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Glomerular Filtration Rate (GFR) - Detailed Explanation

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1. Definition

• Normal GFR: 120 mL/min per 1.73 m² body surface area (~180 L/day)
• Daily tubular reabsorption: ~178.5 L/day → urine output: ~1.5 L/day

"The total glomerular filtration rate (GFR) is the sum of the SNGFRs of functioning nephrons and the normal range is wide, typically cited at 120 mL/min per 1.73 m² surface area." - Comprehensive Clinical Nephrology, 7th Edition

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2. The Starling Forces - The Driving Equation

SNGFR = Kf × [(Pgc - Pbs) - (πgc - πbs)]

Pressure Diagram Along Glomerular Capillary

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3. Filtration Flowchart

BLOOD enters via AFFERENT ARTERIOLE
           |
           ▼
   GLOMERULAR CAPILLARIES
           |
   Forces acting:
   ┌─────────────────────────────────────────┐
   │  PRO-FILTRATION forces (push OUT):      │
   │  Pgc (capillary hydrostatic) = 45 mmHg  │
   │  πbs (Bowman's oncotic) = 0 mmHg        │
   │─────────────────────────────────────────│
   │  ANTI-FILTRATION forces (push IN):      │
   │  πgc (plasma oncotic) = 25 mmHg         │
   │  Pbs (Bowman's hydrostatic) = 10 mmHg   │
   └─────────────────────────────────────────┘
           |
           ▼
   Net Ultrafiltration Pressure = ~10 mmHg
           |
           ▼
   FILTRATE enters BOWMAN'S CAPSULE
     (protein-free, cell-free ultrafiltrate)
           |
           ▼
   Passes through TUBULES for reabsorption
           |
           ▼
           URINE

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4. The Filtration Barrier: Size and Charge Selectivity

Size & Charge Filterability Graph

• Molecules with radius < 1.6 nm are freely filtered regardless of charge
• Anions are filtered LESS than neutral molecules of the same size (GBM's negative charge repels them)
• Albumin (anionic, radius 3.6 nm) - almost no filtration normally
• In minimal change nephropathy, loss of GBM negative charge causes proteinuria despite preserved pore size

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5. The Kf (Ultrafiltration Coefficient)

• The mesangium (mesangial cells have contractile ability) can REDUCE filtration surface area
• Angiotensin II, vasopressin → mesangial contraction → ↓ Kf → ↓ GFR
• The glomerular capillary Kf is much higher than other capillary beds, explaining why 20% of plasma is filtered vs. <1% in systemic capillaries

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6. GFR Measurement (Clearance Concept)

Cy = (Uy × V) / Py

• Cy = clearance of substance y (mL/min)
• Uy = urine concentration
• Py = plasma concentration
• V = urine flow rate

1. Freely filtered at the glomerulus
2. NOT reabsorbed by tubules
3. NOT secreted by tubules
4. NOT metabolized by the kidney

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7. Renal Blood Flow and Filtration Fraction

• Renal blood flow (RBF): ~1200 mL/min (~20% cardiac output)
• Renal plasma flow (RPF): ~650 mL/min
• GFR: ~120 mL/min

• Peritubular capillaries (cortical nephrons) → reabsorption of tubular fluid
• Vasa recta (juxtamedullary nephrons) → medullary blood supply

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8. Autoregulation of GFR

Autoregulation Graph

Two Mechanisms of Autoregulation

A. Myogenic Mechanism (Bayliss Effect)

↑ Arterial Pressure
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        ▼
Stretches afferent arteriole wall
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        ▼
Opens stretch-activated Ca²⁺ channels
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        ▼
↑ intracellular Ca²⁺ in smooth muscle
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        ▼
Smooth muscle CONTRACTION
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        ▼
↑ Afferent arteriolar resistance
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        ▼
RBF and GFR restored to normal

B. Tubuloglomerular Feedback (TGF)

Step 1: ↑ Renal arterial pressure → ↑ RBF → ↑ GFR
            |
Step 2: ↑ Delivery of Na⁺ and Cl⁻ to macula densa
        (specialized cells at thick ascending limb / early distal tubule)
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Step 3: Macula densa senses ↑ NaCl via Na⁺-K⁺-2Cl⁻ cotransporter
        → triggers ATP release
        → ATP → adenosine (via ecto-5'-nucleotidase)
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Step 4: Adenosine acts on A1 receptors on afferent arteriole
        → VASOCONSTRICTION of afferent arteriole
        → ↑ Resistance
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Step 5: ↓ RBF → ↓ GFR → restores back to normal

• Angiotensin II → sensitizes TGF (amplifies vasoconstriction)
• Nitric oxide → blunts TGF
• Adenosine → primary mediator of TGF

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9. Why Autoregulation Matters (Clinical Importance)

• GFR: 180 → 225 L/day
• Tubular reabsorption stays ~178.5 L/day
• Urine output: 1.5 → 46.5 L/day (>30× increase!)
• This would rapidly deplete plasma volume (total plasma = only 3L)

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10. Factors That Alter GFR

Summary Flowchart

                    GFR = Kf × Net Ultrafiltration Pressure

INCREASES GFR:                          DECREASES GFR:
━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━
↑ Pgc                                  ↓ Pgc
  → Afferent dilation (PGE2, NO)         → Afferent constriction
  → Efferent constriction (Ang II)         (catecholamines, high Ang II,
                                           NSAIDs block PGE2)
↓ πgc                                  ↑ πgc
  → Hypoalbuminemia, saline infusion      → Hemoconcentration, ↑ protein
                                          → Volume depletion
↓ Pbs                                  ↑ Pbs
  → Normal                               → Urinary obstruction, tubular
                                           obstruction (casts, edema)
↑ Kf                                   ↓ Kf
  → Relaxation of mesangium              → Mesangial contraction
    (ANP, cAMP-mediated)                   (Ang II, vasopressin, ET-1)
                                         → Loss of nephron mass (CKD)

Hormonal/Vasoactive Effects

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11. CKD Staging by GFR

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12. Master Summary Flowchart

RENAL ARTERY BLOOD
        |
        ▼
AFFERENT ARTERIOLE
(resistance controlled by myogenic reflex + TGF + neurohumoral factors)
        |
        ▼
GLOMERULAR CAPILLARY (Pgc ~45 mmHg)
        |
   FILTRATION EQUATION:
   GFR = Kf × [(Pgc - Pbs) - (πgc - πbs)]
          ↓                    ↓
   Net hydrostatic        Net oncotic
   gradient (~35 mmHg)    pressure (~25 mmHg)
                   ↓
        Net Ultrafiltration = ~10 mmHg
        |
        ▼
BOWMAN'S CAPSULE
(protein-free, cell-free filtrate)
        |
        ▼
PROXIMAL TUBULE → LOOP OF HENLE → DISTAL TUBULE → COLLECTING DUCT
(reabsorb 178.5 L/day out of 180 L/day filtered)
        |
        ▼
URINE (~1.5 L/day)

AUTOREGULATION LOOP:
↑ MAP → ↑ GFR → ↑ NaCl at macula densa → TGF → adenosine
       → ↑ Afferent resistance → ↓ RBF → GFR restored
       (+ Myogenic: stretch → Ca²⁺ → smooth muscle contraction)

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Sources

• Comprehensive Clinical Nephrology, 7th Edition, p. 35-36
• Costanzo Physiology, 7th Edition, p. 264
• Guyton and Hall Textbook of Medical Physiology, p. 343
• National Kidney Foundation Primer on Kidney Diseases, 8th Edition