Glomerular Diseases

Glomerular Structure & Insult - The Kidney's Sieve

• Filtration Barrier (📌 E-B-P): Three critical layers.
  • Endothelium (fenestrated): First size barrier.
  • Basement Membrane (GBM; Type IV collagen, heparan sulfate): Negative charge (-ve) repels albumin; second size/charge barrier.
  • Podocytes: Foot processes with slit diaphragms (nephrin, podocin); final size barrier.
• Mesangium: Intraglomerular cells providing structural support, phagocytosis, and matrix modulation.
• Basic Pathological Responses: Common reactions to injury.
  • Hypercellularity: Increased cells (endothelial, mesangial, epithelial, inflammatory).
  • GBM Thickening: Immune deposits or increased matrix synthesis.
  • Sclerosis: Increased collagenous matrix, scarring.
  • Hyalinosis: Eosinophilic, glassy material deposition.
• Key Immune Mechanisms of Injury:
  • Immune Complex (IC) Deposition: Location is key (subepithelial, subendothelial, mesangial).
  • Anti-GBM Antibody Disease.
  • Pauci-immune Injury (often ANCA-associated).

⭐ Effacement (flattening) of podocyte foot processes is a characteristic finding in nephrotic syndrome, leading to massive proteinuria.

Nephrotic Syndrome - Protein Spill Crisis

• Definition: Clinical tetrad: Hypoalbuminemia (<3g/dL), Edema, Hyperlipidemia, & Heavy Proteinuria. 📌 Mnemonic: Proteinuria, Lipids (Hyper-), Edema, Hypoalbuminemia (PLEH).
• Proteinuria Criteria:
  • Adults: >3.5 g/24h; $U_{P/Cr}$ >3 mg/mg.
  • Children: >40 mg/m²/hr; $U_{P/Cr}$ >2-3 mg/mg.
• Pathophysiology: Podocyte damage → ↑ glomerular permeability → massive protein loss.
• Key Features:
  • Edema: Periorbital, pitting; anasarca (↓ oncotic pressure, Na⁺ retention).
  • Hyperlipidemia & Lipiduria: ↑ hepatic synthesis; oval fat bodies ("Maltese cross").
  • Hypercoagulability: Loss of Antithrombin III, Protein C/S. Risk: DVT, RVT.
  • Infection Risk: ↓ IgG.
• Primary Causes:
  • Children: Minimal Change Disease (MCD).
  • Adults: FSGS, Membranous Nephropathy (MN).

⭐ Renal vein thrombosis is a classic complication, particularly in Membranous Nephropathy.

Nephritic Syndrome - Inflammatory Glom-Jam

• Hallmarks: Hematuria (cola-colored urine, dysmorphic RBCs, RBC casts), HTN, oliguria/anuria, azotemia, edema, mild proteinuria (<3.5 g/day). 📌 Mnemonic: PHAROH (Proteinuria, Hematuria, Azotemia, RBC casts, Oliguria, HTN).
• Pathophysiology: Inflammatory glomerular injury.
• Common Causes:
  • Post-Streptococcal GN (PSGN)
  • IgA Nephropathy (Berger's)
  • Lupus Nephritis (proliferative types)
  • ANCA-associated vasculitis (e.g., GPA, MPA)
  • Anti-GBM Disease (Goodpasture's)
• Rapidly Progressive GN (RPGN): Clinical emergency! >50% crescents on biopsy.
  • Type I: Anti-GBM (Linear IF)
  • Type II: Immune Complex (Granular IF) - e.g., PSGN, IgA, Lupus
  • Type III: Pauci-immune (Negative IF) - e.g., ANCA vasculitis

⭐ PSGN typically presents 1-2 weeks post-pharyngitis or 3-6 weeks post-impetigo. Serum C3 is ↓, ASO titre ↑.

Systemic Disease & Glomeruli - Body's Civil War

• Lupus Nephritis (SLE): IC deposition. "Full house" IF (IgG, IgA, IgM, C3, C1q). Class IV (DPGN) common, severe.
• Diabetic Nephropathy: Top ESRD cause. Kimmelstiel-Wilson nodules. Earliest: microalbuminuria. ACEi/ARBs renoprotective.
• ANCA Vasculitis (GPA, MPA): Pauci-immune GN, RPGN (crescents). c-ANCA (GPA), p-ANCA (MPA).
• Amyloidosis: Congo Red: apple-green birefringence. AL/AA types. Nephrotic syndrome common.
• Goodpasture's Syndrome: Anti-GBM Ab. Affects lungs & kidneys. Linear IgG on IF.

⭐ In Diabetic Nephropathy, Kimmelstiel-Wilson nodules (nodular glomerulosclerosis) are pathognomonic.

High‑Yield Points - ⚡ Biggest Takeaways

• Nephrotic Syndrome: Proteinuria >3.5g/day, hypoalbuminemia, edema, hyperlipidemia.
• Minimal Change Disease: Most common in children; podocyte effacement on EM.
• Membranous Nephropathy: Most common in adults; anti-PLA2R antibodies often present.
• IgA Nephropathy (Berger's): Most common GN; recurrent gross hematuria with URIs.
• Post-Streptococcal GN: 1-3 weeks post-infection; subepithelial humps, ↓C3, nephritic.
• RPGN: Characterized by glomerular crescents and rapid loss of kidney function.
• Alport Syndrome: X-linked; Type IV collagen defect; hematuria, deafness, ocular lesions.