Pathophysiology of Rheumatoid Arthritis Flashcards
what is rheumatoid arthritis?
A chronic, systemic inflammatory condition that develops progressively
what joints are affected 1st?
Interphalangeal joints of fingers and wrist
what is felt and seen at the affected joints?
heat, swollen, redness, increased extracellular fluid
what effect does the extracellular fluid have on the joints?
causes stiffness particularly in the morning
what other diseases does rheumatoid arthritis increase the risk of?
- Cardiovascular disease
- Inflammation around lungs and heart
- Systemic symptoms e.g. malaise / weight loss
what happens to the bone and cartilage around the joint in RA?
they become destroyed
what is septic arthritis?
when there is an infection in the joint causing inflammation
what is post-traumatic arthritis?
inflammation at joint brought about by physical injury
is RA an autoimmune condition?
yes
Is the rheumatoid factor specific for RA?
nope
what causes autoantibody formation in RA?
Citrullinated proteins/peptides
so we get Anti-citrullinated peptide antibodies formed which are what cause the self-harm in autoimmunity
what is citrulline?
an amino acid related to arginine that is NOT used in protein synthesis
what is citrullination?
a mechanism that converts arginine into citrulline
what enzyme catalyses the reaction of citrullination?
peptidylarginine deiminases (PAD)
what does peptidylarginine deiminases do?
- PAD destabilizes proteins and makes them more prone to proteolyisis.
- if there are cells that don’t accept the new proteins containing the citrulline, then they are classed as intolerant so B-cells and T-cells come along
- this is what causes the immunological intolerance at the start of RA development/pathogenesis
what makes up the joint capsule?
Synovial membrane and fibrous layer
what does PAD2 and PAD4 do in the synovial fluid?
they are enzymes that citrullinate unknown proteins in the joint capsule
-this would stimulate an autoimmune reaction when the antictrullinated protein antibodies enter the fluid and cause inflammation
what initiates RA?
joint damage e.g. wound or infection
-this induces inflammation in the joint causing further activation of PAD
why is vascular permeability important in RA?
- it is important in the inflammatory response
2. also allows the antictrullinated protein antibodies to enter the joint capsule
what do CD4T cells differentiate into?
TH-17 and TH-1
what does TH-17 do?
releases IL17 and recruits neutrophils and monocytes
what does TH-1 do?
releases IFN-γ and activates macrophages
Which antibody is specific for RA disease?
Anti-citrullinated protein antibody (ACPA)
Which mediator is actively involved in osteoclast activation?
RANKL
