9 - Normal and Abnormal Synovial Joint - Pathogenesis of RA

Question 1

How many cells thick is the synovial membrane

Answer 1

1-3 cells thick

Question 2

What type of cell is the synovial membrane made up of

Answer 2

Cuboidal synoviocytes

Question 3

What are type A synoviocytes

Answer 3

Bone marrow derived macrophages

Question 4

What are type B synoviocytes

Answer 4

Fibroblast-like connective tissue cell

They produce hyaluronic acid

Question 5

What is the subintima made up of

Answer 5

Loose areolar connective tissue (fat)

Contains fenestrated capillaries

Question 6

What is synovial fluid

Answer 6

Ultrafiltrate of blood with hyaluronic acid

Question 7

What allows plasma to move through the subintima

Answer 7

The loose areolar CT

Question 8

What allows plasma to flow through to the joint cavity

Answer 8

No basement membrane between subintima and synoviocytes

Question 9

Function of synovial fluid

Answer 9

Gives the joint adequate nutrition and removal of waste products

Question 10

What does normal synovial fluid look like

Answer 10

Colourless - pale yellow

Clear (can read text behind it)

Question 11

Red, Brown synovial fluid

Answer 11

Haemorrhage into the joint

Question 12

Yellow and cloudy synovial fluid

Answer 12

Inflammation

Question 13

White/creamy and cloudy/shiny synovial fluid

Answer 13

Crystals (gout/pseudo gout)

Question 14

Colourless to yellow and purulent (lumpy) synovial fluid

Answer 14

Bacterial infection

Question 15

pH of synovial fluid

Answer 15

7.38

Question 16

WBC of synovial fluid

Answer 16

63mm3

Question 17

Hyaluronate of synovial fluid

Answer 17

0.3g/dl

Question 18

Glucose in synovial fluid

Answer 18

4.0mmol/L

Question 19

Protein in synovial fluid

Answer 19

<3g/dl

Question 20

Distance between articular surfaces

Answer 20

50um

Question 21

What keeps the synovial fluid viscous

Answer 21

Hyaluronan

Lubricin

Question 22

How do you test viscoelastic properties of the synovial fluid

Answer 22

String test

Mucin clot test

Question 23

What is the string test

Answer 23

Normal string - 4-6cm

If longer - less oedema, fluid and hydrolysed the hyaluronic acid is

Question 24

What is the mucin clot test

Answer 24

When 2-5% acetic acid added, normal synovial fluid will form a clot surrounded by clear fluid

Question 25

Basic pathophysiology of Rheumatoid Arthritis

Answer 25

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

Question 26

Where do the neutrophils accumulate in RA

Answer 26

Synovial fluid

Question 27

Where do the lymphocytes accumulate in RA

Answer 27

Subintima

Question 28

Apart from joints, where else in the body can Rheumatoid Arthritis affect?

Answer 28

``` Heart GI Eye Kidney - it is a systemic condition so everywhere! ```

Question 29

What is activated in RA after a trigger?

Answer 29

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

Question 30

What is the function of TH17 cells in RA

Answer 30

Orchestrate synovitis | interact with dendritic cells, B cells and macrophages

Question 31

Function of regulatory T cells in RA

Answer 31

Impaired

Question 32

What do B cells do in RA?

Answer 32

Autoantibody secretion Present antigen to T cells Stimulate synovial fibroblasts through secretion of cytokines e.g lymphotoxin B and TNF

Question 33

How do synovial fibroblasts cause joint damage

Answer 33

Secretion of matrix matalloproteinases (MMPs) and cathepsins

Question 34

What causes the bone damage seen in RA?

Answer 34

Osteoclast differentiation and maturation due to signals in the on osteoclast precursors in the subchondral bone

Question 35

What causes synovial joints to be susceptible to inflammatory injury?

Answer 35

- Rich network of fenestrated capillaries | - Limited ways the joint can respond

Question 36

What tissue does the subintima become in RA?

Answer 36

Dense connective tissue

Question 37

What is pannus

Answer 37

Proliferation of the synovial membrane

Question 38

What is pannus filled with

Answer 38

Lymphocytes

Question 39

What forms around small blood vessels?

Answer 39

Lymphoid nodules

Question 40

Why is pannus destructive to the joint

Answer 40

Grows into the bone Secretes cytokines and signalling molecules Involved in the erosion of the articular cartilage and bone

Question 41

What can stimulates bone erosion and how?

Answer 41

ACPA (Anti-citrullinated protein antibodies) can stimulate osteoclast differentiation to the initial bone - causes you to be more probe to RA

Question 42

What is citrullination

Answer 42

Changing arginine to citruline by deamination by peptidyl arginine deaminase

Question 43

What is established RA characterised by

Answer 43

Presence of large bone erosions filled with inflamed, synovially derived pannus tissue

Question 44

What is Dkk-1 and what induces it?

Answer 44

Cytokines induce Dkk-1 | inhibit osteoblast differentiation in RA by inducing sclerostin

Question 45

What other condition can DKK-1 lead to?

Answer 45

Osteopenia in people with osteoarthritis

Question 46

What is the most numerous cell in inflammatory synovial effusion?

Answer 46

Neutrophils | present in synovial fluid in early/active stages of RA

Question 47

What is the synovial fluid like in RA?

Answer 47

Less viscous | Increased volume