Renal Blood Flow and Glomerular Filtration

Renal Blood Flow - Crimson Current

• Key Values:
  • Renal Blood Flow (RBF): ~1 L/min (20-25% of Cardiac Output).
  • Renal Plasma Flow (RPF): ~600 ml/min.
• Vascular Pathway: Renal a. → Segmental a. → Interlobar a. → Arcuate a. → Interlobular a. → Afferent arteriole → Glomerulus → Efferent arteriole → Peritubular capillaries/Vasa recta.
• Measurement:
  • RPF via PAH clearance: $RPF = (U_{PAH} \times V) / P_{PAH}$.
  • RBF from RPF: $RBF = RPF / (1 - Hct)$.

⭐ The kidneys receive approximately 20-25% of the cardiac output, despite constituting only 0.5% of body mass.

Glomerular Filtration & GFR - Mighty Microfilter

• Glomerular Filtration Barrier (GFB): Three layers.
  • 1. Fenestrated endothelium: Stops cells.
  • 2. Glomerular Basement Membrane (GBM): Type IV collagen, heparan sulfate (anionic barrier).
  • 3. Podocyte foot processes: With slit diaphragms (nephrin); final size barrier.
• Selectivity: Filters by size (restricts >4 nm, albumin) & charge (negative charge of GFB, esp. heparan sulfate, repels anionic proteins).
• Starling Forces determine GFR:
  • $GFR = K_f \times [(P_{GC} - P_{BS}) - (\pi_{GC} - \pi_{BS})]$ (Note: $\pi_{BS}$ is usually negligible)
    • $K_f$: Filtration coefficient.
    • $P_{GC}$: Glomerular capillary hydrostatic pressure (favors filtration).
    • $P_{BS}$: Bowman's space hydrostatic pressure (opposes).
    • $\pi_{GC}$: Glomerular capillary oncotic pressure (opposes).
• Normal GFR: ~125 mL/min or 180 L/day.
• GFR Measurement:
  • Ideal marker: Freely filtered; not reabsorbed/secreted.
  • Inulin clearance: Gold standard.
  • Creatinine clearance: Clinical estimate (slight secretion overestimates GFR).

⭐ The glomerular basement membrane (GBM) restricts filtration of molecules based on size and negative charge (due to heparan sulfate).

Regulation of RBF & GFR - Kidney's Command

• Autoregulation (Maintains RBF & GFR over MAP 80-180 mmHg):
  • Myogenic: Afferent arteriole constricts/dilates to stretch.
  • Tubuloglomerular Feedback (TGF): Macula densa senses ↑NaCl in DCT → signals afferent arteriole (adenosine/ATP) → constriction → ↓GFR.
• Neural Regulation: Sympathetic nerves (α1 receptors):
  • Vasoconstriction (Afferent > Efferent arterioles) → ↓RBF, ↓GFR.
• Hormonal Regulation:
  • RAAS (Angiotensin II):
    • Low conc: Potent vasoconstrictor (Efferent > Afferent) → ↑GFR initially or maintains it.
    • High conc: Both afferent & efferent vasoconstriction → ↓GFR.
    • Stimulates aldosterone.
  • Prostaglandins (PGE2, PGI2): Vasodilate afferent arteriole → ↑RBF, ↑GFR. Protective.
  • ANP/BNP: Dilate afferent, constrict efferent → ↑GFR. Inhibit Na+ reabsorption.
  • Endothelin: Vasoconstriction.
  • Bradykinin: Vasodilation.

⭐ Angiotensin II preferentially constricts the efferent arteriole at low concentrations, thereby helping to maintain GFR when renal perfusion pressure drops.

Filtration Fraction - The Net Yield

• Definition: Filtration Fraction ($FF$) = $GFR / RPF$.

• Normal: ~0.2 (20%).

• Factors affecting $FF$:

  Factor	RPF	GFR	$FF$
  Afferent Constriction (NSAIDs)	↓	↓	Variable/↓
  Efferent Constriction (Low Ang II)	↓	↑	↑
  Afferent Dilation	↑	↑	Variable
  Efferent Dilation (ACE-I)	↑	↓	↓
  ↑ Plasma Protein Conc.	↔	↓	↓
  ↓ Plasma Protein Conc.	↔	↑	↑

⭐ ACE inhibitors decrease filtration fraction by dilating the efferent arteriole, which increases RPF and decreases GFR.

High‑Yield Points - ⚡ Biggest Takeaways

• RBF is ~20-25% of cardiac output; RPF = RBF * (1-Hct).
• Normal GFR is ~125 mL/min; Filtration Fraction (FF) = GFR/RPF, typically ~0.2.
• Autoregulation (myogenic & TGF mechanisms) maintains GFR/RBF constant over MAP 80-180 mmHg.
• Afferent constriction (e.g., NSAIDs) ↓RBF & ↓GFR. Efferent constriction (low Ang II) ↑GFR, ↓RBF.
• Inulin clearance measures GFR; PAH clearance estimates RPF.
• Starling forces (glomerular capillary hydrostatic Pgc & oncotic πgc pressures) govern filtration.