Disorders of vasopressin

Question 1

What neurons in the hypothalamus stimulate AVP release, and where do they originate?

Answer 1

magnocellular neurons, in supraoptic and paraventricular nuclei

Question 2

What are the 3 physiological effects of AVP?

Answer 2

Water reabsorption in collecting duct (V2 receptors), vasoconstriction (V1 receptors) and ACTH release

Question 3

How would you view the posterior pituitary gland in imaging, and what is the bright spot?

Answer 3

MRI - appears as a bright spot // bright spot may not be visible for everyone, even in healthy patients

Question 4

What are the two stimuli for vasopressin release, and what receptors detect this change?

Answer 4

increased plasma osmolality - osmoreceptors //
decreased atrial pressure - atrial stretch receptors

Question 5

What are the two brain structures that store osmoreceptors and where are they located (with their special feature)?

Answer 5

Organum vasculosum of lamina terminalis & subfornical organ - around 3rd ventricle - no blood brain barrier

Question 6

How do osmoreceptors regulate vasopressin?

Answer 6

When there is a high osmolality, water leaves osmoreceptor (causes shrinking), leads to more osmoreceptor firing, and hence AVP release

Question 7

How do atrial stretch receptors regulate vasopressin?

Answer 7

Atrial stretch receptors detect pressure in atrium, when stretched there is firing via vagal afferents to inhibit vasopressin

Question 8

Why is vasopressin released after a haemorrhage?

Answer 8

Lower atrial stretch receptor firing means less inhibition of vasopressin release

Question 9

Why is vasopressin release useful after a haemorrhage?

Answer 9

V2 receptor for more water reabsorption - increases pressure in the circulation, V1 receptor for vasoconstriction - increases blood pressure

Question 10

What is the physiological response to water restriction and how will concentrations of plasma and urine change?

Answer 10

Activation of osmoreceptors, increase AVP, there will be a slight increase in plasma osmolality (however body will stabilise) and increase in urine conc and decrease in urine volume

Question 11

What are the three main symptoms of diabetes insipidus and what is the problem with this?

Answer 11

Polyuria, Nocturia, Polydipsia - all the same as diabetes mellitus which has a very different treatment plan

Question 12

What is the clinical presentation of diabetes insipidus? x4

Answer 12

Dilute high volume urine, hyperosmolar plasma, hypernatraemia, normal glucose

Question 13

What are the two types of diabetes insipidus?

Answer 13

Cranial DI - cannot make AVP //
Nephrological DI - cannot respond to AVP

Question 14

What are three causes of CDI? (AVP-D)

Answer 14

pituitary surgery/trauma, metastasis,
autoimmune (sarcoidosis & TB)

Question 15

What is an acquired cause of NDI? (AVP-R)

Answer 15

Lithium drugs (in schizophrenia)

Question 16

What are the 4 blood tests you would do if you suspect DI and why?

Answer 16

blood glucose and HbA1c (for mellitus), sodium concentration (hypernatraemia), plasma osmolality

Question 17

Why do people with DI have polydipsia?

Answer 17

Lose a lot of water in urine, osmoreceptors constantly fire leading to polydipsia

Question 18

When can DI cause death?

Answer 18

When access to water is restricted - by losing all water in urine and not being replaced, plsma osmolarity increases

Question 19

What is psychogenic polydipsia?

Answer 19

Too much water drinking - this leads to similar symptoms as DI

Question 20

How would you differentiate DI and PP?

Answer 20

Water deprivation test - restrict water and monitor weight and urine osmolarity. DI will always stay a low osmolality whereas PP will increase over time. Patient with DI would have a progressive increase in plasma osmolality whereas PP will be lower than normal and increase to a reasonable level.

Question 21

Why would you measure weight in this test?

Answer 21

People with DI can lose a lot of weight due to severe dehydration, stop the test if patient loses more than 3% bodyweight

Question 22

How do you distinguish CDI and NDI?

Answer 22

Administer ddAVP (desmopressin). CDI will respond and urine osmolality will increase, whereas NDI will not

Question 23

How do you treat CDI? (AVP-D)

Answer 23

Administer ddAVP either with a tablet or nasal spray

Question 24

How do you treat NDI? (AVP-R)
rare and difficult to treat successfully

Answer 24

Thiazide diuretics (bendroflumethazide)

Question 25

What is SIADH?

Answer 25

Syndrome of Inappropriate Anti-Diuretic Hormone - ie too much AVP
Excess water reabsorption from the kidney, causing concentrated urine, decreasing plasma osmolality and low sodium

Question 26

What are some of the causes of SIADH?

Answer 26

Pituitary injury, pulmonary disease, malignancy, drug related, CNS (stroke, tumour)

Question 27

What 2 ways do you manage SIADH?

Answer 27

Fluid restrict or vaptan (vasopressin antagonist). Latter is very expensive.

Question 28

Arginine Vasopressin deficiency (AVP-D)

Answer 28

unable to make AVP
CDI
caused by issues with hypothalamus/ posterior pituitary

Question 29

Arginine Vasopressin Resistance (AVP-R)

Answer 29

can make AVP
NDI
Kidney (collecting duct) unable to respond

Question 30

Most common cause of polydipsia, polyuria and nocturia

Answer 30

Diabetes mellitus
symptoms due to osmotic diuresis not vasopressin

Question 31

Congenital NDI

Answer 31

Rare
could be due to mutation in gene encoding V2 receptor
aquaporin 2 water channel

Question 32

Response to desmopressin

Answer 32

AVP-D (CDI) - urine concentrates
AVP-R (NDI) - no increase in urine osmolarity as kidneys cannot respond