Week 4: Rheumatoid Arthritis Flashcards
Describe Pus?
Made from dead leukocytes, primarily neutrophils
What are the risk factors of rheumatoid arthritis?
Females are more suspectible than males
Genetics particularly HLA-DR4
Environmental: Smoking, stress, infection
Define rheumatoid arthritis?
It is a chronic, systemic inflammatory condition due to an autoimmune condition.
Progressive
Usually affecting the hands, feet and wrists.
Usually symmetrical
Most affects the joints but can affect other organ systems
Describe the basic pathophysiology of rheumatoid arthritis?
Autoimmune condition that is typically triggered by an interaction between a genetic factor and the environment. Resulting in autoantibodies “Rheumatoid factor” and activation of CD4 T cells. Rheumatoid factor binds to IgG in the synovial membrane making immune complexes, inducing the inflammation. CD4 T cells produce cytokines recruiting macrophages to the area.
Macrophages present in the synovium start to secrete cytokines in response including TNF-alpha, IL-1 and IL-6. Resulting in inflammation.
Macrophages also produce VEGF and E-selectin causing angiogensis and increase vascular permeability. Increasing the number of immune cells in the area.
These cytokines stimulate the fibroblast-like synoviocytes, causing them to proliferation.
Activated fibroblast-like synoviocytes secrete RANKL express. Stimulate the RANK receptor on osteoclasts. Causing erosion of bone
Activated fibroblast-like synoviocytes secrete proteases, causing articular cartilage degradation. Similarly, neutrophils in the synovial fluid start to secrete proteases.
Activated fibroblast-like synoviocytes are able to migrate to the equivalent joint (e.g. DP joint in Left hand- moves to DP joint on Right hand)- leading to symmetrical arthritis.
T helper cells increase the activity of macrophages.
What are the 3 main pathological changes associated with Rheumatoid arthritis?
1) Rheumatoid synovitis
Synovium appears swollen
2) Articular cartilage degradation
Proteases produced by neutrophils and activated fibroblast-like synviocytes.
3) Bone destruction
Present at the edge of the bone due to osteoclast activity. RANKL is secreted by activated fibroblast-like synoviocytes. Therefore, osteoclast activity is never stopped. Constant destruction.
Describe how rheumatoid arthritis affects organs, not the joints?
Inflammatory cytokines produced at the joint space can travel through the circulatory system.
TNF-alpha, IL-1 and IL-6 can affect the brain causing depression.
TNF alpha and IL-1 affects muscles causing insulin resistance
IL-6 stimulates the liver in producing hepcidin and CRP
IL-6, complement cascade and TNF-alpha stimulates the inflammation of the blood vessels causing plaque formation.
What are the joints most commonly affected in rheumatoid arthritis?
Proximal interphangeal joint
Metacarpal phangeal joint
Metatarsalphalangeal joint
Bilateral joints affected
Describe the other features of rheumatoid arthritis in the head?
“Swan neck” deformity
Distal interphalangeal hyperflexion
Proximal interphalangeal hyperextension
“Boutonnieres” deformity
Distal interphalangeal: Hyperextension
Proximal interphalangeal: Hyperflexion
Ulnar deviation
Inflammation of the metacarpophalangeal joints
Fingers deviated towards the ulnar side
Describe the clinical symptoms of rheumatoid arthritis?
Pain
Stiffness: In the morning less than an hour (lasting longer than osteoarthritis)
Deformity of the fingers: “Swan neck”, “Boutonniere’s”, Ulnar deviation.
Bilateral arthritis affecting commonly affecting PIP, DIP and MCP.
Describe the different phases of rheumatoid arthritis?
Phase A: Genetic risk factors
Phase B: Environmental risk factors
Phase C: Autoimmunity
Phase D: Symptoms
Phase E: Undifferentiated arthritis
Phase F: Rheumatoid arthritis
As the stages progress, the inflammation gets greater
Describe how genetic and environmental factors can cause Rheumatoid arthritis? And the overall process of producing rheumatoid factor
Genetic factors include HLA-DR1 and HLA-DR4
Environmental include smoking and pathogen
Environmental factors leads to the modification of autoantigens
Modification to IgE
Modifies collagen type 2 by a process called citrullination, arginine amino acid is converted into citrulline.
Due to suspectible genes, the immune cells no longer recognise these collagen and IgE molecules as self and start to respond.
Antigen-presenting cells bind to these autoantigens and migrate to the local lymph node and activate CD4 T cells. CD4 T cells stimulate the B cells causing them to proliferate and differentiate into plasma cells.
Plasma cells produce autoantibodies known as Rheumatoid factor
RF and CD4 T cells migrate to the joint space via circulatory system, enducing inflammation
Describe the possible treatments of rheumatoid arthritis?
Chronic, progressive condition with no cure.
Treatment depends on the severity.
NSAIDs and corticosteroids
DMARDs: Disease modifying anti-rheumatic drugs. Supresses inflammatory activity e.g. methotrexate
Can combine NSAIDS and DMARDs
Biological agents: Blocking cytokines prevents the damage.
Flare ups: Using DMARDs to control
What are the differences between osteoarthritis and rhuematoid arthritis?
Osteoarthritis:
Affects weight-bearing joints
Distal interphalangeal joints and Proximal interphalangeal joints
Treatment: Weight-bearing exercise (as obesity is a risk)
Progressive condition
Onset in older generation
Osteophytes + Subchondral sclerosis
Morning stiffness that leaves within 30 mins
Rheumatoid Arthritis:
Proximal interphalangeal joints + Metacarpophalangeal joints
Age of onset between 35-45.
Morning stiffness that last longer than 30 mins, around an hour.
Weight-bearing exercise is not recommended and can cause damage.
Autoimmune disease
Deformities in the fingers
Symmetry arthritis
