Rheumatoid Arthritis 1a Flashcards
Where is synovial membrane located? [1]
A layer of connective tissue that lines the cavities of joints, tendon sheaths, and bursae
What are the two types of synoviocytes [2]
Describe their roles [2]
Which one is more prominent? [1]
Type A bone marrow derived macrophage
Type B fibroblast-like connective tissue cell; make hyaluronic acid - more prominent
Describe the structure of the basement membrane of the synovial membrane [1]
There is no basement membrane
How is synovial fluid produced [1]
Which structures also creates synovial fluid? [2]
Describe the structure of the subintima of the SF [2]
From BV: ultrafiltrate of blood with added hyaluronic acid & lubricin
The subintima is highly vascularised with lots of adipocytes
Which molecules are the most important for causing systemic [1] and within joint [1] effects of rheumatoid arthritis
Systemic: TNF-a
Within the joint: IL-17
Describe the stucture of synovial fluid
- [thick / thin] [1] (Explain)
- colour? [1]
Thick - due to hyaluronic acid
Normal SF is colourless / clear: can read text below it
Synovial fluid anaylsis
What components make SF [3]
Ultrafiltrate of blood
Hyaluronic acid - interacts with proteins like albumin; makes glycoproteic gel
Lubricin
Where does SF come from ? [1]
Synovial fluid is produced due to the fenestrated capillaries surrounding the joint: the semi-permeable fenestrated gaps allow** plasma to leak out into the subintima** but prevents large contents like RBC and WBCs
Synovial fluid of what colour would suggest a bacterial infection
Colourless to pale yellow and clear
Red, brown
Colourless to Yellow and purulent (lumpy)
White/creamy and cloudy/shiny
Yellow and cloudy
Colourless to pale yellow and clear
Red, brown
Colourless to Yellow and purulent (lumpy)
White/creamy and cloudy/shiny
Yellow and cloudy
Which components of synovial fluid structure make glycoproteic gel [3]
hyaluronic acid & glycoproteins (e.g., lubricin) & albumin
Describe how the structure of synovial fluid changes when its in movement [1] and at rest [1]
Viscous at movement:
- molecules align in direction of movement: energy is dissipated as viscous flow
Gels at rest:
- entangled molecular network resists deformation
Perfoming a string test:
How long does normal synoval fluid string before dropping out of pipette? [1]
Normal: 4-6 cm
Describe the mucin clot test [1]
Describe how a patient a healthy patients’’s mucin clot test would present [1]
Describe how a patient with RA’s mucin clot test would present [1]
Mucin clot test:
* Sample of SF into vinegar
* Hyaluronic acid will clot
Healthy:
* Big clot
RA:
* Hyaluronate produced is smaller and not polymerised as long (has less molecular weight), so therefore the clot produced in the mucin clot test will be very loose and not sully solidify.
Describe the pathophysiology of RA [4]
RA is primarily a synovial disease and synovitis (inflammation of the synovial lining) occurs when chemoattractants produced in the joint recruit circulating inflammatory cells
- Over-production of TNF-alpha leads to synovitis
and joint destruction
Type A synoviocytes proliferate:
* increase in number of macrophages
* Early RA: Subintima normal
Infiltration of inflammatory cells:
* Synovial fluid: neutrophils
* Subintima: lymphocytes (CD4 T helpers; dendritic cells; macrophages)
* Both become thicker & more dense
Proliferation of fibroblasts in subinitima causing thickening
Generation of new synovial blood vessels is induced by angiogenic cytokines and activated endothelial cells produce adhesion molecules which FORCE LEUCOCYTES into the synovium - where they can trigger inflammation
The synovium proliferates and grows out over the surface of the cartilage (past the joint margins), producing a tumour-like mass called ‘pannus’
- This pannus of inflamed synovium DAMAGES the underlying cartilage by blocking its normal route for nutrition and by direct effects of cytokines on the chondrocytes
The cartilage becomes thin and the underlying bone exposed
- The pannus DESTROYS the articular cartilage and subchondral bone
resulting in bony erosions
RA pathophysiologyy
Which cells infiltrate the synovial fluid? [1]
Which cells infiltrate the synovial subintima? [1]
- Synovial fluid: neutrophils
- Subintima: lymphocytes
What is a pannus? [1]
Where are pannus created? [1]
What can be the effect of pannus creation ? [2]
Villi like projections caused by proliferation of SF and subintima:
Created at the small microenvironment of bone-cartilage junction
. Concentration of pro-inflammatory cytokines causes increase in osteoclasts and thickening of lining and subintima
Causes synovial membrane to grow over and erode articular cartilage
Describe mechanism of how pannus causes bony erosions [3]
- This pannus of inflamed synovium DAMAGES the underlying cartilage by blocking its normal route for nutrition and by direct effects of cytokines on the chondrocytes
- The cartilage becomes thin and the underlying bone exposed
- The pannus DESTROYS the articular cartilage and subchondral bone
resulting in bony erosions
