Tubuloglomerular Feedback Mechanism

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Questions and Answers

What is the primary function of the tubuloglomerular feedback mechanism?

To regulate kidney oxygen levels

To tightly control RBF and GFR to maintain homeostasis of extracellular fluid volume (correct)

To control the amount of Na+ reabsorbed in the proximal tubule

To stimulate the release of ATP in the macula densa

What is the effect of increased apical NaCl delivery or flow to the macula densa on the tubuloglomerular feedback mechanism?

It increases the fractional reabsorption of Na+ in the proximal tubule

It has no effect on the tubuloglomerular feedback mechanism

It stimulates the release of adenosine, causing vasodilation

It provokes the cells of the macula densa to release ATP, leading to vasoconstriction (correct)

What is the role of ecto-NTPDase1 and ecto-5'-nucleotidase in the tubuloglomerular feedback mechanism?

They are involved in the reabsorption of Na+ in the proximal tubule

They convert ATP to adenosine (correct)

They stimulate the release of ATP from the macula densa

They inhibit the activity of the basolateral Na+-K+-ATPase

What is the frequency of oscillations in the tubuloglomerular feedback mechanism?

30 seconds Signup and view all the answers

What is the effect of adenosine-mediated vasoconstriction on the afferent arteriole?

It reduces RBF and GFR Signup and view all the answers

What is unique to the afferent arteriole regarding adenosine-mediated vasoconstriction?

It is the only site where adenosine-mediated vasoconstriction occurs Signup and view all the answers

What is the result of an increase in RBF and/or GFR without a corresponding increase in fractional reabsorption along the proximal tubule?

An increase in Na+ delivery to the macula densa Signup and view all the answers

What is the relationship between tubular NaCl load and GFR of the same nephron?

Inversely proportional Signup and view all the answers

Which receptors mediate the vasoconstrictor response to interstitial ATP in the afferent arteriole?

P2X purinergic receptors Signup and view all the answers

What is the role of adenosine in the medulla?

Stabilizing medullary energy balance Signup and view all the answers

What happens to TAL sodium reabsorption when ATP levels decline?

It is inhibited Signup and view all the answers

What is the effect of adenosine binding to A1 receptors in the TAL and IMCD?

Inhibiting Na+ reabsorption Signup and view all the answers

What is the effect of activating A2 receptors in the vasa recta?

Increasing blood flow Signup and view all the answers

What is the significance of the fact that TAL sodium reabsorption normally exceeds urinary sodium excretion by 40-fold?

It requires that any significant decline in TAL reabsorption must be compensated for by increasing active transport somewhere else or by reducing GFR through TGF Signup and view all the answers

In the absence of the tubuloglomerular feedback mechanism, what would be the consequence on the kidney's ability to regulate Na+ and volume output?

Homeostasis of extracellular fluid volume would be compromised Signup and view all the answers

What is the role of adenosine A1 receptors in the glomerulus, proximal tubule, or TAL?

Lessening the amount of work imposed on the hypoxic outer medulla Signup and view all the answers

What is the result of adenosine binding to A2 receptors in the deep cortex and medullary vasa recta?

Increasing medullary blood flow Signup and view all the answers

Which of the following is NOT a component of the tubuloglomerular feedback mechanism?

Ecto-nucleoside triphosphate diphosphohydrolase 2 Signup and view all the answers

What is the primary consequence of increased ATP release by the macula densa?

Vasoconstriction of the afferent arteriole Signup and view all the answers

What is the significance of the inverse relationship between tubular NaCl load and GFR of the same nephron?

It enables the kidney to maintain homeostasis of extracellular fluid volume Signup and view all the answers

What is the role of maxi-anion channels in the tubuloglomerular feedback mechanism?

Release of ATP by the macula densa Signup and view all the answers

What is the consequence of oscillations in the tubuloglomerular feedback mechanism?

Rhythmic oscillations in kidney Po2 Signup and view all the answers

Which of the following enzymes is NOT involved in the conversion of ATP to adenosine?

