Disorders of Vasopressin

Question 1

What is the structure of the posterior pituitary?

What are the 2 hormones produced by the posterior pituitary?

How is the anterior pituitary different from the posterior pituitary?

Answer 1

Posterior pituitary = anatomically continous from the hypothalamus. Derived from neuronal tissue - starts from hypothalamic nuclei where the long axons from magnocellular neurons flow down to the posterior pituitary

2 hormones - vasopressin and oxytocin

Anterior Pituitary = glandular tissue and not continuous from hypothalamus

Question 2

What is arginine vasopressin (AVP) also known as?

What does this tell you about the physiological action of vasopressin?

Answer 2

ADH (anti-diuretic hormone)

Diuresis = production of urine

Stimulates water reabsorption in the renal collecting ducts (CDs) by acting via V2 receptors leading to increased blood volume and concentrated urine. Also causes release of more ACTH. And also a vasoconstrictor, acting via V1 receptors.

Question 3

How does vasopressin work to concentrate urine?

Answer 3

AVP travels in the blood to bind to V2 receptors on the basolateral membrane

This triggers intracellular signalling cascade
Causes aquaporin channels to travel to the apical and basolateral membranes

Aquaporin-2 channels on the apical membrane allow water to enter from the tubular lumen, which then travel through the CDC to the aquaporin-3 channels on the basolateral membrane, back into the blood plasma

Question 4

How does the posterior pituitary look on an MRI?

Answer 4

Some people present with a posterior pituitary bright spot

Question 5

What hormone from the anterior pituitary gland does vasopressin stimulate the release of?

Answer 5

ACTH

Question 6

What are the 2 stimuli for vasopressin release?

Answer 6

Osmotic - rise in plasma osmolality (concentration) [NOT H2O CONCENTRATION] sensed by osmoreceptors

Non-osmotic - decrease in atrial pressure sensed by atrial stretch receptors

Question 7

How does osmotic stimulation trigger vasopressin release?

Answer 7

2 special types of nuclei (called the organum vasculosum and subfornical organ) sit around 3rd ventricle
They have no blood brain barrier and are highly vascularised
So can communicate directly with systemic circulation
They communicate with the vasopressinergic neurons in the hypothalamus via neurons

Question 8

How do osmoreceptors regulate vasopressin?

Answer 8

Osmoreceptors are v. sensitive to plasma osmolality
Sense changes in extracellular Na+
Increase in extracellular Na+ causes H2O to leave the osmoreceptor cell via osmosis down the concentration gradient
Osmoreceptor shrinks and changes shape causing neurons to fire off
Triggers vasopressin release from hypothalamic neurons

Question 9

How do atrial stretch receptors interact with vasopressin release?

Answer 9

Atrial stretch receptors detect pressure in the right atrium
When normal, communicates with hypothalamus that everything is normal via vagal afferents and it inhibits vasopressin release
But when bloodcirculating volume and/or BP falls, e.g. with an haemorrhage, there is less stretch of these atrial receptors
So the receptors decrease the inhibition of vasopressin production

Question 10

Why is vasopressin release useful following a fall in blood volume e.g. after a haemorrhage?

Answer 10

Vasopressin acts on:
V2 receptors = increase H2O reabsorption = helps restore circulating volume
V1 receptors = vasoconstriction = maintain normal BP

Question 11

What is the normal physiological response to water deprivation?

Answer 11

Plasma osmolality increases - this stimulates the osmoreceptors
The stimulation of the osmoreceptors stimulates thirst AND release of vasopressin
Vasopressin = increase in water reabsorption from renal CDs = conc. urine, small volume
Water flows into systemic circulation leading to reduced plasma osmolality

Question 12

When there is insufficient vasopressin production, what condition do patients often get?

What symptoms do they present with?

Answer 12

Diabetes insipidus (DI) characterised by: 
Polyuria
Nocturia
Thirst - often extreme 
Polydipsia

Question 13

Symptoms between diabetes mellitus (DM) and diabetes insipidus (DI) are similar.

So what are the differences between DM and DI?

Answer 13

DM = glucose issue, too high BGL so kidney can't filter it out fast enough leading to glucose in the urine
DI = lack of water reabsorption in the renal CDs linked to vasopressin issues

Question 14

What are the 2 types of DI?

