Normal and abnormal joints RA

Question 1

What are the names of the cells found in the synovial membrane. There are 2 types of this cell- name and describe them

Answer 1

Synoviocytes

Type A macrophage (from bone marrow)

Type B connective tissue cell (like fibroblasts)

Question 2

Does the synovial membrane contain a basement membrane?

Answer 2

No?

Question 3

What is a subintima? Where is it found?

Answer 3

Where blood vessels for joints are located

Contains dense network fenestrated capillaries
and
fat (loose areolar connective tissue)

Question 4

What is synovial fluid? - state what it is composed of

Answer 4

It is a ultrafiltrated form of blood that contains hyaluronic acid and proteins (albumin and globulin), and lubricin

Question 5

Describe the structure of the synovial membrane

Answer 5

Cuboidal synoviocytes (intimal cells) sitting directly (no basement membrane) on highly vascular subintima with fenestrated capillaries

Question 6

How is synovial fluid produced?

Answer 6

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

Question 7

Synovial fluid flows easily in and out of joint cavity

- name 2 negative downsides of this

Answer 7

The joint cavity is more easily damaged

Fenestrated capillaries already more leaky = immune cells can leave more easily

Question 8

What is the normal colour of synovial fluid?

Answer 8

Colourless to pale yellow and clear

Question 9

What does it mean when synovial fluid is Red/brown, Yellow /cloudy, White/creamy and cloudy/shiny and Colourless to Yellow and purulent (lumpy)?

Answer 9

Red/brown- Haemorrhage into joint

Yellow /cloudy- Inflammation

White/creamy and cloudy/shiny -Crystals

Colourless to Yellow and purulent (lumpy)- Bacterial infection

Question 10

What is weeping lubrication?

Answer 10

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

Question 11

Which components of synovial fluid enable it to be a gel at rest?

Answer 11

Hyaluronan and lubricin

Question 12

Describe the molecular basis for how synovial fluid responds to movement

Answer 12

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

Question 13

What is the mucin clot test?

Answer 13

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

Question 14

How can the mucin test be used to help diagnose different pathological conditions?

Answer 14

Clear fluid + solid clot = Normal osteoarthritis and trauma bleed

Cloudy fluid + solid clot = Lupus, R.A, reiters

No clot = Gout and Gonorrhea

Question 15

What happens tosynovial membrane in the case of rheumatoid arthritis?

Answer 15

Proliferation of synoviocytes

Infiltration of inflammatory cells
Neutrophils – synovial fluid
Lymphocytes – subintima

Proliferation of fibroblasts in subinitima causing thickening

Question 16

Describe the string test used to test synovial fluid

Answer 16

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

Question 17

Why are synovial joints more susceptible to inflammatory injury?

Answer 17

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

Question 18

In the context of RA what is a pannus?

Answer 18

Proliferated synoviocytes with a fibrotic subintima
Contains granulation tissue (fibroblasts and inflammatory cells)
Is destructive and causes the erosion of articular cartilage and bone

Question 19

Describes the mechanism behind bone erosion in RA

Answer 19

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

Question 20

How do T cells cause damage in RA?

Answer 20

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.

Question 21

How is osteoblast differentiation inhibited in OA?

Answer 21

Cytokines induce expression of Dkk-1 by synovial fibroblasts which inhibits osteoblast differentiation

Question 22

How is the synovial fluid changed in the case of RA?

Answer 22

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

Question 23

Describe the pathogenesis if RA

Answer 23

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