Renal Autoregulation Basics

Renal Autoregulation

• Renal autoregulation is the kidney's ability to maintain a stable blood flow and glomerular filtration rate (GFR) despite fluctuations in blood pressure.
• Intrinsic mechanisms allow the kidney to regulate blood flow and urine output independently.
• Extrinsic mechanisms assist the kidney in regulating blood flow and urine output when blood pressure is extremely low.

Intrinsic Mechanisms

• Myogenic Mechanism:
  • This mechanism involves the smooth muscle cells in the afferent arteriole, responding to changes in blood pressure.
  • High Blood Pressure: Increased stretch of afferent arteriole smooth muscle cells triggers vasoconstriction, reducing blood flow and GFR.
  • Low Blood Pressure: Reduced stretch of afferent arteriole smooth muscle cells triggers vasodilation, increasing blood flow and GFR.
• Tubulo-Glomerular Feedback Mechanism:
  • This mechanism involves specialized macula densa cells in the distal convoluted tubule (DCT) detecting sodium chloride concentration in the filtrate.
  • High GFR: Increased sodium chloride concentration in the DCT triggers the release of adenosine, causing afferent arteriole vasoconstriction and renin release from Juxtaglomerular cells (JG cells).
  • Low GFR: Decreased sodium chloride concentration in the DCT stimulates the release of prostaglandin I2 (PGI2) and nitric oxide (NO), causing afferent arteriole vasodilation.
  • Important Note: The Tubuloglomerular Feedback mechanism is crucial for maintaining stable GFR in response to changes in blood pressure and blood flow.

Extrinsic Mechanisms

• Extrinsic mechanisms are activated when blood pressure is significantly low, or sodium levels in the blood are low.
• Sympathetic Nervous System:
  • Sympathetic nerve stimulation constricts afferent arterioles, reducing blood flow and GFR, directing blood flow to vital organs.
• Renin-Angiotensin-Aldosterone-ADH System (RAAS):
  • Initiated by low blood pressure or low sodium levels, triggering JG cells to release renin.
  • Renin activates angiotensinogen to angiotensin I, then converted to angiotensin II by ACE.
  • Angiotensin II is a powerful vasoconstrictor, increasing blood pressure.
  • Angiotensin II also stimulates the release of aldosterone and ADH, promoting sodium and water retention and increasing water reabsorption.
  • ADH is crucial in maintaining water balance and blood pressure by regulating water reabsorption in the collecting duct.

The Role of Adenosine in Blood Pressure Regulation

• Adenosine inhibits renin release, preventing the activation of RAAS.

Tubuloglomerular Feedback Mechanism – Low Glomerular Filtration Rate (GFR)

• Low GFR triggers macula densa cells to release prostaglandin I2 (PGI2) and nitric oxide (NO). This results in vasodilation of the afferent arteriole and renin release from JG cells.

Sympathetic Nervous System – Low Blood Pressure

• Activated when mean arterial pressure (MAP) drops below 65 mmHg.
• Baroreceptors detect low blood pressure and signal the medulla to activate sympathetic nerves.
• Sympathetic stimulation increases heart rate, contractility, systemic vascular resistance and afferent arteriole vasoconstriction, increasing blood pressure. Important note, it also triggers renin release.

Renin-Angiotensin-Aldosterone-ADH (RAA) Axis – Low Blood Pressure

• Low blood pressure triggers JG cells to release renin.
• Renin converts angiotensinogen (produced by the liver) to angiotensin I, then to angiotensin II.

Angiotensin II Actions

• Angiotensin II exerts numerous actions to increase blood pressure:
  • Stimulates ADH release and increases thirst, regulating water balance and intake.
  • Stimulates aldosterone release, promoting sodium and water reabsorption in the distal convoluted tubule.
  • Causes vasoconstriction of efferent arterioles, increasing pressure within the glomerulus that increases filtration rate.
  • Causes vasoconstriction of systemic vessels, increasing systemic vascular resistance.
  • Acts on proximal convoluted tubules to increase sodium and water reabsorption.

Angiotensin II and Renal Vasoconstriction

• Angiotensin II causes efferent arteriolar vasoconstriction, increasing glomerular hydrostatic pressure.
• This leads to an increase in the glomerular filtration rate (GFR).

Angiotensin II and Sodium & Water Reabsorption

• Angiotensin II enhances sodium and water reabsorption in the proximal convoluted tubule. This increases blood volume and pressure.

Angiotensin II and Systemic Vasoconstriction

• Angiotensin II causes systemic vasoconstriction, enhancing systemic vascular resistance and elevating blood pressure.

Atrial Natriuretic Peptide (ANP)

• ANP is released from the heart's atria in response to high blood pressure and regulates sodium balance and blood pressure.
• ANP's effects oppose those of Angiotensin II and contributes to lowering blood pressure (natriuresis).

ANP's Effect on Angiotensin II

• ANP inhibits ADH, aldosterone and angiotensin II-mediated sodium and water reabsorption and causes systemic vasodilation, counteracting the effects of angiotensin II, lowering blood pressure.