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 is the main receptor that’s responsive to vasopressin & where is it located?
V2 receptor of Kidney
Which receptors mediate vasopressin induced vasocontriction?
V1 receptors
Stimulation of V1 receptors results in what action?
Vasoconstriction
Which hormone is released from the pituitary gland in response to vasopressin?
ACTH
Which protein channels are embedded on the apical membrane of renal tubule cells, facilitating the movement of water molecules?
Aquaporin-2
Describe the response is induced stimulation of V2 receptors by AVP? ***
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?
Posterior Pituitary Bright spot on MRI
What are two main stimuli that stimulates vasopressin release & how are these stimuli detected?
Osmotic: Rise in plasma osmolality 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 the circumventricular nuclei are highly vascularised structures so neurons can respond to changes in the systemic circulation e.g. changes in osmolality
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? Explain with an example
There is an increase in extracellular sodium
- This increase in Plasma Osmolality causes water to flow down concentration gradient out of osmoreceptor to the plasma (the water potential of the plasma altered)
- > Osmoreceptor shrinks & changes shape
- > Increased osmoreceptor firing triggered by shape change
- > Osmoreceptors therefore stimulate 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 found & what do they do?
Atrial Strech Receptors Detect Pressure in the right atrium
Stimulation of atrial stretch receptors result in what?
Inhibit vasopressin release via vagal afferents to the hypothalamus
How does a haemorrhage result in vasopressin release ?
Reduction in circulating volume e.g. due to Haemorrhage
Leads to hypovolemia, this subsequently leads to less stretch and thus reduced stimulation of atrial receptors
Therefore this reduces inhibition of vasopressin - leading to vasopressin release
What is the impact on plasma osmolality in individuals with water deprivation?
Increased plasma osmolality
Describe the physiological responses to water deprivation?
Increased Plasma Osmolality leads to Osmoreceptor Stimulation
Resulting in: Increased thirst and Increased AVP Release
AVP increases water reabsorption from renal collecting ducts
This leads to an Increase in Reduction in Urine Volume
& Increase in Urine Osmolality
And a Reduction in Plasma Osmolality
What are the osmotic symptoms associated with diabetes mellitus?
Polyuria
Nocturia
Thirst- often extreme
Polydypsia
Describe what causes osmotic diuresis in diabetes mellitus
- rephrase explanation ***
In Diabetes Mellitus:
Issue with Insulin leads to increase in glucose in blood -> hyperglycaemia & when sugar in blood greater than 10 mmol/L -> kidney cannot reabsorb anymore & glucose spills over into urine bringing water with it
Therefore Hyperglycaemia increases water retention within the urine & leads 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
Unable to make arginine vasopressin
- ‘Vasopressin Insufficiency’
What is nephrogenic diabetes inspidus?
Can make arginine vasopressin (normal hypothalamus & posterior pituitary)
But the collecting duct of kidney is unable to respond to AVP
- ‘Vasopressin Resistance’
What are the common causes of cranial diabetes inspidus?
Acquired:
- Traumatic brain injury
- Pituitary surgery
- Pituitary tumours
- Metastasis to the pituitary gland e.g. breast
- Granulomatous infiltration of pituitary stalk e.g. TB, sarcoidosis (which is an accumulation of inflammatory cells)
- Autoimmune
What are the causes of nephrogenic diabetes?
Congenital:
Mutation in genes encoding V2 receptor, aquaporin 2 type water channel.
Acquired:
Drugs e.g. Lithium
Which types of drugs can cause nephrogenic diabetes inspidus?
Lithium
What are the symptoms of diabetes insipidus?
Polyuria
Nocturia
Thirst
Polydypsia
Urine:
Very Large Volumes of Hypo-osmolar (Very Dilute) urine
Plasma:
Hyper-osmolar plasma (Increased concentration) as patient becomes dehydrated
- Hypernatremia (Increased sodium) (& Increased Plasma Osmolality)
Glucose is normal (HbA1c) - (only abnormal in Diabetes Mellitus)
What is psychogenic polydypsia?
