1b Disorders of Vasopressin Flashcards
What is the physiological action of vasopressin?
Stimulation of water reabsorption into the renal collecting duct = concentrates the urine
Which receptor does AVP work through?
V2 receptor in the kidney
How does AVP work as a vasoconstrictor?
Via the V1 receptor
Describe how AVP concentrates the urine?
- AVP binds to V2 receptor on basolateral membrane
- This triggers intracellular cascade resulting in the movement of aquaporin-2 molecules onto the apical membrane
- this allows the movement of water from the urine into the blood, therefore concentrating it
What is the bright spot on an MRI of the pituitary?
Posterior Pituitary
What are the two stimuli for vasopressin release?
Osmotic and Non-osmotic
Describe how the osmotic stimuli for vasopressin release works?
rise in plasma osmolality detected by osmoreceptors
Describe how the non-osmotic stimuli for vasopressin works?
decrease in atrial pressure sensed by atrial stretch receptors
What are the names of the nuclei from which AVP is released?
Organum vasulosum and subfornical organ
What enables the organum vasculosum and subfornical oragn to respond to changes in systemic circulation?
Highly vascularised and no blood brain barrier
Where do the neurones of the organosum vasculosum and subfornical organ project to?
the supraoptic nuclei
Describe how osmoreceptors regulate vasopressin?
- Increase in extracellular sodium
- Therefore movement of water out the osmoreceptor by diffusion
- Osmoreceptor shrinks
- This increases osmoreceptor firing
- More osmoreceptor firing leads to more AVP release from the hypothalamic neurones
Describe how the non-osmotic stimulation of Vasopressin works?
- stretch receptors in atrium detect pressure and INHIBIT RELEASE
- Therefore when the volume drops, the stretch receptors are stretched less, so LESS INHIBITION OF VASOPRESSIN
What might trigger the non-osmotic stimulation of Vasopressin Release?
Major haemorrhage
What are the benefits of vasopressin release following major haemorrhage?
- Increase the circulating volume
- Restore the blood pressure which will have dropped
How doe AVP trigger an increase in blood volume following haemorrhage?
Increased water absorption in the kidney via V2 receptor, therefore increasing blood volume and hence pressure as well
Which receptors does AVP initiate vasoconstriction through?
V1 receptors
What is the physiological response to water deprivation?
- Increased plasma concentration
- This stimulates the osmoreceptors to fire, leading to AVP release
- This stimulates water reabsorption from the renal collecting ducts
- Urine volume decreases, and the concentration of the urine increases as more water is kept
- This reduces the plasma concentration
What is the most common cause of polyuria, nocturia and polydipsia?
diabetes mellitus
What are the common symptoms between Diabetes Insipidus and Diabetes Mellitus?
Polyuria
Polydipsia
Nocturia
Thirst
What is the difference between Diabetes Insipidus and Diabetes Mellitus?
Insipidus is due to a problem with AVP, and mellitus is due to osmotic diuresis due to glucose affecting the urine
What are the types of diabetes insipidus?
Cranial Diabetes Insipidus and Nephrogenic Diabetes
What is cranial diabetes insipidus?
A problem with the hypothalamus/pituitary which mean the patient is unable to make their own AVP - could be called vasopressin insufficiency
What is nephrogenic diabetes insipidus?
when the patient makes AVP however the KIDNEY is unable to respond to it
What are some causes of cranial diabetes insipidus?
TBI
Pituitary surgery / tumours
Metastasis to the pituitary
Granulomatous infiltration of pituitary stalk
What are the causes of nephrogenic DI?
mutation in V2 receptor / aquaporin type 2 water
acquired = drugs eg lithium
What is the typical presentation of diabetes insipidus
Polyuria, nocturia, thirst and polydipsia
What happens to the urine of a patient with diabetes insipidus?
Very dilute urine (hypoosmolar) and large volumes
What happens to the plasma of a patient with diabetes insipidus?
plasma concentration increases and becomes hyper
osmolar, as the patient becomes dehydrated as they are continually urinating
what happens to the sodium concentration in the plasma of a patient with diabetes insipidus?
increases
Why do patients with diabetes insipidus have polydipsia?
The AVP problem results in impaired concentration of urine in the renal collecting duct
Therefore large volumes of dilute urine are produced
Increases in plasma osmolarity and sodium
Stimulation of osmoreceptors, leading to polydipsia
How can diabetes insipidus lead to death?
When the patient has polydipsia but no access to water -this
leads to dehydration and death
What is psychogenic polydipsia?
When the patient drinks too much water, and so passes large volumes of water - no problem with AVP
How do symptoms arise from psychogenic polydipsia?
Increased drinking leads to a fall in plasma osmolarity and less AVP being secreted by the posterior pituitary so more urine is secreted
How do you distinguish between diabetes insipidus and psychogenic polydipsia?
Water deprivation test - No access to anything to drink - measuring urine volumes, urine and plasma conc
What is the normal response to hours doing the water deprivation test?
The urine osmolarity increases as AVP helps to concentrate the urine
During the water retention test, what is the difference between psychogenic polydipsia and diabetes insipitus?
Urine osmolarity of the patient with psychogenic polydipsia will increase, however patient with diabetes Insipidus will not (as they have no ADH and therefore cannot concentrate the urine)
Why is it important to measure the weight of the patient regularly?
Stop the test if they lose more than 3% of their total body weight
What happens to the plasma and urine osmolarity in the water deprivation test for a patient with diabetes insipidus?
No change in the urine osmolality,
How to distinguish between Cranial and nephrogenic DI?
give desmopressin or ddAVP
What is the effect in CDI and NDI on giving them ddAVP?
Cranial - the urine osmolarity will increase as the synthetic AVP works like AVP
Nephrogenic - no increase in urine osmolarity with ddAVP as kidneys cannot respond
What are the different presentations of desmopressin?
tablet or intranasal
What is SIADH
?
Syndrome of Inappropriate Anti-Diuretic Hormone
What are the symptoms of SAIDH?
reduced urine output
increased water retention
High urine osmolality
Low plasma osmolality
How is SIADH managed?
Restrict fluids
Use a vasopressin antagonist (Vaptan) which binds to the V2 receptors in the kidney so AVP doesnt work
What happens to sodium levels in SIADH?
low sodium = hypoatrenaemia
