RHEUMATOLOGY REVIEW Flashcards

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1
Q

Degeneration of articular cartilage with hypertrophy of contiguous bone:

DX: joint space loss, subchondral cysts, sclerosis, osteophytes

A

Osteoarthritis (OA)

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2
Q

OA: Predisposing Factors (primary)

A
Age
Obesity
Occupational risks:
Miners: OA hips, knees, shoulders
Weavers: OA hands
Trauma
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3
Q

Osteoarthritis (OA) Joint Involvement:

A

DIP (Heberden’s), PIP (Bouchard’s), 1st CMC
Hips and knees
Spine: cervical and lumbar
First MTP

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4
Q

Osteoarthritis (OA) DX:

A

joint space loss, subchondral cysts, sclerosis, osteophytes

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5
Q

OA: Predisposing Factors secondary

A

Secondary OA:
Inflammatory
Metabolic: hemochromatosis, Wilson’s disease, ochronosis

Sports: in general, no increased risk; exercise may be protective

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6
Q

**Sports: in general, no increased risk for OA; exercise may be _______

A

protective

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7
Q

Collagen: predominantly type II

Proteoglycans (chondroitin and keratin sulfate) linked to hyaluronic acid

Matrix proteins
~Metalloproteinases (MMPs): collagenase, gelatinase, stromelysin
~Tissue inhibitors of metalloproteinases (TIMPS)

Chondrocytes

Water

A

Cartilage components (avascular, no nerves)

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8
Q

In OA, the big problem is

A

cartilage tries to repair itself unsuccessfully

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9
Q

Cartilage in early Osteoarthritis

A

↑ inc chondrocytes
↑ inc metalloproteinases
↑ inc water content

dec TIMP
dec proteoglycan

cartilage changes from a spounge into a dish rag

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10
Q

OA Characteristics

A

Lacks systemic features

Synovial fluid: noninflammatory, type I fluid (200-2000 WBC/mm3)

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11
Q

__________ stimulates MMP production, PGE2, nitric oxide (NO), IL-6 in OA

A

Interleukin-1:

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12
Q

___________: increases MMP production, inhibits proteoglycan synthesis, induces chondrocyte apoptosis in OA

A

Nitric oxide

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13
Q

__________: ↑ production and activation of MMPs in OA

A

Prostaglandins

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14
Q
Complement activation
Adipokines
Interleukin-1:
Nitric oxide
Prostaglandins

present in?

A

OA

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15
Q

Adipokines

A

fat cells may produce IL-6

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16
Q

OA: Knees

A

Joint space loss
Sclerosis
Subchondral cysts
Osteophytes

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17
Q

A systemic, inflammatory, autoimmune disorder of unknown etiology that results predominantly in a peripheral, symmetric synovitis which can result in cartilage and bone destruction

Joint involvement:
Bilateral, symmetric - small joints hands + feet sparing the DIPs
Medium and large joints can be involved

X-rays: marginal joint erosions and deformities

A

Rheumatoid Arthritis (RA)

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18
Q

Rheumatoid Arthritis (RA): A systemic, inflammatory, autoimmune disorder of unknown etiology that results predominantly in a peripheral, ________________ which can result in cartilage and bone destruction

A

symmetric synovitis

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19
Q

Rheumatoid Arthritis (RA) Joint involvement:

A

Bilateral, symmetric - small joints hands + feet sparing the DIPs
Medium and large joints can be involved

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20
Q

Rheumatoid Arthritis (RA) Disease susceptibility and severity associated with shared epitope (QKRAA; in antigen binding groove) in subtypes of _____________ other genes are also involved

A

**HLA-DR4 and HLA-DR1

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21
Q

Antibody directed against the Fc portion of IgG; RF usually IgM, can be IgG or IgA
RF present in 85% of patients with RA
Not specific for RA or CTDs
Produced locally in the synovial tissue

RF-IgG immune complexes are pathogenic

A

Rheumatoid factor (RF):

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22
Q

RF-IgG immune complexes are _______

A

pathogenic

Rheumatoid factor (RF):
Can cause vasculitis or nodules
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23
Q

Rheumatoid factor (RF) ispresent in

A
many disease 
ex
ra
sjordons
sle
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24
Q

Anti-CCP

Anti-Cyclic Citrullinated Peptide Antibodies

A

RF not very specific for RA

reactive with synthetic peptides containing the unusual amino acid citrulline (modified arginine residue) are specifically present in the sera of RA patients:

Anti-CCP abs occur more frequently in individuals with the shared epitope; citrullination of peptides enhances binding

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25
Q

Inflammed tissue of macs, t cells, plasma cells

A

Pannus

in RA

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26
Q

Synovial fluid major cell in RA?

