Rheumatoid Arthritis Pathophysiology / Rheumatoid Arthritis Pathogenesis / Arthritis pathophysiology
Understanding the Pathogenesis of Rheumatoid Arthritis
Overview of Joint Anatomy
- The knee joint is a synovial joint, characterized by a fibrous joint capsule that connects bones or cartilage.
- Articular cartilage serves as a protective cushion between gliding bones, while the fibrous joint capsule is lined with a synovial membrane.
Synovial Membrane and Its Role
- The synovial membrane produces synovial fluid, which lubricates joints and provides nutrition.
- In rheumatoid arthritis, inflammation of the synovial membrane (synovitis) leads to pain and swelling in the joints.
Mechanisms Behind Synovial Inflammation
- The pathogenesis involves genetic, environmental, and immunologic factors causing immune system dysregulation long before clinical symptoms appear.
- Autoantibodies like Rheumatoid factor and anti-CCP antibodies can be detected years prior to disease onset.
Citrullination Process
- Citrullination converts arginine into citrulline; immune cells may misidentify these proteins as foreign antigens.
- Environmental factors such as smoking and pathogens contribute to this process, leading to an autoimmune response.
Activation of Immune Response
- Antigen-presenting cells activate CD4+ T cells in lymph nodes through specific receptor interactions.
- Activated T helper cells secrete cytokines (IFN-γ, TNF-α), stimulating B cells to produce autoantibodies.
Impact on Joints
- Autoantibodies enter circulation and target altered IgG antibodies in joints, forming immune complexes that activate the complement system.
- This activation leads to local tissue destruction; proinflammatory mediators are secreted by macrophages and fibroblasts.
Role of Cytokines in Inflammation
- Tumor necrosis factor α (TNF-α), along with other inflammatory cytokines like IL-1 and IL-6, drives synovial inflammation.
- These cytokines sensitize pain receptors and promote angiogenesis within the joint space.
Bone Destruction Mechanism
- RANK Ligand (RANKL), expressed due to inflammatory cytokines, activates osteoclast precursors leading to bone destruction.
Regulation of Bone Formation