Neurohypophyseal disorders Flashcards
Name the two main nuclei within which neurones of the neurohypophysis have their cell bodies. (2)
Paraventricular Nucleus
Supraoptic Nucleus
Describe the innervation pattern of the hypothalamic PVN and SON nuclei. (3)
- SON neurons are magnocellular
- PVN neurons predominantly magnocellular
- Magnocellular neurons extend into the posterior pituitary
- Some PVN neurons terminate at the median eminence and release e.g. ACTH into the hypophyseal system
What two hormones are produced by the neurohypophysis? (2)
Vasopressin
Oxytocin
What receptors does vasopressin bind to and what are the effects? (2)
- V1 - vasoconstriction
- V2 - increased water reabsorption
What is the mechanism of vasopressins anti-diuretic effect at the kidney? (4)
- Binds to V2 (a GPCR) to activate Ga
- Ga activates adenylate cyclase which produces cAMP from ATP
- cAMP activates PKA
- PKA mediates the cellular effects including:
- AQP2 synthesis/aggrophore insertion (into APICAL membrane)
- Water taken up from tubule lumen (via AQP2) and into interstitial space by AQP3/4 (constitutively active)
How is ADH release regulated? (3)
- Osmoreceptors in the organ vasculosum activated when there is low plasma osmolarity
- Water leaves their cell bodies and into the extracellular space so the cells shrink
- This activates the osmoreceptors and so get increased ADH release at the terminals
- At high plasma osmolarity water enters the neurons and reduces ADH release
List diseases associated with
i) Too little ADH
ii) Too much ADH
i) Diabetes insIpidus
ii) SIADH
What are the two forms of diabetes inspidus and what is the mechanism of each? (2)
1) Cranial DI: failure to produce sufficient ADH (1)
2) Nephrogenic DI: Failure to respond sufficiently to ADH
What is the cause of cranial (aka central) diabetes insipidus? (3)
- Traumatic brain injury
- Pituitary tumour/craniopharyngioma
- Surgery
- Metastasis (from breast cancer)
- Granulomatous infiitration (sarcoidosis)
- In rare cases can be congenital (though usually acquired)
What is the cause of nephrogenic diabetes insipidus? (2)
- In rare cases can be congenital (though usually acquired)
- E.g. mutation in V2 receptor
- Can be caused by drugs/medication e.g. lithium
State some signs and symptoms of diabetes insipidus. (3)
- Polyuria
- Polydipsia
- Hypo-osmolar urine
- Dehydration
- Possible disruption of sleep
- Possible electrolyte imbalance
How does psychogenic polydipsia present? (1)
Polydipsia (excessive thirst and drinking) + polyuria AND ability to produce/respond to ADH is preserved
Compare the biochemical features of diabetes insipidus with those of psychogenic polydipsia. (2)
- DI = hypernatraemia. Psychogenic polydipsia hyponatraemia (another way to see this is that in diabetes inspidus your plasma osmolarity is HIGHER than normal, whilst in psychogenic polydipsia your plasma osmolarity is LOW than normal)
- In diabetes insipidus you get raise plasma urea, you do not in psychogenic polydipsia
- In both you have hypo-osmolar urine
i) What test can you use to distinguish between psychogenic polydipsia and diabetes insipidus? (2)
ii) … between nephrogenic and cranial diabetes inspidus? (2)
i) Do a water deprivation test: as long as the individual can produce and respond appropriately to ADH in water deprived circumstances their urine will become hyperosmolar. In DI your urine will remain hypoosmolar even in water deprived circumstances. In psychogenic polydipsia your urine will become hyperosmolar (even if not quite as much as a normal person). NOTE BEWARE DO NOT WANT TO KILL THE DI PATIENTS!!!
ii) Administer desmopressin. Desmopressin is an ADH anaologue so in cranial DI it will in water deprived circumstances show a more normal response (urine will become hyperosmolar). This will not happen in nephrogenic DI because the problem is with the response to DI rather than the production of it.
How is diabetes insipidus treated? (2)
For cranial DI: desmopressin (an ADH analogue - V2 SPECIFIC)
For nephrogenic DI: thiazides