A

neutrophils

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27
Q

Production of metalloproteinases and other effector molecules
Migration of polymorphonuclear cells
Erosion of ____________ in RA

A

bone and cartilage

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28
Q

CD4+ memory T cells related to RA

A

modulation and amplification of local immune response through antigen recognition (query altered proteoglycans or collagen; citrullinated peptides)

unknown antigen sparks RA, by RA start disease is cleared but RA goes on

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29
Q

Extra-articular manifestations in RA

A

RF-IgG immune complex-induced vasculitis

Rheumatoid nodule formation in tissues/organs

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30
Q

The result of tissue deposition of monosodium urate (MSU) crystals due to hyperuricemia (MSU supersaturation of extracellular fluids)

A

Gout

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31
Q

Gout Joint Involvement:

A

1st MTP (podagra)GRaet Toe

Cool, peripheral joints of lower and upper extremities

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32
Q

Gout Hyperuricemia: over-production or under-excretion of uric acid; _______ (90%) most cases

A

underexcretors

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33
Q

Uric acid is a product of ______ metabolism

A

purine

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34
Q

Humans lack ______ which oxidizes uric acid into allantoin (more soluble compound)

A

uricase

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35
Q

___________of uric acid (X-linked):
PRPP synthetase overactivity
HGPRT deficiency (complete: Lesch-Nyhan)

A

Overproduction

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36
Q

Crystal arthritis is ________________ and crystal identification by polarized microscopy (MSU crystals: needle-shaped, negatively birefringent)

A

diagnosed by arthrocentesis

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37
Q

X-linked inborn errors of Gout

A

inc PRPP synthetase

dec HGPRT

38
Q

_______ inhibited by allopurinol and febuxostat, can treat gout

A

Xanthine oxidase

39
Q

Overproduction of uric acid (X-linked):
__________overactivity
HGPRT deficiency (complete: Lesch-Nyhan)

A

PRPP synthetase

40
Q

IgG-coating promotes phagocytosis by PMNs

IgG: not specific anti-crystal antibodies

A

(Proteins coating the crystals modulate the cellular response)

These are NOT ANTI CRYSTAL AB

41
Q

Apolipoprotein B-coating____________phagocytosis

A

inhibits

Proteins coating the crystals modulate the cellular response

42
Q

Overproduction of uric acid (X-linked):
PRPP synthetase overactivity
__________(complete: Lesch-Nyhan)

A

HGPRT deficiency

43
Q

___________ includes ligamentous-, tendinous-, fibrous-osseous junctions

A

Enthesitis

Seronegative Spondyloarthropathies

44
Q

Phagocytosis of crystals ___________concentration

A

decrease

45
Q

Local heat of inflammation __________MSU solubility

A

increase

46
Q

Calcium Pyrophosphate Dihydrate Deposition Disease

A

Abnormal pyrophosphate (PPi) metabolism

“pseudogout”

47
Q

PPi precipitates with calcium forming CPPD crystals in mid-zonal cartilage layers. Crystal release into the joint space. On xray?

A

Chondrocalcinosis

48
Q

CPPD crystals:

A

rhomboid, positively birefringent

49
Q

Seronegative Spondyloarthropathies hallmark

A

SI joints (sacroiliitis); morning (am) stiffness

50
Q

Seronegative Spondyloarthropathies affect

A

Enthesitis:

ligamentous-, tendinous-, fibrous-osseous junctions

51
Q

Seronegative Spondyloarthropathies Synovium:

A

Synovium: increased expression of TNF

52
Q

HLA-B27 and Ankylosing Spondylitis (AS) Chance of developing AS

A

2% if HLA-B27 positive

20% if HLA-B27 positive with a first-degree relative with AS

53
Q

HLA B27 + has a ___ chance of AS

A

2%

54
Q

HLA B27 + w/ AS FDR has a ___ chance of AS

A

20%

55
Q

Reactive Arthritis

A

Asymmetric, oligoarticular, lower ext arthritis

56
Q

Dactylitis are?

A

sausage digits?

57
Q

Reactive Arthritis Unfolded protein hypothesis: ER stress response

A

in ER HLA b27 misfolds and cannot be released
builds up in ER
stress response to cell
ER stress makes Il-23–> Th17 –> inflammation

58
Q

Reiter’s syndrome: clinical triad of conjunctivitis, urethritis, arthritis

A

Former name of Reactive Arthritis

59
Q

Reiter’s syndrome: clinical triad of ___________

A

conjunctivitis, urethritis, arthritis

60
Q

Systemic Lupus Erythematosus (SLE)

A

A chronic, systemic autoimmune disease which affects multiple organ systems including the skin, joints, serosal surfaces, lungs, kidneys, CNS, and hematologic system

61
Q

SLE - Fundamental defect is the ________________, resulting in an autoimmune process; T cell and B cell process

A

misdirected recognition of self as foreign

62
Q

SLE is a?

