Rheumatoid Arthritis Pathophysiology Flashcards

1
Q

Signs of RA?

A

Morning stiffness
Swelling, heat, redness and pain,
Loss of function
Multiple joints in a symmetrical fashion

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2
Q

Features of RA?

A

3x more women than men

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3
Q

Prevalence?

A

Affects 1%

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4
Q

Autoantibodies?

A

Cyclic citrulinated peptide and rheumatoid factor

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5
Q

Cytokines in RA?

A

IL 1/ 6 and TNF alpha
IL6 triggers liver for acute phase response
And stimulates adipocytes leading to diabetes

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6
Q

Comorbidities of RA?

A
MI 
Stroke
Atherogenesis
Low stress tolerance 
Depression 
Fractures
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7
Q

Where do the antibodies bind?

A

Fc portion of igM, igG

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8
Q

Autoantibodies are found in how many patients?

A

60-70%

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9
Q

How specific are the antibodies for RA?

A

86%

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10
Q

Patients positive with the antibodies are….?

A

Have a more severe disease

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11
Q

Antibodies against CCp are found in patients percentage?

A

70-80%

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12
Q

Antibodies detect?

A

Arginine to citrulline change

Fibronectin, collagen

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13
Q

Mechanism of anti citrullinated antibodies?

A

Activation of inflammatory cells by anti CCP immune complexes
Bind to osteoclast
Producing NETs

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14
Q

Monozygotic identicals getting RA?

A

12-15%

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15
Q

Dizygotic non-identical chances of getting RA?

A

2-5%

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16
Q

Genes associated?

A

HLA DRB1 SE- 30-50% of the overall genetic risk
PTPN22- tyrosine phosphatase
CTLA4, downregulated
A20 downregulated, which normally inhibits NF-kB and TNF alpha mediated apoptosis

17
Q

Environmental factors?

A

Men who have lower testosterone, usually get RA
RA patients often experience remission during pregnancy
Early menopause- RF positive
Oral contraception- decrease of antibodies/ HRT

18
Q

Smoking association?

A

Increased risk, if you have HLA-DR4

Also smoking with HLA DRB1- increases risk of anti- CCP

19
Q

Periodontitis?

A

If you have gum disease, more likely to get RA
P gingivalis can citrullinate our proteins, and if you have the HLA DRB1 then you present through ACPs to activated T cells.

20
Q

Synovitis?

A
Swelling over extensor tendons, wrist and MCP
Synovial hyperplasia ( increase number in cells)
Synovial fibroblasts, sticking to bone and reduced apoptosis
21
Q

What happens in a rheumatoid joint?

A

Synovial membrane becomes thickened- pan us
Immune cells coming from blood and within the synovial fluid, neutrophils doing NETosis
Thinning of cartilage
Fibroblasts grow into places and infiltrate into the bone

22
Q

Molecular members of inflammation present?

A

Macrophages 40%

Fibroblasts and endothelial cells 10-15%

23
Q

Pro inflammatory cytokines?

A

IL 1, 6, 17 and TNF alpha

24
Q

How does cartilage erosion happen?

A

Chondrocytes undergo apoptosis
Fibroblasts adhere to and invade the cartilage
Fibroblasts make matrix metalloproteases, breaking down the cartilage

25
Q

Osteoclasts are activated by?

A

RANKL IL17 TNF alpha IL1 and 6

26
Q

In a year how many RA patients develop resorption pits?

A

80%

27
Q

What do NETs release?

A

Citrullinated proteins

28
Q

TH 17 cause?

A

Release IL 17, favour cartilage resorption

And activate synovial fibroblasts and osteoclasts

29
Q

T regulatory cells are not working due to presence of?

A

TNF

30
Q

Treatment through B cells

A

Anti CD20

31
Q

Most therapies lead?

A

Macrophage cytokine production