Disorders of Vasopressin Flashcards
What tissue is the posterior pituitary made from?
Neuronal tissue
It is also anatomically continuous with the hypothalamus
What are the posterior pituitary neurones and what do they contain?
Hypothalamic magnocellular neurons containing AVP or oxytocin:
-Long, originate in supraoptic and paraventricular hypothalamic nuclei
-Nuclei → stalk →posterior pituitary
What is the physiological action of vasopressin?
Other name = Anti-Diuretic Hormone
Diuresis = production of urine
Main physiological action = stimulation of water reabsorption in the renal collecting duct
This concentrates urine
Acts through the V2 receptor in the kidney
Also a vasoconstrictor (via V1 receptor)
Stimulates ACTH release from anterior pituitary
How does vasopressin concentrate urine?
How do you visualise the posterior pituitary on MRI?
What are the stimuli for vasopressin release?
Osmotic
-Rise in plasma osmolality sensed by osmoreceptors
Non-osmotic
-Decrease in atrial pressure sensed by atrial stretch receptors
What senses plasma osmolality for osmotic stimulation of vasopressin release?
Organum vasculosum & subfornical organ
-both nuclei which sit around the 3rd ventricle (‘circumventricular’)
-no blood brain barrier – so neurons can respond to changes in the systemic circulation
-highly vascularised
-neurons project to the supraoptic nucleus - site of vasopressinergic neurons
How do osmoreceptors regulate vasopressin?
How does non-osmotic stimulation of vasopressin release
Atrial stretch receptors detect pressure in the right atrium
Inhibit vasopressin release via vagal afferents to hypothalamus
Reduction in circulating volume eg haemorrhage means less stretch of these atrial receptors, so less inhibition of vasopressin
Why is vasopressin released following a haemorrhage
(ie reduction in circulating volume)?
Vasopressin release results in increased water reabsorption in the kidney (some restoration of circulating volume) V2 receptors
vasoconstriction via V1 receptors
(NB renin-aldo system will also be important, sensed by JG apparatus)
What is the physiological response to water deprivation
What are the clinical symptoms for diabetes insipidus?
Polyuria
Nocturia
Thirst – often extreme
Polydispia
In diabetes mellitus (hyperglycaemia), these symptoms are due to osmotic diuresis
In diabetes insipidus, these symptoms are due to a problem with arginine vasopressin
Remember – the most common cause of polyuria, nocturia & polydipsia is diabetes mellitus, NOT diabetes insipidus
Urine
-Very dilute (hypo - osmolar)
-Large volumes
Plasma
-Increased concentration (hyper-osmolar) as patient becomes dehydrated
-Increased sodium (hypernatraemia)
-Glucose normal (make sure you ALWAYS check this in a patient with these symptoms)
What are the two types of diabetes insipidus?
Cranial (central) and nephrogenic
What is cranial diabetes insipidus?
Problem with hypothalamus &/or posterior pituitary
Unable to make arginine vasopressin
‘VASOPRESSIN INSUFFICIENCY’
What is nephrogenic diabetes insipidus?
Can make arginine vasopressin (normal hypothalamus & posterior pituitary)
Kidney (collecting duct) unable to respond to it
‘VASOPRESSIN RESISTANCE’
What are the acquired causes of cranial diabetes insipidus?
Traumatic brain injury
Pituitary surgery
Pituitary tumours
Metastasis to the pituitary gland eg breast
Granulomatous infiltration of pituitary stalk eg TB, sarcoidosis
Autoimmune
What are the acquired causes of nephrogenic diabetes insipidus?
Drugs (e.g. lithium)
What are the congenital causes of nephrogenic diabetes insipidus?
rare (e.g. mutation in gene encoding V2 receptor, aquaporin 2 type water channel)
Why do these symptoms occur in diabetes insipidus?
How does diabetes insipidus cause death?
What are the presentations of psychogenic polydipsia?
Similar presentation to diabetes insipidus
-Polydipsia
-Polyuria
-Nocturia
Unlike diabetes insipidus, no problem with arginine vasopressin
Problem is that the patient drinks all the time, so passes large volumes of dilute urine
How do the symptoms in psychogenic polydipsia arise?
How do we distinguish between diabetes insipidus & psychogenic polydipsia?
Water deprivation test
No access to anything to drink
Over time, measure
Urine volumes
Urine concentration (osmolality)
Plasma concentration (osmolality)
What would a graph of water deprivation by urine osmolality look like?
Why are patients weighed regularly during the water deprivation test?
To stop test if lose >3% body weight (a marker of significant dehydration which can occur in diabetes insipidus)
How do we distinguish between cranial & nephrogenic diabetes insipidus?
How to distinguish between diabetes insipidus and psychogenic polydipsia
What is the treatment of diabetes insipidus - cranial?
Want to replace vasopressin
Desmopressin
Selective for V2 receptor (V1 receptor activation would be unhelpful)
Different preparations
-Tablets
-Intranasal
What is the treatment of diabetes insipidus - nephrogenic?
Luckily this is very rare – difficult to treat successfully
Thiazide diuretics eg bendofluazide
Paradoxical! Mechanism unclear
What is Syndrome of Inappropriate Anti-Diuretic Hormone (SIADH)
Too much arginine vasopressin
Reduced urine output
Water retention
High urine osmolality
Low plasma osmolality
Dilutional hyponatraemia
What are the causes of SIADH
CNS
-Head injury, stroke, tumour,
Pulmonary disease
-Pneumonia, bronchiectasis
Malignancy
-Lung cancer (small cell)
Drug-related
-Carbamazepine, Serotonin Reuptake Inhibitors (SSSRIs)
Idiopathic
What can be done for management of SIADH
Common cause of prolonged hospital stay
Fluid restrict
Can use a vasopressin antagonist (vaptan) – binds to the V2 receptors in the kidney (£££££)
