Page 480 - Concise Pathology for Exam Preparation ( PDFDrive )

16 Diseases of the Kidney and Lower Urinary Tract 465

2. Cell-mediated glomerular injury: Cell-mediated immune reactions in the form of
delayed hypersensitivity may be involved in causing glomerular injury.
3. Activation of alternative complement pathway
(a) Direct activation of alternative complement pathway by some polysaccharides,
endotoxins or IgA aggregates deposited in glomeruli may cause glomerular injury.
(b) In membranoproliferative glomerulonephritis II (MPGN II), a circulating antibody
termed C3 nephritic factor (C3NeF) binds to C3 convertase, favouring persistent
splitting of C3 into C3a and C3b, thus activating the alternative pathway and
resulting in hypocomplementaemia.
4. Secondary pathogenic mechanisms: Neutrophils, macrophages, complement, plate-
lets and mesangial cells can cause glomerular injury directly or by producing cytokines,
chemokines, oxidants and enzymes.
5. Nonimmunological mechanisms
(a) Metabolic glomerular injury (diabetic nephropathy)
(b) Haemodynamic glomerular injury (systemic hypertension)
(c) Deposition disease (amyloidosis and cryoglobulinaemia)
(d) Infectious disease (HIV and hepatitis)
(e) Inherited (Alport syndrome)

Q. Write briefly on the aetiopathogenesis and clinicopathological
features of acute proliferative glomerulonephritis.

Ans. Acute proliferative (post-streptococcal or post-infectious) glomerulonephritis:
• Appears 1–4 weeks after a streptococcal infection of the pharynx or skin.
• Occurs most frequently in children between 6 and 10 years of age but can affect
any age.
• Can also be caused by organisms other than streptococcus, eg, Pneumococcus, Staphylococcus
and viral diseases like mumps, measles, chickenpox and hepatitis B and C.

Aetiopathogenesis

• Group A, beta-haemolytic streptococcus has some nephritogenic strains (Types 1, 4 and
12; typing is based on M protein of cell wall).
• Principal antigenic determinants involved in acute post-streptococcal nephritis are
thought to be nephritis-associated streptococcal plasmin receptor (NAPIr), streptococ-
cal pyogenic exotoxin B (SpeB; most common) and its zymogen precursor (zSpeB).
• Immune complexes, preformed by the combination of specific antibodies against streptococ-
cal antigens, localize on the glomerular capillary wall and activate the complement system.
• The immunologic system may be activated by streptococcal antigens that adhere to the
glomerular structures and act as ‘planted antigens’ as well as by altered endogenous
antigens (GBM proteins altered by streptococcal enzymes).
• Glomerular deposition of immune complexes leads to diffuse proliferation and swelling
of glomerular cells as well as infiltration by leukocytes, especially neutrophils.

Clinical Features
• Abrupt onset of malaise and nausea with nephritic syndrome characterized by periorbital
oedema (due to mild to moderate proteinuria), oliguria, azotaemia, hypertension and
gross haematuria (smoky or cocoa-coloured urine).
• Serum complement levels are low.
• Serum antistreptolysin O antibody levels are elevated in post-streptococcal cases.
Prognosis

• In children, recovery occurs in most cases, some children develop RPGN or chronic
renal disease (incidence of chronicity is much less than in adults).
• Fifteen to fifty percent of adults, however, develop end-stage renal disease over a few
years to 1–2 decades.

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