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D2 Fall > Gen Path Exam 3 - Autoimmune Disease - RA > Flashcards

Gen Path Exam 3 - Autoimmune Disease - RA Flashcards

1
Q

Chronic systemic autoimmune inflammatory disease of unknown cause, chiefly affecting synovial membranes of multiple joints

A

Rheumatoid arthritis

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2
Q

This disease has a wide clinical spectrum with considerable variability in joint and extra-articular manifestations

A

RA

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3
Q

T/F: The etiology of RA involves a complex, and still poorly understood, interactions of genetic risk factors, environment, and the immune system

A

True

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4
Q

T/F: RA is 3-5x more common in men than in women

A

FALSE, it is 3-5x more common in women than in men

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5
Q

When is the usual age at onset of RA?

A

20-40

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6
Q

Approximately 50% of the risk of developing RA is related to which genetic factors?

A

HLA-DRB1 locus
Polymorphism in PTPN22 gene

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7
Q

Which gene encodes a tyrosine phosphatase that is postulated to inhibit T cell activation?

A

PTPN22 gene

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8
Q

Usually gradual onset; common prodromal symptoms of weakness, fatigue, and anorexia

A

RA

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9
Q

What is the initial presentation of RA?

A

Symmetric joint involvement in hands and feet

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10
Q

Joint effusions, tenderness, and restricted motion are usually present early in the disease

A

RA

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11
Q

What are the 3 eventual characteristic deformities in RA?

A

Subluxations
Dislocations
Joint contractures

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12
Q

What do the following describe?

-Tendon sheaths and bursae frequently affected by chronic inflammation
-Possible tendon rupture
-Rheumatoid nodules over bony prominences such as the elbow and shaft of the ulna
-Splenomegaly, pericarditis, and vasculitis
-Carpal tunnel syndrome resulting from flexor tenosynovitis

A

Extra-articular findings in RA

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13
Q

The pathologic findings in the joint include chronic ________ with ________ formation

A

synovitis; pannus

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14
Q

What does the pannus erode?

A

Cartilage
Bone
Ligaments
Tendons

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15
Q

Acute, late, or chronic phase?

Effusion and other manifestations of inflammation are common

A

Acute

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16
Q

Acute, late, or chronic phase?

Organization may result in fibrous ankylosis; true bony ankylosis is rare

A

Late

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17
Q

Acute, late, or chronic phase?

Inflammation of soft tissues around the joints may be prominent and is a significant factor in joint damage

A

Acute and chronic

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18
Q

What microscopic finding is most characteristic of RA?

A

Subcutaneous (rheumatoid) nodule

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19
Q

Granuloma with a central zone of fibrinoid necrosis surrounding a palisade of radially arranged elongated CT cells, and a margin of
chronic granulation tissue

A

Subcutaneous (rheumatoid) nodule

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20
Q

Pathologic alterations indistinguishable from those of the ______________ ___________ are occasionally seen in the myocardium, pericardium, endocardium, heart valves, visceral pleura, lungs, sclera, dura mater, spleen, larynx, and other tissues

A

subcutaneous nodule

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21
Q

In the era of more effective treatment, secondary
____________ is now very rare

A

amyloidosis

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22
Q

RA has features of which type of hypersensitivity reaction directed against articular cartilage, bone, and other joint tissues?

A

Type IV hypersensitivity rxn

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23
Q

What does the synovium of RA-affected joints contain?

A

Germinal centers w/ secondary follicles + plasma cells

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24
Q

What do plasma cells produce in the synovium of RA-affected joints?

A

Autoantibodies

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25
Q

Which specific autoantibodies do plasma cells produce in the synovium of RA-affected joints?

A

Rheumatoid factor (RF)
Anti-cyclic citrullinated peptide AB (anti-CCP)
Anti-citrullinanted protein AB (anti-ACPA)

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26
Q

T/F: Destructive arthritis can occur in the absence of autoantibodies due to cytokines

A

True

27
Q

Which cells produce cytokines?

A

Activated T cells

28
Q

What do cytokines recruit?

A

Macrophages

29
Q

What do the product of macrophages cause?

A

Tissue injury

30
Q

What do cytokines activate?

