RA Flashcards

1
Q

Highly variable in their ___ ____

A

phenotypic expression

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2
Q

Can be ___ or ___ inflammtion

A

loaclaized or systemic

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3
Q

Can cause damge to what?

A

musculoskeletal or organ

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4
Q

Clinical and pathologic features are detrmined by what?

A

inital stimuli

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5
Q

Distinguish between acute and chonic IRD

A

Acute:
- initiaing force is recognizable, endogenous or exogenous
- self limiting, flares upon re-exposure
- EX: Gout

Chronic:
- initiating factpr remote and unrecognizable by the time we diagnose the diseas
- self amplifying - autimmune response is driving by sefl antigen - frequent flares
- EG: RA

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6
Q

PLS describe the kinetics of acute and chronic IRD

A

SLIDE 4 diagram

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7
Q

Pathogenesis of inflammation: What cytokines are part of endothelial activation?

A

proinflammatory cytokines: TNF alpha and IL -1 beta

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8
Q

Pathogenesis of inflammation: Cytokines

A

M killer fucntion (effector fucntion) - IL-12 -TH1 (IL-2, TNF alpha, interferon gamma)

B cells activation and genrating antibodies- IL-4 -TH2 (IL-4, 5, 6, 10)

Attracting granulocytes, chronic inflammation and autoimmunity - TGF-gamma, IL-6, Th17 (IL-17)

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9
Q

What are the different kinds of pathogenesis of inflammations?

A

endothelial activation, Cytokines, complement pathway, Myelomonocytic Cells and Immune Complex Formation, Cellualr cytotoxicity

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10
Q

Pathogenesis of inflammation: Complement pathway

A

inflammatory response in cell recruitment and activation

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11
Q

Pathogenesis of inflammation: Myelomonocytic Cells and Immune Complex Formation

A

free radials, proteases, elatase and collagenase

  • Ig fC gamma recpetors
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12
Q

Pathogenesis of inflammation: Cellualr cytotoxicity

A

Cytotoxic T lymphocytes - overkill vs renenwal
- fas/fas ligand pathway
- secretory granules

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13
Q

Rheumatoid arthritis defintion

A

chronic, systemic, inflammtory disease

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14
Q

Characterized by?

A
  • most common inflammtory rheumatoid disease
  • persistent systmetrical inflammation of multple peripheral joints
    -proliferation of synovial lining of diartrodial joint
  • untreated can lead to disability and pre- mature death
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15
Q

Epidemiology most common for women or male?

A

women

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16
Q

peak onset

A

fifth or sixth decade of life

17
Q

What is the cause?

A

autoimmune disease of unknown cause

18
Q

What are some theories on the cause?

A
  • environment factors
  • microbial infection - transient inflammtory arthithis
  • trauma to joint or increased physical stress
  • genetics factors: MHC class II alleles (HLA -DR4)
19
Q

Intiation of RA

A
  • genetic (MHC class II alleles PAD 12 and 14)
  • environmental factors (smoking and infections
  • Autoantibodies (ACPA)
20
Q

Propagation of RA

A

Citrullination and cytokines

21
Q

What does citrullination do?

A

it changes certain proetins whihc can lead to immune response, inflamamtion and damge

-the conversion is catalysed by PAD

22
Q

How do cytokines propagate RA?

A

They promote inflammation, immune cell activation, tissue damage, and the ongoing autoimmune response

23
Q

Outline Pannus formation

A
  1. Initiation phase- changes in the synovial lining between bones
  2. Immune response - influx of immune cells, B and t cells, macrophages, Ab ag complexes
  3. inflammatory response - oxygen radicals, arachidonic acid, and lysosomes destroy synovial tissue
  4. Formation of the pannus - fissures into the bone due to collagenase
24
Q

Clinical presentation of RA

A

morning stiffness last for 1 hour before maximal movement

affects 3 or more joint symmetrically in areas such as the hand, writs, knees, hips, knees and shoulders

demineralization and erosion of the involved joints and bone by synovial inflammation

ongoing inflammation leads to joint deformity (soft tissue destruction in ligaments)

25
Q

Extra - articular manifestations?

A

anemia, vasculitis, osteoporosis arrhythmias, ischemic heart disease, etc

26
Q

what is a key symptom you could have with the progression of the disease?

A

low - grade fever

27
Q

What are some deformities of the hand you can get

A

(refer to pics on slides 18 and 19)
ulnar drift
boutonniere
swan neck deformity

28
Q

Diagnosis of RA

A
  • x-ray
  • Positive for Ra isotypes (IgM, G, A
  • Positive for anti cyclic citrullinated pepetide (anti-ccp)