GFR in pathophysiological states

GFR Fundamentals - The Pressure Game

Glomerular filtration is a battle of pressures, governed by Starling forces across the capillary wall. The net filtration pressure dictates the GFR.

• Core Equation: $GFR = K_f imes (P_{GC} - P_{BS} - oldsymbol{\pi}_{GC})$

  • $P_{GC}$ (Hydrostatic): Favors filtration. Main driver.
  • $P_{BS}$ & $\pi_{GC}$ (Hydrostatic & Oncotic): Oppose filtration.

• Arteriolar Resistance is Key:

  • Afferent Constriction: ↓ Renal Plasma Flow (RPF), ↓ $P_{GC}$, ↓ GFR.
  • Efferent Constriction: ↓ RPF, ↑ $P_{GC}$, ↑ GFR initially.

⭐ Filtration Fraction (FF = GFR/RPF) is normally ~20%. With efferent constriction (e.g., by Angiotensin II), GFR may increase but RPF decreases more, leading to an increased FF.

Pre-Renal Azotemia - When the Tank is Low

• Core Issue: ↓ renal perfusion (hypoperfusion) without intrinsic kidney damage. The kidneys are functional, but the circulatory volume is insufficient.
• Etiologies:
  • Hypovolemia: Hemorrhage, dehydration, burns, diuretics.
  • Low Cardiac Output: Heart failure, cardiogenic shock.
  • Systemic Vasodilation: Sepsis, anaphylaxis, anesthesia.
  • Renal Vasoconstriction: NSAIDs, ACE inhibitors/ARBs (in bilateral renal artery stenosis), hepatorenal syndrome.
• Key Lab Findings:
  • BUN:Cr ratio > 20:1
  • Urine Na⁺ < 20 mEq/L
  • Fractional Excretion of Na⁺ (FENa) < 1%
  • Urine Osmolality > 500 mOsm/kg (concentrated urine)

⭐ In pre-renal states, enhanced proximal tubule reabsorption of Na⁺ and water leads to a passive increase in urea reabsorption, elevating serum BUN disproportionately to creatinine.

Intrinsic & Post-Renal - Clogs and Damage

• Intrinsic Renal Failure: Direct damage to nephron structures.

  • Mechanism: Inflammation & cellular debris → ↓ filtration coefficient ($K_f$) & tubular obstruction → ↓ GFR.
  • Causes:
    • Acute Tubular Necrosis (ATN): Ischemia, nephrotoxins (e.g., contrast dye).
    • Glomerulonephritis (GN): Immune complex deposition.
  • Key Finding: Cellular casts (e.g., muddy brown casts in ATN).

• Post-Renal Azotemia: Outflow obstruction.

  • Mechanism: Blockage → ↑ tubular pressure ($P_T$) → opposes glomerular pressure → ↓ GFR.
  • Causes: BPH, bilateral ureteral stones, tumors.

⭐ In intrinsic ATN, impaired tubular function prevents BUN reabsorption, causing the BUN:Cr ratio to fall below 15:1.

Pharmacologic Effects - Pills & Pressures

• Baseline Tone: Prostaglandins dilate the afferent arteriole; Angiotensin II constricts the efferent arteriole.

• NSAIDs: Inhibit prostaglandins → afferent arteriole constriction → ↓ Renal Blood Flow (RBF) & ↓ GFR.

• ACE Inhibitors / ARBs: Block Angiotensin II → efferent arteriole dilation → ↓ GFR but ↑ RBF. This reduces intraglomerular pressure.

⭐ Concurrent use of NSAIDs and ACE inhibitors can precipitate acute kidney injury (AKI), especially in patients with bilateral renal artery stenosis or volume depletion (e.g., dehydration, heart failure).

High‑Yield Points - ⚡ Biggest Takeaways

• Afferent arteriole constriction (e.g., NSAIDs) leads to a ↓ in both RPF and GFR.
• Efferent arteriole constriction (e.g., low-dose Angiotensin II) ↓ RPF but ↑ GFR, resulting in an ↑ FF.
• Efferent arteriole dilation (e.g., ACE inhibitors) ↑ RPF but ↓ GFR, causing a ↓ FF.
• Increased plasma protein concentration (e.g., multiple myeloma) ↓ GFR by increasing glomerular capillary oncotic pressure.
• Ureteral obstruction increases Bowman's capsule hydrostatic pressure, leading to a progressive ↓ in GFR.