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Blood and Lymph > Rheumatology > Flashcards

Rheumatology Flashcards

1
Q

RA involves ___ joints except for ___

A

small joints
DIP
*** NO thoracic/lumbar spine involvement

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2
Q

Synovial fluid of osteoarthritis

A

Low WBC in synovial fluid (Type I fluid, 200-2,000 WBCs), normal viscosity, negative crystals (uric acid, calcium), normal glucose

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3
Q

Symptoms of OA (3)

A

i. Pain with activity, crepitus, deformity, limited ROM
ii. Pain at END of day
iii. Non-inflammatory pain = worse with use, worse at end of day

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4
Q

X rays of OA

A

asymmetric joint space loss, osteophytes, less cartilage, bony cysts, bone sclerosis

  • Heberden’s (distal interphalangeal joints) and Bouchard’s (proximal phalangeal joints) nodes
      1. Hard, nontender, not warm
  2. Formation of calcified spurs of articular cartilage
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5
Q

Risk factors of OA

A

age, obesity, genetics, prior trauma/surgery to joint, family history

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6
Q

Pathology of OA

A

Imbalance between destruction/production of articular cartilage by chondrocytes - More destruction in late disease

Cartilage is AVASCULAR

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7
Q

4 things made my chondrocytes in cartilage

A

collagen II, proteoglycans, aggrecan, hyaluronic acid

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8
Q

Synovium contains (3)

A

i. Cytokines (IL-1, TNF)
ii. Growth factors (TGF-B, BMP)
iii. Enzymes (MMPs)

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9
Q

Degradation of cartilage in OA

five associated factors

A

catabolic - chondrocytes/synovium release pro-inflammatory cytokines to degrade ECM

i. MMPs (13, 3)
ii. ADAMTS
iii. Cytokines (IL-1, TNF)
iv. NO
v. Prostaglandins

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10
Q

Synthesis of cartilage

5 associated factors

A

anabolic

i. Collagen II
ii. Aggrecan
iii. Link protein
iv. Inhibitory cytokines (IL-4, IL-10, IL-13)
v. Growth factors (TGF-B, BMP)

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11
Q

Treatment of OA

A

NSAIDS, topical NSAIDS, hyaluronic acid matrix injections, analgesics (opioid and nonopioid), PT, surgery

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12
Q

RA manifestations (6)

  • what joint is spared?
  • symmetric or asymmetric?
  • what two kinds of classic deformities?
  • what kinds of extra-articular manifestations?
  • morning or night stiffness?
A
  1. Peripheral, systemic, inflammatory synovitis
  2. Cartilage/bone destruction, and joint deformities
    a. Erosions into the joint space
  3. PIPs and MCPs abnormal (proximal) - warm, tender, soft (spongy/boggy)
    a. DIPs and thumb joint often spared
    b. Cervical spine commonly involved (C1-2)
    c. Often symmetric

4.Swan neck and boutonniere deformity

  1. Fewer extra-articular manifestations
    a. Episcleritis (in eye)
    b. Pulmonary nodules

6.MORNING stiffness, limited ROM

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13
Q

Serologic findings of RA (5)

A
  1. Rheumatoid Factor present in 85%
    a. IgM anti IgG (binds Fc portion of IgG)
  2. Elevated ESR or CRP
  3. Anemia, hypergammaglobulinemia
  4. Anti-cyclic citrullinated peptide (CCP) antibodies present
  5. “Seropositive” when CCP and RF both present
    a. Prognostically bad when both present
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14
Q

Synovial fluid RA

A

inflammatory (> 2000 WBC, neutrophils)

-Low complement and glucose levels

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15
Q

XRAY RA (3)

A
  1. Soft tissue swelling
  2. Erosions in marginal distribution
  3. Symmetric loss of joint space
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16
Q

Risk factors RA

A

genetics, smoking, infections, environmental factors, microbiome, hormones

Risk alleles: encode enzymes/inflammatory pathways we can block

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17
Q

Risk Alleles in RA (2)

A
  1. HLA-DR4

2. HLA-DR-1

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18
Q

HLA-DR4 and HLADR-1

A

biggest risk alleles

Antigen ingested by APC → digest in endosome → goes through golgi and becomes citrullinated (BAD) → put on MHC II - in hypervariable region (QKRAA sequence motif) of HLA-DR4/1 groove (aka SHARED EPITOPE) → presented to T cell

T cell → RF production, CCP, and autoimmunity

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19
Q

RF B cells

A

Can secrete RF or have RF receptors on surface

  • RF-IgG immune complexes are PATHOGENIC
  • RF not ver specific for RA
  1. Results in classical complement activation
  2. RF and complement can deposit in joint, sclera, lungs, skin and cause problems
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20
Q

Late stage RA: synovial tissue

cell types present (4)

A

synovial hyperplasia

1) CD4 T cells
2) Macrophages
3) B cells
4) Th17 cells
5) DCs

NO PMNS

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21
Q

Late stage RA synovial tissue:

macrophages –> ?
B cells –> ?
Th17 cells –> ?

