Rapidly progressive glomerulonephritis pathophysiology
|
Rapidly progressive glomerulonephritis Microchapters |
|
Differentiating Rapidly progressive glomerulonephritis from other Diseases |
|---|
|
Diagnosis |
|
Treatment |
|
Case Studies |
|
Rapidly progressive glomerulonephritis pathophysiology On the Web |
|
American Roentgen Ray Society Images of Rapidly progressive glomerulonephritis pathophysiology |
|
FDA on Rapidly progressive glomerulonephritis pathophysiology |
|
CDC on Rapidly progressive glomerulonephritis pathophysiology |
|
Rapidly progressive glomerulonephritis pathophysiology in the news |
|
Blogs on Rapidly progressive glomerulonephritis pathophysiology |
|
Directions to Hospitals Treating Rapidly progressive glomerulonephritis |
|
Risk calculators and risk factors for Rapidly progressive glomerulonephritis pathophysiology |
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]
Overview
Pathophysiology
Anatomy
The key for the renal corpuscle figure is: A – Renal corpuscle, B – Proximal tubule, C – Distal convoluted tubule, D – Juxtaglomerular apparatus, 1. Basement membrane (Basal lamina), 2. Bowman's capsule – parietal layer, 3. Bowman's capsule – visceral layer, 3a. Pedicels (Foot processes from podocytes), 3b. Podocyte, 4. Bowman's space (urinary space), 5a. Mesangium – Intraglomerular cell, 5b. Mesangium – Extraglomerular cell, 6. Granular cells (Juxtaglomerular cells), 7. Macula densa, 8. Myocytes (smooth muscle), 9. Afferent arteriole, 10. Glomerulus Capillaries, 11. Efferent arteriole.
.Pathogenesis
- Rapidly progressive glomerulonephritis is a disease of the kidney in which the renal function deteriorates in a few days[1][2].
- Atleast 50% reduction in GFR occurs in RPGN in a few days to weeks.
- RPGN occurs from severe and fast damage to the GBM which results in crescent formation, the main pathological finding in RPGN.
- The injury to GBM can be caused by multiple factors.
- Crescent formation is the major pathological finding.
- In some cases crescents might be absent.
Cresent formation
- Crescents are defined as 2 or more layers of proliferating cells in the Bowman's space.[2][3][4]
- The crescents are made up of epithelial cells and macrophages which undergo fibrosis[5][6].
- Crescents are formed after a severe injury to the glomerulus.
- Injury to the glomerulus causes leakage of cells(epithelial, macrophages, coagulation proteins and fibroblasts) and cytokines(IL-12, TNF-alpha) into the Bowmans space.
- The presence of cytokines and coagulation proteins initiates fibrosis around the epithelial cells.
- The fibrosis blocks the glomerulus and filteration is hindered.
- This results in renal failure.
Glomerular injury
- Injury to the glomerulus is the initiating factor for crescent formation.
- Injury can occur by the following.
- Anti GBM antibodies-Type I RPGN
- These are autoantibodies that cross react with type IV collagen of the GBM.
- These can be produced due to genetic causes such as in Goodpasture syndrome or they can be produced after viral URTI or cigarette smoking.
- These autoantibodies react with the GBM resulting in IgG deposition over the GBM.
- The IgG activates helper T cells that attract the inflammatory mediators to the GBM damaging the glomeruli[7].
- This damage causes leakage of cells and inflammatory mediators resulting in crescent formation.
- The anti GBM antibodies can affect the lungs as well as in Goodpasture syndrome resulting in glomerular necrosis and pulmonary haemorrhages.
2. Immune complex- Type II RPGN
- Immune complexes are formed in certain infections, connective tissue diseases, side effects of some drugs and in some myeloproliferative disorders[8].
- These immune complexes are deposited over the GBM.
- The immune complexes activate the complement system which sets off the inflammatory process.
- The complement cascade is activated, attracting inflammatory cells and mediators to the GBM.
- The serum levels of c3 and c4 fall down and is an indicator of immune complex mediated glomerular injury.
- This damages the glomeruli and causes leakage of cells and inflammatory mediators resulting in crescent formation.
- Examples include:
- Postinfectious (staphylococci/streptococci)
- Connective tissue disorders
- Lupus nephritis
- Henoch-Schönlein purpural)
- Immunoglobulin A nephropathy[9]
- Mixed cryoglobulinemia
- Membranoproliferative glomerulonephritis
3. Pauci immune RPGN-Type III RPGN
- No circulating immune complexes or antibodies.
- Glomerular damage is caused by circulating ANCAs(anti nuclear cytoplasmic antibodies) or it can be idiopathic(non ANCA).
- ANCAs cause glomerular damage by releasing lytic enzymes from white blood cells such as neutrophils[10][11][12][13].
- These lytic enzymes damage the GBM and cause leakage of circulating cells and initiate crescent formationin the Bowmans space.
- ANCAs are associated with systemic vasculitis.[14]
- Examples include
- Granulomatosis with polyangiitis (Wegener granulomatosis)
- Microscopic polyangiitis (MPA)
- Renal-limited necrotizing crescentic glomerulonephritis (NCGN)
- Eosinophilic granulomatosis with polyangiitis (EGPA; Churg-Strauss syndrome)
- Drugs- hydralazine, allopurinol and rifampin.
Gross pathology
- The kidneys appear to be having having haemorrhages and necrosed tissue.
- Pulmonary haemorrhages may also be present in Goodpasture syndrome and type III RPGN.
- Type III RPGN may present with petechiae, rashes and purpuras.
Microscopic pathology
Histopathology
- Glomerular inflammation with signs of necrosis are present[15][16].
- .Glomerular caplillary wall rupture and damage to GBM.
- Crescents are present in the Bowmans space.
