ADH and AME

Question 1

Where is AVP synthesised?

Answer 1

1. Magnocellular neurones in SON and PVN of the hypothalamus make AVP and oxytocin
2. Packaged into neurosecretory granules with neurophysin (carrier proteins)
3. Transported in axons of hypothalamus-hypophyseal tract (seen in Herring bodies)
4. Released into posterior pituitary nerve terminals
5. Enter inferior hypophyseal circulation via fenestrated capillaries

NB. Some AVP made in parvocellular neurones for AP to stimulate CRH so more ACTH

:. if tract damaged some AVP still there

Question 2

How is AVP release stimulated?

Answer 2

1. Increased plasma osmolarity
2. Activate osmoreceptors (in 3rd ventricle area in organum vasculosum of lamina terminalis) in hypothalamus
3. Signal drinking behaviour of osmolarity >3%
4. Increased ACh release binding to NACh receptors in PVN/SON
5. More AVP release

Question 3

What influences AVP?

Answer 3

1. Angiotensin II increases sensitivity of osmoreceptors in thalamus and subfornical organ to increased osmalirity (inc. synergy)
2. Baroreceptors have atonic inhibition of this pathway in PVN :. drop in BP means baroreceptors fire less :. less inhibition of this pathway so more AVP released
3. Smoking: nicotine goes to brain and stimulates these nerves to release ADH :. retain more water and not urinate for longer

Question 4

What happens when you phosphorylate AP2?

Answer 4

Translocated from inside of cell to cell membrane

Question 5

What does ADH act on?

Answer 5

1. Short term:

• V1:
  
  • decrease GFR
  • help maintain BP with decreased plasma volume
• V2:
  
  • activate adenylc cyclase :. cAMP up :. PKA up
  • PKA phosporylates AP2 in distal tubule and collecting duct in luminal side
• Also causes water resorption through Na+

Question 6

How does the RAAJ system work?

Answer 6

1. Renin release from JGA:
   * decreased NA⁺ flux in macula densa in DT :. less filtered + SNS + decrease mean transmural pressure (e.g. heamorrhage)
2. Renin converts angiotensinogen to angiotensin I
3. ACE converts angiotensin I to II
4. ATII influence drinking behaviour to bring up BP (heamorrhage people get thirsty) + aldosterone secretion from adrenal cortex

Question 7

What could cause oversecretion of ADH?

Answer 7

1. Head trauma/infection
2. Malignant disease e.g. AVP releasing lung cell cancer
3. Selected narcotics/anelgesis e.g. nicotine, surgery
4. Prolonged strenuous exercise e.g. marathon, hot weather training

Symptoms: hypervolemic hypertension, fatal hyponatremia + conc. urine made

Treat: with fluid restriction, hypertonic saline and/or AVP antagonist (vaptans)

Question 8

What are ligands for MR?

Answer 8

Natural:

1. Aldosterone
2. DOC

Pharm ligands:

1. DOCA
2. Fludrocortisone

Question 9

What are ligands for GR?

Answer 9

Natural:

1. Cortisol

Pharm ligands:

1. Betamethasone
2. Dexamethasone
3. Prednisolone

Question 10

What are aldosterone selective tissue?

Answer 10

1. Kidney
2. Colon
3. Salivary glands
4. Placenta

Question 11

What is the worst inhibitor of 11BHSD2?

Answer 11

Furosemide

Question 12

What are the clinical symptoms of AME?

Answer 12

1. Anti-natriuesis
2. Increased fluid resorption
3. Hypervolemic hypertension due to Na⁺
4. Hypokalemis leading to muscle weakness inc. cardiac arrest

Question 13

What is Barker’s hypothesis?

Answer 13

• High risk of adult disease by epigenetic changes if exposed to high cortisol levels if in utero