Disorders of Vasopressin Flashcards
What two hormones does the posterior pituitary produce?
AVP and Oxytocin
What is the relationship between the hypothalamus and p. pituitary?
Anatomically continuous with the hypothalamus
What connects the hypothalamus and p. pituitary?
supraoptic and paraventricular hypothalamic nuclei that stalk (long axons)
What does diuresis means?
Production of urine
What is the main physiological action of Vasopressin?
Stimulation of water reabsorption in the renal collecting duct
Concentrates the urine
What does Vasopressin act via?
V2 receptor
How does AVP concentrate urine?
AVP binds to V2 receptor
Triggers intracellular signalling cascade
Results in migration of aquaporin 2 to the apical membrane of the collecting duct
Allows passage of water from tubular lumen (aquaporin 2) back to bloodstream via aquaporin 3
How does the posterior pituitary look on a MRI?
‘bright spot’
not visualised in all healthy individuals
What does AVP stimulate?
ACTH stimulation
We don’t really know why
What 2 things stimulate vasopressin release?
Osmotic
- rise in plasm osmolality sensed by osmoreceptors
Non-Osmotic
- decrease in atrial pressure sensed by atrial sense receptors
What are the special types of nuclei that sit around the 3rd ventricle?
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 vasporessoin?
Increase in extracellular sodium
Osmoreceptor around 3rd ventricle senses this change
Senses this because of the change in conc. gradient water flows out of the osmoreceptor causing it to change shape
The change in shape results in increased osmoreceptor firing
Causes AVP release from hypothalamic neurones
How is vasopressin stimulates non-osmotically?
Detect pressure in right atrium
Inhibit vasopressin release via vagal afferents to hypothalamus
Reduction in circulating volume e.g. haemorrhage
Less stretch of the atrial receptors so less inhibition of vasopressin
Why is AVP important following haemorrhage?
Via V2 receptor increased water reabsorption increased circulating volume
Via V1 receptor AVP is a vasoconstrictor
What is the physiological response to water deprivation?
Increased plasma osmolality
Stimulation of osmoreceptors
Causes thirst and increased AVP release
AVP causes increased water reabsorption from renal collecting ducts
Reduces urine volume, increase in urine osmolality
Reduction of plasma osmolality
What are symptoms of diabetes insipidus?
Polyuria
Nocturia
Thirst- often extreme
Polydipsia
What causes diabetes insipidus?
A problem with arginine vasopressin
What causes these symptoms in diabetes mellitus?
Osmotic diuresis
Which form of diabetes is more common?
Diabetes mellitus
What are the two forms of diabetes insipidus?
Cranial (central) diabetes
Nephrogenic diabetes insipidus
What is cranial diabetes insipidus?
Problem with hypothalamus and or posterior pituitary
Unable to make AVP
What are the causes of cranial diabetes insidious?
Traumatic brain injury Pituitary surgery Pituitary tumours Metastasis Granulomatous infiltration of pituitary stalk e.g. TB, sarcoidosis Autoimmune
What are the causes of nephrogenic diabetes insipidus?
Congenital
rare (e.g. mutation in gene encoding V2 receptor)
Acquired
Drugs (e.g. lithium)
What happens to urine in D.I?
Very dilute (hypo-osmolar) Large volumes
What happens to plasma in D.I?
Increased concentration (hyper-osmolar) as patient becomes dehydrated
Increased sodium (hypernatraemia)
Glucose normal (always check this in a patient with these symptoms)
Why do these symptoms occur in D.I?
Not enough/Not responding AVP
Impaired conc. of urine in renal collecting duct
Large volumes of dilute urine
Increase in plasma osmolality (and sodium)
Stimulation of osmoreceptors
Thirst
Maintains circulating volume as long as patient has access to water
What causes nephrogenic diabetes insipidus?
Can make AVP
Collecting duct unable to respond to it
How can D.I cause death?
No access to water
Dehydration
Death
What is psychogenic poludipsia?
Similar presentation to diabetes insipidus
Polyuria
Nocturia
No problem with arginine vasopressin
Problem is that they drink too much
Dilute plasma conc.
Less AVP secreted
Large volumes of dilute urine
Plasma osmolality returns to normal
How do you distinguish between D.I and psychogenic polydipsia?
Water deprecation test
No access to anything to drink
What do you measure during a water deprivation test?
Urine volumes
Urine concentration
Plasma concentration
Weigh regularly stop test if they loose more than 3% of body weight
How would someone with psychogenic polydipsia perform on a water deprivation test?
With time you can increase your urine osmolality (making it more concentrated)
How would someone with D.I perform on a water deprivation test?
Not matter how long they are in the room they cannot concentrate their urine
How do we distinguish between cranial and nephrogenic diabetes insipidus?
At end of water deprivation test
Give ddAVP (synthetic AVP)
Cranial D.I will respond to this and urin concentrates
Nephrogenic D.I there will be no increase in urine osmolality
How do you treat Cranial DI?
Replace
Desmopressin
Selective for V2 receptor
Nasal spray or tablet
How do you treat Nephrogenic DI?
Luckily very rare
Thiazide diuretic e.g. bendofluazide
or NSAIDS
Paradoxical, mechanism nuclear
What is SIADH?
Syndrome of Inappropriate Anti-Diuretic Hormone
More common than DI
What happens in SIADH?
Too much vasopressin
Reduces urin output
Water retention
High urine osmolality
Low plasma osmolality
Dilutional hyponatraemia
What causes SIADH?
CNS: head injury, stoke, tumour Pulmonary disease: pneumonia, bronchiectasis Malignancy: Lung cancer (small cell) Drug-related: Carbamazepine, serotonin Idiopathic
How is SIADH managed?
Common cause prolonged hospital stay
Fluid restrict
Can uses vasopressin antagonist (vaptan)
Prevent binding to V2 receptors in the kidney
Very Expensive ££££
Not prescribed often
Why do we monitor weight during the water deprivation test?
If they do have DI it is important to allow them to drink water or else they can become extremely dehydrated as they have no way to concentrate their urine and will continue to pass large volumes, loosing a great deal of water.
What would be the response to water deprivation in a healthy person?
Urine volumes will decrease with time
Osmolality will increase with time and urine will become more concentrated
AVP preserves plasma osmolality
Why is desmopressin nasal spray potentially better than a tablet?
Acid in stomach reduces biological effect of peptides
Nose is highly vascularised
What are signs of hypovolaemia?
Tachycardia Reduced skin turgor Low urine sodium Low BP Dry membranes
How do you treat hyponatraemia?
Fluid restrict
What causes hypervolaemia?
HF
Cirrhosis
Nephrotic sydnrome
What are signs of hypervolaemia?
Peripheral oedema
Lung crackles
Raised JVP
What happens if you give too much saline too quickly?
Central pontine myelionylysis
Quadruplegia, pseudobulbar palsy
What do give in severe hyponatraemia? Reduced GCS
IV Saline 3%
What causes hypernatremia?
Cushing's Conn's Iatrogenic Sweating GI loses
