3 - Neurohypophysial disorders Flashcards
What are nuclei in the NS?
groups of neuronal cell bodies
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
What is the principal action of vasopressin and how does it carry out this action?
main action is on the V2 receptors in the renal cortical and medullary collecting ducts
It stimulates the synthesis and assembly of aquaporin 2, which then increases water reabsorption and has an antidiuretic effect
What is meant by antidiuresis?
decreased production of urine by increasing water reabsorption
(Diuresis = increase in urine production)
Where are osmoreceptors found?
in the organum vasculosum which project to the PVN (paraventricular nuclei) and SON (supraoptic nuclei)
What are the main actions of oxytocin?
contraction of the myometrium during parturition
involved in milk ejection
Describe how osmoreceptors detect a change a osmolality of an extracellular environment
- in a high osmolality ectracelflulaer environment, water moves out the osmoreceptors, causing them to shrink
- as it shrinks, the cells increase firing, which stimulates vasopressin release from hypothalamic PVN and SON
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
What can cause central diabetes insipidus?
ACQUIRED:
Damage to Neurohypophysial system:
- 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 insipidus?
Acquired - Drugs (e.g. lithium - used for bipolar disorder)
Congenital - rare (e.g. mutation in gene encoding V2 receptor, aquaporin 2 type water channel)
State some signs and symptoms of diabetes insipidus.
Polyuria Polydipsia Hypo-osmolar (dilute) urine Dehydration (if fluid intake is not maintained) Possible disruption of sleep (nocturia)
What is the normal range for plasma osmolality?
275–295 mosm/kg
State a cause of polydipsia that isn’t diabetes.
Define it
Psychogenic polydipsia
This is a central disturbance that increases the drive to drink
(can be caused by ‘dry mouth’ from meds or being told to drink lots by healthcare professionals)
How are the symptoms of psychogenic polydipsia similar to that of diabetes insipidous?
POLYDIPSIA (excess fluid intake - thirst)
POLYURIA (excess urine output)
How is psychogenic polydipsia different to diabetes insipidous?
in PP, the body’s ability to secrete vasopressin in response to osmotic stimuli is preserved
What test can be used to distinguish between normal, psychogenic polydipsia, central DI and nephrogenic DI? Describe the results you would expect.
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)
What test can be used to distinguish between normal, psychogenic polydipsia and diabetes insipidous?
Describe the results you would expect.
Fluid deprivation test
• Normal and psychogenic polydipsia will show a rise in urine osmolality
• the urine osmolality of someone with psychogenic polydipsia will be slightly lower than a normal person
• DI will show little/no change in urine osmolality (don’t have the ability to concentrate the urine)
What test can be used further to distinguish between central DI and nephrogenic DI?
Describe the results you would expect.
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 resistance to VP)
What are the biochemical features of DI?
Hypernatraemia
Raised urea
Increased plasma osmolality
hypo-osmolar (dilute ) urine - ie low urine osmolality
What are the biochemical features of psychogenic polydipsia?
Mild hyponatraemia – excess water intake
Low plasma osmolality
Hypo-osmolar (dilute) urine - ie low 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
Describe the normal change in urine osmolality as plasma osmolality increases.
Describe the changes for someone with DI
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
What is the treatment of cranial DI?
- give selective vasopressin receptor peptidergic agonists (desmopressin)
- give exogenous vasopressin (this will activate all vasopressin receptors, but most importantly the ones in the kidney)
What are the (non-intentional effects) of treating someone with DI with exogenous vasopressin (argipressin)?
there will be V1 action as well as V2
this includes vasoconstriction
Name the selective vasopressin receptor peptidergic agonists and which vasopressin receptors they act on
Which one would be used to treat DI?
TERLIPRESSIN - V1 receptors
DESMOPRESSIN (DDAVP) - V2 receptors
use DDAVP to treat DI, since it acts on V2 receptors
How is desmopressin administered?
Nasally
Orally
Subcutaneously
What is desmopressin used to treat? What is the result of administering it?
cranial diabetes insipidous
results in a reduction in urine volume and concentration
What is the treatment for nephrogenic DI?
THIAZIDE DIURETICS
What is SIADH?
Syndrome of Inappropriate ADH = when the plasma vasopressin concentration is inappropriate (excessive) for the existing plasma osmolality
State some signs of SIADH.
Decreased urine volume Increased urine osmolality HYPONATRAEMIA natriuresis (excretion of sodium) Euvolaemia (normal amount of body fluids)
Why does SIADH cause you to become hyponatraemic?
increased water reabsorption, so the ions in plasma become diluted
What are the symptoms of SIADH?
- can be symptomless
- if [Na+] <120 mM: generalised weakness, poor mental function, nausea
- if [Na+] <110 mM: CONFUSION leading to COMA and ultimately DEATH
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?
Appropriate treatment (e.g. surgery for tumour)
To reduce immediate concern, i.e. hyponatraemia
- Immediate: fluid restriction
- Longer-term: use drugs which prevent vasopressin action in kidneys
How do the drugs used to treat SIADH work (i.e. how do they prevent the action of ADH in the kidney)?
- induce nephrogenic DI ie reduce renal water reabsorption - demeclocyline
- inhibit action of ADH - V2 receptor antagonists (VAPTANS)
What are vaptans?
What do they do?
- Non-competitive V2 receptor antagonists
- Inhibit aquaporin2 synthesis and transport to collecting duct apical membrane, preventing renal water reabsorption
What are vaptans used to treat?
hyponatraemia associated with SIADH
Why is the use of VAPTANS currently limited in the UK?
very expensive
What is aquaresis?
solute-sparing renal excretion of water
contrast with diuretics (diuresis) which produce simultaneous electrolyte loss
Explain the differences in plasma osmolality in a patients with DI and a patient with PP
DI - high plasma osmolality - lots of water excretion (low urine osmolality)
PP - low plasma osmolality - increased water intake with low urine osmolality (hypoosmolar urine)
