circulating immune complex mediated disease Flashcards
Deposition of circulating immune complexes in the glomerulus initiates complement (and/or Fc receptor) mediated leukocyte activation, resulting in glomerular injury
immune complex–mediated diseases, the complexes may be formed with endogenous antigens, as in the GN associated with systemic lupus erythematosus, or the antigens may be exogenous, as is probable in the GN that follows certain bacterial (streptococcal), viral (hepatitis B), parasitic (Plasmodium falciparum malaria), and spirochetal (Treponema pallidum) infections.
antigen-antibody complexes are deposited or formed in the glomeruli, they produce injury by activating complement and recruiting leukocytes. Binding of immune complexes to Fc receptors on leukocytes also may contribute to activation of the cells and injury
electron-dense immune deposits in one or more of three locations: between the endothelial cells and the GBM (subendothelial deposits), between the outer surface of the GBM and the podocytes (subepithelial deposits), or in the mesangium
Deposition of antibodies specific for fixed (intrinsic) or planted (from outside) antigens in the glomerulus is another major pathway of glomerular injury.
Antigens expressed by podocytes have been implicated in membranous nephropathy. Antibodies also may react in situ with previously “planted” nonglomerular antigens, which deposit and become concentrated in the kidney through interaction with various glomerular component
Anti-Glomerular Basement Membrane Antibody–Mediated Glomerulonephritis
Antibody-mediated GN results from the glomerular deposition of autoantibodies directed against protein components of the GBM
Goodpasture disease. In this type of injury, antibodies are directed against fixed antigens in the GBM, creating a linear pattern of staining when visualized with immunofluorescence microscopy
Ensuing complement-mediated injury may result in renal and systemic disease. Two forms of GN (dense deposit disease and C3 GN) and one form of a systemic disease with significant renal manifestations (complement-mediated thrombotic microangiopathy [TMA] or atypical hemolytic uremic syndrome) belong to this category
release proteases, which cause GBM degradation; oxygen-derived free radicals, which cause cell damage; and arachidonic acid metabolites, which contribute to reduction in GFR
of GN in which neutrophils are not prominent, complement-dependent injury may occur through assembly of the C5b-C9 membrane attack complex. TT lymphocytes activated during the immune reaction also have been implicated in glomerular injury. Platelets may aggregate and release mediators, including prostaglandins. Resident glomerular cells (epithelial, mesangial, and endothelial) can be stimulated to secrete mediators such as cytokines (interleukin-1), arachidonic acid metabolites, growth factors, and nitric oxide
GN MCN
Minimal-change disease, a relatively benign disorder, is the most frequent cause of the nephrotic syndrome in children and is characterized by glomeruli that have a normal appearance by light microscopy. Diffuse effacement of podocyte foot processes is seen with electron microscopy. most common between 1 and 7 years of age.
circulating molecules injure podocytes and cause proteinuria with effacement of foot processes.
diffuse effacement of the foot processes of the podocyte.The cytoplasm of the podocytes appears flattened over the external aspect of the GBM, obliterating the network of arcades between the podocytes and the GBM.vacuolization, microvillus formation, and occasional focal detachments, suggesting some form of podocyte injury.
nephrotic syndrome in an otherwise healthy child. There is no hypertension, and renal function is preserved in most of these patients. The protein loss usually is confined to smaller plasma proteins, chiefly albumin (selective proteinuria).
Focal segmental glomerulosclerosis (FSGS) is characterized by sclerosis of some (but not all) glomeruli that involves only a part of each affected glomerulus
HIV infection (HIV nephropathy). FSGS is seen in 5–10% of patients infected with HIV, but the incidence is decreasing with improved antiviral therapy. •Heroin abuse (heroin nephropathy) •Secondary to other forms of GN (e.g., IgA nephropathy) •As a maladaptation to nephron loss Inherited forms, including autosomal dominant forms associated with mutations in cytoskeletal proteins
The deposition of hyaline in the glomeruli is caused by the entrapment of plasma proteins and lipids in foci of injury where sclerosis develops. The recurrence of proteinuria in patients underoing renal transplantion for FSGS, sometimes within 24 hours of transplantation, supports the idea that a circulating mediator leads to podocyte damage in some cases.
affected glomeruli exhibit increased mesangial matrix, obliterated capillary lumina, deposition of hyaline (hyalinosis) and foamy (lipid-laden) macrophages. Inn affected glomeruli, immunofluorescence microscopy often reveals nonspecific trapping of immunoglobulins, usually IgM, and complement in the areas of hyalinosis. On electron microscopy, the podocytes exhibit effacement of foot processes, as in minimal-change disease.
A morphologic variant called collapsing glomerulopathy is characterized by collapse of the glomerular tuft and epithelial cell hyperplasia
Both are associated with nephrotic syndrome, but the incidence of hematuria and hypertension is higher in individuals with FSGS
