The Science of Rheumatoid Arthritis Flashcards
What are some functions of the Synovium?
Maintenance of intact tissue surface.
Lubrication
Control of synovial fluid volume and composition (hyaluronan, lubricin)
Nutrition of chondrocytes within joints.
What is Rheumatoid Arthritis?
Chronic symmetric, polyarticular inflammatory joint disease which particularly affects the small joints of the hands and feet.
It is characterised by inflammatory cell infiltration, synoviocyte proliferation and neoangiogenesis. The synovial fluid also contains neutrophils, especially during acute flares.
Eventually causes bone and. cartilage destruction.
What autoantibodies are commonly associated with RA?
Rheumatoid factor
Anti-citrullinated protein antibodies.
What is the function of autoantibodies?
Recognise either joint antigens such as type II collagen or systemic antigens such as glucose phosphate isomerase. They potentially contribute to inflammation through several mechanisms including activation of complement.
What is Rheumatoid factor?
An auto-antibody to self IgG Fc.
How are genes related to RA?
Genes play a key role in susceptibility to RA.
HLA-DRB1 locus association
Other genetic associations including polymorphisms in PTPN22, CTLA4, c-REL .
They are very complex and involve many genes.
What are some environmental factors that predispose individuals to RA?
Smoking
Bronchial stress
Infectious agents e.g viruses, e.coli, mycoplasma, periodontal disease, microbiome.
What is citrullination?
The conversion of the amino acid arginine in a protein into the amino acid citrulline.
What is Synovitis?
Inflammation of the synovial membrane.
Intimal lining hyperplasia and sublining infiltration (migration) with mononuclear cells, especially CD4 + T cells, macrophages, and B cells.
What is the function of inflammatory cytokines?
Induce expression of endothelial-cell adhesion molecules.
Activate synovial fibroblasts
Promote angiogenesis
Suppress T regulatory cells
Activated leukocytes
Promote autoAb production
IL-6 mediates systemic effects - acute phase, anaemia, cognitive dysfunction, lipid metabolism dysregulation.
What is Neoangiogenesis?
Formation of blood vessels in tumour tissue.
It provides nutrients to the hyperplastic synovium.
What factors enhance blood vessel proliferation in the synovium?
Hypoxic conditions
IL-8
VEGF
What causes cartilage and bone destruction in RA?
Classes of proteases including metalloproteinases and aggrecanases are produced by intimal lining layer.
Synovial lining cells can attach and invade cartilage.
Osteoclasts mediate bone destruction, which are activated under the influence of RANKL produced in synovium.
What are some systemic consequences of RA?
Vasculitis Nodules Scleritis Amyloidosis Cardiovascular disease - altered lipid metabolism, elevated acute phase reactants, increased endothelial activation, IL-6. Fatigue and reduced cognitive function. Liver disease - elevated acute phase response, anaemia of chronic disease. Lungs - interstitial disease, fibrosis Sacropoenia Osteoporosis Sjorgren's syndrome.
