Lecture 19; Regulation of Na and water balance

Question 1

What is water balance?

Answer 1

Water Input = Water output

Question 2

Give some relative values for water input?

Answer 2

2. 2L/day Food and Drink
3. 3L/day Metabolism

= 2.5L/day

Question 3

Give some relative values for water output;

Answer 3

Skin + Lungs (insensible loss) = 0.9L/day
Urine = 1.5L/day
Feces = 0.1L/day

Question 4

What is the role of the kidneys;

Answer 4

They can only conserve fluid

Question 5

Describe some mechanisms of fluid reabsorption in the kidney;

Answer 5

• Water is reabsorbed in the descending LOH, due to the intense extra loop osmolarity
• When aquaporins are inserted into the DCT & CD

Question 6

Describe the LOH;

Answer 6

Very strong osmolarity in the loop, draws out water through the decending LOH that is not permeable to ions making it hyperosmolar, this fluid then ascends the ALOH and ions are draw out into the LOH but no water, making the fluid hypo-osmotic

Question 7

What is the function of ADH?

Answer 7

• Regulates water excretion by the kidney
- acts on the distal convoluted tubule to
increase permeability to water, increase
water absorption and increase urine
concentration (aquaporin 2 insertion to apical membrane)
• Potent vasoconstrictor

Question 8

What receptors do ADH (AVP) work on?

Answer 8

V1 and V2, both are GPCRs

V1= Coupled with Ga(s)
V2= Coupled with ATRAP

Question 9

What does ADH on V1 do?

Answer 9

Increase phosphatidylinositol (PI) metabolism
increases intracellular calcium levels
increase vascular smooth muscle contraction

Question 10

What does ADH on V2 do?

Answer 10

Increases cAMP production + phosphorylation
of intracellular proteins aquaporin-2 (AQP2) vesicles to move to the apical membrane and fuse with it.
now the cell is permeable to water.

Question 11

Describe aquaporin 2 insertion;

Answer 11

1) ADH binds to membrane receptor
2) Receptor activates cAMP secondary messanger system
3) Cells insert AQ2 into apical membrane of DCT
4) Water is absorbed by osmosis into the blood

Question 12

What regulates ADH production?

Answer 12

1. Serum Osmolarity
2. Blood Volume
3. Blood O2 and CO2 tension

Question 13

Describe how serum osmolarity regulates ADH production;

Answer 13

• high (dehydration) leads to increased AVP
  release, increased water retention and decreased osmolarity
• low (e.g. water intoxication) leads to decreased
  AVP release, decreased water retention and increased
  osmolarity

Serum Osmolarity is sensed in the hypothalamus

Question 14

How does blood volume regulate ADH production?

Answer 14

• fall in blood volume >8% (e.g. haemorrhage)
  leads to increased AVP release and vasoconstriction

This is sensed by atrial stretch receptors

Question 15

How does blood oxygen and CO2 tensions effect ADH?

Answer 15

• Increased arterial O2 partial pressure leads to increase AVP
• Decreased arterial CO2 partial pressure leads to increase AVP

This will be sensed by the carotid bodies. The carotid bodies also sense blood pressure and when this is low, it will signal for increased ADH release

Question 16

What are some additional factors that regulate ADH production?

Answer 16

• Hormones - angiotensin II, epinephrine, cortisol,
  sex steroids
  •Pain and trauma associated with surgery increase in
  circulating AVP
  •Nausea and vomiting increase AVP production
  •A rise in temperature prior to any change in plasma
  osmolarity increase AVP release

Question 17

What is vascular volume maintenance dependant on?

Answer 17

• Maintenance of vascular volume is dependent on
sodium balance

Addition of salt to the body raises osmolarity -
triggers AVP release and thirst. (increasing BV)

Question 18

Describe what happens when salt is ingested;

Answer 18

Increase blood Osmolarity
= 
Increased ADH release -> Fluid retention
Increased Thirst
= 
Increased ECF volume and increased BP
- Salt and water excreted slowly over time
- CV effects to reduce BP

Question 19

What governs Na loss

Answer 19

Regulated by the renin-angiotensin-aldosterone
system and atrial natriuretic hormone which
maintains blood pressure

Question 20

What is the half life of aldosterone?

Answer 20

• Aldosterone circulates with a half life of ~ 20 -30
minutes at ~ 1000 fold lower concentration than
cortisol

Question 21

Which receptor does aldosterone act on?

Answer 21

• Acts in cells by binding to the mineralcorticoid (zona glomerulosa) receptor (MR) and acts in the cell nucleus to influence gene expression (proteins that alter proteins for K excretion and Na reabsoprtion)

Glucocorticoid; Cortisol can also bind to this (Antagonises this)

Question 22

Because cortisol and aldosterone share the same MR, what prevents constant cortisol antagonism?

Answer 22

Specificity; at major sites of mineralcorticoid
action (distal tubule and collecting tubule of
kidney), the enzyme HSD11B2 is produced to
inactivate cortisol to cortisone to allow aldosterone
to bind MR

(cortisone cant bind effectively)

Question 23

What is aldosterones role and where does it act?

Answer 23

• Promotes sodium resorption from the urine and
potassium excretion
• Primary site of action is principal cells or P cells
in the distal tubule and collecting duct of kidney

Question 24

What regulates aldosterone release?

Answer 24

Blood pressure, osmolarity and potassium

levels regulate aldosterone secretion

Question 25

What causes Aldosterone release?

Answer 25

• Primary signal for aldosterone release is a trophic
hormone known as angiotensin II (ANG II)
• Renin- angiotensin-aldosterone system maintains
blood pressure
• The enzyme, renin, is synthesised in the kidney in the
juxtaglomerular apparatus. Decreased volume
stimulates renin synthesis.
• Renin acts on its circulating inactive substrate,
angiotensinogen to generate angiotensin I.
• An enzyme in the blood called angiotensin converting
enzyme (ACE) converts ANG I to ANG II.

Question 26

What receptor does ANG2 bind to for aldosterone production and what are the additonal effects of ANG2?

Answer 26

• ANG II binds to the type 1 angiotensin II receptor
(G protein coupled receptor) in the zona
glomerulosa cells of the adrenal cortex to
stimulate aldosterone synthesis and release.
• ANG II has additional effects directed at raising
blood pressure through both direct and indirect
pathways.

Question 27

What hormones promote water and na loss?

Answer 27

• Atrial natriuretic peptide (ANP)

* Related brain naturiuretic peptide (BNP)

Question 28

Where are ANP and BNP produced?

Answer 28

• Produced in myocardial cells of the heart and others found in the brain and cause sodium and water loss

Question 29

What do these natriuretic peptides bind to?

Answer 29

• ANP and BNP bind and activate cell membrane guanylate cyclase receptors and increase the second messenger, cGMP.
• Short half lives in plasma

Question 30

What are the effects of natriuretic peptides?

Answer 30

Hypothalamus = less ADH
Kidney = Increased GFR and decreased Rening
Adrenal Cortex = less Aldosterone

= Na and H2O excretion

Decrease Renin and Increased natriuretics act on the medulla oblongata to decrease blood pressure

(decreased Renin and ACE activity)

Question 31

What is also essential?

Answer 31

Go through all the flow diagrams and make sure you understand them and can reproduce them

Draw them out