Neurohypophysial Disorders Flashcards
Name the two main nuclei within which neurones of the neurohypophysis have their cell bodies.
Paraventricular Nucleus
Supraoptic Nucleus
What two hormones are produced by the neurohypophysis?
Vasopressin
Oxytocin
NB: neurohypophysis = posterior pituitary
adenohypophysis = anterior pituitary
What is the principal action of vasopressin and how does it carry out this action?
ANTI-DIURETIC (ADH)
Vasopressin’s main action is on the V2 receptors (it binds to them) in the renal cortical and medullary collecting ducts
It stimulates the synthesis and assembly of aquaporin 2 into the membrane of teh lumen, which then increases water reabsorption from the nephron and has an antidiuretic effect
What are the main actions of oxytocin?
It is a contractile molecule that binds to oxytocin receptors It causes contraction of the myometrium during parturition and is involved in milk ejection It also has central effects
What part of the brain is responsible for regulating vasopressin release? What enables it to have this function?
Organum vasculosum - has osmoreceptors (=neurones) which project to the hypothalamic PVN and SON
Organum vasculosum is devoid of a BBB so it can communicate with systemic ciruclation
Describe how osmoreceptors regulate vasopressin release.
- Osmoreceptors ae very sensitive to changes in EC OSMOLALITY
- An increase in EC sodium causes plasma osmolality to increase and the osmoreceptor to shrink
- This leads to more osmoreceptor firing
- Causing VP release from hypothalamic PVN and SON neurones
Describe the normal response to thirst.
Results –> reuced urine volume, increase in urine osmolality, reduction in serum osmolality.
What are the consequences of a lack of the neurohypophysial hormones?
(Lack of Oxytocin – not clinically significant )
Lack of Vasopressin – Diabetes Insipidus
What are the two forms of diabetes insipidus?
Central (cranial) and Nephrogenic Diabetes Insipidus
(Either th body not making enough from the poosterior pituitary or kidneys not responding to vasopressin - nephrogenic is uncommon)
What can cause central diabetes insipidus?
Acquired (more common):
- Damage to neurohypophysial system (injury, surgery, pituitary tumours, metastasis to pituitary gland, granulomatous infiltration of median eminence e.g. sarcoidosis)
Congenital (rare)
What can cause nephrogenic diabetes insipidus?
Congenital (rare) - e.g. mutation in gene encoding V2 receptor, aquaporin 2 type water channel
Acquired - Drugs e.g. lithium
State some signs and symptoms of diabetes insipidus. (Recall the process that causes these).
- Polyuria
- Polydipsia
- Hypo-osmolar urine
- Dehydration (and its consequences)
- Possible disruption of sleep
Can patients die from diabetes insipidus?
Yes - e.g. if they do not have access to water in a hospital and their sodium levels rise to ver high concentrations in the blood they can die.
State another cause of polydipsia that isn’t diabetes.
Psychogenic polydipsia - “dry mouth”
This is a central disturbance that increases the drive to drink
Describe the symptoms associated with psychogenic polydipsia. How is it different from diabetes insipidus?
Excess fluid intake (polydipsia) and excess urine output (polyuria) -
BUT unline DI, ability to secrete vasopressin in response to osmotic stimuli is maintained.
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
- Normals and psychogenic polydipsia will show a rise in urine osmolality
- Central and nephrogenic diabetes insipidus will show little or no change in urine osmolality
Fluid deprivation with administration of DDAVP (Desmopressin)
- Central diabetes insipidus will show a rise in urine osmolality
- Nephrogenic DI will still have a low urine osmolality (because of end-organ resistance)
- NB: This is bascially an injection of vasopressin
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
Describe the normal change in urine osmolality as plasma osmolality increases.
Normally, urine osmolality will increase as plasma osmolality increases (in a graph of urine osmolality against plasma osmolality it will show a sigmoid shape)
In DI, there is little change in urine osmolality as plasma osmolality increases
Describe changes in plasma vasopressin following administration of hypertonic saline in a normal subject, psychogenic polydipsia, central DI and nephrogenic DI.
Hypertonic saline will increase the plasma osmolality and hence
will increase the vasopressin secretion in patients that have the capacity to produce vasopressin (normal, psychogenic polydipsia and nephrogenic DI)
Patients with central DI can’t produce vasopressin at all so the hypertonic saline will show no change in plasma vasopressin
List the biochemical features of diabetes insipidus.
