Disorders of Vasopressin Flashcards
What pituitary is anatomically continuous with the hypothalamus?
Posterior pituitary
What kind of hypothalamic neurones are related to the posterior pituitary?
Magnocellular neurones
What kind of hypothalamic neurones are related to the anterior pituitary?
Parvocellular neurones
What hypothalamic neurones are long?
Magnocellular
Where do hypothalamic magnocellular neurones originate?
Supraoptic and paraventricular hypothalamic nuclei
What is the other name for vasopressin?
Anti-Diuretic Hormone
What is the other name for anti-diuretic hormone?
Vasopressin
What is diuresis
Production of urine
What is the production of urine called?
Diuresis
What is the main physiological action of vasopressin?
Stimulation of water reabsorption in the renal collecting duct -> concentrates urine
What does the main physiological action of vasopressin act through?
V2 receptor in kidney (basolateral membrane)
What other actions does vasopressin have?
A vasoconstrictor (via V1 receptor) Stimulates ACTH release from anterior pituitary
Where does the main physiological action of vasopressin occur?
Renal collection duct
What is the osmotic stimuli for vasopressin release?
Rise in plasma osmolality
sensed by osmoreceptors
What is the non-osmotic stimuli for vasopressin release?
Decrease in atrial pressure sensed by atrial stretch receptors
What is the physiological response to water deprivation?
- Increased plasma osmolality
- Stimulation of osmoreceptors
- Thirst
- Increased AVP release
- Increased water absorption from renal collection ducts
- Reduction in urine volume, increase in urine osmolality
- Reduction in plasma osmolality
What are the symptoms of diabetes insipidus?
- Polyuria
- Nocturia
- (Often extreme) thirst
- Polydipsia
What are the symptoms due to in diabetes insipidus vs diabetes mellitus?
Diabetes mellitus -> osmotic diuresis
Diabetes insipidus -> problem with arginine vasopressin
What is the most common cause of polyuria, nocturia and polydipsia?
Diabetes mellitus, not insipidus
What are the two types of diabetes insipidus?
- Cranial (central)
2. Nephrogenic
What type of diabetes insipidus is ‘vasopressin insufficiency’?
Cranial
What type of diabetes insipidus is ‘vasopressin resistance’?
Nephrogenic
What is cranial diabetes insipidus?
- Problem with hypothalamus &/or posterior pituitary
- Unable to make arginine vasopressin
What is nephrogenic diabetes insipidus?
- Can make arginine vasopressin (normal hypothalamus & posterior pituitary)
- Kidney (collecting duct) unable to respond to it
What are the causes of cranial diabetes insipidus?
- Acquired
1. Traumatic brain injury
2. Pituitary surgery
3. Pituitary tumours
4. Metastasis to the pituitary gland eg breast
5. Granulomatous infiltration of pituitary stalk eg TB, sarcoidosis
6. Autoimmune
-Congenital (rare)
What are the causes of nephrogenic diabetes insipidus?
-Congenital
rare (e.g. mutation in gene encoding V2 receptor, aquaporin 2 type water channel)
-Acquired
Drugs (e.g. lithium)
What type of diabetes insipidus is more common?
Cranial
What is psychogenic polydipsia?
Patient drinks all the time, so passes large volumes of dilute urine
(no problem with AVP)
How do symptoms arise in psychogenic polydipsia?
- Increased drinking (polydipsia)
- Plasma osmolality falls (diluted)
- Less AVP secreted by posterior pituitary
- Large volumes of dilute (hypotonic) urine
- Plasma osmolality returns to normal
How can we distinguish between diabetes insipidus and psychogenic polydipsia?
Water deprivation test
What is a water deprivation test?
No access to anything to drink Over time, measure -Urine volumes -Urine concentration (osmolality) -Plasma concentration (osmolality)
Why is it important to weight the patient regularly in a water deprivation test?
Stop test if lose >3% body weight (a marker of
significant dehydration which can occur in diabetes insipidus)
How does water deprivation test distinguish between diabetes insipidus and psychogenic polydipsia?
Urine osmolality not increase with diabetes insipidus
Does with psychogenic polydipsia
How do we distinguish between cranial & nephrogenic diabetes insipidus?
Give ddAVP
How does administrating ddAVP distinguish between cranial & nephrogenic diabetes insipidus?
Cranial diabetes insipidus – response to ddAVP, urine concentrates
Nephrogenic diabetes insipidus – no increase in urine osmolality with ddAVP, as kidneys can’t respond
How is cranial DI treated?
Desmopressin
- Tablets
- Intranasal
How is nephrogenic DI treated?
Thiazide diuretics e.g. bendofluazide
How does desmopressin work?
Selective for V2 receptor (V1 receptor activation unhelpful)
What is SIADH?
Syndrome of Inappropriate Anti-Diuretic Hormone
- Too much AVP
- Reduced urine output
- Water retention
What are causes of SIADH?
- CNS
- Pulmonary disease
- Malignancy
- Drug-related
- Idiopathic
What is the management of SIADH?
- Fluid restrict
2. Can use vaptan - vasopressin antagonist - costly
What are the physiological consequences of SIADH?
- High urine osmolality
- Low plasma osmolality
- Dilutional hyponatraemia
How does vaptan work
Vasopressin antagonist
Binds to the V2 receptors in the kidney
What are CNS causes of SIADH?
- head injury
- Stroke
- Tumour
What are pulmonary disease causes of SIADH?
- Pneumonia
2. Bronchiectasis
What are malignancy causes of SIADH?
Lung cancer (small cell)
What are drug-related causes of SIADH?
- Carbamazepine (an antiepileptic)
2. SSSRIs - serotonin reuptake inhibitors
What are responsible for the osmotic stimulation of vasopressin release?
- Organum vasculosum
2. Subfornical organ
What are the organum vasculosum and subfornical organ?
Nuclei which sit around the 3rd ventricle - circumventricular
What are the properties of the organum vasculosum and subfornical organ?
- No blood brain barrier – so neurons can respond to changes in the systemic circulation
- Highly vascularised
What do the organum vasculosum and subfornical organ do?
Neurons project to the supraoptic nucleus - site of vasopressinergic neurons
How do osmoreceptors regulate vasopression?
- 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 hypothalamic neurones
What is responsible for the non-osmotic stimulation of vasopressin release?
Atrial stretch receptors
What do atrial stretch receptors do?
- Detect pressure in the right atrium
- Inhibit vasopressin release via vagal afferents to hypothalamus
- Reduction in circulating volume eg haemorrhage means less stretch of these atrial receptors, so less inhibition of vasopressin
Why is vasopressin released following a haemorrhage (ie. reducing in circulating volume)?
-Vasopressin release results in increased water reabsorption in the kidney (some restoration of circulating volume) V2 receptors
-Vasoconstriction via V1 receptors
(NB renin-aldo system will also be important, sensed by JG apparatus)
What is the presentation of diabetes insipidus?
- Polyuria
- Nocturia
- Thirst – often extreme
- Polydispia
What is the presentation of diabetes insipidus relating to urine?
- Very dilute (hypo-osmolar)
- Large volumes
What is the presentation of diabetes insipidus relating to 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)
Why do the symptoms occur in diabetes insipidus?
- Arginine vasopressin problem
- Not enough-CDI
- Not responding-NDI - Impaired concentration of urine in renal collecting duct
- Large volumes of dilute (hypotonic) urine
- Increase in plasma osmolality (and sodium)
- Stimulation of osmoreceptors
- Thirst - polydipsia
- Maintains circulating volume as long as patient has access to water
What happens if person with diabetes insipidus has no access to water?
Dehydration and death
