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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

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
Which normal cells are involved in joint damage and hows
Synovial fibroblasts | Through secretion of matrix metalloproteinases and cathepsins
26
Why are synovial joints more susceptible to inflammatory injury
Rich network fenerstrated capillaries | Limited ways it can respond
27
How does a RA appear different to a healthy joint
Thick and fibrotic subintima | Lymphocytes and B cells form aggregates
28
What is pannus
Synovial membrane which is growing and proliferatin | Grows in articular cartilage and underlying bone
29
What bone is the main site of erosion and attack
Subchondral bone
30
How are lymphoid nodules formed
CD4 T cells collect around smaller blood vessels, forming lymphoid nodules
31
How is pannus destructive
Secretes cytokines and other signalling molecules
32
What are ACPAs
Anti-citrullinayed protein antibodies | Stimulate osteoclast differentiation leading to initial bone loss
33
What are the consequences of the synovitis at the beginning of the disease
Leads to production of cytokines which stimulates osteoclast proliferation and differentiation
34
What is the involvement of the RANKL system in RA
Inducing expression of RANLK to enhance bone erosion by more osteoclast differentiation
35
How is established RA characterised
Large bone erosions filled with inflammed, synovially derived pannus tissue
36
What is the most direct hallmark of RA
CD4+ T cell infiltration
37
What is secreted by Th17
IL-17
38
Describe the action of IL-17 in terms of RA
- Induces RANKL on synovial fibroblasts - Stimulates local inflammation - Activates synovial macrophages to secrete proinflam cytokines
39
Name some pro-inflammatory cytokines released by synovial macrophages
TNF IL-1 IL-6
40
What is Dkk-1 expression induced by, and cells cells express it
Cytokines | Expressed by synovial fibroblasts
41
What does dkk-1 do
- Inhibits osteoblast differentation | - Induces expression of another anti-anaboic molecule (scleostin) by osteocytes
42
What cells are seen most in synovial fluid at early disease stage
Neutrophils
43
What do neutrophils do inside the synovial fluid
Mount a respiratory burst producing superoxide anion radical | More free radical damage
44
Is synovial fluid more or less viscous in RA? Why
- Less | - Shorter hyaluronic acid strands
45
Is synovial volume increased or decreased in RA
- Increased | - Leakier vessels from release of cytokines
46
Summarise the 4 steps of RA pathogenesis
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
What auto-antibodies are produced in RA
- Rheumatoid factors and anti-citrullinated ab

LOCO 2 (25 decks)

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