A

Resident synovial cells

31
Q

What do resident synovial cells produce?

A

Proteolytic enzymes

32
Q

What is an example of a proteolytic enzyme?

A

Collagenase

33
Q

What facilitates destruction of cartilage, ligaments, and tendons of joints?

A

Collagenase

34
Q

What do activated T cells produce?

A

Cytokines

35
Q

Which 5 inflammatory cells from the products of macrophages cause tissue injury?

A

IFN-gamma
IL-17
RANKL
TNF
IL-1

36
Q

Inflammatory cell from TH1 cell

A

IFN-gamma

37
Q

Inflammatory cell that activates macrophages and synovial cells

A

IFN-gamma

38
Q

Inflammatory cell from TH17 cell

A

IL-17

39
Q

Inflammatory cell that recruits neutrophils and monocytes

A

IL-17

40
Q

Inflammatory cell that is expressed on activated T cells and stimulates osteoclasts/bone resorption

A

RANKL

41
Q

Inflammatory cells that stimulate resident synovial cells to secrete proteases that destroy hyaline cartilage

A

TNF
IL-1

42
Q

Inflammatory cells from macrophages

A

TNF
IL-1

43
Q

What contributes to the bone destruction in RA?

A

Increased osteoclast activity in joints

44
Q

What causes the increased osteoclast activity in joints and bone destruction in RA?

A

TNF cytokines

45
Q

Which cytokine plays a pivotal role in RA?

A

TNF

46
Q

Many of the newer therapeutic agents for RA are directed at the suppression of which final mediators of inflammation?

A

Monoclonal AB specific for human TNF-alpha

(TNF-alpha inhibitors)

47
Q

What are 3 examples of monoclonal ABs specific for human TNF-alpha (TNF-alpha inhibitors)?

A

Etanercept
Infliximab
Adalimumab

48
Q

Which autoantibodies bind to the Fc portions of their own IgG?

A

IgM (more common)
IgA (less common)

49
Q

Where do IgM and IgA bind to?

A

Fc portion of their own IgG

50
Q

Autoantibodies (IgM, IgA) that bind to the Fc portions of their own IgG

A

Rheumatoid factor (RF)

51
Q

A nonspecific assay for pentameric IgM antibodies in the blood and will be present in 70 to 80% of patients with RA

A

Rheumatoid factor (RF)

52
Q

20% of RA patients will remain ___________ __________ __________, despite other signs RA

A

Rheumatoid factor (RF) negative

53
Q

What is a poor screening tool with a positive predictive value (PPV) of only 20% in asymptomatic pts?

A

Rheumatoid factor (RF)

54
Q

More specific than Rheumatoid factor for RA; up to 98% specificity

A

Anti-citrullinated protein ABs (ACPA)

55
Q

Positive in 30-60% of pts with RA

A

Anti-nuclear ABs (ANA)

56
Q

Common finding in RA due to inflammation

A

Elevated acute phase reactants

57
Q

What are the 2 elevated acute phase reactants commonly found in pts with RA?

A

Erythrocyte sedimentation rate (ESR)
C-reactive protein (CRP)

58
Q

What type of anemia is found in many pts with RA?

A

Mild, normocytic normochromic anemia

59
Q

Forms a poor mucin clot; elevated WBC count with an increase in neutrophils

A

Turbid joint fluid

60
Q

Name the 11 complications of RA

A
  1. Erosive arthritis + joint destruction
  2. Skin vasculitis
  3. Pericarditis
  4. Intracardiac rheumatoid nodules
  5. Pleural/subpleural disease; interstitial fibrosis
  6. Ocluar disease
  7. Mononeuritis multiplex
  8. Median nerve entrapment
  9. Felty’s syndrome
  10. Sjogren’s
  11. TMJ
61
Q

What do intracardiac rheumatoid nodules cause?

A

Valvular or conduction abnormalities (arrhythmias)

62
Q

What is ocular disease in RA due to?

A

Scleral nodules

63
Q

Severe sensorimotor neuropathy in RA

A

Mononeuritis multiplex

64
Q

Immune neutropenia associated with seropositive nodular RA and splenomegaly

A

Felty’s syndrome

D2 Fall (37 decks)

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