Answer 14

1. Cranial Diabetes Insipidus (CDI) = damage directly to posterior pituitary or hypothalamus so they are unable to make vasopressin
2. Nephrongenic diabetes insipidus (NDI) = vasopressin is being produced, but renal CDs are not responding to the vasopressin

Question 15

Causes of Cranial Diabetes Insipidus (CDI)?

HINT: congenital Vs acquired

Answer 15

Congenital issues = rare
Acquired: traumatic brain injury, pituitary surgery, pituitary tumours, metastasis to pituitary gland, granulomatous infiltration of pituitary stalk e.g. TB or sarcoidosis, autoimmune damage

Question 16

Causes of nephrogenic diabetes insipidus (NDI)?

(HINT: congenital Vs acquired)

Are CDIs or NDIs more common?

Answer 16

Congenital = rare (e.g. gene mutations encoding for V2 receptors, aquaporin-2 channels, etc.)
Acquires: drugs e.g. lithium

CDIs are more common than NDIs, but DI is not very common in general

Question 17

During DI, what causes the symptoms of polyuria, nocturia, thirst and polydipsia?

Answer 17

Polyuria and nocturia: Very dilute and large volumes of urine (hypo-osmolar) due to lack of reabsorption in renal CDs via vasopressin stimulation

Thirst and polydipsia: Plasma = increased conc. (hyper-osmolar) due to losing large volumes of water in urine,
leads to increased sodium (hypernatraemia)
Stimulates osmoreceptors, which stimulate thirst to maintain circulating volume as long as patient has access to water
Glucose levels stay normal in DI

Question 18

How can DI cause death?

Answer 18

As long as you can drink, you can just about keep up with it

Lack of access to water, leads to severe dehydration, and eventually death

Question 19

What is psychogenic polydipsia (PP)?

Answer 19

Present similarly to DI (similar symptoms)
However, unlike in DI, no issue with vasopressin
Patient simply drinks huge amounts of water, hence the normal response is to urinate it all out - leads to passing of large volumes of very dilute urine

Question 20

How do you test to see if the patient has PP or DI?

What volume and concentration of urine do healthy people pass over time in a water deprivation test and how do they compare to PP and DI?

What measures are put in place to ensure true DI patients do not die from severe dehydration?

Answer 20

Water deprivation test - overtime measure urine volume, urine concentration (osmolality), and plasma concentration (osmolality)

e.g. over 8 hours, normally, produce smaller volumes and more concentrated urine
PP follows a similar curve

DI cannot dilute their urine at all, so over time they do not follow the regular curve of increase in conc and decrease in volume of urine over time

Weigh patients regularly. If they loose more than 3% of their body weight, stop the test due to severe dehydration

Question 21

How to distinguish between CDI Vs NDI following the water deprivation test?

Answer 21

Give synthetic vasopressin (ddAVP)
CDI = responds to vasopressin so they are able to concentrate their urine
NDI = renal CDs do not respond to synthetic vasopressin, hence are still unable to concentrate their urine

Question 22

DI vs PD? Main difference in a blood test:

Answer 22

DI = increased plasma osmolality
PD = decreased plasma osmolality due to excessive drinking of water diluting the plasma, urinating a lot is a result of excessive drinking

Question 23

What is the treatment given to CDI patients?

Answer 23

Given desmopressin nasal spray or tablet (selective to V2 receptors)

Question 24

What is the treatment given to NDI patients?

Answer 24

V. rare, difficult to treat

Given thiazide diuretics (mechanism unclear to why it works)

Question 25

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

How common is this compared to DI?

Answer 25

Too much vasopressin production, leads to water retention hence reduced urine output

Leads to high urine osmolality, low plasma osmolality, and dilutional hyponatraemia (low plasma Na+)

Much more common than DI

Question 26

What are some causes of SIADH?

Answer 26

CNS - head injury, stroke, tumour
Lung issues - pneumonia, brochietasis, lung cancer
Drug related - Carbamazepine, Serotonin Reuptake Inhibitors (SSRIs)

Question 27

How are SIADH patients managed?

Answer 27

Common cause of prolonged hospital stay
Fluid restriction
Or alternatively given a vasopressin antagonist (vaptan) - binds to V2 receptors in the kidney so vasopressin in unable to access / bind onto the V2 receptors. Expensive = unlikely to be prescribed