Nephritic syndrome pathophysiology
|
Nephritic syndrome Microchapters |
|
Treatment |
|---|
|
Case Studies |
|
Nephritic syndrome pathophysiology On the Web |
|
American Roentgen Ray Society Images of Nephritic syndrome pathophysiology |
|
Risk calculators and risk factors for Nephritic syndrome pathophysiology |
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Yazan Daaboul, Serge Korjian
Overview
It is believed that glomerular inflammation requires the activation of both the humoral and the cell-mediated immune system. Various glomerular disease have different pathophysiology, but the final cellular changes, immunological activation, and renal scarring are shared outcomes.
Pathophysiology
Role of Antibodies
Immunological mechanisms mediated by antibodies are required in the pathogenesis of glomerulonephritis. Antibodies are thought to bind either intrinsic glomerular components or specific compounds with unique physiochemical features that are present surrounding the glomerulus. Type IV collagen is an intrinsic glomerular component involved in Goodpasture's syndrome; whereas histone-DNA complexes in systemic lupus erythematosus are not intrinsic compounds to the glomerulus.[1][2][3] However, presence of antibodies alone is not sufficient for glomerular inflammation.[4] Complexes formed by the antibody-antigen complexes must in fact be able to evade clearance by the reticuloendothelial system to effectively deposit at the glomerulus.[1][5]
Role of Neutrophils
When complement pathway is activated, complement-derived neutrophil chemotactic factors facilitate the infiltration of neutrophils.[6] Neutrophils undergo respiratory burst to release toxic oxygen metabolites that are nephritogenic.[7][8] Hydrogen peroxide interacts with myeloperoxidase enzyme derived form the neutrophils leading to a direct injury to the glomerular basement membrane.[8] Damage to the capillary wall and proteinuria have also been shown to be induced by elastase and cathepsin G, both of which are serine proteases derived from neutrophils.[9][10]
Role of Platelets
Platelets play a role in the neutrophil-mediated injury as well. It is believed that platelets exacerbate the injury caused by neutrophils in a mechanism that is yet to be understood.[10]
Role of Macrophages
Macrophages are involved in glomerular injury through the release of oxidants and proteases. These compounds help in the synthesis of tissue factor that leads to deposition of fibrin material on the glomerulus. Subsequently, cytokines and growth factors, such as IL-1 and TGF-B, are released and cause the abnormal production of extracellular matrix.[11][12]
Role of T Cells
T cells are important for inducing glomerular hypercellularity.[13] T cells are present in both proliferative and non-proliferative glomerular diseases.[14] Pro-inflammatory pathways are activated following initial injury to induce further synthesis of cytokines, complement activation, influx of circulating leukocytes, release of proteolytic enzymes, and activation of coagulation pathway.[15][16] These changes make the glomerular cell itself, in addition to the infiltrating glomerular cells, an active component of destruction and subsequent restoration.[16][17][18]
Matrix Remodeling
Matrix remodeling is in part involved in the activation and proliferation of glomerular cells. The resident and the infiltrating cells will both receive unique signals following matrix remodeling that are involved in the activation of pro-inflammatory pathways in these cells.[1] Autocrine activation of platelet-derived growth factors (PDGF) B-chain and B-receptors is believed to cause the proliferation of mesangial cells during glomerular injury.[19] Growth factors ultimately cause the increase in proteinase synthesis and matrix expansion.[20][21]
Adaptive Mechanisms
Due to ongoing injury, adaptive changes take place in order to help in the resolution of glomerulonephritis. Hyperfiltration, intraglomerular hypertension, and irregular intravascular stress and shear are all processes that may on one hand worsen the renal injury, but are also crucial for the remainder of the functioning glomerulus.[16][17][18][22]
Resolution of Disease
Apoptosis, defined as programmed cell death, plays a significant role in defining the resolution of disease and in the renal scarring following glomerulonephritis.[23]
References
- ↑ 1.0 1.1 1.2 Hricik DE, Chung-Park M, Sedor JR (1998). "Glomerulonephritis". N Engl J Med. 339 (13): 888–99. doi:10.1056/NEJM199809243391306. PMID 9744974.
- ↑ Kalluri R, Sun MJ, Hudson BG, Neilson EG (1996). "The Goodpasture autoantigen. Structural delineation of two immunologically privileged epitopes on alpha3(IV) chain of type IV collagen". J Biol Chem. 271 (15): 9062–8. PMID 8621555.
- ↑ Jacob L, Viard JP, Allenet B, Anin MF, Slama FB, Vandekerckhove J; et al. (1989). "A monoclonal anti-double-stranded DNA autoantibody binds to a 94-kDa cell-surface protein on various cell types via nucleosomes or a DNA-histone complex". Proc Natl Acad Sci U S A. 86 (12): 4669–73. PMC 287332. PMID 2660143.
