Page 479 - Concise Pathology for Exam Preparation ( PDFDrive )

464 SECTION II Diseases of Organ Systems

Q. Classify glomerular diseases.

Ans. Based on clinicopathological features, glomerular diseases are classified broadly into
primary and secondary (Table 16.3).

TABLE 16.3. Clinicopathological classification of glomerular diseases

Secondary (systemic diseases with
Primary glomerulonephritis glomerular involvement) Hereditary nephritis
• Acute proliferative glomerulonephritis DM Alport syndrome
• RPGN Amyloidosis Fabry disease
• Membranous glomerulonephritis SLE
• Minimal change disease Polyarteritis nodosa
• Focal segmental glomerulosclerosis Microscopic polyangiitis
• Membranoproliferative glomerulonephritis Wegener granulomatosis
• Dense deposit disease. Henoch–Schonlein purpura
• IgA nephropathy Bacterial endocarditis
• Chronic glomerulonephritis

Q. Write in detail on the pathogenesis of glomerular injury.

Ans. The various immune mechanisms involved in the pathogenesis of glomerular
injury are:
1. Antibody-mediated injury
(a) In situ immune complex deposition
(i) Fixed intrinsic tissue antigens:
- Good pasture antigen (anti-GBM nephritis): Antibody is directed against an
intrinsic fixed antigen that is a normal component of the GBM (noncollag-
enous domain of the alfa-3 chain of collagen type IV). The deposits show a
homogeneous, diffuse and linear pattern.
- PLA2R antigen (membranous glomerulonephritis): Antibody is directed against
M-type phospholipase A2 receptor (PLA2R) located on the glomerular epi-
thelial cell membrane. This antigen complex is partially homologous to
Heymann antigen found in rats. Granular, interrupted deposits are seen
along the subepithelial aspect of the GBM.
- Mesangial antigens
- Others
(ii) Planted antigens: These are nonglomerular antigens, which get planted in the
glomerulus by interacting with various intrinsic components in the glomerulus, eg,
- Cationic molecules, which can bind to the glomerular capillary anionic sites.
- Larger aggregated proteins like IgG which can deposit in mesangium.
- DNA which has affinity for GBM components.
Many exogenous (infectious agents and drugs) and endogenous (DNA, immu-
noglobulins and immune complexes) antigens can act as planted antigens.
(b) Circulating immune complex deposition
(i) Injury is caused by trapping of circulating antigen–antibody complexes within
glomeruli because of their physicochemical properties and the prevailing hae-
modynamics of glomeruli
(ii) Subendothelial (rarely subepithelial) granular deposits either along basement
membrane or mesangium or both are seen
(iii) The antigens involved could be endogenous antigens (DNA and tumour anti-
gens) or exogenous antigens (infectious products)
(c) Cytotoxic antibodies: Antibodies directed against glomerular cell components
can lead to glomerular injury. For example, antibodies against endothelial cell an-
tigen can cause endothelial injury and intravascular thrombosis. Antibody directed
against visceral epithelial cell antigen can cause proteinuria.

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