Endo - Disorders of Vasopressin

Question 1

What type of neurones are found in the PPG?

Answer 1

Mangocellular neurones

Question 2

Why is the PPG neural in origin?

Answer 2

it develops continuously with the hypothalamus

Question 3

Where do magnocellular neurones originate from?

Answer 3

Supraoptic and paraventricular nucleus

Question 4

What are the PPG hormones?

Answer 4

AVP

Oxytocin

Question 5

What is the physiological action of AVP?

Answer 5

Concentrations urine in the collecting duct

Question 6

What does AVP bind to?

Answer 6

V2 receptors

Question 7

What type of receptor is V2?

Answer 7

G protein coupled

Question 8

What does V2 binding stimulate?

Answer 8

Adenylate cyclase leads to cAMp and protein kinase A activity which leads to aquaporin 2 channels to move to the apical membrane of tubular cells

Question 9

What does the PPG normally show in an MRI?

Answer 9

Bright spot

Question 10

Is the PPG always seen in health?

Answer 10

No

Question 11

What are the 2 ways vasopressin release is stimulated?

Answer 11

Osmotic and non osmotic

Question 12

What is the osmotic route of AVP stimulation?

Answer 12

Increase in plasma osmolarity is sensed by hypothalamic osmoreceptors

Question 13

What is the non osmotic route of AVP stimulation?

Answer 13

Decreased blood volume leads to less atrial stretch detected by stretch receptors

Question 14

Where are osmoreceptors found mainly?

Answer 14

In the hypothalamus in the subfornical organ and the organum vasculosum

Question 15

What is an advantage of the osmoreceptors?

Answer 15

They lack a blood brain barrier therefore respond directly to the systemic circulation

Question 16

Where do osmoreceptor neurones project?

Answer 16

Into the supraoptic nucleus which is a site of vasopressinergic neurones

Question 17

Outline how water deprivation increases AVP secretion

Answer 17

Increase in plasma Na means that water leaves the osmorecpetors due to osmotic balance, osmoreceptor shrinking leads to increased firing and thus increased AVP release

Question 18

Where are atrial stretch receptors found?

Answer 18

Right atrium

Question 19

How do atrial stretch receptors work?

Answer 19

They are usually inhibitory on AVP secretion via the vagus nerve

Question 20

Outline how water deprivation causes AVP release non osmotically?

Answer 20

Decrease in water
Decrease in blood volume
Less stretch detected
Disinhibition by less firing 
AVP release

Question 21

Why is AVP released following a haemorrhage?

Answer 21

Following a haemorrhage there us a lower circulating volume, this allows for us to try and increase our blood pressure

Question 22

Alongside AVP release, what else happens during a haemorrhage?

Answer 22

We get vasoconstriction by AVP acting on V1 receptors

Junta glomerular apparatus stimulates aldosterone release to increase blood volume

Question 23

Alongside AVP release, how else do we correct plasma osmolarity?

Answer 23

Stimulation of osmoreceptors increases thirst therefore plasma osmolarity is reduced when drinking

Question 24

What is diabetes insipidus?

Answer 24

When there is a problem with insufficient AVP effect

Question 25

What are the symptoms for diabetes insipidus?

Answer 25

Polyuria Polydipsia/extreme thirst Nocturia

Question 26

What is the more common form of diabetes?

Answer 26

Mellitus

Question 27

Why does diabetes mellitus cause osmotic symptoms?

Answer 27

Increase in blood glucose Water enters blood due to osmotic effect Increased water loss in urine

Question 28

Describe urine production in diabetes insipidus

Answer 28

Large volume, hypo-osmoloar urine

Question 29

Describe the plasma in diabetes insipidus

Answer 29

Hyper-osmolar with increasing thirst Hypernatremia Normal glucose

Question 30

What are the 2 types of diabetes insipidus

Answer 30

Cranial | Nephrogenic

Question 31

What is the more common form of diabetes insipidus

Answer 31

Cranial

Question 32

What happens in cranial diabetes insipidus

Answer 32

Problem with hypothalamus or pituitary whereby we don't make sufficient AVP

Question 33

What happens in nephrogenic diabetes insipidus

Answer 33

AVP production is normal but collecting duct doesn't respond - vasopressin resistance