Polydipsia is excessive or abnormal thirst, accompanied by intake of excessive quantities of water or fluid.
Psychogenic polydipsia (PPD), is characterised by excessive volitional water intake and is often seen in patients with (severe) mental illness (and/or developmental disability). Patient unlike in Diabetes Insipidus has no problems with Arginine Vasopressin
What test can be conducted to distinguish between diabetes insipidus and psychogenic polydipsia?
Water deprivation test
How can the results of the water deprivation test distinguish diabetes insipidus & psychogenic polydipsia
Diabetes Insipidus: There is no increase in urine osmolarity (AVP is suppressed)
Psychogenic Polydipsia: Urine Osmolality increases although sometimes can be abnormal (lower than usual?)
At what parameter should the water deprivation test be stopped?
If there is a loss of 3% body weight (marker of dehydration)
How is cranial 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 as kidneys can’t respond
What is the treatment for cranial diabetes insipidus?
Desmopressin to replace vasopressin
Desmopressin is selective for v2 receptor
- can be given as Tablets or intranasal preparation
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?
Too much arginine vasopressin 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 (Small Cell)
Drug related
-Carbazepine, serotonin reuptake inhibitors
Idiopathic
What is the available management for SIADH?
Vaptan (Vasopressin antagonist), binds to V2 renal receptors.
Fluid restriction
When trying to observe the posterior pituitary bright spot what is something important to remember?
Posterior pituitary ‘bright spot’ on MRI
Not visualised in all healthy individuals, so absence may be normal variant
Why is vasopressin released following a haemorrhage?
Paraphrasing is allowed
Loss of Blood in Haemorrhage results in reduction in circulating volume, so Vasopressin restores circulating volume (1) & plays a role in trying to restore blood pressure & systemic vascular resistance
(1) Vasopressin release results in increased water reabsorption in the kidney via V2 receptors -> some restoration of circulating volume
(2) Vasopressin release results in Vasoconstriction via V1 receptors -> increase blood pressure & systemic vascular resistance to more normal levels
Most common cause of the following cluster of symptoms?
Polyuria
Nocturia
Thirst- often extreme
Polydypsia
Diabetes Mellitus
What are rarer causes of cranial diabetes inspidus
Congenital
Which is more common out of Cranial & Nephrogenic Diabetes Insipidus
Cranial Diabetes Insipidus
What is Lithium used for?
Managing Mental Health - Bipolar Affective Disorder
Why important to check Glucose in patients with:
Polyuria
Nocturia
Thirst
Polydypsia
If normal -> Diabetes Insipidus
If abnormal -> Diabetes Mellitus
Why do the following symptoms occur in diabetes insipidus?
Polyuria
Nocturia
Thirst
Polydypsia
*** Rephrase explanation
1) ARGININE VASOPRESSIN PROBLEM Not enough (CDI) Not responding (NDI)
2) Impaired concentration of urine in renal collecting duct
3) -> Large volumes of dilute (hypotonic) urine
4) -> Increase in plasma osmolality (and sodium)
5) This stimulates osmoreceptors
6) Thus causing Thirst - polydipsia
7) Maintains circulating volume as long as patient has access to water
Why might diabetes insipidus cause death?
***Rephrase explanation
1) Arginine Vasopressin Problem Not enough (CDI) Not responding (NDI)
2) Impaired concentration of urine in renal collecting duct
3) -> Large volumes of dilute (hypotonic) urine
4) -> Increase in plasma osmolality (and sodium)
5) This stimulates osmoreceptors
6) Thus causing Thirst - polydipsia
7) However due to lack of access to water patient dehyrdates & dies
Why might drugs cause psychogenic polydipsia
Certain drugs used for mental health treatment can cause dry mouth as a side effect and so have their thirst stimulated more
Describe the water deprivation test
Water deprivation test Place patients in room with no access to anything to drink (remove plant pots too lol) Over time, measure Urine volumes Urine concentration (osmolality) Plasma concentration (osmolality)
