Page 681 - Textbook of Pathology, 6th Edition

GN and lupus nephritis. Neutrophils can mediate glomerular to increased deposition of mesangial matrix and proliferation 665
injury by activation of complement as well as by release of of mesangial cells, endothelial and epithelial cell injury, and
proteases, arachidonic acid metabolites and oxygen-derived eventually to progressive glomerulosclerosis and end-stage
free radicals. These agents cause degradation of GBM and renal failure.
cell injury.
SPECIFIC TYPES OF GLOMERULAR DISEASES
2. MONONUCLEAR PHAGOCYTES. Many forms of
human and experimental proliferative GN are associated Classification of different forms of glomerular diseases is
with glomerular infiltration by monocytes and macrophages. already presented in Table 22.4. Features of individual types
Accumulation of mononuclear phagocytes is considered an are described below and a summary of major forms of
important constituent of hypercellularity in these forms of primary glomerulonephritis is given in Table 22.11 at the
GN aside from proliferation of mesangial and endothelial end of this discussion.
cells. Activated macrophages release a variety of biologically
active substances which take part in glomerular injury. I. PRIMARY GLOMERULONEPHRITIS
Acute Glomerulonephritis
3. COMPLEMENT SYSTEM. The pathogenetic role of
classical and alternate pathway of activation of complement (Synonyms: Acute Diffuse Proliferative GN,
has already been highlighted above. Besides the components Diffuse Endocapillary GN)
of complement which mediate glomerular injury via Acute GN is known to follow acute infection and charac-
neutrophils already mentioned, C5bC6789 (MAC, acronym teristically presents as acute nephritic syndrome. Based on
for membrane attack complex, also called terminal complex) etiologic agent, acute GN is subdivided into 2 main groups:
is capable of inducing damage to GBM directly. acute post-streptococcal GN and acute non-streptococcal GN,
the former being more common.
4. PLATELETS. Platelet aggregation and release of
mediators play a role in the evolution of some forms of GN. ACUTE POST-STREPTOCOCCAL GN
Increased intrarenal platelet consumption has been found to
occur in some forms of glomerular disease. Acute post-streptococcal GN, though uncommon and
sporadic in the Western countries, is a common form of GN CHAPTER 22
5. MESANGIAL CELLS. There is evidence to suggest that in developing countries, mostly affecting children between
mesangial cells present in the glomeruli may be stimulated 2 to 14 years of age but 10% cases are seen in adults above 40
to produce mediators of inflammation and take part in years of age. The onset of disease is generally sudden after
glomerular injury. 1-2 weeks of streptococcal infection, most frequently of the
throat (e.g. streptococcal pharyngitis) and sometimes of the
6. COAGULATION SYSTEM. The presence of fibrin in
early crescents in certain forms of human and experimental skin (e.g. streptococcal impetigo).
GN suggests the role of coagulation system in glomerular ETIOPATHOGENESIS. The relationship between
damage. Fibrinogen may leak into Bowman’s space and act streptococcal infection and this form of GN is now well
as stimulus for cell proliferation. Crescents usually transform established. Particularly nephritogenic are types 12,4,1 and
into scar tissue under the influence of fibronectin which is Red Lake of group A β-haemolytic streptococci (compare the
regularly present in crescents in human glomerular disease. etiologic agent with that of RHD, page 438). The glomerular
lesions appear to result from deposition of immune
II. NON-IMMUNOLOGIC MECHANISMS complexes in the glomeruli. The evidences cited in support The Kidney and Lower Urinary Tract
are as under:
Though most forms of GN are mediated by immunologic i) There is epidemiological evidence of preceding strepto-
mechanisms, a few examples of glomerular injury by non- coccal sore throat or skin infection about 1-2 weeks prior to
immunologic mechanisms are found: the attack.
1. Metabolic glomerular injury e.g. in diabetic nephropathy ii) The latent period between streptococcal infection and onset
(due to hyperglycaemia), Fabry’s disease (due to sulfatidosis). of clinical manifestations of the disease is compatible with
2. Haemodynamic glomerular injury e.g. systemic hyper- the period required for building up of antibodies.
tension, intraglomerular hypertension in FSGS. iii) Streptococcal infection may be identified by culture or
3. Deposition diseases e.g. amyloidosis. may be inferred from elevated titres of antibodies against
4. Infectious diseases e.g. HBV, HCV, HIV, E. coli-derived streptococcal antigens. These include the following:
nephrotoxin. anti-streptolysin O (ASO);
5. Drugs e.g. minimal change disease due to NSAIDs. anti-deoxyribonuclease B (anti-DNAse B);
6. Inherited glomerular diseases e.g. Alport’s syndrome, nail- anti-streptokinase (ASKase);
patella syndrome. anti-nicotinyl adenine dinucleotidase (anti-NADase); and
The evolution of end-stage renal failure in glomerular injury anti-hyaluronidase (AHase).
is explained on the basis of adaptive glomerular hypertrophy iv) There is usually hypocomplementaemia indicating
of unaffected glomeruli that results in increased glomerular involvement of complement in the glomerular deposits.
blood flow and increased glomerular capillary pressure v) It has also been possible to identify antigenic component
inducing intraglomerular hypertension. These events lead of streptococci which is cytoplasmic antigen, endostreptosin.