Normal and abnormal joints RA Flashcards
(23 cards)
What are the names of the cells found in the synovial membrane. There are 2 types of this cell- name and describe them
Synoviocytes
Type A macrophage (from bone marrow)
Type B connective tissue cell (like fibroblasts)
Does the synovial membrane contain a basement membrane?
No?
What is a subintima? Where is it found?
Where blood vessels for joints are located
Contains dense network fenestrated capillaries
and
fat (loose areolar connective tissue)
What is synovial fluid? - state what it is composed of
It is a ultrafiltrated form of blood that contains hyaluronic acid and proteins (albumin and globulin), and lubricin
Describe the structure of the synovial membrane
Cuboidal synoviocytes (intimal cells) sitting directly (no basement membrane) on highly vascular subintima with fenestrated capillaries
How is synovial fluid produced?
Fenestrated capillaries
Leaky allows plasma out
Loose areolar connective tissue allows plasma to move through subintima
No basement membrane between subintima and synoviocytes allows plasma to flow through to joint cavity
Synovial fluid flows easily in and out of joint cavity
- name 2 negative downsides of this
The joint cavity is more easily damaged
Fenestrated capillaries already more leaky = immune cells can leave more easily
What is the normal colour of synovial fluid?
Colourless to pale yellow and clear
What does it mean when synovial fluid is Red/brown, Yellow /cloudy, White/creamy and cloudy/shiny and Colourless to Yellow and purulent (lumpy)?
Red/brown- Haemorrhage into joint
Yellow /cloudy- Inflammation
White/creamy and cloudy/shiny -Crystals
Colourless to Yellow and purulent (lumpy)- Bacterial infection
What is weeping lubrication?
When synovial fluid seeps into articular cartilage
It produces a Slippery weight-bearing film which reduces friction between cartilages
Forms reserve volume
Helps nourish articular cartilage
Which components of synovial fluid enable it to be a gel at rest?
Hyaluronan and lubricin
Describe the molecular basis for how synovial fluid responds to movement
Low/slow frequency movement - Hyaluronan chain molecules align in the direction of movement
- energy is dissipated as viscous flow
High/fast frequency movement
- hyaluronan and globular proteins form entangled molecular network acts as a shock absorber
Energy is stored as elasticity
What is the mucin clot test?
A tests that involves adding acetic acid to synovial fluid. What should happen - a clot of hyaluronic acid should form surrounded by clear fluid
Tough the clot, less hydrolyzed the hyaluronic acid is
How can the mucin test be used to help diagnose different pathological conditions?
Clear fluid + solid clot = Normal osteoarthritis and trauma bleed
Cloudy fluid + solid clot = Lupus, R.A, reiters
No clot = Gout and Gonorrhea
What happens tosynovial membrane in the case of rheumatoid arthritis?
Proliferation of synoviocytes
Infiltration of inflammatory cells
Neutrophils – synovial fluid
Lymphocytes – subintima
Proliferation of fibroblasts in subinitima causing thickening
Describe the string test used to test synovial fluid
synovial fluid is normally viscous and when dripped from a pipette forms a string. Normal is 4-6cm
<3cm – low viscosity due to reduced hyaluronan and reduced polymerisation in inflammatory condition and infection
Why are synovial joints more susceptible to inflammatory injury?
Presence of rich network of fenestrated capillaries,
Are more leaky to begin with
Limited ways it can respond
Pro-inflammatory cytokines induce proliferation and/or direct osteoclast differentiation
In the context of RA what is a pannus?
Proliferated synoviocytes with a fibrotic subintima
Contains granulation tissue (fibroblasts and inflammatory cells)
Is destructive and causes the erosion of articular cartilage and bone
Describes the mechanism behind bone erosion in RA
Anti-Citrullinated protein antibodies (ACPA) can stimulate osteoclast differentiation from monocytes leading to initial bone loss
Osteoclasts produce IL8 that induces more osteoclasts by autocrine feedback
Synovitis - inflammation of synovial tissue leads to production of cytokines, which stimulate osteoclast proliferation and differentiation
Inducing expression of RANKL to enhance bone erosion by more osteoclast differentiation
How do T cells cause damage in RA?
CD4 T (helper) lymphocytes collect around small blood vessels, forming lymphoid nodules.
CD4+T-cell infiltration is a hallmark of RA pathogenesis (TH17 cells)
TH17 cells secrete lots of IL-17,
TH17-
induces RANKL on synovial fibroblasts
stimulates local inflammation
activates synovial macrophages to secrete proinflammatory cytokines, such as TNF, IL-1 and IL-6.
How is osteoblast differentiation inhibited in OA?
Cytokines induce expression of Dkk-1 by synovial fibroblasts which inhibits osteoblast differentiation
How is the synovial fluid changed in the case of RA?
It is infiltrated with immune cells the most numerous being neutrophils
Neutrophils cause free radical damage
Synovial fluid is less viscous
Shorter hyaluronic acid strands
Increased volume
Leakier vessels from release of cytokines
Normal knee 2 ml in RA can remove 20ml from knee
Describe the pathogenesis if RA
Activated synovial fibroblasts stimulate osteoclasts and production of MMPs
Degrade cartilage and bone matrix
B-cells mature to plasma cells produce auto-antibodies
Rheumatoid factors and, Anti-citrullinated antibodies
T-cells
Produce pro-inflammatory cytokines that orchestrate synovitis and systemic symptoms
Macrophages
Produce pro-inflammatory cytokines
Can differentiate into osteoclasts
Neutrophils
NETosis (apoptosis) degranulation activate B-cells and release PAD modified citrullinated peptides
Reactive oxygen directly damages hyaluronic acid
