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Topics: Nephrotic syndrome, Kidney diseases, Immune system Pages: 15 (1840 words) Published: July 16, 2013
Pathogenesis of Glomerular Diseases PBL Resource Session
Prof.J.Jose,M.D.

Diseases of kidney-classification


Classified into those that affect the following 4 compartments: each one has distinct manifestations 
  

Glomeruli Tubules, Interstitium Blood vessels


Disease of one compartment will eventually affect the entire structure.

Clinical manifestations of renal diseases




1.Nephritic syndrome ("nephritis")  Indicates acute inflammation of glomeruli  hematuria (including red cell casts)  mild to moderate proteinuria  oliguria, hypertension and mild edema 2.Nephrotic syndrome  Indicates excessive permeability of the filtration membrane to plasma proteins.

Clinical manifestations of renal diseases (contd..)
   

heavy proteinuria (adult more than 3.5 gm/day) hypoalbuminemia (less than 3.0 gm/dL) severe generalized edema Hyperlipidemia and lipiduria


     

3.Asymptomatic proteinuria or haematuria or both 4.Acute renal failure 5.Chronic renal failure 6.Renal tubular defects-polyuria,electrolyte disorders 7.Urinary tract infection 8.Nephrolithiasis 9.Urinary tract obstruction and renal tumors

Glomerular diseases-classification


1.Primary glomerulopathies


Acute diffuse proliferative glomerulonephritis- post streptococcal, Rapidly Progressive GlomeruloNephritis (RPGN), lipoid nephrosis, membranous GN,MPGN, chronic glomerulo nephritis ( classified by histologic changes as aetiology is unknown in many glomerulopathies)



2.Systemic diseases with glomerular involvement
 

SLE, DM, Amyloidosis, Henoch- Schonlein purpura, infective endocarditis Vasculitis Alport syndrome



3.Hereditary disorders


Review of Glomerular structure and function

Glomerular filter consisting from bottom to top,of fenestrated endothelium, BM and foot processes of epithelial cells. Note filtration slits and diaphragm

Structure of type IV collagen triple-helical molecule in the BM

Porous anionic suprastructure of GBM

Characteristics of glomerular filtration




High permeability to water and small solutes Impermeability to proteins-glomerular barrier function allows for size and charge dependent filtration of molecules 

Albumin is not at all filtered as it is anionic even though the molecule is small enough to pass through the pores.

TABLE 20-4 (RBD) --

Immune Mechanisms of Glomerular Injury


1.ANTIBODY-MEDIATED INJURY  1.1 IN SITU IMMUNE COMPLEX DEPOSITION 

1.1.1 Fixed intrinsic tissue antigens
 




NC1 domain of collagen type IV antigen (anti-GBM nephritis) Heymann antigen (membranous glomerulopathy) Mesangial antigens Exogenous (infectious agents, drugs) Endogenous (DNA, nuclear proteins, immunoglobulins, immune complexes, IgA)

1.1.2 Planted antigens
 

 

1.2 CIRCULATING IMMUNE COMPLEX DEPOSITION  Endogenous antigens (e.g., DNA, tumor antigens)  Exogenous antigens (e.g., infectious products)  1.3 CYTOTOXIC ANTIBODIES 2.CELL-MEDIATED IMMUNE INJURY 3.ACTIVATION OF ALTERNATIVE COMPLEMENT PATHWAY 

Antibody-mediated glomerular injury can result either from the deposition of circulating immune complexes (A) or from in situ formation of complexes exemplified by anti-GBM disease (B) or Heymann nephritis (C). Two patterns of deposition of immune complexes as seen by immunofluorescence microscopy: granular, characteristic of circulating and in situ immune complex nephritis (D), and linear, characteristic of classic anti-GBM disease (E).

1.1 IN SITU IMMUNE COMPLEX DEPOSITION
1.1.1 Fixed intrinsic tissue antigens  Normal components (part of noncollagenous domain (NC1) of the α3 chain of collagen type IV ) of BM act as antigen (Ag), deposition of Antibodies (Ab) produces a linear pattern of immunofluroscence (IF) 



E.g. Goodpasture syndrome – Ab also cross reacts with pulmonary alveolar BM. Masugi nephritis ( experimental model of anti GBM nephritis)



Heymann nephritis-...
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