Brainscape's Knowledge GenomeTM

Browse over 1 million classes created by top students, professors, publishers, and experts.


See full index

LOCO 2 > Pathogenesis of RA > Flashcards

Pathogenesis of RA Flashcards

1
Q

How thick is the synovial membrane?

What cells is it made of and what shape are they?

A

1-3 cells thick

Synoviocytes - cuboidal

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

What are the two types of synoviocytes?

A

Type A - bone marrow derived macrophage

Type B - fibroblast-like connective tissue cell

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

Describe the basement membrane and subintima.

A

No basement membrane (to allow plasma to flow through to joint cavity)
Subintima contains dense network of fenestrated capillaries (it is highly vascular) and fat (loose areolar connective tissue to allow plasma to move through subintima).

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

What is synovial fluid?

What does it do?

A

Ultrafiltrate of blood with added hyaluronic acid

Forms a thin film over the articular surfaces

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

What is the benefit of fenestrated capillaries?

A

Leaky so allows plasma out

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

Synovial fluid flows easily in and out of joint due to fenestrated capillaries, no basement membrane and loose areolar connective tissue in the subintima.
What are the disadvantages of this? (2)

A

More easily damaged

Reduced immune surveillance

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

Synovial fluid that is colourless to pale yellow and clear?

A

Normal

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

Synovial fluid that is red/brown?

A

Haemorrhage into joint

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

Synovial fluid that is yellow and cloudy?

A

Inflammation

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

Synovial fluid that is white/creamy and cloudy/shiny?

A

Crystals

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

Synovial fluid that is colourless to yellow and purulent (lumpy)?

A

Bacterial infection

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

What is the pH of synovial fluid?

A

7.38

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

What is synovial fluid composed of? (6)

A 
WBCs
Hyaluronate
Glucose
Protein (60% albumin and 40% globulin)
Ions, lactate etc
Lubricin
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

A small amount of synovial fluid occupies all free spaces between articulating surfaces. How much?

A

Approx 50µm

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

Synovial fluid also seeps into articular cartilages - what is this called?
What is the purpose of this? (3)

A

“Weeping lubrication”
Slippery weight-bearing film - reduces friction between cartilages
Forms reserve volume
Helps nourish articular cartilage

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

Synovial fluid is viscous and gels at rest. Why?

A

Due to the hyaluronan and lubricin

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

What is the synovial fluid response to low/slow frequency movement?

A

Molecules align in the direction of movement

Energy is dissipated as viscous flow

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

What is the synovial fluid response to high/fast frequency movement?

A

Entangled molecular network resists deformation and acts as a shock absorber
Energy is stored as elasticity

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
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.
The tougher the clot, the less hydrolysed the hyaluronic acid. In RA, a solid clot forms in cloudy fluid, whereas in OA the fluid is clear. In gout no clot forms.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
20
Q

What is the string test?

What is the normal string length?

A

You drop the fluid from a pipette and a string forms. The longer the string, the less oedema fluid and the less hydrolysed the hyaluronic acid.
4-6 cm

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
21
Q

What is seen in the synovium in RA?

A

Osteoclasts, fibroblasts, macrophages, dendritic cells, T and B cells, plasma cells, extensive angiogenesis, mast cell and hyperplastic synovial lining.

22
Q

In RA, the synovial membrane becomes infiltrated with various __________ cell types, which synergize to cause ____ __________ .
It is clear that __ ____ are important (in particular, _____ cells) - what do these do?

A 
inflammatory
joint destruction
T cells (TH17) - may orchestrate synovitis and damage through interactions with dendritic cells, macrophages and B cells.
23
Q

What cells’ function seems to be impaired in RA?

A

Regulatory T cells

24
Q

What cells’ presence correlates with symptoms?

A

Macrophages

25
Q

What is the role of B cells in RA? (3)

A

Auto-antibody secretion
Present antigen to T cells
Stimulate synovial fibroblasts through the secretion of cytokines

26
Q

How are fibroblasts involved?

A

They produce joint damage through secretion of MMPs

27
Q

What causes bone damage?

A

The convergence of several signals on osteoclast precursors in the subchondral bone, inducing their differentiation and maturation.

