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
