Tuesday, August 09, 2011

Pathogenesis of Arthritis

Arthritis is the painful disorder of joints, a leading cause for the disability in geriatrics. Osteoarthritis (OA), rheumatoid arthritis (RA), gout, lupus etc. are the common types of arthritis. OA is a disease aquired by 'wear and tear', and injury leading to cartilage degradation. RA is chronic inflammatory disorder attacking mainly the joints. Gout develops due to monosodium urate (MSU) crystal deposition in synovial fluid.

Pathogenesis of arthritis is mainly due to the following reasons. The activation of immune cells because of cross reactivity with bacteria, virus, pollen grains etc., which share common epitope with synovium or defects in genes like HLA-DRB1*0401, single nucleotide polymorphism (PTPN22, STAT4, CDK6, etc.). Complement complex, C5b678(9)n are deposited on synovial lining and opsonize it. These immune cells release pro-inflammatory cytokines, which intitaites  proliferation of fibroblast and osteoclast, and ultimately demineralize and destroy the bone matrix. Agonist of RANK, TLR2, etc. trigger the activation of NF-kB, which ultimately produces matrix metalloproteinase, nitric oxide and other bone degenarating enzymes. Due to obesity, axial  force as well as varus malalignment increases, hence cartilage begin to erode. Uric acid (purine) is overproduced due to some hyperactive enzymes or overturn of nucleic acid rich dietary source, and renal failure (not removing of urate).

Joint damage and pain due to arthritis can be reduced using ice, joint replacement, physiotherapy, hyaluronic acid administration, avoiding purine rich diet, administration of drugs such as methotrexate, etanercept, infliximab, rituximab, tocilizumab, Ibuprofen, corticosteroids, colchicine, diclofenac,  allopurinol, etc.
(To be Continue.....) (Update: View part II)
References
  1. Porth, C.M, and Matfin, G. Pathophysiology, concept of altered health states, 8th edition, Lippincott Willian and Wilkins Publisher (2009)
  2. Firestein, G.S. Evolving concepts of rheumatoid arthritis. Nature 423, 356-361(2003)
  3. El-Gabalawy H. S. et al.,  Non-HLA genes modulate the risk of rheumatoid arthritis associated with HLA-DRB1 in a susceptible North American Native population, Genes and Immunity, Doi :10.1038/gene.2011.30(2011)
  4. Loughlin, J. Osteoarthritis: All types of trouble-defining OA in the genomic era. Nature Reviews Rheumatology 7, 200-201(2011)

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