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Lecture 40

Physiology 3120 Lecture Notes - Lecture 40: Macula Densa, Angiotensin, Juxtaglomerular Cell


Department
Physiology
Course Code
PHYSIO 3120
Professor
Tom Stavraky
Lecture
40

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Lecture 40 Hormone Regulation of Sodium
Hormonal regulation of sodium balance
- In the collecting duct, there are transporters and channels that respond to hormones so we
can modify the amount of sodium that is excreted and reabsorbed
- Sodium balance: multiple hormones acting (for high and low)
- Water balance: one hormone acting (ADH)
Two hormone systems to regulate body levels of sodium:
- 1. Renin-Angiotensin-Aldosterone System (RAAS)
o Sodium levels are low, RAAS pathway is activated
- 2. Atrial Natriuretic Peptide (ANP)
o Sodium levels are high, ANP is released (this is more common)
- There is a link between sodium and extracellular fluid volume = can detect BP changes
- When sodium levels are high, the ECF volume increases (conserve more water to maintain
osmolarity) as does blood pressure
o Ingest too much sodium = expansion of ECF volume = increase blood pressure
- Have receptors to detect changes in blood pressure and filtrate composition to activate
these pathways
o There are barcoreceptors and volume receptors and we have the ability to detect
the composition of the tubule filtrate
o What is in the filtrate is related to what was in the blood
- There is an integration of multiple things that tells the body how if a hormone needs to be
released and how much (low sodium pathway is most integrated)
RAAS Pathway
- There is an enzyme that is produced + 2 hormones
- Liver produces angiotensinogen (plasma protein that is constitutively produced)
o Liver is constantly making it
o It does not have a function and contributes to the colloid osmotic pressure of blood
o Large protein (452 AA) cleavage products are much smaller
- Within the blood, angiotensinogen is cleaved to a smaller product, angiotensin I (10 AA)
o AngI is cleaved because there is a presence of the enzyme that comes from
juxtaglomerular cells
- Juxtaglomerular cells (granular cells) are next to macula densa cells and secrete renin into
the blood
o Renin is only released with specific stimuli
o It is not constitutively secreted into the blood
o There are triggers for the juxtaglomerular cells to release the renin
o When it is secreted into the blood, we have the production of ang I
- Renin is the enzyme that will cleave angiotensinogen into ang I
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- Angiotensin I does nothing: it is a small peptide without a biological function that floats in
the blood
- The capillaries are made of endothelial cells and they have an enzyme embedded in them
that cleaves ang I to ang II (8 AA peptide hormone)
o Enzyme embedded in the membrane of endothelial cells is called ACE
o Endothelial cells in the entire circulation express ACE but the highest level of ACE
expression is found in the capillary bed of the lungs
- In the lungs, there is the highest expression of the membrane bound enzyme, ACE
o All of the blood must pass by the lungs for reoxygenation and to drop off carbon
dioxide
o All blood is efficiently transported in lung capillary beds
o Any angI in the blood will be converted to ang II very efficiently and rapidly
- Ang II is the first hormone in the pathway
- RATE LIMITING STEP: what limits the production of ang II?
o Production of the enzyme renin
o Renin is rate limiting and is only put into the blood when there is the right trigger
from the body
- Ang II travels through the blood and since it is a hormone, there are receptors that
recognize ang II
o Receptors are on a number of cells and not just the kidney
- Ang II stimulates the adrenal glands that sit on the kidneys
o Adrenal cortex layer within the gland is the specific layer of cells that produce and
secrete aldosterone
- Aldosterone: steroid hormone that is triggered for release by the presence of Ang II in the
RAAS pathway
Angiotensin II
- Made by sequential cleavage of angiotensinogen to angiotensin I to angiotensin II
- Peptide hormone (small 8 amino acids in length)
- Stimulated by renin release
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o Renin itself does not produce ang II but it is the rate limiting step
o Renin acts on angiotensinogen to make ang I but the production of ang II is because
of the renin that is rate limiting
- RAAS pathway is activated when sodium levels are low in the blood plasma
o Function of ang II in the kidneys: increase sodium reabsorption
o When sodium is being filtered, want to reabsorb more if levels are low
o Cells respond very quickly when ang II is in the blood more efficiently reabsorb
sodium changes functions of transporters by increasing their activity causing
conformational changes to occur faster
- Acts to increase sodium reabsorption
o In the proximal tubule:
Increase activity of Na+/H+ exchanger
Increase activity of Na+/K+ ATPase
Angiotensin II action
- Increasing sodium reabsorption in the proximal tubule
- Since Ang II is in the blood, ang II can either act on a basolateral ang II receptor on proximal
tubule cells OR on luminal membrane receptors
o Ang II gets in the filtrate because it is a small peptide and is capable of getting
filtered
- When there is binding of the receptor on the luminal membrane:
o There is an increase of the sodium hydrogen exchanger on the luminal membrane
because of binding of the luminal receptor to ang II
o = more sodium reabsorbed, more hydrogen secreted
- Basolateral activation of ang II by binding to basolateral receptor:
o Causes an increase in the sodium-potassium ATPase on the basolateral membrane
o = more effectively absorbing sodium
- There is a location specific response
o Local changes in the receptor causes that protein to change function
o Just because there is activation on the luminal membrane does not mean ang II
signaling cascade that is elicited will affect the basolateral membrane
o Also have to have binding of ang II basolaterally to the basolateral receptor
o Change in function of signaling cascades are LOCAL
o Local changes in signaling cascades occur on either the basal or luminal membrane
o The same type of receptor exists on both sides
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