Disorders of Vasopressin Flashcards
Hypothalamus and pituitary connections
Parvocellular neurons - Median eminence - Portal circulation - anterior pituitary
Magnocellular neurons - contain AVP or oxytocin - anatomically continuous ny pituitary stalk to posterior pituitary
Physiological action of vasopressin
Acts through the V2 receptor in the kidney
Also a vasoconstrictor (via V1 receptor)
Stimulates ACTH release from anterior pituitary
Posterior pituitary on MRI
Posterior pituitary ‘bright spot’ on MRI
Not visualised in all healthy individuals, so absence may be normal variant
Stimuli for vasopressin release
Osmotic
Rise in plasma osmolality sensed by osmoreceptors
Non-osmotic
Decrease in atrial pressure sensed by atrial stretch receptors via vagal afferents
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
Diabetes insipidus symptoms
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
Causes of cranial diabetes insipidus
Acquired (more common)
Traumatic brain injury
Pituitary surgery
Pituitary tumours
Metastasis to the pituitary gland eg breast
Granulomatous infiltration of pituitary stalk eg TB, sarcoidosis
Autoimmune
Congenital rare
Causes of nephrogenic diabetes insipidus
Much less common than cranial diabetes insipidus
Congenital rare (e.g. mutation in gene encoding V2 receptor, aquaporin 2 type water channel)
Acquired
Drugs (e.g. lithium)
Presentation of 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)
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
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)
Weigh regularly –stop test if lose >3% body weight (a marker of significant dehydration which can occur in diabetes insipidus)
Distinguish between cranial & nephrogenic diabetes insipidus
Give ddAVP
This will work ‘like’ vasopressin
Cranial diabetes insipidus – response to ddAVP – urine concentrates
Nephrogenic diabetes insipidus – no increase in urine osmolality with ddAVP, as kidneys can’t respond
Treatment of diabetes insipidus
Cranial DI Want to replace vasopressin Desmopressin Selective for V2 receptor (V1 receptor activation would be unhelpful) Different preparations Tablets Intranasal
Nephrogenic DI
Luckily this is very rare – difficult to treat successfully
Thiazide diuretics eg bendofluazide
Paradoxical! Mechanism unclear
Syndrome of Inappropriate Anti-Diuretic Hormone (SIADH)
Too much arginine vasopressin Reduced urine output Water retention High urine osmolality Low plasma osmolality Dilutional hyponatraemia
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
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 (£££££)
