Pathogenesis Of Rheumatoid Arthritis

Question 1

2 types of synoviocytes

Answer 1

Type a bone marrow derived macrophage
Type b fibroblast like connective tissue cell

Question 2

Characteristics of synovial membrane basement membrane

Answer 2

No basement membrane

Question 3

What is contained in the sub intima of the synovial membrane

Answer 3

Dense network of Fenestrated capillaries
Fat
Loose areola CT

Question 4

What is synovial fluid

Answer 4

Ultrafiltrate of blood with added hylauronic acid which forms a thin film over articulate surfaces

Question 5

Histological structure of synovial membrane

Answer 5

Synoviocytes sitting directly on highly vascular subintima

Question 6

How is synovial fluid produced

Answer 6

Leaky Fenestrated capillaries allow plasma out

Question 7

Characteristics of synovial membrane that allows plasma/synovial fluid to easily flow in and out between blood membrane and joint cavity

Answer 7

Fenestrated capillaries
Loose areola or CT
No basement membrane between subintima and synoviocytes

Question 8

Normal colour of synovial fluid

Answer 8

Colourless to clear pale yellow
Can read text through

Question 9

What causes red or brown synovial fluid

Answer 9

Haemorrhage into joint

Question 10

What causes yellow cloudy synovial fluid

Answer 10

Inflammation

Question 11

What causes white or cream and cloudy or shimmery synovial fluid

Answer 11

Crystals

Question 12

What causes yellow, purulent, or lumpy synovial fluid

Answer 12

Bacterial infection

Question 13

Synovial fluid pH

Answer 13

7.38

Question 14

How many g/L of hylauronate is in synovial fluid

Answer 14

3g/L

Question 15

Why is synovial fluid thicker at rest and thins on movement

Answer 15

Protects cartilage at start of movement
Hylauronic acid and proteins inc lubricin interact more at rest and detangle on movement

Question 16

How far apart are articulating surfaces kept by synovial fluid

Answer 16

50um

Question 17

What is synovial fluid seeping into articulate cartilage called

Answer 17

Weeping lubrication

Question 18

Purpose of weeping lubrication

Answer 18

Reduce friction
Reserve volume
Nourish articulate cartilage

Question 19

string length of normal synovial fluid and synovial fluid in RA

Answer 19

4-6cm normal
RA <1cm

Question 20

Why is synovial fluid less viscoelastic in RA than normal

Answer 20

Less hylauronic acid

Question 21

Mucin clot test

Answer 21

2-5% acetic acid added to synovial fluid, clot surrounded by clear fluid forms in health, no clot in RA

Question 22

Mucin clot test result in RA

Answer 22

no clot or clot that breaks up easily
Due to less hylauronic acid

Question 23

Features of RA

Answer 23

Synoviocyte proliferation
Infiltration of inflammatory cells
Subintima fibroblast proliferation

Question 24

Do type a or type b synoviocytes proliferate more in RA

Answer 24

Type a

Question 25

Which types of inflammatory cells infiltrate the synovial fluid and subintima in RA

Answer 25

Syn fluid - neutrophils Subintima - lymphocytes

Question 26

Why is the subintima of the synovial membrane thickened in RA

Answer 26

Fibroblast proliferation

Question 27

Why are synovial joints susceptible to inflammatory injury

Answer 27

Fenestrated capillaries so immune cells can easily enter Limited responses

Question 28

Pannus

Answer 28

Inflamed synovial membrane

Question 29

How does pannus cause joint and bone erosion

Answer 29

Secretes cytokines, autoantibodies, and signalling mols that increase Clast activity

Question 30

What forms lymphoid nodules in pannus and where do they form

Answer 30

Collections of Th17 subset of CD4 T lymphocytes Form around small blood vessels

Question 31

What tissue does pannus invade

Answer 31

Bone

Question 32

What molecules lead to bone erosion in RA

Answer 32

Anti citrullinated protein antibodies IL8 RANKL Cytokines from Synovitis DKK1 Sclerostin

Question 33

How does anti citrullinated protein antibodies cause bone erosion

Answer 33

Stimulates osteoclast differentiation

Question 34

Role of IL8 in RA

Answer 34

Produced by osteoclasts Induces more osteoclasts by Autocrine feedback Sensitises nociceptors increasing pain Attracts neutrophils and induces NETosis

Question 35

How do cytokines from Synovitis cause bone erosion

Answer 35

Stimulate osteoclast prolif and differentiation Induce RANKL expression

Question 36

Rheumatoid factor

Answer 36

IgM autoantibody that attacks IgG increasing inflammation

Question 37

Role of IL-17 in RA

Answer 37

secreted by Th17 cells infiltrating joint Induce RANKL on synovial fibroblasts Stim local inflam Activate synovial macrophages to secrete pro inflammatory cytokines

Question 38

How do pro inflammatory cytokines released from pannus switch off the repair mechanism of bone in RA

Answer 38

Induce DKK1 expression by synovial fibroblasts -> inhibit osteoblasts and induces sclerostin expression by osteocytes -> sclerostin inhibits osteoblasts

Question 39

Which cells are most numerous in inflammatory synovial effusion

Answer 39

Neutrophils

Question 40

How do neutrophils increase free radical damage in RA

Answer 40

Cause respiratory burst producing superoxide anion radical

Question 41

How does RA effect synovial fluid volume

Answer 41

Increase Cytokines make vessels more leaky

Question 42

Roles of activated synovial fibroblasts, b cells, T cells, macrophages, and neutrophils in RA

Answer 42

ACFs - stim osteoclasts and MMP production to degrade cartilage and bone matrix B cells - mature to plasma cells and produce autoantibodies T cells - pro inflammatory cytokines Macrophages - pro inflammatory ctokines and differentiate to osteoclasts Neutrophils - NETosis, free radical damage

Question 43

What causes damage to hylauronic acid in RA

Answer 43

Free radical damage by oxygen