Lecture 19; Regulation of Na and water balance Flashcards
(31 cards)
What is water balance?
Water Input = Water output
Give some relative values for water input?
- 2L/day Food and Drink
- 3L/day Metabolism
= 2.5L/day
Give some relative values for water output;
Skin + Lungs (insensible loss) = 0.9L/day
Urine = 1.5L/day
Feces = 0.1L/day
What is the role of the kidneys;
They can only conserve fluid
Describe some mechanisms of fluid reabsorption in the kidney;
- Water is reabsorbed in the descending LOH, due to the intense extra loop osmolarity
- When aquaporins are inserted into the DCT & CD
Describe the LOH;
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
What is the function of ADH?
• 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
What receptors do ADH (AVP) work on?
V1 and V2, both are GPCRs
V1= Coupled with Ga(s) V2= Coupled with ATRAP
What does ADH on V1 do?
Increase phosphatidylinositol (PI) metabolism increases intracellular calcium levels increase vascular smooth muscle contraction
What does ADH on V2 do?
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.
Describe aquaporin 2 insertion;
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
What regulates ADH production?
- Serum Osmolarity
- Blood Volume
- Blood O2 and CO2 tension
Describe how serum osmolarity regulates ADH production;
- 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
How does blood volume regulate ADH production?
- fall in blood volume >8% (e.g. haemorrhage)
leads to increased AVP release and vasoconstriction
This is sensed by atrial stretch receptors
How does blood oxygen and CO2 tensions effect ADH?
- 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
What are some additional factors that regulate ADH production?
- 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
What is vascular volume maintenance dependant on?
• Maintenance of vascular volume is dependent on
sodium balance
Addition of salt to the body raises osmolarity -
triggers AVP release and thirst. (increasing BV)
Describe what happens when salt is ingested;
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
What governs Na loss
Regulated by the renin-angiotensin-aldosterone
system and atrial natriuretic hormone which
maintains blood pressure
What is the half life of aldosterone?
• Aldosterone circulates with a half life of ~ 20 -30
minutes at ~ 1000 fold lower concentration than
cortisol
Which receptor does aldosterone act on?
• 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)
Because cortisol and aldosterone share the same MR, what prevents constant cortisol antagonism?
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)
What is aldosterones role and where does it act?
• 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
What regulates aldosterone release?
Blood pressure, osmolarity and potassium
levels regulate aldosterone secretion
