Disorders of vasopressin Flashcards
Which hypothalamic neurones secrete AVP and oxytocin?
Hypothalamic magnocellular neurones
Which part of the pituitary gland secretes AVP and oxytocin?
Posterior pituitary gland
Which pituitary gland is anatomically continuous with the hypothalamus?
Posterior pituitary gland
Which hormones are secreted by the neurohypophysis?
Vasopressin
Oxytocin
Which hypothalamic nuclei contain the magnocellular neurone cell bodies?
Supraoptic and paraventricular nuclei
What is the main physiological action of vasopressin?
Stimulation of water reabsorption in the renal collecting duct.
-Concentrates urine
Which renal receptors are responsive to vasopressin?
V2 receptor
Which receptors are responsive to vasopressin induced vasocontriction?
V1 receptors
Stimulation of V1 receptors results in what action?
Vasoconstriction
Which hormone is released in response to vasopressin from the pituitary gland?
ACTH
Which protein channels are embedded on the apical membrane of renal tubule cells, facilitating the movement of water molecules?
Aquaporin-2
What response is induced by AVP-V2 stimulation?
G-protein coupled response, formation of a secondary messenger.
- Adenylate cyclase activity elevates cAMP concentration and protein kinase A.
- Migration and synthesis of aquaporin-2 channels to apical membrane.
Which aquaporin channels are embedded on the basolateral membrane?
Aquaporin-3
How is the posterior pituitary gland identified on a pituitary MRI?
Bright spot
What are two main stimuli that stimulates vasopressin release?
Osmotic: Rise in plasma osmolarity sensed by osmoreceptors.
Non-osmotic: Decreases atrial pressure sensed by atrial stretch receptors
Which receptors respond to non-osmotic changes?
Atrial stretch receptors
Which circumventricular nuclei respond to changes in systemic circulation and thus stimulate vasopressin release?
Organ vasculosum
Subfornical organ
Where are the organ vasculosum and subfornical organs located?
Reside around the 3rd ventricle (circumventricular)
How can the circumventricular nuclei detect immediate changes to systemic circulation?
There is no blood-brain barrier and are highly vascularised structures
Which hypothalamic structure communicates with projections of the organum vasculosum and subfornical organ?
Supraoptic nucleus
Which hypothalamic nucleus contains vasopressinergic neurones?
Supraoptic nucleus
What type of receptors are sensitive to plasma osmolarity?
Osmoreceptors
How do osmoreceptors detect changes in plasma osmolarity?
There is an increase in extracellular sodium
- This alters the water potential of the plasma
- Water flows from the osmoreceptor to the plasma
- Osmoreceptor shrinks
- Increased osmoreceptor firing
- AVP release from magnocellular hypothalamic neurones of the supraoptic nucleus
What happens to the structural shape of osmoreceptors in response to an increase plasma osmolarity?
Osmoreceptors shrink
Where are atrial stretch receptors predominantly fonud?
Within the right atrium
Stimulation of atrial stretch receptors result in what?
Inhibit vasopressin release
Vagal afferents to the hypothalamus
How does a haemorrhage result in vasopressin release?
The circulating volume decreases, leading to hypovolemia, this subsequently leads to less stretch and stimulation of atrial receptors, therefore this reduces inhibition of vasopressin - leading to vasopressin release (Increased water reabsorption) and vasoconstriction via v1 receptors.
What is the impact on plasma osmolarity in individuals with water deprivation?
Increased plasma osmolarity
What are the physiological responses to water deprivation?
Increased thirst and released AVP (Reduces plasma osmolarity through increased water reabsorption.
What are the osmotic symptoms associated with diabetes?
Polyuria
Nocturia
Thirst- often extreme
Polydypsia
What is osmotic diuresis?
Hyperglycaemia increases water retention within the urine, leading to decreased water reabsorption
What pathology is associated with diabetes insipidus?
Issue with arginine vasopressin.
What are the two types of of diabetes insipidus?
- Cranial (central) diabetes insipidus
- Nephrogenic diabetes insipidus
What is central diabetes insipidus?
Problem concerned with hypothalamus/posterior pituitary gland
There is an insufficient secretion of arginine vasopressin.
What is nephrogenic diabetes inspidus?
Arginine vasopressin production is normal from the posterior pituitary gland and hypothalamus
The collecting duct is unable to respond to AVP.
What are the common causes of cranial diabetes inspidus?
Acquired:
- Traumatic brain injury
- Pituitary surgery
- Pituitary tumours
- Metastasis to the pituitary gland (breast)
- Granulomatous infiltration of pituitary stalk: TB, sarcoidosis (Accumulation of inflammatory cells)
- Autoimmune
What are the common causes of nephrogenic diabetes?
Mutation encoding V2 receptor, aquaporin 2 type water channel.
Lithium drugs
Which types of drugs are concerned with causing nephrogenic diabetes inspidus?
Lithium
What are the symptoms of diabetes insipidus?
Polyuria Nocturia Thirst Polydypsia Hypo-osmolar urine (and in large volumes)
Hyper-osmolar plasma
-Hypernatremia
Glucose is normal (HbA1c)
What is psychogenic polydypsia?
Polydipsia is excessive or abnormal thirst, accompanied by intake of excessive quantities of water or fluid. Psychogenic polydipsia (PPD), or primary polydipsia, is characterised by excessive volitional water intake and is often seen in patients with severe mental illness and/or developmental disability.
What test can be conducted to distinguish between diabetes insipidus and psychogenic polydipsia?
Water deprivation test
In patients with diabetes insipidus, what are the likely results of the water deprivation test?
There is no increase in urine osmolarity (AVP is suppressed)
At what parameter should the water deprivation test be stopped?
If there is a loss of 3% body weight (marker of dehydration)
How is central diabetes insipidus distinguished from nephrogenic diabetes?
Administer ddAVP (behaving like vasopressin) -in central diabetes, ddAVP will interact with V2 receptors facilitating water reabsorption and leading to a significant increase in urine osmolarity
This is unresponsive in nephrogenic diabetes
What is the treatment for diabetes insipidus?
Desmopressin to replace vasopressin
Selective v2 receptor
(Tablets, intranasal)
What is the available treatment for nephrogenic diabetes insipidus?
Thiazide diuretics
Which disorder is associated with an increase in AVP?
Syndrome of inappropriate ADH
What are the features of SIADH?
Reduced urine output Water retention high urine osmolarity Low plasma osmolarity Dilutional hyponatremia
What are the causes of SIADH?
CNS
-Head injury, stroke, tumour
Pulmonary disease
-Pneumonia, bronchiectasis
Malignancy
-Lung cancer
Drug related
-Carbazepine, serotonin reuptake inhibitors
Idiopathic
What is the available management for SIADH?
Vaptan (Vasopressin antagonist), binds to V2 renal receptors.
Fluid restrict
