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PHA223 > Rheumatiod Arthritis 1 (SD) > Flashcards

Rheumatiod Arthritis 1 (SD) Flashcards

1
Q

What type of disorder is RA?

A

chronic autoimmune inflammatory disorder

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2
Q

Where does RA occur?

A

within synovial joints

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3
Q

symptoms of RA

A

pain
swelling
stiffness
joint erosion and destruction

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4
Q

What other places does RA affect? (inflammation elsewhere)

A 
blood vessels
bone marrow
GI tract
lungs
eyes
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5
Q

What causes mortality with RA?

A

cardiovascular disease

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6
Q

When is symptom onset of RA?

A

> 25 years of age

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7
Q

male:female

A

1:2.7

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8
Q

swelling

A

synovial tissue in caps of joints becomes damaged causing tissue to thicken and swell

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9
Q

stiffness

A

inflammed joints stiffen and are difficult to move correctly
especially in mornings or after long rest
can last for hours

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10
Q

pain

A

cartilage and bone within the joints will wear down over time
muscles, ligaments and tendons weaken and no longer stabilise joints
causes intense pain and joint damage

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11
Q

redness

A

joints can be warm

may appear pink/red on the outside during flare/when inflammed

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12
Q

What are the 3 bones in the finger called?

A

distal phalanx
middle phalanx
proximal phalanx

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13
Q

What are the 3 joints in the fingers called?

A

distal interphalangeal joint - DIP
proximal interphalangeal joint - PIP
metacarpophalangeal joint - MCP

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14
Q

symptoms in early stage RA

A

ulnar deviation - hand less straight, inflammation in metacarpal region
boutonniere deformity - DIP hyperextended and PIP flexed (bend)
swan-neck deformity - DIP flexed and PIP hyperextended

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15
Q

healthy bone/joint

A

articular cartilage provides a lubricated surface for the opposing bones
synovial membrane produces/contains synovial fluid
synovial fluid provides lubrication and removes debris

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16
Q

What are autoantigens?

A

antigens produced by the body that are attacked by the immune system

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17
Q

What do autoantigens cause?

A

an immune response

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18
Q

What genes regulate the immune system?

A

human leukocyte antigen (HLA)

genes on chromosone 6

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19
Q

What are HLA genes part of?

A

MHC 1 and MHC 2 complex

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20
Q

at risk patients related to HLA genes

A

patients with alterations to HLA-DR1 and HLA-DR4 alleles at increased risk of RA

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21
Q

mutation of what is involved in activation of inflammatory cells

A

PTP2N22 mutation
-> encodes the protein tyrosine phosphatase
involved in the activation and control of inflammatory cells, including T cells

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22
Q

What is produced that is thought to be an environmental factor for RA?

A

environmental arthritogen

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23
Q

What environmental factors may cause RA?

A 
viruses
gut bacteria
smoking
gum disease
obesity
diet
citrullinated proteins
-> lead to autoantigen generation
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24
Q

What is citrullination?

A

citrullination is a post translational conversion of arginine to citrulline in proteins by an enzyme called PAD

-> Peptidyl Arginine Deminiase

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25
Q

citrullination of proteins in RA

A
  • this becomes disregulated in RA
  • lead to alterations of proteins in the synovium
  • the protein AA sequence is changed
  • the immune system thinks this protein is not normal, thinks it’s a foreign protein
  • the immune system attacks these protiens
  • it can lead to autoantigens being formed which are then no longer recognised as self antigens by the immune system
  • anti-citrullinated protein antibodies (ACPA) are produced that attact these proteins
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26
Q

How does periodontal infection/gum disease cause RA?

A

gum disease releases PAD enzymes at sites of infection
this causes citrullination of bacterial and human proteins
activates ACPA production

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27
Q

How does smoking cause RA?

A

PAD is released from inflammation, apoptosis and necrosis in the lungs
citrullination of proteins
ACPA production

28
Q

What is MHC?

A

major histocompatibility complex

29
Q

What does MHC complex do?

A

binds antigens
presents antigens to T cells to activate the immune response
(destroyed)

30
Q

What does MHC contain that can cause RA?

A

HLA complex
HLA-DRbeta1 contains a binding site of the arthritogen that initiates the inflammatory synovitis
- alterations in genetics that cause RA

31
Q

What is synovitis?

A

inflammation of the synovial joint/fluid

32
Q

example of an auto-antigen

A

citrullinated protein

33
Q

What is activated when an auto-antigen is detected?