- Hypernatraemia
- Raised urea
- Increased plasma osmolality
- Dilute (hypo-osmolar) urine - ie low urine osmolality
What are the biochemical features of psychogenic polydipsia?
- Mild hyponatraemia – excess water intake
- Low plasma osmolality
- Dilute (hypo-osmolar) urine - ie low urine osmolality
Where are V1 and V2 receptors found?
V1
- Vascular smooth muscle
- Non-vascular smooth muscle
- Anterior pituitary
- Liver
- Platelets
- CNS
V2
- Kidney
- Endothelial cells
State two selective peptidergic vasopressin selective agonists.
V1 – Terlipressin
V2 - Desmopressin (DDAVP)
How is desmopressin administered?
- Nasally
- Orally
- SC
What are the effects of desmopressin? What must you tell a patient who is taking desmopressin?
- Effects: Reduction in urine volume and concentration in cranial DI
- CARE – to tell patient starting this NOT to continue drinking large amounts of fluid – risk of hyponatraemia
State one treatment used for nephrogenic diabetes insipidus and its possible mechanism of action.
Thiazide Diuretics (e.g. bendroflumethiazide)
- This inhibits the Na+/Cl- pump in the DCT leading to a diuretic effect
- This leads to volume depletion resulting in a compensatory increase in Na+ reabsorption from the PCT (plus small decrease in GFR etc)
- This increases proximal water reabsorption so less water reaches the collecting duct
- This ultimately leads to reduced urine volume
What is SIADH?
Syndrome of Inappropriate ADH = when the plasma vasopressin concentration is inappropriately HIGH for the existing plasma osmolality
State some signs of SIADH.
- Decreased urine volume (initially)
- Increased urine osmolality
- Decreased p[NA+] (hyponatraemia) mainly due to increased water reabsorption
State some symptoms of SIADH that are caused by the hyponatraemia.
Can be symptomless
At relatively mild hyponatraemia (p[Na+]<120mM) = generalized weakness, poor mental function, nausea
Severe hyponatraemia (p[Na+]<110mM) = confusion, coma, death
What is the main consequence of SIADH?
HYPONATRAEMIA
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?
Provide appropriate treatment when the cause is identified (e.g. surgery for a tumour)
To reduce immediate concern i.e. hyponatraemia:
- Immediate: Fluid Restriction
- Long term: use drugs wihich prevent vasopressin action in kidneys
- e.g. induce nephrogenic DI - DEMECLOCYLINE (reduces renal water reabsorption)
- inhibit action of ADH - V2 RECEPTOR ANTAGONIST
What are vaptans?
Non-competitive V2 receptor antagonists
Inhibit AQP2 synthedid and transport to collectig duct apical membrane, preventing renal water reabsorption
How are vaptans better than diuretics?
They cause aquaresis = solute sparing renal excretion of water.
Diuretics produce electrolyte loss
What stops the use of vaptans more?
although they are licensed for use of hyponatraemia with SIADH in the UK they are VERY EXPENSIVE - limits their use.
State some drugs that increase or decrease vasopressin secretion.
Increase vasopressin secretion = nicotine
Decrease vasopressin secretion = alcohol + glucocorticoids
State some other actions of vasopressin.
- Vasoconstriction
- Corticotrophin release
- Factor VIII and von Willebrand factor
- Central effects
Diabetes insipidus:
- may be due to a deficiency of circulating vasopressin
- can be a consequence of lithium treatment
- is characterised by the excretion of large volumes of dilute urine
- can usually be diagnosed on the basis of the response - to a water deprivation test
- is treated with a V1 receptor agonist
- True
- True
- True
- True
- False
Desmopressin:
- is an analogue of aldosterone
- promotes water reabsorption in the collecting ducts
- is a treatment for diabetes mellitus
- is used in the treatment of cranial diabetes insipidus
- is normally administered by subcutaneous injection
- False
- -True
- -False
- -True
- -False
The Syndrome of Inappropriate ADH (SIADH):
- is associated with a low urine osmolality
- is associated with a hyponatraemia
- is associated with fluid overload
- causes polyuria
- is usually treated by surgical removal of the posterior pituitary
- False
- True
- False
- False
- False