28
Q

Why are synovial joints susceptible to inflammatory injury? (2)

A

Rich network of fenestrated capillaries

Limited ways it can respond

29
Q

CD4 T (helper) lymphocytes collect around small blood vessels, forming…?

A

Lymphoid nodules

30
Q

What is pannus?

A

An abnormal layer of fibrovascular tissue or granulation tissue.
Destructive (secretes cytokines and other signalling molecules) and is involved in the erosion of the articular cartilage and bone, eventually destroying joint.

31
Q

What is central to the pathogenesis of RA?

A

Inflamed synovium

32
Q

The synovium shows increased ________, cellular _________, influx of ___________ cells, changes in the expression of cell surface adhesion molecules, and many cytokines.

A

angiogenesis
hyperplasia
inflammatory

33
Q

The synovial lining becomes ________, with infiltration of the sublining with mononuclear cells including T-cells, B cells, macrophages, and plasma cells.

A

hyperplastic

34
Q

What causes the erosions seen in RA?

A

Formation of locally invasive synovial tissue

35
Q

What cytokines are most abundant in the joint?

A

TNF
IL-1
IL-6

36
Q

What do the cytokines do in RA?

A

Stimulate proliferation, metalloproteinase expression, adhesion molecule expression, and further secretion of other cytokines.

37
Q

Anti-Citrullinated protein antibodies - what do these stimulate?

A

Osteoclast differentiation leading to initial bone loss

38
Q

Synovitis leads to production of…? What do these do? What do they induce the expression of?

A

Cytokines (that stimulate osteoclast proliferation and differentiation, induce expression of RANKL, plus synergize with RANKL to enhance bone erosion). Cytokines induce expression of Dkk-1 by synovial fibroblasts which inhibits directly osteoblast differentiation. Dkk-1 induces expression of another anti-anabolic molecule, sclerostin, by osteocytes.

39
Q

What is established RA characterised by?

A

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

40
Q

The infiltration of what cell is a hallmark of RA pathogenesis?

A

CD4+T-cell (TH17 cells)

41
Q

What do TH17 cells secrete?

A

IL-17

42
Q

What does IL-17 cause? (3)

A

Induces RANKL on synovial fibroblasts
Stimulates local inflammation
Activates synovial macrophages to secrete pro-inflammatory cytokines (TNF, IL-1 and IL-6)

43
Q

What are the most numerous cells in inflammatory synovial effusion, present in synovial fluid in early or active stages of the disease?

A

Neutrophils

44
Q

What do neutrophils mount? What does this mean?

A

A respiratory burst producing the superoxide anion radical. This means more free radical damage.

45
Q

What is the synovial fluid like in RA?

A 
Less viscous (shorter hyaluronic acid strands)
Increased volume (leakier vessels from release of cytokines) - can remove 20ml from knee
46
Q

Summarise the pathogenesis of RA.

A
  1. Activated synovial fibroblasts stimulate osteoclasts and production of MMPs - degrade cartilage and bone matrix
  2. B-cells mature to plasma cells produce auto-antibodies - rheumatoid factors and, Anti-citrullinated antibodies
  3. T-cells produce pro-inflammatory cytokines
  4. Macrophages - produce pro-inflammatory cytokines
47
Q

Describe normal synovial fluid.

Colour, clarity, viscosity, white cell count, % neutrophils, crystals, bacteria

A

Colourless, clear, high (4-6cm string), <150, <5, no, no

48
Q

Describe synovial fluid in OA.

Colour, clarity, viscosity, white cell count, % neutrophils, crystals, bacteria

A

Colourless, clear, high to medium (1-2cm string), 100-2000, <5, 5% have crystals, no

49
Q

Describe synovial fluid in RA.

Colour, clarity, viscosity, white cell count, % neutrophils, crystals, bacteria

A

Yellow, cloudy, low (<1cm string), 2000-50,000, 30-80, no, no

50
Q

Describe synovial fluid in gout.

Colour, clarity, viscosity, white cell count, % neutrophils, crystals, bacteria

A

Yellow, cloudy, low (<1cm string), 5,000 – 50,000, 50-80, yes (urate), no

LOCO 2 (28 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2024 Bold Learning Solutions. Terms and Conditions