▪ secondary e.g. tumour/ histiocytosis, sarcoidosis, encephalitis, meningitis, vascular insults, autoimmune o symptoms ▪ polyuria ▪ polydipsia (provided thirst sensation remains intact) o treatment ▪ DDAVP (desmopressin) • What is Hypothalamic Syndrome? growth in hypothalamus disregulating range of homeostatic functions e.g. disordered thirst (→ DI), appetite, temperature, sleep and hypopituitarism • Nephrogenic Diabetes Insipidus o What is the pathophisiology of Nephrogenic Diabetes Insipidus? renal tubules resistant to AVP o Aetiology ▪ genetic: mutation of receptor or aquaporin ▪ metabolic: calcium or potassium ▪ chronic kidney disease ▪ drugs e.g. lithium ▪ idiopathic o What can this cause? polydipsia o Treatment ▪ correct cause ▪ thiazide diuretics: mild hypovolemia → aid with solute absorption in proximal tubule ▪ NSAIDs: block prostoglandin production, enhance urine concentraion + anti-diuretic effects • Primary Polydipsia (psychogenic) o Aetiology polydipsia → ▪ plasma osmolality → AVP secretion → polyuria renal interstitial solute lost → reduced renal concentrating ability Pathophysiology of SIADH • What is SIADH? when patient is clinically euvolaemic with low Na and plasma osmolality, but have inappropriately high urine Na concentraions and high urine osmolality • • What can cause SIADH? o renal, adrenal or thyroid (endocrine) problems o neoplasia o neurological disorders o lung disease If underlying cause is not found, how would you treat SIADH? o o fluid restriction until Na levels return to normal How does demeclocycline work? induce mild nephrogenic DI o vasopressin antagonists Investigations • What investigations would you do in regards to Polyuria and Polydipsia? What would you want to exclude? o medical history o 24 hour fluid balance: intake + output o water deprivation test ▪ How is it done? no water, inject AVP measure plasma + urine osmolality, weight ▪ What would be a normal response? normal plasma osmolality high urine osmolality ▪ What would be the results in CDI? poor urine osmolality after dehydration rise in urine osmolality after desmopressin ▪ What results would you get with NDI? poor urine osmolality after dehydration no rise in urine osmolality after desmopressin • • exclude: DM, hypercalcaemia/hypokalaemia Hyponatraemia o Symptoms ▪ asymptomatic ▪ non-specific: headache, nausea, mood change, cramps, lethargy ▪ chronic: brain adapts o o ▪ severe or sudden: confusion, drowsiness, seizures, coma What should you exclude before decided patient is hyponatraemic? ▪ drugs e.g. thiazides ▪ high concentrations of other substances in blood e.g. glucose, plasma lipids or proteins How else is hyponatraemia classified? by extracellular volume status e.g. hypo-, normo- or hypervolaemia o When treating, what should you be careful of? Why? Who is at most risk? correct slowly → rapid correction risks oligodendrocyte degeneration + CNS myelinolysis ▪ ▪ may be permanent alcoholics + malnorished at particular risk What is DIDMOAD? - genetic condition causing diabetes and other things