Glomerular diseases overview

Glomerular Anatomy - The Kidney's Sieve

• Glomerular Filtration Barrier (GFB): A three-layered sieve controlling passage from blood to urine.
  • 1. Fenestrated Capillary Endothelium: First layer; blocks cells but allows plasma through.
  • 2. Glomerular Basement Membrane (GBM): Middle layer; with Type IV collagen and negatively charged heparan sulfate.
  • 3. Podocyte Foot Processes: Outer layer with slit diaphragms between them.
• Selective Permeability:
  • Size Barrier: Prevents passage of molecules > 70 kDa.
  • Charge Barrier: Anionic heparan sulfate in the GBM repels negatively charged molecules like albumin.

⭐ High-Yield Fact: Podocyte effacement (flattening of foot processes) is the characteristic finding in Minimal Change Disease, leading to selective albuminuria.

Nephritic vs. Nephrotic - A Clinical Duel

• Nephritic Syndrome: "Inflammation"

  • Pathophysiology: Immune complex deposition → glomerular inflammation (hypercellularity).
  • Hallmarks: Hematuria (dysmorphic RBCs, RBC casts) & Azotemia (↑ BUN/Cr).
  • Clinical: Abrupt onset of oliguria, hypertension, and mild periorbital edema from salt/water retention.
  • Proteinuria: Mild to moderate, always < 3.5 g/day.

• Nephrotic Syndrome: "Podocyte Damage"

  • Pathophysiology: Podocyte effacement → loss of negative charge barrier → massive protein leak.
  • Hallmarks: Heavy proteinuria (> 3.5 g/day) & severe hypoalbuminemia (< 3.0 g/dL).
  • Clinical: Insidious onset of anasarca (pitting edema, ascites), hyperlipidemia (fatty casts, oval fat bodies), and frothy urine.
  • 📌 PALE Mnemonic: Proteinuria, HypoAlbuminemia, HyperLipidemia, Edema.

⭐ Loss of antithrombin III in nephrotic syndrome urine creates a hypercoagulable state, predisposing patients to thrombosis, particularly renal vein thrombosis.

Pathology Parade - Rogues' Gallery

• Nephrotic Syndrome: Massive proteinuria (>3.5 g/day), hypoalbuminemia, edema, hyperlipidemia/uria.
  • 📌 PALE: Proteinuria, Albuminemia (hypo), Lipidemia (hyper), Edema.
  • Minimal Change (MCD): #1 in kids. LM normal; EM shows podocyte effacement.
  • FSGS: #1 in adults (esp. Black). LM shows sclerosis; EM effacement.
  • Membranous Nephropathy: #2 in adults. LM thick GBM; IF granular; EM "spike & dome."
• Nephritic Syndrome: Inflammation. Hematuria (RBC casts), HTN, oliguria, azotemia.
  • Post-strep (PSGN): LM hypercellular glomeruli; IF "starry sky"; EM subepithelial humps.
  • IgA Nephropathy (Berger): Most common cause worldwide. Episodic hematuria post-URI/GI infection.
  • RPGN: Crescents on LM. Poor prognosis.

⭐ Subepithelial "humps" on EM are characteristic of PSGN, representing immune complex deposition.

High‑Yield Points - ⚡ Biggest Takeaways

• Nephritic syndrome: Inflammatory process causing hematuria (RBC casts), oliguria, and hypertension.
• Nephrotic syndrome: Massive proteinuria (>3.5 g/day), hypoalbuminemia, edema, and hyperlipidemia.
• Linear IF is pathognomonic for Goodpasture syndrome; most others are granular.
• Podocyte effacement on EM is the hallmark of Minimal Change Disease.
• Look for "spike and dome" in Membranous Nephropathy and "tram-tracks" in MPGN.
• FSGS is the most common cause of nephrotic syndrome in adults.