Disorders of Vasopressin

Question 1

What is the main physiological action of ADH?

Answer 1

Stimulation of water reabsorption in the renal collecting duct

This concentrates urine

Question 2

What receptor does ADH act through in the kidney?

Answer 2

V2 Recptor

Question 3

What receptor does ADH act through as a vasoconstrictor?

Answer 3

V1 Recptor

Question 4

Which hormone does ADH stimulate the release of?

Answer 4

ACTH from the anterior pituitary

Question 5

What is the definition of osmolality?

Answer 5

Concentration of particles dissolved within a fluid

Question 6

What are the names of the nuclei involved in the osmotic stimulation of vasopressin release?

Answer 6

Organum vasculosum and subfornical organ

Question 7

Where are these nuclei (Organum vasculosum and subfornical organ) in the brain?

Answer 7

Both sit around the 3rd ventricle (‘circumventricular’)

So they are highly vascularised

Question 8

What enables the neurons to be able to respond to changes in the systemic circulation?

Answer 8

There is no blood brain barrier

Question 9

Where do these neurons project to?

Answer 9

Hypothalamic Supraoptic nucleus - site of vasopressinergic neurons

Question 10

Supraoptic nucleus - site of vasopressinergic neurons

Answer 10

Increase in plasma osmolality leading to loss of H20 via osmosis in the osmoreceptors

Osmoreceptor shrinks leading to increased osmoreceptor firing and AVP is released from the hypothalamic neurons in the supraoptic nucleus

Question 11

Describe the non-osmotic stimulation of vasopressin release

Answer 11

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

This increases vasoconstriction

Question 12

Why is ADH released following a haemorrhage (reduction in circulating volume)?

Answer 12

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 as sensed by the JG apparatus

Question 13

Describe the physiological response pathway to water deprivation

Answer 13

Increased plasma osmolality → Stimulation of osmoreceptors → Thirst as well as Increased AVP release → Increased water reabsorption from renal collecting ducts → Reduced urine volume, Increased urine osmolality → Reduction in plasma osmolality

Question 14

What are the 4 clinical symptoms of diabetes insipidus?

Answer 14

Polyuria

Nocturia

Thirst - often extreme

Polydipsia

Question 15

Is the most common cause of polyuria, nocturia and polydipsia diabetes mellitus or diabetes insipidus?

Answer 15

Mellitus

Question 16

What is cranial diabetes insipidus?

Answer 16

Problem with hypothalamus and/or posterior pituitary

Unable to make ADH

Question 17

What is nephrogenic diabetes insipidus?

Answer 17

Can make ADH (normal hypothalamus and posterior pituitary)

Kidney collecting duct unable to respond to it

Question 18

What are the acquired causes of cranial diabetes insipidus?

Answer 18

Traumatic brain injury

Pituitary surgery

Pituitary tumours

Metastasis to the pituitary gland e.g. - breast

Granulomatous infiltration of pituitary stalk e.g. TB Sarcoidosis

Autoimmune

Question 19

What are some of the acquired causes of nephrogenic diabetes insipidus?

Answer 19

Drugs - Lithium

Question 20

What are possible congenital causes of nephrogenic diabetes insipidus?

Answer 20

Rare (e.g. mutation in gene encoding V2 receptor, aquaporin 2 type water channel)

Question 21

What presentations would be seen in the urine of someone with diabetes insipidus?

Answer 21

Very dilute (hypo-osmolar)

Large volumes

Question 22

What presentations would be seen in the plasma of someone with diabetes insipidus?

Answer 22

Increased concentration (hyper-osmolar) as patient becomes dehydrated

Increased sodium (hypernatraemia) due to excess free water losses

Glucose normal (make sure you always check this in a patient with these symptoms)

Question 23

Why do these symptoms occur in diabetes insipidus?

Answer 23

AVP insufficiency (CDI) or resistance (NDI) → Impaired concentration of urine in renal collecting duct → Large volumes of hypotonic urine → Increase in plasma osmolality and sodium → Stimulation of osmoreceptors → Polydipsia due to thirst → Maintains circulating volume as long as patient has access to water

Question 24

What happens if a patient with diabetes insipidus does not quench their thirst?

Answer 24

They dehydrate and die

Question 25

What is psychogenic polydipsia

Answer 25

Similar presentation to diabetes insipidus with polydipsia, polyuria and nocturia however there is no issue with AVP, it is just that the patient drinks all the time so they pass large volumes of dilute urine

Question 26

Describe the pathophysiology of psychogenic polydipsia

Answer 26

Increased drinking (polydipsia) → Plasma osmolality falls → less AVP secreted by posterior pituitary → Large volumes of hypotonic urine → Plasma osmolality returns to normal

Question 27

What tests do we do to distinguish between diabetes insipidus and psychogenic polydipsia?

Answer 27

Water deprivation test No access to anything to drink Measure over time: Urine volumes Urine concentration (osmolality) Plasma concentration (osmolality) Weigh regularly Stop test if lose >3% of body weight as this is a marker of significant dehydration which can occur in diabetes insipidus

Question 28

What are the results from this test that distinguish between psychogenic polydipsia and diabetes insipidus?

Answer 28

Psychogenic polydipsia - Slight decrease in max urine osmolality relative to normal, however it still increases ( and fairly significantly relative to pts with Diabetes Insipidus) Diabetes insipidus - No increase in urine osmolality from start as there is an issue with AVP so there is no way of removing the water from urine and so it is hypotonic (very dilute)

Question 29

Do you expect to see a progressive increase in urine osmolality in a patient with diabetes insipidus during a water deprivation test?

Answer 29

No you would see a progressive increase in plasma osmolality as there is no way for them to concentrate their urine so the water leaves the plasma making the plasma more concentrated

Question 30

How do we distinguish between cranial and nephrogenic diabetes insipidus?

Answer 30

Give ddAVP which is a synthetic analogue to vasopressin Cranial diabetes insipidus - Response to ddAVP is the urine will become concentrated (increased urine osmolality) Nephrogenic diabetes insipidus - No increase in urine osmolality with ddAVP as kidneys cannot respond (no change to urine osmolality)

Question 31

How do you treat cranial diabetes insipidus?

Answer 31

Replace ADH by giving ddAVP (desmopressin) Selective for V2 receptor (V1 receptor activation would be unhelpful) Different preparations: Tablets Intranasal

Question 32

How do you treat nephrogenic diabetes insipidus?

Answer 32

Thiazide diuretics e.g. bendofluazide (Mechanism unclear)

Question 33

What is the issue in Syndrome of Inappropriate Anti-Diuretic Hormone (SIADH)?

Answer 33

Too much ADH

Question 34

What are the symptoms in SIADH?

Answer 34

Reduced urine output Water retention

Question 35

How would you describe the urine and plasma osmolality and sodium concentrations in SIADH?

Answer 35

High urine osmolality Low plasma osmolality Dilutional hyponatraemia

Question 36

What are the CNS related causes of SIADH?

Answer 36

Head injury, stroke and tumour

Question 37

What are the other causes of SIADH?

Answer 37

Pulmonary disease - Pneumonia, bronchiectasis Malignancy - Lung cancer Drug related - Carbamazepine, Serotonin Reuptake Inhibitors (SSRIs) Idiopathic

Question 38

How would you manage a patient with SIADH?

Answer 38

Fluid restriction Can use a vasopressin antagonist (vaptan) to bind to the V2 receptors in the kidney