Page 489 - Concise Pathology for Exam Preparation ( PDFDrive )

474 SECTION II Diseases of Organ Systems

Clinical Features
• Affects children and adults.
• Occurs after mucosal (respiratory, gastrointestinal or urinary tract) infections (increased
IgA synthesis in response to viruses, bacteria, food allergens, etc.).
• Presents with gross or microscopic haematuria and/or proteinuria.
• Five to ten percent present as acute nephritic syndrome.
• Course of disease variable; many individuals maintain normal renal function for
decades.
• Chronic renal failure (CRF) may occur in as many as 50% cases.
• Henoch–Schönlein purpura (a systemic disorder characterized by purpura, abdominal
pain and arthritis) has many similarities with IgA nephropathy.

Morphology
• Mesangial widening and segmental inflammation confined to certain glomeruli (focal
proliferative GN) or overt crescent formation (crescentic GN) or diffuse mesangial pro-
liferation (mesangioproliferative GN) may be seen.
• Mesangium shows electron-dense deposits.
• IF shows mesangial deposition of IgA, C3, properdin and small amounts of IgG/IgM.
Pathogenesis (Flowchart 16.4)
• Involves abnormality in IgA production and clearance (IgA is the main immunoglobulin
in mucosal secretions).

Abnormality in glycosylation of IgA (hereditary or acquired)

Decreased clearance of IgA

IgA-containing immune complexes get entrapped in mesangium

Activation of mesangial cells, release of cytokines and growth factors, recruitment of inflammatory cells and
activation of alternate complement pathway

Initiation of glomerular injury
FLOWCHART 16.4. Pathogenesis of IgA nephropathy.

• Normally serum IgA levels are low and it exists predominantly in monomeric form.
Polymeric form, which is catabolised by the liver, has a greater tendency of forming
immune complexes.
• Plasma polymeric IgA levels are increased in IgA nephropathy
• IgA nephropathy is initiated by either, an increase in production of IgA or formation
of circulating IgA-containing immune complexes (due to an abnormality of immune
regulation). Increased frequency of IgA nephropathy is noted in celiac disease (char-
acterized by presence of intestinal mucosal defects) and liver disease (characterized by
defective hepatobiliary clearance of IgA complexes). Another key factor in the patho-
genesis of IgA nephropathy is abnormal glycosylation of IgA due to a hereditary or
acquired defects. This abnormally glycosylated IgA may either itself deposit in the
glomeruli or initiate an autoimmune response leading to formation of IgG autoanti-
bodies against it. This leads in the formation of circulating immune complexes which
deposit in the mesangium.

Q. Differentiate between nephritic and nephrotic syndrome.
Ans. Differences between nephritic and nephrotic syndrome are listed in Table 16.4.

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