Confused about myogenic mechanisms and tubuloglomerular feedback in kidney

[kevv]

I am very confused by the regulation of glomerular filtration rate (GFR) and renal blood flow (RBF), and I have spent hours in going through textbooks and websites, but I still do not understand clearly.

In myogenic mechanisms:
when arterial pressure ↓ -> RBF↓, GFR↓, stretch in afferent arteriole↓ -> secretion of renin ↑ by granular cells -> contraction of vascular smooth muscle -> arterial pressure ↑ ->RBF↑, GFR↑

In tubuloglomerular feedback:
when GFR↑ and RBF ↑ -> ↑uptake of NaCl by macula densa via NKCC2 -> ↑ [ATP] and ↑[adenosine] (because water ↑ by osmosis and cell swells) -> ATP binds to P2X receptor while adenosine binds to adenosine A1 receptor on smooth muscle cells of afferent arteriole -> ↑[Ca2+] in smooth muscle cells of afferent arteriole-> vasoconstriction -> GFR↓ and RBF↓

Macula densa also affects renin secretion in granular cells:
Using the situation in tubuloglomerular feedback...
when GFR↑ and RBF ↑ -> ↑uptake of NaCl by macula densa via NKCC2 -> ↓secretion of prostaglandin E2 by macula densa -> ↓renin secretion by granular cell -> vasodilation in afferent artiole -> GFR↓ and RBF↓

The steps unerlined seem to be contradictory. Which steps are wrong?

Some of the sources I looked into:
Tubuloglomerular feedback - Wikipedia
"The binding of adenosine to the A1 receptor causes a complex signal cascade involving the Gi subunit deactivating Ac, thus reducing cAMP and the Go subunit activating PLC, IP3 and DAG.[11] The IP3 causes the release of intracellular calcium, which spreads to neighboring cells via gap junctions creating a "TGF calcium wave".[7] This causes afferent arteriolar vasoconstriction, decreasing the glomerular filtrate rate."

"PGE2 acts on EP2 and EP4 receptors in juxtaglomerular cells and causes renin release.[4] Renin release activates RAAS leading to many outcomes including an increased GFR."
(so renin ↑ causes GFR↑ because of vasoconstriction. However, why would the above paragraph say that vasoconstriction decreases GFR?)


Natalie's Casebook
"This causes cell swelling and adenosine (or ATP which subsequently breaks down to adenosine) is released, constricting the nearby afferent artery, reducing GFR."




Thank you very much.

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[DefinitelyNotTaylorSwift]

Not really sure what your question is but are you confusing afferent vs efferent arteriole?


Your first statement that increased renin leads to both increased gfr AND rpf is what is at fault here- constriction of the efferent arteriole will decrease RPF but increase GFR

 

[kevv]

Not really sure what your question is but are you confusing afferent vs efferent arteriole?


Your first statement that increased renin leads to both increased gfr AND rpf is what is at fault here- constriction of the efferent arteriole will decrease RPF but increase GFR

Sorry. I should clarify my question a bit.

In statement 1, about myogenic mechanisms,
renin secretion -> vasoconstriction -> arterial pressure increases -> renal blood flow (RBF) increases and glomerular filtration rate (GFR) increases

However, in statement 2, tubuloglomerular feedback
vasoconstriction -> RBF decreases and GFR decreases

So, does vasoconstriction increase or reduce RBF and GFR?
As you said, renin causes vasoconstriction in efferent arterioles, so then is such renin vasoconstriction different from the vasoconstriction caused by tubuloglomerular? Do these two mechanisms have different effects on afferent and efferent arterioles?

I am guessing -
- So, myogenic mechanism causes vasoconstriction in the whole body, and hence this increasing arterial pressure increases GFR and RBF. While vasoconstriction also occurs in afferent arterioles that intends to reduce RBF and GFR, such effect is smaller than the systemic increase in arterial pressure (causing greater GFR and RBF) and also smaller than the vasoconstriction in efferent arterioles (causing greater GFR but smaller RBF). So, the overall effect is that GFR increases but RBF decreases.
- For tubuloglomerular feedback, such vasoconstriction is limited locally to afferent arteriole, so that both RBF and GFR decrease
- In statement 3, macula densa activiating renin secreting in granular cells
this is simply the same concept as statement 1 - overall change in whole-body arterial pressure and change in local efferent arterioles overcomes changes in local afferent arterioles.

Is this correct then??
Thank you.

 

[Rahas]

Both mechanisms serve to autoregulate RBF / GFR. Since this is autoregulation, neither mechanism will affect the entire body.

The myogenic mechanism depends on the intrinsic property of smooth to contract if its stretch, which helps modulate RBF / GFR. Too much blood flow --> the smooth muscle in the renal vasculature will stretch --> this will cause it to vasoconstrict --> this will limit the increase in RBF / GFR.

The tubuloglomerular feedback involves feedback from the tubules (specifically, the MD of the DCT) to locally autoregulate the RBF / GFR. The macular dense measures the NaCl delivery to the DCT, which is an indirect indicator of the RBF / GFR. Too much NaCl would imply too much RBF / GFR, which needs to be limited, and vice versa. The MD accomplishes this by the release of either adenosine or activation of the RAAS, which can cause vasodilation or vasoconstriction of the renal vasculature to modulate the RBF / GFR. (I may be mistaken about the specific mediators as its been a while since I read this, but I hope you understand the basic idea).

 

[DefinitelyNotTaylorSwift]

S
So, does vasoconstriction increase or reduce RBF and GFR?
As you said, renin causes vasoconstriction in efferent arterioles, so then is such renin vasoconstriction different from the vasoconstriction caused by tubuloglomerular? Do these two mechanisms have different effects on afferent and efferent arterioles?

Yea the tubuloglomerular feedback has two different things going on when salt load is high :

1) decreased renin (affects efferent arteriole downstream leading to reduced gfr but increased rpf)
2) paracrine mechanism through adenosine/thromboxane/atp or whatever (clamps down afferent arteriole reducing both gfr and rpf)

Overall effect is prob to reduce gfr while maintaining rpf so the filtration fraction decreases- im presuming this is to preserve renal blood flow for oxygen purposes


The myogenic mechanism involves auto regulation of afferent and efferent arterioles; when pressure/volume is too high it'll vasoconstrict both to reduce flow

I don't know how they interplay but I presume if myogenic mechanism isn't enough to reduce gfr through reducing flow the tubuloglomerular feedback backs it up to reduce gfr even more without affecting rpf that much more since a further drop would lead to ischemia