Question 34

What are the causes of congenital cranial diabetes insipidus

Answer 34

Very rare

Question 35

What are the causes for acquired cranial diabetes insipidus

Answer 35

``` Traumatic brain injury Pituitary surgery Pituitary tumours Metastasis (breast to pituitary) Granulomatous infiltration of pituitary stalk e.g. TB, sarcoidosis. Autoimmune ```

Question 36

How does granuloma cause cranial diabetes insipidus?

Answer 36

Stalk inflammation causes thickening thus preventing passage of AVP

Question 37

What are the causes of congenital nephrogenic diabetes insipidus

Answer 37

Rare e.g. V2 receptor or aquaporin 2 gene mutation

Question 38

What are the causes of acquired nephrogenic diabetes insipidus

Answer 38

Drugs e.g. lithium

Question 39

What is the treatment for cranial diabetes insipidus

Answer 39

Desmopressin - oral or intranasal

Question 40

What does desmopressin act on?

Answer 40

V2 receptors - not V1 receptors

Question 41

What is the treatment for nephrogenic diabetes insipidus?

Answer 41

Thiazide diuretics e.g. bendrofluazide

Question 42

How can diabetes insipidus cause death?

Answer 42

We constantly lose water through lack of AVP mechanism therefore if we don't drink water and the DI is not managed correctly, we die

Question 43

qWhat is psychogenic polydipsia?

Answer 43

Mental health disorder in which the patient drinks too much water - seen in the context of other mental health disorders

Question 44

What are the symptoms of psychogenic polydipsia?

Answer 44

Polyuria Nocturia Polydipsia

Question 45

How do we distinguish DI from PD?

Answer 45

Water deprivation test

Question 46

What happens in a water deprivation test?

Answer 46

We give the patient nothing to drink over the course of a few hours

Question 47

What do we measure in water deprivation test?

Answer 47

Urine volume Urine osmolarity Plasma concentration Body weight

Question 48

When do we stop a water deprivation test?

Answer 48

If patient loses more than 3% of their body weight indicating significant dehydration

Question 49

What do we see in a water deprivation test for normal patient

Answer 49

As we have less water, AVP increases therefore urine osmolarity increases

Question 50

What do we see in a water deprivation test for PD

Answer 50

Water deprivation means AVP still works, but it is generally lower osmolarity than normal person due to large amounts of dilute urine

Question 51

What do we see in a water deprivation test for DI

Answer 51

AVP problem therefore urine is never concentrated, osmolarity stays low

Question 52

How do we distinguish between CDI and NDI?

Answer 52

We give desmopressin

Question 53

What do we see in CDI deprivation test?

Answer 53

CDI responds, urine osmolarity rises

Question 54

What do we see in NDI deprivation test?

Answer 54

NDI is resistant to ddAVP therefore osmolarity of urine is unaffected

Question 55

What is a normal plasma osmolality

Answer 55

280 mOsm/kg H20

Question 56

What is the plasma osmolarity for DI?

Answer 56

290

Question 57

What is the plasma osmolarity for PD?

Answer 57

270

Question 58

What is Syndrome of Inappropriate ADH?

Answer 58

Too much AVP

Question 59

What are the effects of SIADH?

Answer 59

``` Water retention Low urine output High urine osmolarity Low plasma osmolarity Dilution hyponatremia ```

Question 60

What are the 5 main causes of SIADH?

Answer 60

``` Drugs Idiopathic Pulmonary disease Malignancy CNS causes ```

Question 61

What malignancies cause SIADH

Answer 61

Small cell lung cancer

Question 62

What drugs cause SIADH

Answer 62

SSRIs | Carbamazepine

Question 63

What pulmonary diseases cause SIADH

Answer 63

Bronchiectasis | Pneumonia

Question 64

What CNS problems cause SIADH

Answer 64

Head injury Stroke Tumour

Question 65

How do we manage SIADH

Answer 65

Vaptan - V2 receptor antagonist (very expensive)