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LOCO > 9 - Normal and Abnormal Synovial Joint - Pathogenesis of RA > Flashcards

9 - Normal and Abnormal Synovial Joint - Pathogenesis of RA Flashcards

1
Q

How many cells thick is the synovial membrane

A

1-3 cells thick

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2
Q

What type of cell is the synovial membrane made up of

A

Cuboidal synoviocytes

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3
Q

What are type A synoviocytes

A

Bone marrow derived macrophages

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4
Q

What are type B synoviocytes

A

Fibroblast-like connective tissue cell

They produce hyaluronic acid

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5
Q

What is the subintima made up of

A

Loose areolar connective tissue (fat)

Contains fenestrated capillaries

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6
Q

What is synovial fluid

A

Ultrafiltrate of blood with hyaluronic acid

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7
Q

What allows plasma to move through the subintima

A

The loose areolar CT

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8
Q

What allows plasma to flow through to the joint cavity

A

No basement membrane between subintima and synoviocytes

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9
Q

Function of synovial fluid

A

Gives the joint adequate nutrition and removal of waste products

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10
Q

What does normal synovial fluid look like

A

Colourless - pale yellow

Clear (can read text behind it)

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11
Q

Red, Brown synovial fluid

A

Haemorrhage into the joint

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12
Q

Yellow and cloudy synovial fluid

A

Inflammation

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13
Q

White/creamy and cloudy/shiny synovial fluid

A

Crystals (gout/pseudo gout)

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14
Q

Colourless to yellow and purulent (lumpy) synovial fluid

A

Bacterial infection

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15
Q

pH of synovial fluid

A

7.38

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16
Q

WBC of synovial fluid

A

63mm3

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17
Q

Hyaluronate of synovial fluid

A

0.3g/dl

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18
Q

Glucose in synovial fluid

A

4.0mmol/L

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19
Q

Protein in synovial fluid

A

<3g/dl

20
Q

Distance between articular surfaces

A

50um

21
Q

What keeps the synovial fluid viscous

A

Hyaluronan

Lubricin

22
Q

How do you test viscoelastic properties of the synovial fluid

A

String test

Mucin clot test

23
Q

What is the string test

A

Normal string - 4-6cm

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

24
Q

What is the mucin clot test

A

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

25
Q

Basic pathophysiology of Rheumatoid Arthritis

A

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

26
Q

Where do the neutrophils accumulate in RA

A

Synovial fluid

27
Q

Where do the lymphocytes accumulate in RA

A

Subintima

28
Q

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

A 
Heart
GI
Eye
Kidney
- it is a systemic condition so everywhere!
29
Q

What is activated in RA after a trigger?

A

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

30
Q

What is the function of TH17 cells in RA

A

Orchestrate synovitis

interact with dendritic cells, B cells and macrophages

31
Q

Function of regulatory T cells in RA

A

Impaired

32
Q

What do B cells do in RA?

A

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

33
Q

How do synovial fibroblasts cause joint damage

A

Secretion of matrix matalloproteinases (MMPs) and cathepsins

34
Q

What causes the bone damage seen in RA?

A

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

35
Q

What causes synovial joints to be susceptible to inflammatory injury?

A
  • Rich network of fenestrated capillaries

- Limited ways the joint can respond

36
Q

What tissue does the subintima become in RA?

A

Dense connective tissue

37
Q

What is pannus

A

Proliferation of the synovial membrane

38
Q

What is pannus filled with

A

Lymphocytes

39
Q

What forms around small blood vessels?

A

Lymphoid nodules

40
Q

Why is pannus destructive to the joint

A

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

41
Q

What can stimulates bone erosion and how?

A

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

42
Q

What is citrullination

A

Changing arginine to citruline by deamination by peptidyl arginine deaminase

43
Q

What is established RA characterised by

A

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

44
Q

What is Dkk-1 and what induces it?

A

Cytokines induce Dkk-1

inhibit osteoblast differentiation in RA by inducing sclerostin

45
Q

What other condition can DKK-1 lead to?

A

Osteopenia in people with osteoarthritis

46
Q

What is the most numerous cell in inflammatory synovial effusion?

A

Neutrophils

present in synovial fluid in early/active stages of RA

47
Q

What is the synovial fluid like in RA?

A

Less viscous

Increased volume

LOCO (25 decks)

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