Basolateral Na+-K+-ATPase Signup and view all the answers

What is the significance of the unique response of the afferent arteriole to adenosine-mediated vasoconstriction?

It is a distinct feature of the tubuloglomerular feedback mechanism Signup and view all the answers

Study Notes

Tubuloglomerular Feedback (TGF)

TGF is a mechanism that tightly controls RBF (Renal Blood Flow) and GFR (Glomerular Filtration Rate) to maintain homeostasis of extracellular fluid volume.

Regulation of RBF and GFR

Increased RBF and/or GFR leads to increased salt delivery to the macula densa, triggering the TGF response.
TGF response is dependent on the basolateral Na+-K+-ATPase to maintain the inward-directed Na+ gradient.
Increased apical NaCl delivery or flow to the macula densa provokes cells to release ATP into the interstitium.

ATP Release and Adenosine Production

ATP is released via maxi-anion channels.
Released ATP is converted to adenosine by local ecto-nucleoside triphosphate diphosphohydrolase 1 (ecto-NTPDase1) and ecto-5'-nucleotidase.
Adenosine activates A1 adenosine receptors on the afferent arteriole, causing vasoconstriction.

TGF Response and GFR Regulation

Arteriolar constriction reduces RBF and GFR until Na+ delivery to the macula densa is realigned.
An inverse relationship is established between tubular NaCl load and the GFR of the same nephron.

TGF System Characteristics

The TGF system is prone to oscillate with a period of around 30 seconds.
Rhythmic oscillations of kidney Po2 occur at the same frequency as TGF-mediated oscillations in tubular flow.

Adenosine and Purinergic Receptors

Adenosine mediates TGF as a vasoconstrictor, unique to the afferent arteriole.
Adenosine A1 receptors are sufficient to explain the TGF response.
P2X purinergic receptors, also expressed on the afferent arteriole, mediate a vasoconstrictor response to interstitial ATP, essential for pressure-mediated RBF autoregulation.

Tubuloglomerular Feedback (TGF) Mechanism

The TGF mechanism tightly controls RBF and GFR to prevent significant fluctuations in RBF, GFR, and filtered Na+ load, which would compromise homeostasis of extracellular fluid volume.
An increase in RBF and/or GFR leads to an increase in salt delivery to the macula densa, triggering the TGF response.
The TGF response involves the release of ATP from the macula densa cells into the interstitium surrounding the afferent arterioles, which is dependent on the basolateral Na+-K+-ATPase.

ATP Release and Adenosine Conversion

ATP is released via maxi-anion channels.
Some fraction of the released ATP is converted to adenosine by local ecto-nucleoside triphosphate diphosphohydrolase 1 (ecto-NTPDase1) and ecto-5'-nucleotidase.

Adenosine-Mediated Vasoconstriction

Adenosine activates A1 adenosine receptors on the afferent arteriole, causing vasoconstriction.
This vasoconstriction reduces RBF and GFR until Na+ delivery to the macula densa is realigned.
Adenosine-mediated vasoconstriction is unique to the afferent arteriole, whereas in other beds, adenosine exerts a vasodilatory effect mediated by A2 receptors.

TGF Oscillations and Oxygen Levels

The TGF system is prone to oscillate with a period of around 30 seconds.
Rhythmic oscillations of kidney Po2 occur at the same frequency as TGF-mediated oscillations in tubular flow.
This illustrates the simultaneous influence of TGF over minute-to-minute tubular flow rate and oxygen levels in the kidney.

Adenosine's Role in Medullary Energy Balance

Adenosine plays an important role in stabilizing medullary energy balance through local adjustments in blood flow and transport.
Adenosine binds to adenosine A1 receptors and inhibits Na+ reabsorption in the TAL and IMCD, increasing Po2 by reducing Qo2.
Adenosine also activates vascular adenosine A2 receptors in the deep cortex and medullary vasa recta to increase blood flow.

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Description

Learn about the tubuloglomerular feedback mechanism that regulates renal blood flow and glomerular filtration rate to maintain homeostasis of extracellular fluid volume.