Physiology 3120 Lecture Notes - Lecture 42: Angiotensin-Converting Enzyme, Hyperkalemia, Juxtaglomerular Cell
2 May 2018
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Human Physiology Lecture 42
Renal Physiology – Part 4
Hormonal Regulation of Sodium Balance
- In the collecting duct, there are transporters and channels that respond to hormones
o Modify the amount of sodium that is excreted and reabsorbed
- Sodium balancing – have multiple hormones that are acting
o BUT in water balancing, there is only one hormone (ADH)
- Two hormone systems to regulate body levels of sodium:
o 1. Renin-Angiotensin-Aldosterone System (RAAS)
▪ Sodium levels are low
o 2. Atrial Natriuretic Peptide (ANP)
▪ Sodium levels are high
▪ When sodium levels are high, the ECF volume increases as does blood pressure
• There is a link between [sodium] and ECF volume allows us to detect BP
changes
• Conserve more water when high [sodium] = increased ECF volume
o Do not want the plasma osmolarity to change too much
• More blood volume = higher BP
▪ Have receptors to detect changes in blood pressure and filtrate composition to
activate these pathways
• Have the ability to detect composition of the filtrate fluid
• What is in the filtrate is related to what is in the blood in terms of ions
▪ We are usually in the high sodium pathway
- LOW SODIUM RAAS
- HIGH SODIUM ANP
- The kidney control osmolarity of the ECF volume
o If ion levels like sodium are too high in the body, ECF volume expands
o NOTE: plasma is included in ECF, therefore increased ECF means increased total blood
volume
o Increase blood volume = increase BP
- Body detect changes in BP to regulate sodium content since the sodium concentration, ECF volume
and BP are closely connected
RAAS Pathway
- There is an enzyme that is produced and two hormones
- Liver: produces plasma proteins, angiotensinogen
o Constitutively produced (liver is always producing it)
o Has no function – just contributes to colloid osmotic pressure of the blood
o Large – 452 a.a (sequential cleavage products are much smaller)
- Within the blood, angiotensinogen is cleaved into a smaller peptide, angiotensin I
o Much smaller, 10 a.a
o It is cleaved due to the enzyme from the Juxtaglomerular cells (cells next to the macula densa
cells in the corpuscle)
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- Juxtaglomerular cells: secrete renin into the blood at low levels of sodium
o Renin cleave angiotensinogen into angiotensin 1 (10 a.a peptide)
o ONLY released with specific stimuli – there are triggers for the juxtaglomerular cells
▪ NOT constitutively produced
o When renin is triggered for secretion into the blood, then we have the production of
angiotensin 1
o NOTE: angiotensin 1 has NO function small peptide without any biological function
- Endothelial cells: Angiotensin converting enzyme (ACE) – enzyme embedded in the membrane
o ACE is abundant
o ACE cleaves angiotensin 1 to angiotensin 2
o Angiotensin 2 is an 8 a.a peptide hormone
▪ FIRST HORMONE IN THE PATHWAY
o Epithelial cells in entire circulation do express some of this enzyme, BUT highest level of ACE
expression is found in the capillary beds of our lungs
▪ In lung, have highest expression of membrane bound enzyme, ACE
▪ This is a good thing: all of the blood has to pass by the lungs for pick up oxygen, drop
off carbon dioxide
• All of blood is efficiently transported in lung capillary beds – all of the blood
has to go there
o ANY angiotensin 1 in the blood will be converted to angiotensin 2 efficiently and rapidly
o Note: angiotensin 2 has function in the body
▪ There are receptors that recognize it found on cell surface
- RATE LIMITING STEP (what limits the production of Angiotensin 2): production of enzyme, renin
o Renin is only put in the blood when there are the right triggers from the body
- Angiotensin 2 will stimulate the adrenal glands that sit on the kidneys
o One of the layers = adrenal cortex
o Adrenal cortex layer is the specific layer of cells that produce and secrete aldosterone
o Aldosterone is a steroid hormone that is triggered for release by the presence of angiotensin
2 (one mechanism to release it)
o Aldosterone conserves sodium in the blood
Angiotensin II
- MADE BY: sequential cleavage of angiotensinogen to angiotensin I to angiotensin II
- HORMONE PROPERTIES: Peptide hormone, released into the blood when triggered
- Small – 8 a.a. in length
- STIMULUS: renin release
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o Renin itself does NOT produce angiotensin 2, it acts on angiotensinogen to produce
angiotensin 1
o Renin is the RATE LIMITING STEP
- Function in kidney = acts to increase sodium reabsorption
o In the proximal tubule:
▪ Increase activity of Na+/H+ exchanger
• Changes its function by incrasing activity – conformational change occur
faster in presence of Ang 2
▪ Increase activity of Na+/K+ ATPase
▪ VERY quick response – once Ang2 is in the blood, it can more efficiently reabsorb
sodium
o Note: RAAS pathway activated when sodium levels are low in the blood
o When filtering sodium, you want to reabsorb more than usual if your blood plasma levels are
low
- ACTION OF ANGIOTENSIN 2: Will cause an increase in sodium reabsorption in the proximal tubule
by:
o Increasing activity of the Na+/H+ exchanger
o Increasing the activity of the Na+/K+ ATPase
o Constricting both the afferent and efferent arterioles
▪ GFR is decreased in response
Angiotensin II Action
- Increasing sodium reabsorption in the proximal tubule
- Angiotensin 2 can EITHER act on a basolateral angiotensin 2 receptor (because angiotensin 2 is in the
blood) OR act on luminal membrane receptors
- Angiotensin 2 gets into the filtrate because it is small – it is a small peptide that are capable of being
filtered
- When we have binding of the receptors, we have increase of the Na+/H+ exchanger on the luminal
membrane because of the binding of the luminal receptor to Ang 2
o More sodium gets reabsorbed and more hydrogen is secreted
- Basolateral activation by Ang2 causes increase in the Na+/K+ ATPase on the basolateral membrane
o More effectively reabsorb sodium across the basolateral membrane
- There is a location specific response
o Local changes in the receptor causes the protein to change function
o Just because we have activation on the luminal membrane DOES NOT mean that the
angiotensin 2 signaling cascade that is elicited will also affect the basolateral membrane
find more resources at oneclass.com
find more resources at oneclass.com
Document Summary
In the collecting duct, there are transporters and channels that respond to hormones: modify the amount of sodium that is excreted and reabsorbed. Sodium balancing have multiple hormones that are acting. Two hormone systems to regulate body levels of sodium: but in water balancing, there is only one hormone (adh, 1. The kidney control osmolarity of the ecf volume. If ion levels like sodium are too high in the body, ecf volume expands: note: plasma is included in ecf, therefore increased ecf means increased total blood volume. Body detect changes in bp to regulate sodium content since the sodium concentration, ecf volume and bp are closely connected. There is an enzyme that is produced and two hormones. Liver: produces plasma proteins, angiotensinogen: constitutively produced (liver is always producing it, has no function just contributes to colloid osmotic pressure of the blood, large 452 a. a (sequential cleavage products are much smaller)
