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Dr Bashir ahmed dar associate professor medicine chinkipora sopore kashmir presently working in medical college malaysia describes rheumatoid arthritis which is a autoimmune disorder in which Immune system identifies the synovial membrane as "foreign" and begins attacking it.

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  2. Dr Bashir and Dr Yashodhra leading group of medical students to meet noble prize winner in medicine at KL Malaysia

  3. Dr Bashir at PBL Conference

  4. Noble prize winner Prof Barry .J Marshall in recognition of his discovery Helicobacter pylori-most common cause for peptic ulcer

  5. Precious moments with noble prize winner

  6. RHEUMATOID ARTHRITIS • Rheumatoid arthritis isautoimmune disorder in which Immune system identifies the synovial membrane as "foreign" and begins attacking it. • Synovial membrane shown in picture

  7. RHEUMATOID ARTHRITIS • With long-term or intensive exposure to the antigen, normal antibodies become auto-antibodies that target self-antigens in the synovial membrane.

  8. RHEUMATOID ARTHRITIS • Once the antigen or immune complex reaches the synovial membrane .The antigen presenting cell deals with it.

  9. RHEUMATOID ARTHRITIS • First, the APC usually a macrophage in synovium engulfs the antigen. • Enzymes (peroxides) inside the APC break down the antigen into smaller particles.

  10. RHEUMATOID ARTHRITIS • The processed antigens are transported to the surface of the APC, where it binds with MHC (major histocompatibility complex).

  11. RHEUMATOID ARTHRITIS • This complex ie (part of a foreign substance and MHC) is now presented to T-cells (CD4 cells ie T-helper cell ) or CD8 (cytotoxic T cells) which the T-cell receptor (TCR) recognizes and binds to.

  12. RHEUMATOID ARTHRITIS • Once the T-cell binds to the Antigen / MHC complex, the APC then secrete cytokines like • Interleukin-1 (IL-1) • Interferon-alpha (IFN-a) • Interferon-gamma (IFN-g) • Tumor necrosis factor (TNF) • And other factors that activate lymphocytes and other immune cells to respond to the antigens.

  13. RHEUMATOID ARTHRITIS • APC also Secretes • Lysozymes, Elastases and Collagenases these enzymes cause cartilage breakdown. • FGF & Angiogenesis Factors add to pannus formation • Chemokines mediates chemo attraction (chemotaxis)

  14. Effects of IL-1 • On exposure to IL-1, synoviocytes proliferate and produce following factors • Interleukin-6 (IL-6) • Prostaglandin's (e.g. , PGE2) , and platelet-activating factor, which are involved in the pain mechanism. • Matrix Metalloproteases(e.g. stromelysin) that cause activation of collagenase, an enzyme required for cartilage breakdown.

  15. Effects of IL-1 • IL-1 also activates endothelial cells and induce stimulation of adhesion molecule expression on endothelial cells. • Enhances activity of NK cells and leads to Pyrogen (cause fever).

  16. Effects of IL-1 • IL-1 also causes increased production of inducible nitric oxide synthase and consequently high levels of nitric oxide kill chondrocytes, the cells responsible for cartilage remodeling. • Induce osteoblast apoptosis and thereby prevent new bone formation • Prevent formation of the cartilage matrix by inhibition of proteoglycan synthesis.

  17. Effects of IL-1 • The end result of these of IL-1 and TNF-a include activation and migration of leukocytes and lymphocytes from the blood into inflammatory tissues as well as formation of pannus and damage to cartilage and surrounding normal cells.

  18. Effects of IL-1

  19. MICROSCOPY- RA • Micro: dense perivascular inflammatory infiltrate of T lymphocytes, plasma cells (often with eosinophilic cytoplasmic inclusions called Russell bodies) • inflammation extends to subchondral bone (relatively specific for rheumatoid arthritis); proliferative synovitis with synovial cell hyperplasia and hypertrophy, necrobiotic nodules and fibrosis; • increased vascularity with hemosidrin deposition; organizing fibrin floating in joint space as rice bodies; neutrophils present on synovial surface;

  20. MICROSCOPY- RA • Neutrophils, lymphocytes, plasma cells, macrophages, and fibroblasts are responsible for increased cellularity. • Superficial areas of necrosis are present and masses of inflammatory cells can be seen free above the synovial surface.


  22. MICROSCOPY- RA • The synovium is red due to blood vessel dilatations and thickened due to inflammation and cellular infiltration.

