9 - Normal and Abnormal Synovial Joint - Pathogenesis of RA Flashcards
How many cells thick is the synovial membrane
1-3 cells thick
What type of cell is the synovial membrane made up of
Cuboidal synoviocytes
What are type A synoviocytes
Bone marrow derived macrophages
What are type B synoviocytes
Fibroblast-like connective tissue cell
They produce hyaluronic acid
What is the subintima made up of
Loose areolar connective tissue (fat)
Contains fenestrated capillaries
What is synovial fluid
Ultrafiltrate of blood with hyaluronic acid
What allows plasma to move through the subintima
The loose areolar CT
What allows plasma to flow through to the joint cavity
No basement membrane between subintima and synoviocytes
Function of synovial fluid
Gives the joint adequate nutrition and removal of waste products
What does normal synovial fluid look like
Colourless - pale yellow
Clear (can read text behind it)
Red, Brown synovial fluid
Haemorrhage into the joint
Yellow and cloudy synovial fluid
Inflammation
White/creamy and cloudy/shiny synovial fluid
Crystals (gout/pseudo gout)
Colourless to yellow and purulent (lumpy) synovial fluid
Bacterial infection
pH of synovial fluid
7.38
WBC of synovial fluid
63mm3
Hyaluronate of synovial fluid
0.3g/dl
Glucose in synovial fluid
4.0mmol/L
Protein in synovial fluid
<3g/dl
Distance between articular surfaces
50um
What keeps the synovial fluid viscous
Hyaluronan
Lubricin
How do you test viscoelastic properties of the synovial fluid
String test
Mucin clot test
What is the string test
Normal string - 4-6cm
If longer - less oedema, fluid and hydrolysed the hyaluronic acid is
What is the mucin clot test
When 2-5% acetic acid added, normal synovial fluid will form a clot surrounded by clear fluid
Basic pathophysiology of Rheumatoid Arthritis
1) Proliferation of synoviocytes
2) Infiltration of inflammatory cells e.g Neutrophils and Lymphocytes
3) Proliferation of fibroblasts in subintima cause thickening
Increase of synovial fluid and increase in osteoclasts
Where do the neutrophils accumulate in RA
Synovial fluid
Where do the lymphocytes accumulate in RA
Subintima
Apart from joints, where else in the body can Rheumatoid Arthritis affect?
Heart GI Eye Kidney - it is a systemic condition so everywhere!
What is activated in RA after a trigger?
1) T cells are activated
2) T cells produce TH17 (t helper cell)
3) TH17 produces 1L1, IL6, TNFa and B cells (autoantibodies such as RF)
4) Induces osteoclast differentiation and maturation
Joint destruction
What is the function of TH17 cells in RA
Orchestrate synovitis
interact with dendritic cells, B cells and macrophages
Function of regulatory T cells in RA
Impaired
What do B cells do in RA?
Autoantibody secretion
Present antigen to T cells
Stimulate synovial fibroblasts through secretion of cytokines e.g lymphotoxin B and TNF
How do synovial fibroblasts cause joint damage
Secretion of matrix matalloproteinases (MMPs) and cathepsins
What causes the bone damage seen in RA?
Osteoclast differentiation and maturation due to signals in the on osteoclast precursors in the subchondral bone
What causes synovial joints to be susceptible to inflammatory injury?
- Rich network of fenestrated capillaries
- Limited ways the joint can respond
What tissue does the subintima become in RA?
Dense connective tissue
What is pannus
Proliferation of the synovial membrane
What is pannus filled with
Lymphocytes
What forms around small blood vessels?
Lymphoid nodules
Why is pannus destructive to the joint
Grows into the bone
Secretes cytokines and signalling molecules
Involved in the erosion of the articular cartilage and bone
What can stimulates bone erosion and how?
ACPA (Anti-citrullinated protein antibodies) can stimulate osteoclast differentiation to the initial bone
- causes you to be more probe to RA
What is citrullination
Changing arginine to citruline by deamination by peptidyl arginine deaminase
What is established RA characterised by
Presence of large bone erosions filled with inflamed, synovially derived pannus tissue
What is Dkk-1 and what induces it?
Cytokines induce Dkk-1
inhibit osteoblast differentiation in RA by inducing sclerostin
What other condition can DKK-1 lead to?
Osteopenia in people with osteoarthritis
What is the most numerous cell in inflammatory synovial effusion?
Neutrophils
present in synovial fluid in early/active stages of RA
What is the synovial fluid like in RA?
Less viscous
Increased volume
