Neurohypophysial Disorders Flashcards
Name the two main groups of hypothalamic nuclei which terminate in the neurohypophysis?
Paraventricular Nucleus Supraoptic Nucleus NOTE: nucleus = group of cell bodies in CNS
What two hormones are produced by the neurohypophysis?
Vasopressin Oxytocin
What is the principal action of vasopressin and how does it carry out this action?
Vasopressin = ADH (anti-diuretic hormone) Vasopressin’s main action is on the V2 receptors in the renal cortical and medullary collecting ducts cells which are impermeable to water It stimulates aquaporin 2 synthesis and the ones which are stored inside vesicles to be inserted into the apical membrane (facing lumen) This increases water reabsorption by making the collecting duct cells permeable to water and has an antidiuretic effect NOTE: diuresis = increase in urine production
What is diabetes insipidus?
A disease which causes production of large volumes of dilute urine (polyuria) and excessive thirst (polydipsia)
What are the two forms of diabetes insipidus?
Cranial (central) = absence or lack of circulating vasopressin Nephrogenic = end-organ (kidneys) resistance to vasopressin
What can cause cranial diabetes insipidus?
ACQUIRED (more common) - by damage to the neurohypophysial system, e.g. by: Traumatic brain injury Pituitary surgery Pituitary tumours, craniopharyngioma (benign tumours which grow just above the pituitary gland near the base of the brain - they affect the pituitary gland as they grow so close to it) Metastasis to the pituitary gland (e.g breast cancer) Granulomatous infiltration of median eminence eg TB, sarcoidosis - i.e. spread of infection to the median eminence resulting in a granuloma (mass of macrophages and other immune cells - formed in inflammatory response) CONGENITAL (rare)
What can cause nephrogenic diabetes insipidus?
Congenital (rare) - e.g: mutation in gene encoding V2 receptor so the receptor doesn’t respond to vasopressin → MAIN mutation in aquaporin 2 so it isn’t embedded into the collecting duct basolateral membrane properly Acquired - by drug use, e.g: lithium - accumulates in collecting duct cells and interfere with cell response to vasopressin
State some signs and symptoms of diabetes insipidus.
Polyuria - large volumes of urine production Hypo-osmolar urine - very dilute Polydipsia - excessive thirst and drinking Dehydration (and consequences) if fluid intake not maintained - can lead to DEATH Possible disruption of sleep due to nocturia Possible electrolyte imbalance if dehydration occurs leading to hyper-osmolar plasma
State another cause of polydipsia that isn’t diabetes.
Psychogenic polydipsia This is a central disturbance so is most commonly seen in psychiatric patients that increases the drive to drink - the exact cause (aetiology) for this is unclear Anticholineregic drugs can be used in psychiatry - this can lead to a ‘dry mouth’ which also stimulates the feeling of a need to drink This psychiatric effect can also be seen in patients who are told to ‘drink plenty’ by healthcare professions
What test can be used to distinguish between normal, psychogenic polydipsia, central DI and nephrogenic DI? Describe the results you would expect.
Fluid deprivation test: Normal and psychogenic polydipsia will show a rise in urine osmolality (more concentrated urine being produced over time and in lower amounts) Central and nephrogenic diabetes insipidus will show little or no change in urine osmolality (and volume) Fluid deprivation with administration of DDAVP (Desmopressin) = vasopressin substitute: Central diabetes insipidus will show a rise in urine osmolality (lower volumes of more concentrated urine produced) Nephrogenic DI will still have a low urine osmolality (and volume) because of end-organ resistance
Why is the urine osmolality of someone with psychogenic polydipsia lower (mainly in the fluid deprivation test) than a normal subject?
Because there is a constant passage of large volumes of water through the kidneys, this will reduce the osmotic gradient which is necessary for vasopressin to have its effect, resulting in slightly less water reabsorption, therefore slightly lower urine osmolality (more dilute urine)
Describe the normal change in urine osmolality as plasma osmolality increases. How does this differ in DI?
Normally, urine osmolality will increase as plasma osmolality increases - due to increased water reabsorption and production of concentrated urine to maintain plasma osmolality In DI, there is little change in urine osmolality as plasma osmolality increases - still large volumes of dilute urine being produced
What is SIADH?
Syndrome of Inappropriate ADH When the plasma vasopressin concentration is inappropriately high for the existing plasma osmolality
What are the symptoms of SIADH?
Can be symptomless However if p[Na+] <120 mM: generalised weakness, poor mental function, nausea If p[Na+] <110 mM: CONFUSION leading to COMA and ultimately DEATH Hyponatreamia causes problems with neural transmission (AP generation requires Na+ influx) - the extent of the hyponatreamia determines the symptoms (i.e. extent of neurological disruption)
State some causes of SIADH.
CNS SAH, stroke, tumour, TBI Pulmonary disease Pneumonia, bronchiectasis Malignancy Lung (small cell) Drug-related Carbamazepine, SSRI Idiopathic
How is SIADH treated?
Fluid Restriction Provide appropriate treatment when the cause is identified (e.g. surgery for a tumour) NOTE: if someone is hyponatraemic you need to deal with that as soon as possible – e.g. use drugs that prevent vasopressin action in the kidneys
State two selective vasopressin receptor peptidergic agonists.
V1 selective – Terlipressin V2 selective - Desmopressin (used to treat CRANIAL diabetes insipidus to reduce unwanted effects by acting on other vasopressin receptors)
