renal hormones Flashcards
Describe the renin angiotensin system
- Renin cleaves angiotensinogen/renin substrate
- Angiotensin I (decapeptide) is acted on by ACE into
-
Angiotensin II, which binds
- AT1 receptors: does most of the work
- AT2 receptors: works most during fetal development
What activates the renin-angiotensin system?
What suppresses it?
- Activated by:
- Extracellular fluid volume depletion –> decreased arterial pressure
- Sodium depletion
- Stress/trauma
- Inhibited by:
- Extracellular fluid volume expansion
- Sodium repletion
The roles of the RAS system
Conservation of extracellular fluid volume
Maintenance of extracellular fluid volume
Maintenance of arterial blood pressure
Where is renin synthesized?
Juxtaglomerular cells (modified smooth muscle cells) lining the terminal portion of afferent arteriole.
Path of renin after synthesis
After synthesis by juxtaglomerular cells in teh afferent arteriole,
- 1/2 goes through the glomerulus and out the renal vein into general circulation where it does its work (lots of ACE in lung)
- 1/2 gets released into the kidney’s interstitial environment, where it will work on the angiotensinogen from proximal tubule
Where is the of ACE outside of the kidney?
Where is it inside the kidney?
Outside the kidney, most ACE is in the lungs
Inside the kidney, ACE is on the basolateral side of the proximal tubule cells
What is the rate limiting step for activation of the RAS system?
The amount of renin synthesized by the JG cells
To stimulate JG cells to release renin, either ___ has to decrease or ___ has to increase.
Cytosolic Ca2+ decreases
cAMP increases
Baroreceptor mechanism of regulating renin secretion
- Increased mean arterial pressure will activate stretch receptors on the JG cell membrane.
- Opens Ca2+ channels on the membrane so Ca2+ enters the JG cells.
- Increased [Ca2+]JG cells suppresses renin secretion
Thus, low mean arterial pressure would increase renin secretion.
Sympathetic system of regulating renin
- Increased sympathetics –> norepinephrine
- Norepinephrine will bind B1 receptors on JG cells to increase [cAMP]
- cAMP increases renin secretion
Macula densa mechanism of regulating renin secretion
- Increased NaCl delivery to the macula densa
- Macula densa releases Prostaglandin E2
- PGE2 inhibits renin secretion from JG cells.
Which would increase renin secretion (click all that apply)?
- Increased Ca++ conc in the JG cells
- Increased NaCl delivery to the macula densa
- Increased activity of the sympathetic nervous sytem
- Decreased cAMP in the JG cells
Increased sympathetics
Major actions of angiotensin II
-
Kidney.
- Reduce RBF
- Increase absolute reabsorption.
- Adrenal. Aldosterone
- Vascular. Vasoconstrictor
- Heart. Increased contractility
- Intestine. NaCl & H2O reabsorption
-
CNS.
- Thirst & salty appetite
- ADH release
- Sympathetics
- PNS. Adrenergic transmission (release more norepinephrine from sympathetics)
Whe macula densa NaCl delivery goes up, renin secretion goes __
down
Angiotensin II on the kidney (3)
- *Vasoconstrictor of the efferent arteriole –> decreases renal blood flow & maintains GFR*
-
Decreases Kf(reduces GFR a lil)
- Contraction of the intraglomerular mesangial cells reduces the surface area for filtration.
- Decreases proximal & distal tubule NaCl & H2O reabsorption
Aldosterone from the adrenal gland acts where?
Late distal tubule & collecting duct cells
What is the effect of aldosterone in the late dt and cd?
Synthesizes and stimulates the insertion of
- Na,K-ATPases
-
Apical Na+ channels
- Thus, it also promote K+ secretion
- Krebs cycle enzymes.
All renal prostaglandins are synthesized from ___.
___ will oxygenate it to form inactive ___ and ___.
The final prostaglandin products are: __, __, and __.
Synthesized from arachidonic acid, which will be oxygenated by COX1 or 2 to form inactive PGG and PGH.
These will be acted upon by enzymes to form PGI2, PGE2, and thromboxane
Which of the renal prostaglandins are vasodilators? Which are vasoconstrictors?
PGE2 & PGI2(prostacyclin) - vasodilator of aff & eff arterioles
Thromboxane - vasoconstrictor of the aff arteriole
Prostaglandins are called local hormones/autacoids because
they act on the cells that synthesized them
Actions of PGE2 and PGI2
Vasodilation of aff & eff arterioles –> increases RBF (not much change in GFR)
Decreases NaCl reabsorption by the thick ascending loop of Henle & the collecting duct.
Thus, the prostglandin system is like the opposite of the RAS system
In a regular sodium replete state, your prostaglandin levels are
very low
What stimulates PGE2 & PGI2 synthesis?
- Depleted ECFV
- Decreased mean arterial pressure
When these happen, this increases Angiotensin II levels, norepinephrine, and ADH all acting to reduce RBF. These prostaglandins make sure that the kidney does not completely fail
Counteracting mechanism
When ECFV is decreased and MAP drops, the RAS system will increase angII, norepinephrine, and ADH to cause vasoconstriction.
PGE2 and PGI2 cause vasodilation to keep RBF going so the kidney doesn’t fail
Kallikrein-kinin system
- Renal kallikrein is synthesized in the cells of the connecting tubule (late dt), released into the interstitium
- Acts on kininogens to form kallidin
- Aminopeptidase turns kallidin into bradykinin, which will oppose the effects of angII, norepi, and ADH (just like prostaglandins).
How does bradykinin mediate itse effects?
It binds to B2-bradykinin receptors to
- Stimulate the production of NO and PGE2 by vascular endothelial cells –> vasodilation
- Decrease NaCl reabsorption at the thick ascending limb and the late dt
Erythropoietin
Stimulates RBC synthesis in the bone marrow.
90% is released by the kidney
what stimulates erythropoietin production?
Decreased oxygenation
- Low blood volume
- Anemia
- Low hemoglobin
- Poor blood flow
- Pulmonary disease
- Chronic renal vasoconstriction by angiotensin II, norepi, ADH