  23. MICROSCOPY- RA • There is also granulation formation over the synovial membrane now called as pannus.

  24. Early bone destruction in RA

  25. MICROSCOPY- RA • The inflammation can spread to soft tissues as shown in fig and destroy these structure causing laxity and deformity of joint. • Muscles /tendons /ligaments





  30. Mast Cells • Mast cells are implicated in the pathology of autoimmune disorders like rheumatoid arthritis. • Mast cells are basophils that have "homed in" on tissues characteristically surrounding blood vessels and contains many granules rich in histamine and heparin.

  31. Mast Cells • Mast cells has a receptor for the Fc region of IgE. • As a result, mast cells are coated with IgE. • Mast cells usually remain inactive until an allergen binds to IgE already in association with the cell. • It appears that binding of two or more IgE molecules is required to activate the mast cell.

  32. Mast Cells

  33. Mast Cells • The molecules thus released by mast cell into the extracellular environment include: • Cytokines • Histamine/Serotonin/Heparin • Eosinophil chemotactic factor • Prostaglandin D2 • leukotrienes C4 • Platelet-activating factor • TNFa

  34. Mast Cells • Histamine and serotonin dilates capillaries activates the endothelium, and increases blood vessel permeability. This leads to local edema (swelling), warmth, redness, and the attraction of other inflammatory cells to the site of release.

  35. RHEUMATOID ARTHRITIS • Increase in the permeability of blood vessels in the synovial membranes. This attracts several types of leukocytes and lymphocytes to the synovial membrane out of the circulation. • Synovial inflammation (synovitis)

  36. RHEUMATOID ARTHRITIS • The phagocytes of inflammation (neutrophils and macrophages) ingest the immune complexes which releases powerful enzymes that degrade synovial tissue and articular cartilage.

  37. RHEUMATOID ARTHRITIS • Inflammation causes hemorrhage, coagulation, and fibrin deposits on the synovial membrane, in the intracellular matrix, and in the synovial fluid.

  38. RHEUMATOID ARTHRITIS • On the denuded areas of the synovial membrane, fibrin gets deposited and develops into granulation tissue called pannus, which is the earliest tissue produced in the healing process.

  39. RHEUMATOID ARTHRITIS • The pannus is a sheet of inflammatory granulation tissue that spreads from the synovial membrane and invades the joint in rheumatoid arthritis ultimately leading to fibrous ankylosis.

  40. RHEUMATOID ARTHRITIS • The synovial membrane undergoes hyperplasic thickening as its cells abnormally proliferate and enlarge. • These vascular derangements decrease blood flow to the synovial tissue and compromised circulation. This, coupled with increased metabolic needs due to hypertrophy and hyperplasia, causes hypoxia (oxygen depletion) and metabolic acidosis.

  41. RHEUMATOID ARTHRITIS • Acidosis stimulates the release of hydrolytic enzymes from synovial cells into the surrounding tissue, initiating erosion of the articular cartilage and inflammation spreads into the supporting ligaments and tendons.

  42. RHEUMATOID ARTHRITIS • The synovitis or inflammation, results in the warmth, redness, swelling, and pain that are typical symptoms of RA.

  43. RHEUMATOID ARTHRITIS • In this disease process, an interaction between antibodies and antigens occurs, and causes alterations in the composition of the synovial fluid. Infiltration of cells in it etc.

  44. RHEUMATOID ARTHRITIS • Once the composition of this fluid is altered, it is less able to perform the normal functions and results in soft tissue destruction that eventually leads to laxity in tendons and ligaments.

  45. RHEUMATOID ARTHRITIS • Stage One: • Congestion and edema of the synovial membrane and joint capsule. • Stage Two: • Formation of pannus occurs, covering the cartilage and eventually destroying the joint capsule and bone.

  46. RHEUMATOID ARTHRITIS • Stage Three: • Fibrous ankylosis, which is a fibrous invasion of pannus and scar tissue that fills the joint space. • Mal-alignment cause visible deformities and disrupt the articulation of opposing bones. This, in turn, causes muscle atrophy and imbalance that may also include partial dislocations (subluxation).

  47. RHEUMATOID ARTHRITIS • Stage Four: • Fibrous tissue begins to calcify, resulting in bony ankylosis (total immobility).

  48. Epidemiology • RA affects 0.5-1.0% of population in USA • Females > males 3:1 • but people of any age can be affected • Peak age 45-65 but onset early from age 20-45 yrs • Smoking risk factor • Genetic • 70% of patients with RA express HLA-DR4 • twins indicate a concordance of about 15%–20%

  49. Epidemiology • It occurs worldwide, affecting more than 6.5 million people in the U.S. alone. • About 75% of these are women. • The disease strikes women three times more often than men.

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