Neurohypophysial disorders Flashcards
What are magnocellular neurones?
Neurones that project into the neurohypophysis and have herring bodies
What are the 2 neurohypophysial hormones?
Oxytocin and vasopressin
What does vasopressin do?
It is an anti-diuretic and it acts by increasing water reabsorption
How does vasopressin act? (summary)
By increasing water reabsorption from the renal cortical and medullary collecting ducts via V2 receptors
What is the detailed action of VP?
- VP binds to V2 receptors which are Gs receptors
- Aquaporin 2 molecules are created which move to the apical membrane in aggraphores
- The AQA2 insert in the apical membrane to allow water reabsorption
Where are osmoreceptor neurones located? What’s special about this place
In the organum vasculosum which has no blood brain barrier
What is the homeostatic response of osmoreceptors when blood osmolarity goes up?
Water moves out of osmoreceptor cells and the osmoreceptors shrink which triggers them to send more signals to the hypothalamus to release VP and also stimulates thirst. This increases water reabsorption from renal collecting ducts, reduction in blood plasma osmolarity and reduced urine volume but a higher urine osmolarity
What are the two types of diabetes insipidus?
Cranial/Central and Nephrogenic
How can cranial DI be acquired? (More common than congenital)
Traumatic brain injury Pituitary surgery Pituitary tumours, craniopharyngioma Metastasis to pituitary gland Granulomatous infiltration of median eminance
How can you aquire a nephrogenic DI?
Drug use eg lithium
What are examples of mutations that can cause congenital nephrogenic DI?
Mutation in gene encoding V2 receptor
AQA2 type water channels
What is the fundamental cause of diabetes insipidus?
Insufficient ADH/Vasopressin
What are signs and symptoms of DI?
Polyuria Hypo-osmolar urine Polydipsia Dehydration Disruption to sleep and fatigue
What is psychogenic polydipsia?
Excess fluid intake and polyuria but VP secretion ability preserved
What is a possible aetiology of psychogenic polydipsia?
Anti-cholinergic effects of medication stimulating a ‘dry mouth’ effect
What type of people frequently show signs of psychogenic polydipsia?
Psychiatric patients and in-patients told to ‘drink plenty’ by healthcare professionals
What is the plasma osmolarity difference in people with DI and PP?
People with DI will have a HIGH plasma osmolarity but people with PP will have a LOW plasma osmolarity even though they both drink a lot- due to differences in VP
How is the water deprivation test done?
No water given to patient. A cannular inserted to take regular readings, and patient’s weight is taken regularly to make sure they don’t become too dehydrated
What is DDAVP?
Synthetic AVP that differentiates between cranial and central readings - used in water deprivation tests and to treat DI
Why are the results of PP very similar to normal levels in a water deprivation test?
It is mostly psychogenic! PP is slightly lower because polydipsia has ‘washed away’ the concentration gradient in the medulla slightly
What are biochemical features of DI?
Hypernatraemia, raised urea, increased plasma osmolarity, hypoosmolar urine
What are biochemical features of PP?
Mild hyponatraemia, low plasma osmolarity and hypoosmolar urine
What is the treatment for cranial diabetes insipidus?
Only want to target V2 kidney receptors so use selective VP receptor agonists
- V1 Terlipressin
- V2 Desmopressin (DDAVP)
How can DDVAP be administered?
Nasal spray, orally or subcutaneous
What does DDVAP do?
Reduce urine conc and volume in cranial DI however patients must be told to NOT CONTINUE drinking large volumes of water
What is the treatment for nephrogenic DI?
Thazides eg bendroglumethazide which inhibits the Na+/Cl- transport in DCT in kidneys therefore promotes diuresis. This leads to volume depletion and an increase in Na+ reabsorption in PCT. This increases water reabsorption in PCT and reduces urine volume.
Why is nephrogenic DI hard to treat
Problem lies in kidneys, not the hormone itself
What is SIADH
Syndrome of inappropriate ADH is where there is an excessively high ADH , natriuresis and eurolaemia
What are the signs of SIADH
Small volumes of conc urine, hyponatraemia
What are the symptoms of SIADH
Can be symptomless, but can also if hyponatraemia <120mM show weak, poor mental function and nausea or <110mM can lead to coma or death
What can be the causes of SIADH
Primary brain injury – e.g. meningitis. subarachnoid haemorrhage (SAH)
Malignancy – e.g. small-cell lung cancer
Drugs – e.g. carbamazepine, SSRIs, amitriptyline
Infectious – e.g. atypical pneumonia, cerebral abscess
Hypothyroidism
What are treatment plans for SIADH
Remove tumour
Fluid restriction - immediate
Demeclocyline - long term which induces nephrogenic DI by reducing renal water absorption to prevent VP action in the kidneys
VAPTANS which are non competitive V2 receptor antagonists that inhiit AQA2 synsthesis and transport and causes aquaresis - solute sparing renal excretion of water but are very expensive
