Pathogenesis Of Rheumatoid Arthritis Flashcards
2 types of synoviocytes
Type a bone marrow derived macrophage
Type b fibroblast like connective tissue cell
Characteristics of synovial membrane basement membrane
No basement membrane
What is contained in the sub intima of the synovial membrane
Dense network of Fenestrated capillaries
Fat
Loose areola CT
What is synovial fluid
Ultrafiltrate of blood with added hylauronic acid which forms a thin film over articulate surfaces
Histological structure of synovial membrane
Synoviocytes sitting directly on highly vascular subintima
How is synovial fluid produced
Leaky Fenestrated capillaries allow plasma out
Characteristics of synovial membrane that allows plasma/synovial fluid to easily flow in and out between blood membrane and joint cavity
Fenestrated capillaries
Loose areola or CT
No basement membrane between subintima and synoviocytes
Normal colour of synovial fluid
Colourless to clear pale yellow
Can read text through
What causes red or brown synovial fluid
Haemorrhage into joint
What causes yellow cloudy synovial fluid
Inflammation
What causes white or cream and cloudy or shimmery synovial fluid
Crystals
What causes yellow, purulent, or lumpy synovial fluid
Bacterial infection
Synovial fluid pH
7.38
How many g/L of hylauronate is in synovial fluid
3g/L
Why is synovial fluid thicker at rest and thins on movement
Protects cartilage at start of movement
Hylauronic acid and proteins inc lubricin interact more at rest and detangle on movement
How far apart are articulating surfaces kept by synovial fluid
50um
What is synovial fluid seeping into articulate cartilage called
Weeping lubrication
Purpose of weeping lubrication
Reduce friction
Reserve volume
Nourish articulate cartilage
string length of normal synovial fluid and synovial fluid in RA
4-6cm normal
RA <1cm
Why is synovial fluid less viscoelastic in RA than normal
Less hylauronic acid
Mucin clot test
2-5% acetic acid added to synovial fluid, clot surrounded by clear fluid forms in health, no clot in RA
Mucin clot test result in RA
no clot or clot that breaks up easily
Due to less hylauronic acid
Features of RA
Synoviocyte proliferation
Infiltration of inflammatory cells
Subintima fibroblast proliferation
Do type a or type b synoviocytes proliferate more in RA
Type a
Which types of inflammatory cells infiltrate the synovial fluid and subintima in RA
Syn fluid - neutrophils
Subintima - lymphocytes
Why is the subintima of the synovial membrane thickened in RA
Fibroblast proliferation
Why are synovial joints susceptible to inflammatory injury
Fenestrated capillaries so immune cells can easily enter
Limited responses
Pannus
Inflamed synovial membrane
How does pannus cause joint and bone erosion
Secretes cytokines, autoantibodies, and signalling mols that increase Clast activity
What forms lymphoid nodules in pannus and where do they form
Collections of Th17 subset of CD4 T lymphocytes
Form around small blood vessels
What tissue does pannus invade
Bone
What molecules lead to bone erosion in RA
Anti citrullinated protein antibodies
IL8
RANKL
Cytokines from Synovitis
DKK1
Sclerostin
How does anti citrullinated protein antibodies cause bone erosion
Stimulates osteoclast differentiation
Role of IL8 in RA
Produced by osteoclasts
Induces more osteoclasts by Autocrine feedback
Sensitises nociceptors increasing pain
Attracts neutrophils and induces NETosis
How do cytokines from Synovitis cause bone erosion
Stimulate osteoclast prolif and differentiation
Induce RANKL expression
Rheumatoid factor
IgM autoantibody that attacks IgG increasing inflammation
Role of IL-17 in RA
secreted by Th17 cells infiltrating joint
Induce RANKL on synovial fibroblasts
Stim local inflam
Activate synovial macrophages to secrete pro inflammatory cytokines
How do pro inflammatory cytokines released from pannus switch off the repair mechanism of bone in RA
Induce DKK1 expression by synovial fibroblasts -> inhibit osteoblasts and induces sclerostin expression by osteocytes -> sclerostin inhibits osteoblasts
Which cells are most numerous in inflammatory synovial effusion
Neutrophils
How do neutrophils increase free radical damage in RA
Cause respiratory burst producing superoxide anion radical
How does RA effect synovial fluid volume
Increase
Cytokines make vessels more leaky
Roles of activated synovial fibroblasts, b cells, T cells, macrophages, and neutrophils in RA
ACFs - stim osteoclasts and MMP production to degrade cartilage and bone matrix
B cells - mature to plasma cells and produce autoantibodies
T cells - pro inflammatory cytokines
Macrophages - pro inflammatory ctokines and differentiate to osteoclasts
Neutrophils - NETosis, free radical damage
What causes damage to hylauronic acid in RA
Free radical damage by oxygen
