GLOMERULAR DISEASES
Glomerular components (Filtration membrane components)
1. Fenestrated endothelium of glomerular capillaries
2. Basement membrane
3. Modified epithelial cell layer (pedicles/foot processes + podocytes + filtration slits)
4. Entire glomerular tuft is supported by the mesangium (matrix and cells)
*What supports the entire glomerular tuft? —> mesangium which is comprised of
matrix and mesangial cells
Diagnosis of Glomerular Diseases (RUSC)
1. Clinical history and physical examination
2. Urine analysis - Proteinuria/Hematuria/Type of casts
3. Serum analysis - BUN/Creatinine levels/Serum electrolytes levels
4. Renal biopsy - LM with special stains such as H+E/Silver stain, EM and
Immunofluorescence
Glomerulopathy/Glomerular Diseases
What? —> one of the most common causes of renal failure
Types:
A) Primary: Begins in kidneys and primarily affects the kidneys
B) Secondary: Glomerular damage occurs secondary to systemic diseases
Immune mechanisms involved in glomerulopathy (Pathogenesis):
- Ag-AB reaction
- Cell-mediated response
- Alternative complement activation pathway
Pathogenesis of Glomerular Injury
1. Antibody-Mediated Injury
In Situ Immune Complex Deposition
A) Fixed intrinsic tissue antigen
• NPC1 domain of collagen type IV antigen (seen in anti-GBM nephritis)
• Heymann antigen (seen in membranous nephropathy)
*Note that Heymann antigen is an extensively studied model that replicates the
mechanism of membranous nephropathy in rats
, B) Planted antigen
• Exogenous (drugs, infectious agents)
• Endogenous (DNA, nuclear proteins, immunoglobulins, IgA, immune complexes)
Circulating Immune Complex Deposition
A) Exogenous (infectious products)
B) Endogenous (DNA, tumor antigens)
2. Cell-Mediated Injury
3. Alternative Complement Pathway Activation
Summary Point of Antibody Mediated Injury —> Large proportion of cases involve
immune deposition that is GRANULAR + along basement membrane/mesangium
Primary Glomerulopathies
1. Minimal change disease
2. Membranous nephropathy
3. Focal segmental glomerulosclerosis
4. Membranoproliferative glomerulonephritis
5. IgA nephropathy (Berger’s disease)
6. Acute proliferative glomerulonephritis (post-infectious/others)
7. Chronic proliferative glomerulonephritis
8. Crescentic rapid progressive glomerulonephritis
Secondary/Systemic Glomerulopathies (SAD Girl Wants Her Boyfriend More)
1. SLE
2. Diabetes
3. Amyloidosis
4. Goodpasture
5. Wegener’s
6. HS Purpura
7. Microscopic polyarteritis/polyangitis
8. Bacterial endocarditis
Glomerular components (Filtration membrane components)
1. Fenestrated endothelium of glomerular capillaries
2. Basement membrane
3. Modified epithelial cell layer (pedicles/foot processes + podocytes + filtration slits)
4. Entire glomerular tuft is supported by the mesangium (matrix and cells)
*What supports the entire glomerular tuft? —> mesangium which is comprised of
matrix and mesangial cells
Diagnosis of Glomerular Diseases (RUSC)
1. Clinical history and physical examination
2. Urine analysis - Proteinuria/Hematuria/Type of casts
3. Serum analysis - BUN/Creatinine levels/Serum electrolytes levels
4. Renal biopsy - LM with special stains such as H+E/Silver stain, EM and
Immunofluorescence
Glomerulopathy/Glomerular Diseases
What? —> one of the most common causes of renal failure
Types:
A) Primary: Begins in kidneys and primarily affects the kidneys
B) Secondary: Glomerular damage occurs secondary to systemic diseases
Immune mechanisms involved in glomerulopathy (Pathogenesis):
- Ag-AB reaction
- Cell-mediated response
- Alternative complement activation pathway
Pathogenesis of Glomerular Injury
1. Antibody-Mediated Injury
In Situ Immune Complex Deposition
A) Fixed intrinsic tissue antigen
• NPC1 domain of collagen type IV antigen (seen in anti-GBM nephritis)
• Heymann antigen (seen in membranous nephropathy)
*Note that Heymann antigen is an extensively studied model that replicates the
mechanism of membranous nephropathy in rats
, B) Planted antigen
• Exogenous (drugs, infectious agents)
• Endogenous (DNA, nuclear proteins, immunoglobulins, IgA, immune complexes)
Circulating Immune Complex Deposition
A) Exogenous (infectious products)
B) Endogenous (DNA, tumor antigens)
2. Cell-Mediated Injury
3. Alternative Complement Pathway Activation
Summary Point of Antibody Mediated Injury —> Large proportion of cases involve
immune deposition that is GRANULAR + along basement membrane/mesangium
Primary Glomerulopathies
1. Minimal change disease
2. Membranous nephropathy
3. Focal segmental glomerulosclerosis
4. Membranoproliferative glomerulonephritis
5. IgA nephropathy (Berger’s disease)
6. Acute proliferative glomerulonephritis (post-infectious/others)
7. Chronic proliferative glomerulonephritis
8. Crescentic rapid progressive glomerulonephritis
Secondary/Systemic Glomerulopathies (SAD Girl Wants Her Boyfriend More)
1. SLE
2. Diabetes
3. Amyloidosis
4. Goodpasture
5. Wegener’s
6. HS Purpura
7. Microscopic polyarteritis/polyangitis
8. Bacterial endocarditis
