RA - Pathology/Aetiology Flashcards
What guidelines do we use to classify RA?
2010 EULAR/ACR Classification (European Leaque against Rheumatism/American College of Rheumatology)
What criteria do we use to classify the types/levels of RA?
Under the 2010 EULAR/ACR Classification its done by:
- No./size of joints involved
- Serology (-ve/low +ve or high +ve tests for RF & ACPA)
- Acute Phase Reactants (ESR/CRP)
- Duration (>6wks of symptoms)
Who gets RA?
3x more common in women
Can occur at any point after 16yrs but mostly in 4th/5th decade
What factors contribute to Development of RA?
Genetics
Environmental:
- Certain infections
- Silica Exposure
- Smoking
What infections predispose to RA?
Viruses e.g. CMV/EBV
E. Coli
Mycoplasma
Periodontal Disease (Porphyromonas Gingivalis)
Gut Microbes
In short how does RA work?
repeated insults to the synovium in genetically predisposed patients leads to immune complex & ACPA/RF production –> Chronic inflammation + Neovascularisation of the synovium
What do we call the fibrovascular tissue that forms over the hyperplastic intimal lining?
Pannus
What cell types are involved in Rheumatoid Synovitis?
T Cells
B Cells
Macrophages
Fibroblasts
What major inflammatory mediators are involved in Rheumatoid Synovitis?
ACPA (anti-citrullinated Protein Antibodies)
Rheumatoid Factor
TNF-Alpha
IL-6
IL-17
IFN-gamma
What inflammatory cell predominates in the synovial fluid ?
Neutrophils
How is cartilage damaged during RA?
Synovial fibroblasts from the intimal layer invade the articular cartilage & produce several classes of proteases (E.g. Metalloproteinases) that break down cartilage matrix allowing it to wear down under mechanical pressures
How is bone damaged during RA?
RANKL produced by Synovial Fibroblasts and macrophages activate osteoclasts
How does RA affect CVD?
Altered Lipid Metabolism –> Increased coronary artery disease
How does fatigue & Reduced cognitive function come about from RA?
Dysregulates the HPA (Hypothalamic-Pituitary-Adrenal) Axis
How does RA affect the liver?
Elevated Acute-phase response
Also IL-6 increases Hepcidin hormone production –> Iron dysregulation –> Anaemia
