RANKL expression → osteoclasts (from Type B) Early morning stiffness >30 mins Synovitis > 3 joints, symmetrical MMPs (from Type A) Hands: MCP, PIP Foot: metatarsophalyngeal joints Hydrostatic pressure → oedema Synovitis ↑MMP: TIMP Endothelial activation – adhesion molecule expression Cartilage and bone erosion Ulnar deviation, Swan neck, Boutonniere Extracellular matrix degradation C1-C2 pannus, subaxial sublixation Neutrophils in fluid Immune cell ingress into synovial space ↓ Oestrogen CD4 lymphocytes, macrophages, NK cells, DCs in tissue VEGF Vascular proliferation Genetics + environment DRB1 0401 / 0404 B cell germinal centres ➔ High endothelial venules Cytokines: IFN-G, IL-3, granular macrophage CSF Smoking, EBV, P.ging, SES Immune complex exudate Anti-apoptosis genes Inc synovial pressure Autoantibodies RF → targets IgG Increased pressure on fronds Anti-CCP ↑Type A synoviocytes IL-1 and TNF Basic fibroblast growth factor ↑HIF-1alpha ↑Type B synoviocytes Fusion into giant cells Early morning stiffness >30 mins Synovitis > 3 joints, symmetrical Hands: MCP, PIP Foot: metatarsophalyngeal joints Synovial villi Ulnar deviation, Swan neck, Boutonniere Synovial pannus C1-C2 pannus, subaxial sublixation Early morning stiffness > 30 minutes. Upper limbs: MCP and PIP Lower limbs: Metartarso phalyngeal joints WCC normal, ddx from septic arthirits Soft tissue swelling → para articular erosion → paraarticular OP