|
|
| (9 intermediate revisions by 2 users not shown) |
| Line 1: |
Line 1: |
| __NOTOC__
| | #Redirect[[Nephritic syndrome#Pathophysiology]] |
| {{Nephritic syndrome}}
| |
| {{CMG}}
| |
| | |
| ==Pathophysiology==
| |
| It is believed that glomerular inflammation requires the activation of both the humoral and the cell-mediated immune system.<ref>{{cite book | last = Cibrik |first = DM | authorlink = | coauthors = Sedor JR | title = Immunopathogenesis of renal disease. In: Breenberg A, ed. Primer on kidney diseases. 2nd ed. | publisher = Academic Press |date = 1997 | location = San Diego, Calif | pages = 141-9 | url = | doi = | id = | isbn = }}</ref> Various glomerular disease have different pathophysiology, but the final cellular changes, immunological activation, and renal scarring are shared outcomes.
| |
| | |
| ===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.<ref name="pmid9744974">{{cite journal| author=Hricik DE, Chung-Park M, Sedor JR|title=Glomerulonephritis. | journal=N Engl J Med | year= 1998 | volume= 339 | issue= 13 | pages= 888-99 |pmid=9744974 | doi=10.1056/NEJM199809243391306 | pmc= |url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=9744974 }} </ref><ref name="pmid8621555">{{cite journal| author=Kalluri R, Sun MJ, Hudson BG, Neilson EG| title=The Goodpasture autoantigen. Structural delineation of two immunologically privileged epitopes on alpha3(IV) chain of type IV collagen. | journal=J Biol Chem | year= 1996 | volume= 271 | issue= 15 | pages= 9062-8 | pmid=8621555 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=8621555 }} </ref><ref name="pmid2660143">{{cite journal| author=Jacob L, Viard JP, Allenet B, Anin MF, Slama FB, Vandekerckhove J et al.| title=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. | journal=Proc Natl Acad Sci U S A | year= 1989 | volume= 86 | issue= 12 | pages= 4669-73 | pmid=2660143 | doi= | pmc=PMC287332 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=2660143 }} </ref> However, presence of antibodies alone is not sufficient for glomerular inflammation. 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.<ref name="pmid9744974">{{cite journal| author=Hricik DE, Chung-Park M, Sedor JR| title=Glomerulonephritis. | journal=N Engl J Med | year= 1998 | volume= 339 | issue= 13 | pages= 888-99 | pmid=9744974 | doi=10.1056/NEJM199809243391306 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=9744974 }} </ref><ref>{{cite book | last = Wilson |first = CB | authorlink = | coauthors = | title = The renal response to immunologic injury. In: Brenner BM, Recror FC Jr, eds. The Kidney. 4th ed. | publisher = W.B. Saunders |date = 1991 | location = Philadelphia | pages = 1062-181 | url = | doi = | id = | isbn = }}</ref>
| |
| | |
| ===Role of Neutrophils===
| |
| When complement pathway is activated, complement-derived neutrophil chemotactic factors facilitate the infiltration of neutrophils.(41) Neutrophils undergo respiratory burst to release toxic oxygen metabolites that are nephritogenic.<ref name="pmid3033023">{{cite journal| author=Johnson RJ, Couser WG, Chi EY, Adler S, Klebanoff SJ| title=New mechanism for glomerular injury. Myeloperoxidase-hydrogen peroxide-halide system. | journal=J Clin Invest | year= 1987 | volume= 79 | issue= 5 | pages= 1379-87 | pmid=3033023 | doi=10.1172/JCI112965 | pmc=PMC424393 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=3033023 }} </ref><ref name="pmid2822992">{{cite journal| author=Johnson RJ, Klebanoff SJ, Ochi RF, Adler S, Baker P, Sparks L et al.| title=Participation of the myeloperoxidase-H2O2-halide system in immune complex nephritis. | journal=Kidney Int | year= 1987 | volume= 32 | issue= 3 | pages= 342-9 | pmid=2822992 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=2822992 }} </ref> Hydrogen peroxide interacts with myeloperoxidase enzyme derived form the neutrophils leading to a direct injury to the glomerular basement membrane.<ref name="pmid2822992">{{cite journal| author=Johnson RJ, Klebanoff SJ, Ochi RF, Adler S, Baker P, Sparks L et al.| title=Participation of the myeloperoxidase-H2O2-halide system in immune complex nephritis. | journal=Kidney Int | year= 1987 | volume= 32 | issue= 3 | pages= 342-9 | pmid=2822992 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=2822992 }} </ref> 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.(43,47)
| |
| | |
| ===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.<ref name="pmid2971672">{{cite journal|author=Johnson RJ, Alpers CE, Pritzl P, Schulze M, Baker P, Pruchno C et al.| title=Platelets mediate neutrophil-dependent immune complex nephritis in the rat. | journal=J Clin Invest | year= 1988 |volume= 82 | issue= 4 | pages= 1225-35 | pmid=2971672 | doi=10.1172/JCI113720 | pmc=PMC442673 |url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=2971672 }} </ref>
| |
| | |
| | |
| ===Role of Macrophages===
| |
| Macrophages are involved in glomerular injury through the release of xidants 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.(48,49)
