Wk 15: Rheumatoid arthritis Flashcards
What is the principle pathology of rheumatoid arthritis?
Inflammation w/in synovial joints causing pain, swelling, stiffness + erosion
Swelling
Synovial tissue in cap of joins = damaged, tissue thicken + swell
Stiffness
Inflamed joints stiffen + difficult to move esp in morning/long periods of rest
Pain
Cartilage + bone w/in joint wear down
What are the symptoms of early stage RA?
- Fixed flexion + fixed hyperextension of PIP joint: impairs hand function
- Swelling + dorsal subluxation of ulnar styloid: wrist pain + finger extensor tendons rupture
What are the features of healthy bones + joints?
- Articular cartilage: lubricate surface for opposing bones of joint
- Synovial membrane prod + contains synovial fluid
- Synovial fluid: remove debris + lubrication
What is the pathogenesis of RA?
Genetic/env trigger:
- Autoantigens generated
- Autoimmune response
- Onset of RA
Which genes inc the risk of developing RA?
- HLA
- MHCI + MHCII complex
- Genetic alterations to HLA-DR1 + HLA-DR4 alleles
- PTP2N22 mutation
Which complex present antigen to T cell?
MCH complex - activates immune response
What initiates inflammatory synovitis?
HLA-DRβ1 has binding site for arthritogen
Outline the mechanism of action of the pathogenesis of RA
- Autoantigens bind to antigen presenting cell
- APC couple to T-cell releasing cytokines
- Feedback + activates T-Helper cells releasing more cytokines (IFNy + IFN17)
- Activates B-cells = prod antibodies
- Recruits macrophage which attack foreign invader: release cytokines to stimulate synovial cells to proliferate (TNF-a, IL1 + 6)
- Cytokines release: Chrondocyte (attack cartilage), synovial fibroblasts (prod matrix metalloproteinases causing inflammation + degrade cartilage) + osteoclast (attack bone)
Describe what you would find in a RA joint
- Synovial membrane inflamed
- Thick pannus
- Bone + cartilage eroded
- Cytokines (TNF-a, IL1+6)
- Inc fibroblast like synoviocytes
- MLS proliferate producing RANKL
