Rheumatoid Arthritis Flashcards
How many cells thick is the synovium
1-3 cells
3 cell types that make up the synovium
Synoviocytes
Type A bone marrow derived macrophages
Type B fibroblast like connective tissue
What is synovial fluid
An ultrafiltrate of blood with added hyaluronic acid
What is the subintima
Contains the dense network of fenestrated capillaries and loose areolar connective tissue
What shape are synoviocytes/ intimal cells
Cuboidal
Is the subintima highly vascular
Yes
Name 3 mechanisms/ structures than ensure the proper production of synovial fluid
- Fenestrated capillaries
- Loose areolar connective tissue ensuring plasma can move through subintima
- No basement membrane between subintima and synoviocytes allow plasma to flow through joint cavity
What are the consequences of synovial fluid being able to flow in and out the joint cavity easily
More easily damaged
Reduced immune surveillance
What does it mean if synovial fluid is colourless to pale yellow
Normal/ no pathology
What does it mean if synovial fluid is red/ brown
Haemorrhage into joint
What does it mean if synovial fluid is yellow and cloudly
Inflammation
What does it mean if synovial fluid is white/ creamy and cloudy/shiny
Crystals
What does it mean if synovial fluid is colourless to yellow and purulent
Bacterial infection
What is the ph of synovial fluid
7.38
What proteins are found in synovial fluid
Albumin (60%) and globulin (40)
Name the molecules found in synovial fluid
WBC Hyaluronate Glucose Protein Ions, lactate Lubricin
Where is synovial fluid found
Occupies free space between articulating surfaces
Seeps into articular cartilages- weeping lubrication
What is the function of the synovial fluid in the articular cartilages
Reduces friction
Forms reserve volume
Nourishes articular cartilage
How does synovial fluid appear at rest
Gel
What molecules enable synovial fluid to gel
Lubricin and hyaluronan
3 pathological aspects of rheymatoid athritis
Proliferation of synoviocytes
Infiltration of inflammatory cells
Proliferation of fibroblasts in subintima causing thickening
What inflammatory cells infilitrate in RA and where
Neutrophils infilitrate the synovial fluid
Lymphocytes infilitrate subintima
What T cells and thought to be involved in RA and hoq
Th17 cells
Orchestrate synovitis and damage through interactions with dendritic cells, macrophages and B cells
What evidence is there for B cell involvement in RA
B cell antibody therapy appears succesful
Which normal cells are involved in joint damage and hows
Synovial fibroblasts
Through secretion of matrix metalloproteinases and cathepsins
Why are synovial joints more susceptible to inflammatory injury
Rich network fenerstrated capillaries
Limited ways it can respond
How does a RA appear different to a healthy joint
Thick and fibrotic subintima
Lymphocytes and B cells form aggregates
What is pannus
Synovial membrane which is growing and proliferatin
Grows in articular cartilage and underlying bone
What bone is the main site of erosion and attack
Subchondral bone
How are lymphoid nodules formed
CD4 T cells collect around smaller blood vessels, forming lymphoid nodules
How is pannus destructive
Secretes cytokines and other signalling molecules
What are ACPAs
Anti-citrullinayed protein antibodies
Stimulate osteoclast differentiation leading to initial bone loss
What are the consequences of the synovitis at the beginning of the disease
Leads to production of cytokines which stimulates osteoclast proliferation and differentiation
What is the involvement of the RANKL system in RA
Inducing expression of RANLK to enhance bone erosion by more osteoclast differentiation
How is established RA characterised
Large bone erosions filled with inflammed, synovially derived pannus tissue
What is the most direct hallmark of RA
CD4+ T cell infiltration
What is secreted by Th17
IL-17
Describe the action of IL-17 in terms of RA
- Induces RANKL on synovial fibroblasts
- Stimulates local inflammation
- Activates synovial macrophages to secrete proinflam cytokines
Name some pro-inflammatory cytokines released by synovial macrophages
TNF
IL-1
IL-6
What is Dkk-1 expression induced by, and cells cells express it
Cytokines
Expressed by synovial fibroblasts
What does dkk-1 do
- Inhibits osteoblast differentation
- Induces expression of another anti-anaboic molecule (scleostin) by osteocytes
What cells are seen most in synovial fluid at early disease stage
Neutrophils
What do neutrophils do inside the synovial fluid
Mount a respiratory burst producing superoxide anion radical
More free radical damage
Is synovial fluid more or less viscous in RA? Why
- Less
- Shorter hyaluronic acid strands
Is synovial volume increased or decreased in RA
- Increased
- Leakier vessels from release of cytokines
Summarise the 4 steps of RA pathogenesis
1) Activated synovial fibroblasts stimulate osteoclasts and produce MMP
2) B cells mature to plasma cells, producing auto-antibodies
3) T cells produce pro-inflammatory cytokines
4) Macrophages produce pro-inflammatory cytokines
What auto-antibodies are produced in RA
- Rheumatoid factors and anti-citrullinated ab