Glomerular Diseases

Glomerular Structure & Injury - Filtration Fortress Facts

• Components: Endothelium (fenestrated), GBM (collagen IV, negative charge), Podocytes (foot processes, slit diaphragms - nephrin), Mesangium (support).
• Filtration Barrier: Size & charge selective (restricts albumin).
• Injury Mechanisms:
  • Immune Complexes: Subepithelial (MN), subendothelial (LN, MPGN), mesangial (IgAN).
  • Anti-GBM Disease: Linear IgG (Goodpasture's).
  • Pauci-immune: ANCA-associated.
  • Cell-mediated.

⭐ The GBM's negative charge (heparan sulfate) is crucial for repelling albumin.

Nephrotic Syndrome - The Great Protein Leak

• Hallmarks:

  • Proteinuria ($>$ 3.5g/24h)
  • Hypoalbuminemia ($<$ 3 g/dL)
  • Edema
  • Hyperlipidemia/Lipiduria
  • 📌 PALE H: Proteinuria, Albumin low, Lipids high, Edema, Hypercoagulability.

• Key Diseases & Biopsy:

  • Minimal Change Disease (MCD):

    • Children; excellent steroid response.
    • LM: Normal. IF: Negative.
    • EM: Diffuse podocyte foot process effacement.

  • Focal Segmental Glomerulosclerosis (FSGS):

    • LM: Segmental sclerosis. IF: Often negative (may be IgM, C3).
    • EM: Foot process effacement.
    • Assoc: HIV, heroin, obesity.

  • Membranous Nephropathy (MN):

    • Adults; PLA2R Ab.
    • LM: Thick GBM. IF: Granular IgG, C3.
    • EM: Subepithelial deposits ("spike & dome").
    • Assoc: HBV, HCV, SLE, malignancy.

  • Diabetic Nephropathy:

    • LM: Mesangial expansion, Kimmelstiel-Wilson nodules.
    • EM: Thick GBM.
    • Most common ESRD cause.

⭐ Kimmelstiel-Wilson nodules are pathognomonic for diabetic nephropathy.

Nephritic Syndrome - Fiery Filter Fight

• Definition: Hematuria (RBC casts, cola-urine), Oliguria, Hypertension (HTN), Azotemia, Mild proteinuria (<3.5g/d).

• Post-Streptococcal GN (PSGN):

  • LM: Diffuse proliferative GN, hypercellular.
  • IF: Granular IgG, C3 ("lumpy-bumpy").
  • EM: Subepithelial humps.
  • Clinical: Post-strep infection (pharyngitis/impetigo), ↓C3.
  • ⭐ > PSGN: Classic subepithelial humps on EM; C3 typically recovers in 6-8 weeks.

• IgA Nephropathy (Berger's Disease):

  • LM: Mesangial proliferation.
  • IF/EM: Mesangial IgA deposits.
  • Clinical: Episodic gross hematuria, often with URI/GI infection. Most common GN. Normal C3.
  • 

• Rapidly Progressive GN (RPGN):

  • LM: Crescent formation in Bowman's space. Rapid renal failure.
  • 📌 RPGN Types (1-2-3):
    • Type I: Anti-GBM (Goodpasture's) - Linear IF.
    • Type II: Immune Complex (e.g., PSGN, IgA, Lupus) - Granular IF.
    • Type III: Pauci-Immune (ANCA-associated) - Negative IF.

%%{init: {'flowchart': {'htmlLabels': true}}}%% flowchart TD

Start["🩺 RPGN Diagnosis
• Crescents on LM• Rapid renal loss"]

IF["🔬 IF Pattern
• Immunofluorescence• Staining pattern"]

Type1["🩺 Type I Disease
• Anti-GBM disease• Goodpasture synd."]

Type2["🩺 Type II Disease
• Immune complexes• PSGN, IgA, Lupus"]

Type3["🩺 Type III Disease
• ANCA-associated• GPA or MPA"]

Start --> IF IF -->|Linear IgG| Type1 IF -->|Granular| Type2 IF -->|Pauci-Immune| Type3

style Start fill:#F7F5FD, stroke:#F0EDFA, stroke-width:1.5px, rx:12, ry:12, color:#6B21A8 style IF fill:#FFF7ED, stroke:#FFEED5, stroke-width:1.5px, rx:12, ry:12, color:#C2410C style Type1 fill:#F7F5FD, stroke:#F0EDFA, stroke-width:1.5px, rx:12, ry:12, color:#6B21A8 style Type2 fill:#F7F5FD, stroke:#F0EDFA, stroke-width:1.5px, rx:12, ry:12, color:#6B21A8 style Type3 fill:#F7F5FD, stroke:#F0EDFA, stroke-width:1.5px, rx:12, ry:12, color:#6B21A8

*   **Lupus Nephritis (LN):** (Nephritic forms)
    -   Class III (Focal Proliferative GN), Class IV (Diffuse Proliferative GN - most common/severe).
    -   LM (Class IV): "Wire-loop" lesions.
    -   IF: "Full house" (IgG, IgA, IgM, C3, C1q). EM: Subendothelial deposits.


## Glomerular Biopsy Interpretation - Glomerular Detective Work

*   **Immunofluorescence (IF)**:
    *   Linear: IgG along GBM (e.g., Anti-GBM disease).
    *   Granular (Immune complexes):
        +   Mesangial (e.g., IgA Nephropathy).
        +   Subepithelial (e.g., Membranous Nephropathy - "spikes & domes").
        +   Subendothelial (e.g., Lupus Nephritis - "wire loops").
*   **Electron Microscopy (EM)**:
    *   Deposits: Location (subepithelial, subendothelial, mesangial, intramembranous), density.
    *   Foot process effacement (common in proteinuria).
    *   GBM: Thickening, thinning, splitting (e.g., "basket-weave" in Alport).

*   **Alport Syndrome**: ***COL4A5*** defect (Type IV collagen); hematuria, sensorineural deafness, ocular defects (lenticonus). EM: GBM splitting/lamellation ("basket-weave" appearance).
*   **Thin Basement Membrane Disease**: Benign familial hematuria; diffuse GBM thinning on EM.
> ⭐ Pauci-immune glomerulonephritis (e.g., ANCA-associated vasculitis) shows minimal or no immune deposits on IF, despite active glomerular inflammation (glomerular crescents may be present).

## High‑Yield Points - ⚡ Biggest Takeaways

> *   **Nephrotic Syndrome**: **Proteinuria >3.5g/day**, hypoalbuminemia, edema, hyperlipidemia.
> *   **Minimal Change Disease**: Top nephrotic cause in **children**; **podocyte effacement** on EM.
> *   **FSGS**: Key nephrotic syndrome in **adults**; linked to **HIV, sickle cell, obesity**.
> *   **Membranous Nephropathy**: **Subepithelial "spike and dome" deposits**; common adult nephrotic cause.
> *   **Nephritic Syndrome**: **Hematuria (RBC casts)**, oliguria, hypertension, mild proteinuria.
> *   **PSGN**: Post-strep nephritic syndrome; EM shows **subepithelial "humps"**.
> *   **IgA Nephropathy**: **World's most common GN**; **mesangial IgA deposits** on IF.