Hormonal influences on GFR

RAAS - The Pressure Player

Triggered by ↓ renal blood pressure or ↓ Na⁺ delivery to the macula densa. The juxtaglomerular (JG) cells release renin, initiating a cascade to restore blood pressure and GFR.

• Angiotensin II (AT-II) Actions:
  • Potent systemic vasoconstrictor → ↑ Mean Arterial Pressure.
  • Preferentially constricts the efferent arteriole > afferent arteriole.
    • Increases glomerular hydrostatic pressure ($P_{GC}$) → ↑ GFR.
    • Increases filtration fraction (FF = GFR/RPF).
  • Stimulates aldosterone release from the adrenal cortex → ↑ Na⁺ and H₂O reabsorption.
  • Promotes ADH secretion and thirst.

⭐ In bilateral renal artery stenosis, giving an ACE inhibitor (e.g., lisinopril) can cause acute kidney injury. It blocks the vital efferent arteriole constriction needed to maintain GFR, leading to a precipitous drop.

ANP & BNP - The Volume Relievers

• Source: Released from atrial (ANP) & ventricular (BNP) myocytes in response to ↑ stretch (volume expansion).
• Primary Action: Counteract volume overload by promoting natriuresis and diuresis.
• Renal Effects on GFR:
  • Dilates afferent arteriole → ↑ Renal Blood Flow.
  • Constricts efferent arteriole.
  • Both actions synergistically ↑ Glomerular Hydrostatic Pressure → ↑ GFR.
• Other Renal Actions:
  • Inhibits renin secretion.
  • Reduces Na⁺ reabsorption in the collecting duct.

⭐ Clinically, BNP levels are a crucial biomarker in diagnosing and assessing the severity of heart failure; a level > 100 pg/mL is a key threshold.

Prostaglandins - The Local Protectors

• Source: Synthesized locally within the kidneys, primarily Prostaglandins E₂ (PGE₂) and I₂ (PGI₂).
• Primary Action: Vasodilation of the afferent arteriole.
  • This action ↑ Renal Blood Flow (RBF) and helps maintain the Glomerular Filtration Rate (GFR).
  • Crucially counteracts potent vasoconstrictors (e.g., Angiotensin II, norepinephrine), especially during periods of systemic hypotension or volume depletion.
• Clinical Significance:
  • Non-steroidal anti-inflammatory drugs (NSAIDs) inhibit prostaglandin synthesis.
  • This inhibition removes the protective vasodilation, leading to unopposed afferent arteriole constriction, ↓ RBF, and ↓ GFR.

⭐ In patients with reduced effective renal perfusion (e.g., heart failure, dehydration), NSAID use can precipitate acute kidney injury by blocking this essential compensatory mechanism.

High‑Yield Points - ⚡ Biggest Takeaways

• Angiotensin II preferentially constricts the efferent arteriole, preserving GFR; high levels constrict both, ↓ GFR.
• ANP and BNP dilate the afferent arteriole while constricting the efferent, leading to an ↑ in GFR.
• Prostaglandins maintain GFR by dilating the afferent arteriole; NSAIDs block this protective vasodilation.
• Sympathetic stimulation strongly constricts the afferent arteriole, causing a significant ↓ in both GFR and RBF.
• Endothelin is a potent vasoconstrictor of both arterioles, which ↓ GFR.