A 
T helper cells activated
they activate B cells
B cells produce antibodies
fibroblast like synoviocytes activated
macrophages activated
34
Q

Why do auto-antigens activate the cells of an immune response?

A

it thinks it’s a foreign body
doen’t know it’s our own cells
it it attacking it

35
Q

How does destruction occur?

A
  • T helper cells activate fibroblast like synoviocytes and macrophages
  • these activate osteoclasts, pannus, somatic mutations, proteases
36
Q

What are osteoclasts?

A

cells that break down bone

37
Q

What are cytokines?

A

small secreted proteins relesaed by cells that have a specific effect on the interaction and communications between cells
(cause a biological effect)

38
Q

What do cytokines bind to?

A

cytokine receptors

39
Q

What do cytokines regulate?

A

innate and adaptive immune system

process of inflammation

40
Q

Why do we block cytokines in RA?

A

to block the immune response/inflammation/RA

41
Q

autocrine cytokines

A

feed back onto themselves

42
Q

paracrine cytokines

A

affect nearby cells and activate them

43
Q

endocrine cytokines

A

released into the bloodstream, circulate and activate cells elsewhere

44
Q

main cytokines for RA

A

interleukins: IL-1, IL-6
interferons: INF-gamma
tumour necrosis factors: TNF-alpha

45
Q

antigen presentation

A
  1. antigen binds to APC (antigen presenting cell)
  2. APCs couple to T cells
  3. T cells release cytokines IFN gamma, IFN17
  4. T cells recruit macrophages and B cells
  5. macrophages release cytokines TNF-alpha, IL1, IL6
  6. T cells, macrophages, B cells attack the invader/bacteria and destroy it
  7. synovial cells release MMPs and RANKL
46
Q

What does an RA joint look like?

A
  • synovial membrane is inflammed
  • thick pannus
  • bone and cartilage is eroded
  • macrophages release cytokines (TNF alpha, IL1, IL6)
  • increased fibroblast like synoviocytes
  • macrophage like synovicytes (MLS) line the membrane
47
Q

another name for APC

A

dendritic cell

48
Q

What is a the pannus?

A 
inflammed synovial membrane
contains:
- osteoclasts
- macrophages
- T cells
- dendritic cells (APC)
- B cells
- leukocytes
- plasma cells
49
Q

What does IL-1 induce?

A

inflammation

50
Q

What does IL-6 stimulate?

A

osteoclast stimulation

51
Q

Where are fibroblast like synoviocytes located?

A

they line the RA joint

52
Q

Where are macrophage like synoviocytes located?

A

the line the membrane

53
Q

What do macrophage like synoviocytes (MLS) do?

A

proliferate in response to cytokines

produce RANKL

54
Q

What stimulates the release of fibroblast like synoviocytes (FLS)?

A

IL-1
TNF
(from macrophages)

55
Q

What doe FLS (fibroblast like synoviocytes) release?

A

cytoines

RANKL

56
Q

What does RANKL do?

A

stimulates osteoclasts which degrade bone

57
Q

What can the pannus lead to?

A

scar tissue
cartilage damage
bone erosion

58
Q

diagosis of RA

A
  • FH
  • pain Hx and examination of joints
  • blood tests
  • scans: x-rays, ultrasound, MRI (determines if RA is the cause of erosion)
59
Q

What blood tests are done to diagnose RA?

A

positive Rheumatoid Factor (RF)
positive anti-cyclic citrullinated peptide (anti-CCP)
high erythrocyte sedimentation rate (ESR)
positive c-reactive protein (CRP)

60
Q

How does RA decrease life expectancy?

A

decreases life expectancy by 3-7 years

61
Q

other problems caused by RA

A

heart disease
infection
GI bleeding

62
Q

factors for poor prognosis

A 
causasians
women
patients with subcutaneous nodules
advanced age at onet
inflammation >20 joints
early erosion
smoking
high ESR
high levels of RF
high anticyclic cirtullinated protein
63
Q

What causes other problems like CV/CNS/liver with RA

A

IL-6 that goes into the bloodstream

64
Q

CNS affects of RA

A

depression

fatigue

65
Q

CV affects of RA

A

accelerated CVD

increased myocardial electric instability

66
Q

affects on adipose tissue of RA

A

insulin resistance

67
Q

affects RA can have on the liver

PHA223 (43 decks)

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