- ↑ Cibrik, DM (1997). Immunopathogenesis of renal disease. In: Breenberg A, ed. Primer on kidney diseases. 2nd ed. San Diego, Calif: Academic Press. pp. 141–9. Unknown parameter
|coauthors=ignored (help) - ↑ Wilson, CB (1991). The renal response to immunologic injury. In: Brenner BM, Recror FC Jr, eds. The Kidney. 4th ed. Philadelphia: W.B. Saunders. pp. 1062–181.
- ↑ Danoff, TM (1997). The role of chemoattractants in renal disease (Chapter 24). In: Nielson EG, Couser WG, eds Immunologic renal diseases. Philadelphia, PA: Lippincott-Raven Publishers. pp. 495–512. Unknown parameter
|coauthors=ignored (help) - ↑ Johnson RJ, Couser WG, Chi EY, Adler S, Klebanoff SJ (1987). "New mechanism for glomerular injury. Myeloperoxidase-hydrogen peroxide-halide system". J Clin Invest. 79 (5): 1379–87. doi:10.1172/JCI112965. PMC 424393. PMID 3033023.
- ↑ 8.0 8.1 Johnson RJ, Klebanoff SJ, Ochi RF, Adler S, Baker P, Sparks L; et al. (1987). "Participation of the myeloperoxidase-H2O2-halide system in immune complex nephritis". Kidney Int. 32 (3): 342–9. PMID 2822992.
- ↑ Johnson, RJ (1997). Neutrophils (Chapter 25). In: Nielson EG, Couser WG, eds Immunologic renal diseases. Philadelphia, PA: Lippincott-Raven Publishers. pp. 512–541. Unknown parameter
|coauthors=ignored (help) - ↑ 10.0 10.1 Johnson RJ, Alpers CE, Pritzl P, Schulze M, Baker P, Pruchno C; et al. (1988). "Platelets mediate neutrophil-dependent immune complex nephritis in the rat". J Clin Invest. 82 (4): 1225–35. doi:10.1172/JCI113720. PMC 442673. PMID 2971672.
- ↑ Nikolick-Patterson, DJ (1997). Macrophages (Chapter 28). In: Nielson EG, Couser WG, eds Immunologic renal diseases. Philadelphia, PA: Lippincott-Raven Publishers. pp. 567–586. Unknown parameter
|coauthors=ignored (help) - ↑ Floege, J (1997). Growth factors and cytokines (Chapter 20). In: Nielson EG, Couser WG, eds Immunologic renal diseases. Philadelphia, PA: Lippincott-Raven Publishers. pp. 415–452. Unknown parameter
|coauthors=ignored (help) - ↑ Bhan AK, Collins AB, Schneeberger EE, McCluskey RT (1979). "A cell-mediated reaction against glomerular-bound immune complexes". J Exp Med. 150 (6): 1410–20. PMC 2185734. PMID 315992.
- ↑ Main IW, Atkins RC (1995). "The role of T-cells in inflammatory kidney disease". Curr Opin Nephrol Hypertens. 4 (4): 354–8. PMID 7552103.
- ↑ Couser WG (1993). "Pathogenesis of glomerulonephritis". Kidney Int Suppl. 42: S19–26. PMID 8361123.
- ↑ 16.0 16.1 16.2 Johnson RJ (1994). "The glomerular response to injury: progression or resolution?". Kidney Int. 45 (6): 1769–82. PMID 7933825.
- ↑ 17.0 17.1 Sedor JR, Konieczkowski M, Huang S, Gronich JH, Nakazato Y, Gordon G; et al. (1993). "Cytokines, mesangial cell activation and glomerular injury". Kidney Int Suppl. 39: S65–70. PMID 8468928.
- ↑ 18.0 18.1 Johnson RJ (1997). "What mediates progressive glomerulosclerosis? The glomerular endothelium comes of age". Am J Pathol. 151 (5): 1179–81. PMC 1858081. PMID 9358740.
- ↑ Johnson RJ, Raines EW, Floege J, Yoshimura A, Pritzl P, Alpers C; et al. (1992). "Inhibition of mesangial cell proliferation and matrix expansion in glomerulonephritis in the rat by antibody to platelet-derived growth factor". J Exp Med. 175 (5): 1413–6. PMC 2119215. PMID 1569407.
- ↑ Lovett DH, Johnson RJ, Marti HP, Martin J, Davies M, Couser WG (1992). "Structural characterization of the mesangial cell type IV collagenase and enhanced expression in a model of immune complex-mediated glomerulonephritis". Am J Pathol. 141 (1): 85–98. PMC 1886574. PMID 1321565.
- ↑ Border WA, Noble NA (1994). "Transforming growth factor beta in tissue fibrosis". N Engl J Med. 331 (19): 1286–92. doi:10.1056/NEJM199411103311907. PMID 7935686.
- ↑ Brenner BM, Lawler EV, Mackenzie HS (1996). "The hyperfiltration theory: a paradigm shift in nephrology". Kidney Int. 49 (6): 1774–7. PMID 8743495.
- ↑ Savill J, Mooney A, Hughes J (1996). "Apoptosis and renal scarring". Kidney Int Suppl. 54: S14–7. PMID 8731187.