Disorders Of Vasopressin Flashcards
What structure is the posterior pituitary continuous with?
Hypothalamus
Where are AVP and oxytocin contained in the hypothalamus?
In hypothalamic magnocellular neurons - supraoptic and paraventricular nuclei
What are the physiological actions of vasopressin?
Stimulation of water reabsorption in the renal collecting duct - concentrates urine
Acts on V2 receptor in the kidney
Also a vasoconstrictor (via V1 receptor)
Stimulates ACTH release from anterior pituitary
How does vasopressin concentrate urine?
How does the posterior pituitary show up on an MRI?
As a ‘bright spot’ posterior to anterior pituitary
Is the ‘bright spot’ (posterior pituitary) visualised in all healthy individuals?
No
What are the stimuli for vasopressin release?
Osmotic:
- Rise in plasma osmolality sensed by osmoreceptors
Non-osmotic:
- Decrease in atrial pressure detected by atrial stretch receptors
How are the organum vasculosum and subfornical organ involved in osmotic stimulation of vasopressin release?
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 directly to the supraoptic nucleus - site of vasopressinergic neurons
How do the organum vasculosum and subfornical organ work?
Osmoreceptors
When there is an increase in extracellular Na+ concentration, water diffuses out of the osmoreceptor causing it to shrink
Shrinkage -> increase in osmoreceptor firing -> AVP release from hypothalamic neurons
Outline 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 (e.g. haemorrhage) means less stretch of these atrial receptors, so less inhibition of vasopressin
Why is vasopressin released following a haemorrhage (i.e. reduction in circulating volume)?
Vasopressin release results in increased water reabsorption in the kidney (some restoration of circulating volume) - acts on V2 receptors
Vasoconstriction via V1 receptors
Note: Renin-aldo system will also be important, sensed by JG apparatus)
Outline the physiological response to water deprivation
Increased plasma osmolality -> stimulation of osmoreceptors
Leads to thirst + increased AVP release -> increased water reabsorption from renal collecting ducts
Leads to reduced urine volume + increased urine osmolality -> reduction in plasma osmolality
What are the symptoms of Diabetes Insipidus?
Polydypsia
Polyuria
Noturia
Thirst (often extreme)
Compare the cause of symptoms in Diabetes Insipidus with Diabetes Mellitus
DM - symptoms due to osmotic diuresis
DI - symptoms due to problem with AVP
The most common cause of polyuria, polydypsia and nocturia is Diabetes Insipidus. True or false?
False, the most common cause is Diabetes Mellitus
What are the two types of Diabetes Insipidus and what causes them?
Cranial (central) diabetes insipidus:
- Problem with hypothalamus &/or posterior pituitary
- Unable to make arginine vasopressin
- ‘VASOPRESSIN INSUFFICIENCY’
Nephrogenic diabetes insipidus:
- Can make arginine vasopressin (normal hypothalamus & posterior pituitary)
- Kidney (collecting duct) unable to respond to it
- ‘VASOPRESSIN RESISTANCE’
What are the causes of cranial Diabetes Insipidus?
Acquired:
- Traumatic brain injury
- Pituitary surgery
- Pituitary tumours
- Metastasis to the pituitary gland, e.g. breast
- Granulomatous infiltration of pituitary stalk eg TB, sarcoidosis - stalk thickens and AVP can’t travel to PP
- Autoimmune
Congenital: rare
What are the 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)
Describe the presentation of DI with reference to urine and plasma
Urine:
- very dilute (hypo-osmolar)
- large volumes
Plasma:
- 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 DI?
Arginine vasopressin insufficiency/resistance -> impaired concentration of urine in renal collecting duct -> large volumes of dilute (hypotonic) urine -> increase in plasma osmolality and sodium -> osmoreceptor stimulation -> thirst -> circulating volume is maintained as long as patient has water access
How can DI lead to death?
If a patient with DI has no access to water, they can get severely dehydrated and die
How does psychogenic polydypsia mimic DI?
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
Outline how plasma osmolality is maintained in psychogenic polydypsia
Increased drinking (polydypsia) -> plasma osmolality falls -> less AVP secreted by posterior pituitary -> large volumes of dilute hypotonic urine -> plasma osmolality returns to normal
How do we distinguish between diabetes insipidus & psychogenic polydipsia?
Carry out a water deprivation test
What does a water deprivation test involve?
No access to anything to drink
Over time, measure urine volumes, urine concentration (osmolality) and plasma concentration (osmolality)
Why should weight be checked regularly during a water deprivation test?
Risk of severe dehydration - Diabetes Insipidus
Stop test if lose >3% body weight (a marker of significant dehydration)
Why must weight be checked regularly during a water deprivation test?
Risk of severe dehydration - Diabetes Insipidus
Stop test if lose >3% body weight (a marker of significant dehydration)
How do we distinguish between cranial & nephrogenic diabetes insipidus?
Give ddAVP - works ‘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
Would the plasma osmolality be higher in a person with DI or psychogenic polydypsia?
DI because they are more dehydrated (PP they are over hydrated - slightly lower plasma osmolality than normal)
How is cranial DI treated?
Replace vasopressin with Desmopressin
Selective for V2 receptor (V1 receptor activation would be unhelpful)
Different preparations:
- Tablets
- Intranasal
How can DI be poorly managed in a healthcare setting?
- Can be wrongly regarded as the same as DM
- Nasal spray can be easily disregarded as non-urgent in hospital admission
- Preventing a patient with DI from drinking/not giving IV fluids (if they can’t drink) can cause death
How is nephrogenic DI treated?
Very rare
Difficult to treat successfully
Thiazide diuretics e.g. bendofluazide are used
What is SIADH and what are the symptoms
Syndrome of Inappropriate Anti-Diuretic Hormone
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
How can SIADH be managed?
Fluid restrict
Vaptan - Vasopressin antagonist (binds to V2 receptor) - however very expensive
