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LOCO2 > Pathogenesis of RA > Flashcards

Pathogenesis of RA Flashcards

1
Q

What does the synovial membrane contain?

A
  • cuboidal synoviocytes
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2
Q

What are cuboidal synoviocytes?

A
  • type A and B
  • A = bone marrow derived macrophages (immune cells)
  • B = fibroblast like CT cells (make up majority, produce hyaluronic acid)
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3
Q

What is the subintima?

A
  • loose CT so fluid moves easily through
  • dense fenestrated capillary network so synovial fluid leaves to enter cavity
  • below synovial membrane, no basement membrane between
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4
Q

What is synovial fluid?

A
  • ultrafiltrate of blood plasma from fenestrated capillaries + hyaluronic acid from type B synoviocytes
  • flows in and out of joint cavity
  • constantly replaced
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5
Q

What is the function of synovial fluid?

A
  • nourishes cartilage cells and synoviocytes
  • removes CO2
  • reduces friction between cartilages
  • forms reserve volume
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6
Q

What are the disadvantages of loose membrane?

A
  • more easily damaged

- reduced immune surveillance (hard to remove material)

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7
Q

What does synovial fluid normally look like?

A
  • colourless to pale yellow and clear
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8
Q

What does synovial fluid look like when there is a haemorrhage in the joint?

A

Red/brown colour

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9
Q

What does synovial fluid look like when there is inflammation?

A

Yellow and cloudy

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10
Q

What does synovial fluid look like in a bacterial infection?

A

Colourless to yellow and purulent

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11
Q

What does synovial fluid contain?

A
  • WBC
  • hyaluronate
  • glucose
  • protein (abumin and globulin)
  • lubricin
  • ions/lactate
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12
Q

How is synovial fluid hydrophobic?

A
  • hyaluronate interacts with albumin and globulin

- more hyaluronate = more viscous

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13
Q

How is synovial fluid viscoelastic?

A
  • thixotropic = viscosity not constant

- when resting viscosity is greater (more interaction between hyaluronate and proteins)

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14
Q

What are the 2 synovial fluid tests?

A
  • string test

- mucin clot test

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15
Q

What is the string test?

A
  • normally 4-6cm string per drop of synovial fluid from syringe
  • inflammation = decreased viscosity so smaller string as hyaluronate is shorter sections
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16
Q

What is the mucin clot test?

A
  • add acetic acid to synovial fluid
  • normally forms a clot surrounded by clear fluid
  • inflammation = clot soft and hyaluronate not formed
17
Q

What structural changes to synovial fluid are there in rheumatoid arthritis?

A
  • proliferation of synoviocytes
  • infiltration of inflammatory cells (T cells, neutrophils into fluid, lymphocytes into membrane)
  • proliferation of fibroblasts in subintima causes thickening
18
Q

Why are synovial joints susceptible to inflammatory injury?

A
  • rich fenestrated capillary network

- limited responses (pro-inflammatory cytokines induce proliferation and osteoclast differentiation)

19
Q

What is pannus?

A
  • end destructive synovial membrane
  • joint erosion at joint margin
  • makes joint unstable and destroys it
  • due to inflammation and synovium proliferation
  • grows over into cartilage and bone
  • secretes cytokines
  • syvonectomy to remove but will regrow as disease progress continues
20
Q

What are ACPA?

A

Anti-citrullinated protein antibodies

  • made by B cells
  • directly stimulate osteoclast differentiation which produce IL8 to induce more osteoclasts via autocrine feedback
  • leads to bone loss
21
Q

What is the function of IL8?

A
  • produced by osteoclasts to induce more osteoclasts via autocrine feedback
  • sensitises nociceptors = increased pain
22
Q

What is established RA characterised by?

A
  • large bone erosions filled with inflamed synovial derived pannus tissues
23
Q

What does synovitis lead to in RA?

A
  • production of cytokines stimulating osteoclast prolif and diff.
  • this induces RANKL expression enhancing bone erosion
24
Q

What is a hallmark of RA pathogenesis?

A

Th17 cells

CD4+ T cell infiltration

25
Q

What do Th17 cells do?

A

secrete lots of IL-17 which:

  • induces RANKL on synovial fibroblasts
  • stimulates local inflammation
  • activates synovial macrophages to secrete proinflammatory cytokines -> induce Dkk-1 expression by synovial fibroblasts
26
Q

What is Dkk-1?

A
  • inhibits osteoblast differentiation

- induces sclerostin expression

27
Q

How does synovial fluid change in RA?

A
  • neutrophils most numerous cells
  • produce superoxide anion radical = free radical damage
  • less viscous as shorter hyaluronate strands
  • increased volume as leaker vessels from cytokines release
28
Q

What do B cells do?

A
  • produce auto-antibodies (rheumatoid factor and ACPA)
29
Q

What do T cells do?

A
  • produce pro-inflammatory cytokines which orchestrate synovitis and systemic symptoms
30
Q

What do macrophages do?

A
  • produce pro-inflammatory cytokines

- can differentiate into osteoclasts

LOCO2 (26 decks)

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