A

T AND B CELL PROCESS

63
Q

SLE Antibody responses toward autoantigens are antigen-driven and require ____________

A

CD4+ T cells

64
Q

SLE Loss of T cell tolerance permitting autoreactive B cell stimulation: ? central or peripheral abnormality in_____________ lymphocyte deletion or anergy

A

self-reactive

65
Q

Association with HLA-DR3 and C4A null allele (greatest risk)

A

SLE

66
Q

SLE Association with HLA-DR3 and _________ (greatest risk)

A

C4A null allele

67
Q

SLE- Loss of T cell tolerance permitting ___________: ? central or peripheral abnormality in self-reactive lymphocyte deletion or anergy

A

autoreactive B cell stimulation

68
Q

Antinuclear Antibodies (ANA)

A

SLE: > 95% patients have + ANAs
Not specific for SLE
Antibodies are directed to multiple nuclear antigens
CD4 directed

69
Q

Systemic Lupus Erythematosus (SLE)

A

Genetics (polygenic):

C4A null allele (greatest risk)

70
Q

ANA specific for SLE?

A

NOPE

71
Q

Anti-dsDNA antibodies:

A

renal disease

72
Q

Anti-histone antibodies:

A

SLE and drug-induced lupus

73
Q

Anti-phospholipid antibodies: block prothrombin activation in the clotting cascade; associated with increased _______ ? neutralize anticoagulant effect of 2 GP1; do not cause a vasculitis

A

clotting

Specific antibody-mediated disease (Type II):

74
Q

Inflammation within or through the vessel wall resulting in damage to vessel integrity/flow

A

Vasculitis

75
Q

Vasculitis Pathology

A

Varying degree of infiltrating lymphs, monocytes, histiocytes, eosinophils, and PMNs
Granulomas and/or giant cells in vessel wall in some types of vasculitis
Fibrinoid necrosis of vessel wall secondary to immune complex deposition
Focal and segmental nature of vascular lesions common to all types of vasculitis

76
Q

Vasculitis Pathology

Immune complexes: inflamm→ PAFs→ ↑vascular permeability→ IC deposition; __________

A

palpable purpura

77
Q

Vasculitis Pathology- Pathophysiology:

Immune complexes: inflamm→ PAFs→ ↑___________→ IC deposition; palpable purpura

A

vascular permeability

78
Q

Vasculitis Pathology- Pathophysiology:

T cell dependent-mediated endothelial cell injury: (HLA-DR4 and giant cell arteritis; suggests ___________ vascular inflammation)

A

antigen-driven

79
Q

HLADR4 in Vasculitis is not related to?

A

RA HLADR4

80
Q

Vasculitis- Sources of antigen for immune complexes:

A

Drugs
Bugs: infectious agents
Connective tissue disease: autoimmune process
Malignancy

81
Q

ANCA Vasculitis

A

Antineutrophil Cytoplasmic Antibodies. Seperates small Vasculitis

82
Q

*Cytoplasmic ANCA (c-ANCA):

A

Proteinase-3 (PR3) in primary granules of PMNs

Associated with generalized GPA (Wegener’s)

83
Q

*Perinuclear ANCA (p-ANCA):

A

Myeloperoxidase (MPO) in primary granules of PMNs

Associated with microscopic polyangiitis (MPA)

84
Q
Inflammatory myopathies are characterized by:
Muscle weakness (proximal) and low endurance
Usually idiopathic but may occur in association with neoplastic diseases or in “overlap” with CTDs
A

Polymyositis / Dermatomyositis (PM/DM)

85
Q

-DM presents with typical skin rashes:

A
Gottron’s papules 
Heliotrope rash 
V-sign and shawl-sign 
Mechanic’s hands 
Periungual changes/erythema
86
Q

*Anti-synthetase Syndrome

A

PM or DM presenting with:
Interstitial lung disease (ILD): 60%*****

Anti-synthetase antibodies:
Anti-aminoacyl-tRNA synthetases (cytoplasm)
Anti-Jo-1 = anti-histadyl-tRNA synthetase
Not pathologic or myotoxic antibodies

87
Q

Anti-synthetase antibodies:
Anti-aminoacyl-tRNA synthetases (cytoplasm)
Anti-Jo-1 = ______________
Not pathologic or myotoxic antibodies

A

anti-histadyl-tRNA synthetase (antiJo1)

Not pathologic or myotoxic antibodies- IT IS A MARKER OF DISEASE

88
Q

Endomysial distribution of inflammatory cells (CD8+ T cells) surrounding and invading muscle fibers

A

Polymyositis

89
Q

Perivascular (CD4+ T cells) and perifascicular inflammatory infiltrate

A

Dermatomyositis

Around vasical

90
Q

Polymyositis / Dermatomyositis Evidence suggesting a _________ etiology:

A

viral

Viral particles by EM and viral RNA detected in muscle from PM/DM patients. NO live virus has been cultured from muscle

91
Q

Osteoarthritis (OA) Joint Involvement:

A
Joint Involvement:
DIP (Heberden’s), PIP (Bouchard’s), 1st CMC
Hips and knees
Spine: cervical and lumbar
First MTP