The Korean Journal of Medicine

The Korean Association of Internal Medicine (대한내과학회)
권호 표지

Pathophysiology of Gout

통풍의 병태 생리

  • Lee, Kwang-Hoon (Department of Internal Medicine, Yonsei University College of Medicine) ;
  • Lee, Soo-Kon (Department of Internal Medicine, Yonsei University College of Medicine)
  • 이광훈 (연세대학교 의과대학 내과학교실) ;
  • 이수곤 (연세대학교 의과대학 내과학교실)
  • Published : 2011.03.01
⟨ Previous Next ⟩

Abstract

We reviewed the pathophysiology of gout in this review article. Gout occurs as a response to monosodium urate crystal (MSU) that is present in joints, bones and soft tissue. Hyperuricemia in gout is mainly due to the decreased renal clearance of uric acid and is considered to be the cause of MSU formation. However, hyperuricemia alone does not explain the development of gout. Acute gout attack is due to the response to MSU, which is derived by innate immunity. Tophi are deposits of MSU and cell debris surrounded by granulomatous inflammation.

Keywords

References

  1. McCarty DJ, Hollander JL. Identification of urate crystals in gouty synovial fluid. Ann Intern Med 1961;54:452-460. https://doi.org/10.7326/0003-4819-54-3-452
  2. Buchanan WW, Klinenberg JR, Seegmiller JE. The inflammatory response to injected microcrystalline monosodium urate in normal, hyperuricemic, gouty, and uremic subjects. Arthritis Rheum 1965;8:361-367. https://doi.org/10.1002/art.1780080304
  3. Riches PL, Wright AF, Ralston SH. Recent insights into the pathogenesis of hyperuricaemia and gout. Hum Mol Genet 2009; 18:R177-R184. https://doi.org/10.1093/hmg/ddp369
  4. Klinenberg JR. The effectiveness of allopurinol in the treatment of gout. Arthritis Rheum 1965;8:891-895. https://doi.org/10.1002/art.1780080453
  5. Perez-Ruiz F, Calabozo M, Erauskin GG, Ruibal A, Herrero- Beites AM. Renal underexcretion of uric acid is present in patients with apparent high urinary uric acid output. Arthritis Rheum 2002;47:610-613. https://doi.org/10.1002/art.10792
  6. Hall AP, Barry PE, Dawber TR, McNamara PM. Epidemiology of gout and hyperuricemia: a long-term population study. Am J Med 1967;42:27-37. https://doi.org/10.1016/0002-9343(67)90004-6
  7. Fields TR, Abramson SB, Weissmann G, Kaplan AP, Ghebrehiwet B. Activation of the alternative pathway of complement by monosodium urate crystals. Clin Immunol Immunopathol 1983;26: 249-257. https://doi.org/10.1016/0090-1229(83)90143-5
  8. Guerne PA, Terkeltaub R, Zuraw B, Lotz M. Inflammatory microcrystals stimulate interleukin-6 production and secretion by human monocytes and synoviocytes. Arthritis Rheum 1989;32: 1443-1452. https://doi.org/10.1002/anr.1780321114
  9. di Giovine FS, Malawista SE, Thornton E, Duff GW. Urate crystals stimulate production of tumor necrosis factor alpha from human blood monocytes and synovial cells: cytokine mRNA and protein kinetics, and cellular distribution. J Clin Invest 1991; 87:1375-1381. https://doi.org/10.1172/JCI115142
  10. Terkeltaub RA, Dyer CA, Martin J, Curtiss LK. Apolipoprotein (apo) E inhibits the capacity of monosodium urate crystals to stimulate neutrophils: characterization of intraarticular apo E and demonstration of apo E binding to urate crystals in vivo. J Clin Invest 1991;87:20-26. https://doi.org/10.1172/JCI114971
  11. Getting SJ, Christian HC, Flower RJ, Perretti M. Activation of melanocortin type 3 receptor as a molecular mechanism for adrenocorticotropic hormone efficacy in gouty arthritis. Arthritis Rheum 2002;46:2765-2775. https://doi.org/10.1002/art.10526
  12. Akahoshi T, Namai R, Murakami Y, et al. Rapid induction of peroxisome proliferator-activated receptor gamma expression in human monocytes by monosodium urate monohydrate crystals. Arthritis Rheum 2003;48:231-239. https://doi.org/10.1002/art.10709
  13. Dalbeth N, Pool B, Gamble GD, et al. Cellular characterization of the gouty tophus: a quantitative analysis. Arthritis Rheum 2010;62:1549-1556. https://doi.org/10.1002/art.27356
  14. Schweyer S, Hemmerlein B, Radzun HJ, Fayyazi A. Continuous recruitment, co-expression of tumour necrosis factor-alpha and matrix metalloproteinases, and apoptosis of macrophages in gouttophi. Virchows Arch 2000;437:534-539. https://doi.org/10.1007/s004280000282
  15. Hsieh MS, Ho HC, Chou DT, et al. Expression of matrix metalloproteinase- 9 (gelatinase B) in gouty arthritis and stimulation of MMP-9 by urate crystals in macrophages. J Cell Biochem 2003;89:791-799. https://doi.org/10.1002/jcb.10530