Neurohypophysial Disorders Flashcards
Name the two main nuclei within which neurones of the neurohypophysis have their cell bodies. State the types of neurones for each
Paraventricular Nucleus - Parvocellular and Magnocellular
Supraoptic Nucleus - just Magnocellular
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’s binds to V2 receptors in the renal cortical and medullary collecting ducts.
It stimulates the synthesis and assembly of aquaporin 2 (via Gs protein coupled receptor pathway), which then increases water reabsorption and has an antidiuretic effect => increased urine osmolality, reduced serum osmolality
State some other actions of vasopressin
- Vasoconstriction
- Corticotrophin release
- Factor VIII and von Willebrand factor synthesis
Describe how vasopressin release is regulated
Osmoreceptors shrink in response to and increase in extracellular osmolality (increased Na+) => increased osmoreceptor firing => increased VP release
Where are osmoreceptors found within the brain?
Organum vasculosum of the lamina terminalis
What are the two types of Diabetes Insipidus, and characterise the two?
Cranial (or central) = Absence or lack of circulating vasopressin
Nephrogenic = Kidneys resistant to vasopressin
Cranial DI is mainly as a result of damage to the neurohypophysial system. List possible causes for such damage.
- Traumatic brain injury
- Pituitary surgery
- Pituitary tumours, craniopharyngioma
- Metastasis to the pituitary gland eg breast
- Granulomatous infiltration of median eminence eg TB, sarcoidosis
- Congenital (rare)
What can cause nephrogenic diabetes?
- Congenital (e.g. V2 receptor/ AQP2 channel gene mutation)
- Acquired due to drugs (e.g. lithium)
What are the signs and symptoms of diabetes insipidus?
Polyuria Polydipsia Hypo-osmolar urine Dehydration Possible disruption of sleep
State another cause of polydipsia that isn’t diabetes.
Psychogenic polydipsia
This is a central disturbance that increases the drive to drink (VP secretion and response is normal)
What is the approximate plasma osmolality for DI and PP?
DI = 290 mOsm/kg H2O PP = 270 mOsm/kg H2O
Normal (hydrated) range = 280
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 = rise in urine osmolality
- Central and nephrogenic diabetes insipidus will show little or no change in urine osmolality
- After fluid deprivation with administration of DDAVP (Desmopressin), only Central diabetes insipidus will show a rise in urine osmolality
Why is the urine osmolality of someone with psychogenic polydipsia lower (in the fluid deprivation test) than a normal subject?
Over time, the constant passage of large volumes of water through the kidneys will wash out the osmotic gradient that is necessary for AVP to exert its diuretic effect
List the biochemical features of diabetes insipidus
- Hypernatraemia
- Raised urea
- Increased plasma osmolality
- Dilute (hypo-osmolar) urine (i.e. low urine osmolality)
List the biochemical features of psychogenic polydipsia
- Mild hyponatraemia
- Low plasma osmolality
- Dilute (hypo-osmolar) urine (i.e. low urine osmolality)
State two selective vasopressin receptor peptidergic agonists
V1 –TERLIPRESSIN
V2 – DESMOPRESSIN (DDAVP)
Why is exogenous vasopressin NOT used in the treatment of cranial DI?
Exogenous vasopressin would activate all receptors (V1a, V1b and V2) affecting other tissues/organs (e.g. vasculature, liver)
How may cranial DI be treated?
- Administration (nasally, orally or subcutaneous) of desmopressin
- Note that the patient must be told NOT to continue drinking large amounts of fluid for risk of hyponatraemia
How may nephrogenic DI be treated?
Thiazides (e.g. bendroflumethiazide)
Describe the possible mechanism for thiazides in the treatment of nephrogenic DI?
- Inhibits Na+/Cl- transport in distal convoluted tubule and so sodium reabsorption (diuretic effect)
- Compensatory increase in Na+ reabsorption from the proximal tubule (plus small decrease in GFR)
- Increased proximal water reabsorption
- Decreased fluid reaches collecting duct
- Reduced urine volume
Define Syndrome of Inappropriate ADH
Plasma vasopressin concentration is inappropriately high for the existing plasma osmolality
What are the effects of inappropriately increased vasopressin?
- Increased water reabsorption => raised urine osmolality
- Expansion of ECF volume (=>hyponatraemia)
- Release of atrial natriuretic peptide from right atrium => natriuresis => hyponatraemia + euvolaemia
List some symptoms of SIADH
- Can be symptomless
If p[Na+] <120 mM => generalised weakness, poor mental function, nausea
If p[Na+] <110 mM => CONFUSION leading to COMA and ultimately DEATH
List potential causes of SIADH
CNS: e.g. Sub-arachnoid Haemorrhage, stroke, tumour
Pulmonary disease: e.g.
Pneumonia, bronchiectasis
Malignancy: Lung cancer (small cell)
Drug-related: e.g. Carbamazepine, Selective Serotonin Re-uptake Inhibitors
Idiopathic
What is the treatment for SIADH?
To reduce the immediate concern of hyponatraemia:
- Fluid restriction (immediate)
- Drugs to inhibit action of ADH and induce nephrogenic DI (e.g. demeclocyline, V2 receptor antagonists)
What are Vaptans?
Non-competitive V2 receptor antagonists.
Cause solute-sparing renal excretion of water (i.e. no simultaneous electrolyte loss)