| |
| | |
| ===Role of T Cells===
| |
| T cells are important for inducing glomerular hypercellularity.<ref name="pmid315992">{{cite journal| author=Bhan AK, Collins AB, Schneeberger EE, McCluskey RT| title=A cell-mediated reaction against glomerular-bound immune complexes. | journal=J Exp Med | year= 1979 | volume= 150 | issue= 6 | pages= 1410-20 | pmid=315992 | doi= | pmc=PMC2185734 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=315992 }} </ref> T cells are present in both proliferative and non-proliferative glomerular diseases.<ref name="pmid7552103">{{cite journal| author=Main IW, Atkins RC| title=The role of T-cells in inflammatory kidney disease. | journal=Curr Opin Nephrol Hypertens | year= 1995 | volume= 4 | issue= 4 | pages= 354-8 | pmid=7552103 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=7552103 }} </ref> 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.<ref name="pmid8361123">{{cite journal| author=Couser WG| title=Pathogenesis of glomerulonephritis. | journal=Kidney Int Suppl | year= 1993 | volume= 42 | issue= | pages= S19-26 | pmid=8361123 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=8361123 }} </ref><ref name="pmid7933825">{{cite journal| author=Johnson RJ| title=The glomerular response to injury: progression or resolution? | journal=Kidney Int | year= 1994 | volume= 45 | issue= 6 | pages= 1769-82 | pmid=7933825 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=7933825 }} </ref> These changes make the glomerular cell itself, in addition to the infiltrating glomerular cells, an active component of destruction and subsequent restoration.<ref name="pmid7933825">{{cite journal| author=Johnson RJ| title=The glomerular response to injury: progression or resolution? | journal=Kidney Int | year= 1994 | volume= 45 | issue= 6 | pages= 1769-82 | pmid=7933825 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=7933825 }} </ref><ref name="pmid8468928">{{cite journal| author=Sedor JR, Konieczkowski M, Huang S, Gronich JH, Nakazato Y, Gordon G et al.| title=Cytokines, mesangial cell activation and glomerular injury. | journal=Kidney Int Suppl | year= 1993 | volume= 39 | issue= | pages= S65-70 | pmid=8468928 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=8468928 }} </ref><ref name="pmid9358740">{{cite journal| author=Johnson RJ| title=What mediates progressive glomerulosclerosis? The glomerular endothelium comes of age. | journal=Am J Pathol | year= 1997 | volume= 151 | issue= 5 | pages= 1179-81 | pmid=9358740 | doi= | pmc=PMC1858081 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=9358740 }} </ref>
| |
| | |
| ===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.<ref name="pmid9744974">{{cite journal| author=Hricik DE, Chung-Park M, Sedor JR| title=Glomerulonephritis. | journal=N Engl J Med | year= 1998 | volume= 339 | issue= 13 | pages= 888-99 | pmid=9744974 | doi=10.1056/NEJM199809243391306 | pmc= |url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=9744974 }} </ref>
| |
| | |
| ===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.<ref name="pmid7933825">{{cite journal| author=Johnson RJ| title=The glomerular response to injury: progression or resolution? | journal=Kidney Int | year= 1994 | volume= 45 | issue= 6 | pages= 1769-82 | pmid=7933825 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=7933825 }} </ref><ref name="pmid8468928">{{cite journal| author=Sedor JR, Konieczkowski M, Huang S, Gronich JH, Nakazato Y, Gordon G et al.| title=Cytokines, mesangial cell activation and glomerular injury. | journal=Kidney Int Suppl | year= 1993 | volume= 39 | issue= | pages= S65-70 | pmid=8468928 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=8468928 }} </ref><ref name="pmid9358740">{{cite journal| author=Johnson RJ| title=What mediates progressive glomerulosclerosis? The glomerular endothelium comes of age. | journal=Am J Pathol | year= 1997 | volume= 151 | issue= 5 | pages= 1179-81 | pmid=9358740 | doi= | pmc=PMC1858081 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=9358740 }} </ref><ref name="pmid8743495">{{cite journal| author=Brenner BM, Lawler EV, Mackenzie HS| title=The hyperfiltration theory: a paradigm shift in nephrology. | journal=Kidney Int | year= 1996 | volume= 49 | issue= 6 | pages= 1774-7 | pmid=8743495 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=8743495 }} </ref>
| |
| | |
| ===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.<ref name="pmid8731187">{{cite journal| author=Savill J, Mooney A, Hughes J| title=Apoptosis and renal scarring. | journal=Kidney Int Suppl | year= 1996 | volume= 54 | issue= | pages= S14-7 | pmid=8731187 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=8731187 }} </ref>
| |
| | |
| ==References==
| |
| {{reflist|2}}
| |
| {{WH}}
| |
| {{WS}}
| |
| [[Category:Needs content]]
| |
| [[Category:Disease]]
| |
| [[Category:Nephrology]]
| |
| [[Category:Syndromes]]
| |
| [[Category:Pediatrics]]
| |