Neurohypophysial Disorders Flashcards
what are magnocellular neurones?
neurones that project into the neurohypophysis with herring bodies
come from the paraventricular nucleus of the hypothalamus
the 2 neurohypophysis hormones
- oxytocin
- vasopressin (ADH)
what receptors does VP bind to?
V2 receptors in the renal cortical and medullary collecting ducts
the pathway of VP action
1) VP binds to V2 receptor
2) G protein activates the conversion of ATP to cAMP
3) PKA is activated
4) mediators lead to the synthesis of AQP2
5) AQP2 move towards the apical membrane in aggraphores
6) APQ2 insertion leads waster in from the lumen
(APQ 3 and 4 let it into the circulation)
what is the response to water deprivation?
- increased plasma osmolarity
- stimulation of osmoreceptors (thirst)
- increased VP release
- increased water reabsorption from renal collecting ducts
- reduction in plasma osmolarity
- reduce urine volume, increase in urine osmolarity
what are the two forms of Diabetes Insipidus (DI)?
- cranial/ central
- nephrogenic
difference between cranial/central and nephrogenic DI
Cranial DI is not making enough VP
nephrogenic DI is the target organ being resistant to VP
acquired cranial DI
more common due to: - traumatic brain injury - pit. surgery - pit. tumours, craniopharygioma - metastases to pit. gland - granulotamous infiltration of median eminence e.g. TB
congenital cranial DI is rare
causes of acquired and congenital nephrogenic DI
acquired- drugs e.g. lithium
congenital- rare, due to mutation in V2 receptor encoding gene, AQP2 channel gene
signs and symptoms of DI
- polyuria (urine volume increases)
- very dilute urine (hypo-osmolar
- polydipsia
- dehydration
- sleep distruption, fatigue e
what is psychogenic polydipsia?
excess fluid intake causing polyuria but there is nothing wrong with VP system
where is psychogenic polydipsia seen?
in psychiatric patients, possibly due to the anti-cholinergic effects of medication causing a “dry mouth” effect
also seen in those that drink plenty of water when instructed to by health professionals
what is the difference between those with DI and those with PP?
DI patients have a high plasma osmolarity while PP patients have a low plasma osmolarity despite the same intake of water
what is the normal range of plasma osmolarity?
270-290 mOsm/kg H2O
<270 –> psychogenic polydipsia
> 290 –> diabetes insipidus
what are the biochemical features of DI?
- hypernatraemia
- raised urea
- increased plasma osmolarity
- hypo-osmolar urine
biochemical features of primary polydipsia?
- mild hyponatraemia
- low plasma osmolarity
- hypo-osmolar urine
what needs to be taken into consideration in the treatment of DI?
as all vasopressin receptors will be activated, they need to be specific to kidney receptors
treatment of cranial DI
V1- terlipressin
V2- desmopressin (DDVAP0
DDVAP is a synthetic AVP
what is DDVAP used for?
for cranial DI (as the kidneys are still sensitive, therefore not used in nephrogenic)
administered as nasal spray, orally or sub-cutaneous
- reduces urine concentration and volume
what must be told to a patient if they are told to take DDAVP?
they should not continue drinking large volumes of water as this could lead to hyponatraemia
what is the treatment of nephrogenic DI?
thiazides e.g. bendroflumethiazide (diuretic)
- causes mild hypovolaemia and therefore encourages salt and water reuptake in the PCT
mechanism of thiazides for nephrogenic DI
inhibition of Na+/Cl- transport in the DCT in kidneys this promotes diuresis volume depletion increase in Na+ reabsorption in PCT increase water reabsorption reduce urine volume
what is SIADH?
Syndrome of Inappropriate ADH
excessively high ADH
what is natriuresis and euvolaemia?
natriuresis- excretion of sodium in the urine (consequence of SIADH)
euvolaemia- state of normal body fluid volume
signs and symptoms of SIADH
Small volumes of concentrated urine,
hyponatraemia (leads to poor nerve conduction–> confusion and unsteadiness)
can be symptomless
what are the different symptoms seen with different hyponatraemia levels?
<120mM- weakness, poor mental function and nausea
<110mM- coma and death
causes of SIADH
- CNS: SAH, stroke, tumour, traumatic brain injury
- pulmonary disease: pneumonia, bronchiectasis
- malignancy: small cell lung cancer
- drug-induced: carbamazepine, SSRI
- idiopathic
what are the SIADH treatment options?
1) remove the tumour
2) reduce immediate concern e.g. hyponatraemia
- fluid restriction
3) VAPTANS (v2 receptor antagonists–> prevent AQ2 synthesis)
long term treatment of SIADH
demeclocycline
induces nephrogenic DI, reduce renal water reabsorption
prevent VP action in the kidneys
what are VAPTANS?
non-competitive V2 receptor antagonists
- inhibits AQP2 synthesis and transport to the apical membrane
- causes aquaresis (solute sparing excretion of water; electrolytes are not lost)
- however very expensive
how is desmopressin administered?
as a nasal spray usually
what type of DI does desmopressin respond to best?
cranial DI
nephrogenic DI patients dont respond to DDAVP as they do not recognise it
