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LOCO 2 > Rheumatoid Arthritis > Flashcards

Rheumatoid Arthritis Flashcards

1
Q

How many cells thick is the synovium

A

1-3 cells

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2
Q

3 cell types that make up the synovium

A

Synoviocytes
Type A bone marrow derived macrophages
Type B fibroblast like connective tissue

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3
Q

What is synovial fluid

A

An ultrafiltrate of blood with added hyaluronic acid

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4
Q

What is the subintima

A

Contains the dense network of fenestrated capillaries and loose areolar connective tissue

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5
Q

What shape are synoviocytes/ intimal cells

A

Cuboidal

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6
Q

Is the subintima highly vascular

A

Yes

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7
Q

Name 3 mechanisms/ structures than ensure the proper production of synovial fluid

A
  • Fenestrated capillaries
  • Loose areolar connective tissue ensuring plasma can move through subintima
  • No basement membrane between subintima and synoviocytes allow plasma to flow through joint cavity
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8
Q

What are the consequences of synovial fluid being able to flow in and out the joint cavity easily

A

More easily damaged

Reduced immune surveillance

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9
Q

What does it mean if synovial fluid is colourless to pale yellow

A

Normal/ no pathology

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10
Q

What does it mean if synovial fluid is red/ brown

A

Haemorrhage into joint

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11
Q

What does it mean if synovial fluid is yellow and cloudly

A

Inflammation

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12
Q

What does it mean if synovial fluid is white/ creamy and cloudy/shiny

A

Crystals

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13
Q

What does it mean if synovial fluid is colourless to yellow and purulent

A

Bacterial infection

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14
Q

What is the ph of synovial fluid

A

7.38

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15
Q

What proteins are found in synovial fluid

A

Albumin (60%) and globulin (40)

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16
Q

Name the molecules found in synovial fluid

A 
WBC
Hyaluronate
Glucose
Protein
Ions, lactate
Lubricin
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17
Q

Where is synovial fluid found

A

Occupies free space between articulating surfaces

Seeps into articular cartilages- weeping lubrication

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18
Q

What is the function of the synovial fluid in the articular cartilages

A

Reduces friction
Forms reserve volume
Nourishes articular cartilage

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19
Q

How does synovial fluid appear at rest

A

Gel

20
Q

What molecules enable synovial fluid to gel

A

Lubricin and hyaluronan

21
Q

3 pathological aspects of rheymatoid athritis

A

Proliferation of synoviocytes
Infiltration of inflammatory cells
Proliferation of fibroblasts in subintima causing thickening

22
Q

What inflammatory cells infilitrate in RA and where

A

Neutrophils infilitrate the synovial fluid

Lymphocytes infilitrate subintima

23
Q

What T cells and thought to be involved in RA and hoq

A

Th17 cells

Orchestrate synovitis and damage through interactions with dendritic cells, macrophages and B cells

24
Q

What evidence is there for B cell involvement in RA

A

B cell antibody therapy appears succesful

25
Q

Which normal cells are involved in joint damage and hows

A

Synovial fibroblasts

Through secretion of matrix metalloproteinases and cathepsins

26
Q

Why are synovial joints more susceptible to inflammatory injury

A

Rich network fenerstrated capillaries

Limited ways it can respond

27
Q

How does a RA appear different to a healthy joint

A

Thick and fibrotic subintima

Lymphocytes and B cells form aggregates

28
Q

What is pannus

A

Synovial membrane which is growing and proliferatin

Grows in articular cartilage and underlying bone

29
Q

What bone is the main site of erosion and attack

A

Subchondral bone

30
Q

How are lymphoid nodules formed

A

CD4 T cells collect around smaller blood vessels, forming lymphoid nodules

31
Q

How is pannus destructive

A

Secretes cytokines and other signalling molecules

32
Q

What are ACPAs

A

Anti-citrullinayed protein antibodies

Stimulate osteoclast differentiation leading to initial bone loss

33
Q

What are the consequences of the synovitis at the beginning of the disease

A

Leads to production of cytokines which stimulates osteoclast proliferation and differentiation

34
Q

What is the involvement of the RANKL system in RA

A

Inducing expression of RANLK to enhance bone erosion by more osteoclast differentiation

35
Q

How is established RA characterised

A

Large bone erosions filled with inflammed, synovially derived pannus tissue

36
Q

What is the most direct hallmark of RA

A

CD4+ T cell infiltration

37
Q

What is secreted by Th17

A

IL-17

38
Q

Describe the action of IL-17 in terms of RA

A
  • Induces RANKL on synovial fibroblasts
  • Stimulates local inflammation
  • Activates synovial macrophages to secrete proinflam cytokines
39
Q

Name some pro-inflammatory cytokines released by synovial macrophages

A

TNF
IL-1
IL-6

40
Q

What is Dkk-1 expression induced by, and cells cells express it

A

Cytokines

Expressed by synovial fibroblasts

41
Q

What does dkk-1 do

A
  • Inhibits osteoblast differentation

- Induces expression of another anti-anaboic molecule (scleostin) by osteocytes

42
Q

What cells are seen most in synovial fluid at early disease stage

A

Neutrophils

43
Q

What do neutrophils do inside the synovial fluid

A

Mount a respiratory burst producing superoxide anion radical

More free radical damage

44
Q

Is synovial fluid more or less viscous in RA? Why

A
  • Less

- Shorter hyaluronic acid strands

45
Q

Is synovial volume increased or decreased in RA

A
  • Increased

- Leakier vessels from release of cytokines

46
Q

Summarise the 4 steps of RA pathogenesis

A

1) Activated synovial fibroblasts stimulate osteoclasts and produce MMP
2) B cells mature to plasma cells, producing auto-antibodies
3) T cells produce pro-inflammatory cytokines
4) Macrophages produce pro-inflammatory cytokines

47
Q

What auto-antibodies are produced in RA

A
  • Rheumatoid factors and anti-citrullinated ab

LOCO 2 (25 decks)

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