- Crescents are formed by proliferating epithelial cells and monocytes
- Fibroblasts migrate to the Bowman’s space and synthesize collagen.
- When cellular components are mixed with collagen the lesion is called fibroepithelial crescent.
- Renal vessels can show transmural vasculitis, with necrosis and lymphocyte infiltrates.
- Tubular necrosis may also be present.
- Interstitial granulomas in the glomeruli indicate Wegener’s granulomatosis.
.jpg){kind=link}
Immunoflourescence
- In type I RPGN- diffuse and linear deposition of IgG along the GBM.
- In ttype II RPGN- diffuse and irregular deposition of IgG and C3 in the mesangial matrix.
- In type III RPGN- no finding.
Electron microscopy
- In type I and type III, no electron dense deposits are seen.
- In type II RPGN, subepithelial electron dense deposits indiacting the presence of immune complexes are seen.
Genetics
People with HLA DP1,DQ and DRB4 are more susceptible to develop RPGN[17]. {{#ev:youtube|CqSyj4cVZPE}}
References
- ↑ Couser WG (1988). "Rapidly progressive glomerulonephritis: classification, pathogenetic mechanisms, and therapy". Am J Kidney Dis. 11 (6): 449–64. PMID 3287904.
- ↑ 2.0 2.1 Couser WG (1998). "Pathogenesis of glomerular damage in glomerulonephritis". Nephrol Dial Transplant. 13 Suppl 1: 10–5. PMID 9507491.
- ↑ Roy S, Murphy WM, Arant BS (1981). "Poststreptococcal crescenteric glomerulonephritis in children: comparison of quintuple therapy versus supportive care". J Pediatr. 98 (3): 403–10. PMID 7205449.
- ↑ Atkins RC, Nikolic-Paterson DJ, Song Q, Lan HY (1996). "Modulators of crescentic glomerulonephritis". J Am Soc Nephrol. 7 (11): 2271–8. PMID 8959617.
- ↑ Bariéty J, Bruneval P, Meyrier A, Mandet C, Hill G, Jacquot C (2005). "Podocyte involvement in human immune crescentic glomerulonephritis". Kidney Int. 68 (3): 1109–19. doi:10.1111/j.1523-1755.2005.00503.x. PMID 16105041.
- ↑ Tipping PG, Timoshanko J (2005). "Contributions of intrinsic renal cells to crescentic glomerulonephritis". Nephron Exp Nephrol. 101 (4): e173–8. doi:10.1159/000088165. PMID 16155400.
- ↑ Huang XR, Tipping PG, Apostolopoulos J, Oettinger C, D'Souza M, Milton G; et al. (1997). "Mechanisms of T cell-induced glomerular injury in anti-glomerular basement membrane (GBM) glomerulonephritis in rats". Clin Exp Immunol. 109 (1): 134–42. PMC 1904710. PMID 9218836.
- ↑ Izzedine H, Camous L, Deray G (2007). "New insight on crescentic glomerulonephritis". Nephrol Dial Transplant. 22 (5): 1480–1. doi:10.1093/ndt/gfl742. PMID 17164315.
- ↑ "Chapter 10: Immunoglobulin A nephropathy". Kidney Int Suppl (2011). 2 (2): 209–217. 2012. doi:10.1038/kisup.2012.23. PMC 4089745. PMID 25018935.
- ↑ Heeringa P, Brouwer E, Klok PA, Huitema MG, van den Born J, Weening JJ; et al. (1996). "Autoantibodies to myeloperoxidase aggravate mild anti-glomerular-basement-membrane-mediated glomerular injury in the rat". Am J Pathol. 149 (5): 1695–706. PMC 1865281. PMID 8909258.
- ↑ Yang G, Tang Z, Chen Y, Zeng C, Chen H, Liu Z; et al. (2005). "Antineutrophil cytoplasmic antibodies (ANCA) in Chinese patients with anti-GBM crescentic glomerulonephritis". Clin Nephrol. 63 (6): 423–8. PMID 15960143.
- ↑ de Lind van Wijngaarden RA, Hauer HA, Wolterbeek R, Jayne DR, Gaskin G, Rasmussen N; et al. (2006). "Clinical and histologic determinants of renal outcome in ANCA-associated vasculitis: A prospective analysis of 100 patients with severe renal involvement". J Am Soc Nephrol. 17 (8): 2264–74. doi:10.1681/ASN.2005080870. PMID 16825335.
- ↑ Bomback AS, Appel GB, Radhakrishnan J, Shirazian S, Herlitz LC, Stokes B; et al. (2011). "ANCA-associated glomerulonephritis in the very elderly". Kidney Int. 79 (7): 757–64. doi:10.1038/ki.2010.489. PMID 21160463.
- ↑ Chen M, Yu F, Wang SX, Zou WZ, Zhao MH, Wang HY (2007). "Antineutrophil cytoplasmic autoantibody-negative Pauci-immune crescentic glomerulonephritis". J Am Soc Nephrol. 18 (2): 599–605. doi:10.1681/ASN.2006091021. PMID 17215440.
- ↑ Berden AE, Ferrario F, Hagen EC, Jayne DR, Jennette JC, Joh K; et al. (2010). "Histopathologic classification of ANCA-associated glomerulonephritis". J Am Soc Nephrol. 21 (10): 1628–36. doi:10.1681/ASN.2010050477. PMID 20616173.
- ↑ Bonsib SM (1988). "Glomerular basement membrane necrosis and crescent organization". Kidney Int. 33 (5): 966–74. PMID 3392885.
- ↑ Jagiello P, Gross WL, Epplen JT (2005). "Complex genetics of Wegener granulomatosis". Autoimmun Rev. 4 (1): 42–7. doi:10.1016/j.autrev.2004.06.003. PMID 15652778.