A

macrophages –> cytokine cascade (IL-1, IL-6, TNFa, MMPs)

B cells –> activated by T cells, RF and anti-CCP abs –> complement

Th17 cells –> IL-17

CD4+ memory T cells –> modulate and amplify local immune response through antigen recognition + IL-6

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22
Q

Pannus

A

Present in Late stage RA

organized mass of granulation tissue

Consists of: macrophages, T cells, B cells, fibroblasts

Arises due to inflamed synovium and cytokines
→ Bony destruction

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23
Q

Extra-articular disease in RA is mediated by…

A

complement pathway destruction

-Complement induced vasculitis and Rheumatoid nodule formation

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24
Q

You can get hyperuricemia with…

A

overproduction

underexcretion

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25
Q

Increased production of urate typically due to super-activity in __________ or deficiency in ___________

A

superactivity of PRPP (phosphoribosyl-pyrophosphate) synthetase

OR

deficiencies in HGPRT (hypoxanthine-guanine phosphoribosyltransferase)

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26
Q

Increase production of urate defined as urinary excretion of UA > _______

A

750 mg per 24 hours

Overproduction gout is usually genetic

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27
Q

Lesch-Nyhan

A

complete deficiency of HGPRT

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28
Q

Decreased excretion of urate defined as urinary excretion of UA less than _______

A

750 mg per 24 hours

MAJORITY of primary gout patients are UNDER EXCRETORS of uric acid

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29
Q

Uricase

A

enzyme that oxidizes uric acid to allantoin (highly soluble)

Humans DO NOT have this enzyme

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30
Q

MSU crystals are formed when…

what decreases urate solubility?

A

supersaturation of uric acid (hyperuricemia)→ gout crystal formation

Decreased urate solubility with: low temp, dehydration, trauma, low pH

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31
Q

MSU crystals cause an inflammatory response. This can involve…(4)

A

1) inflammatory response PMN dependent
2) TLR 2 and 4 (on PMN)
3) NLRP3 Inflammasome (in PMN) –> IL-1B production
4) activate complement

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32
Q

IL-1 + TNF –>

A

endothelial activation (allowing PMN infiltration)

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33
Q

MSU crystals bind TLR 2 and 4 on PMNs –> ?

A

intracellular cascade that causes GENE UPREGULATION

→ critical to inflammatory response

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34
Q

MSU crystals engage _______ –> NLRP3 inflammasome activated in PMN –> release of what cytokine?

A

caspase-1

IL-1B

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35
Q

MSU crystals can also be coated with IgG. This results in…

A

→ promotion of phagocytosed into PMN

IgG binding MSU crystals in NONSPECIFIC anti-crystal antibodies

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36
Q

___________ coating of crystals inhibits phagocytosis and cellular response

A

Apolipoprotein-B

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37
Q

Acute Gouty Arthritis

A
  • abrupt onset
  • VERY painful, warm, red swollen joint

-MTP joint of great toe most often involved, also ankles, heels, knees, wrists, fingers, and elbows
[Podagra = painful condition of big toe]

  • Spontaneously resolve over 3-10 days
  • Predilection for cooler, acral sites (MSU crystals have lower solubility)

ASYMMETRIC

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38
Q

Synovial fluid in gout (3)

A

MSU crystals present (needle-shaped, negatively birefringent)

Inflammatory - 2,000-100,000 WBCs (neutrophils predominantly)

Elevated ESR (test of inflammation)

39
Q

Gout vs. pseudogout

A

Gout = MSU crystal

  • Process of supersaturation
  • Diet, pH and temperature are all variables - DO NOT matter in pseudogout
  • Tissue deposition of monosodium urate (MSU) crystals due to hyperuricemia (MSU supersaturation of extracellular fluids)

Psuedogout = CPPD crystals (calcium crystals)

  • MTP rarely involved
  • Usually in women and older patients
  • due to abnormal pyrophosphate metabolism
40
Q

Calcium Phosphate Dihydrate Deposition Disease (psuedogout)

Pathology

A
  • CPDD crystals are rhomboid-shaped, blue, positively birefringent - PREFORMED, NOT SOLUBILTY EVENT
  • due to abnormal pyrophosphate metabolism
41
Q

What causes pseudogout?

A

Due to abnormal pyrophosphate metabolism

1) ANKH gene mutation: membrane transporter of pyrophosphate in chondrocytes → CPPD crystal formation due to excess PPi being pushed out of chondrocytes
2) NTP pyrophosphohydrolase defect that converts NTP –> NMP + Pi –> more Pi extracellularly

Too much extracellular pyrophosphate precipitates with calcium → CPPD

42
Q

“Shedding Phenomena” (aka strip mining)

A

preformed CPPD crystals released into synovial fluid

43
Q

Allopurinol and febuxostat are…

A

Xanthine Oxidase Inhibitor

Anti-hyperuricemic medications

decrease uric acid production

44
Q

Risk factors for gout

A

dietary obesity, genetic factors, HTN, certain meds

Dairy is protective!

45
Q

Large and medium-vessel vasculitis pathophysiology

A

infiltration of WBCs through vessel wall, associated with granuloma, disruption of elastic lamina, thickening of intima → obliteration of vessel lumen (same as medium vessel)

46
Q

Small-vessel vasculitis pathophysiology

A

typically leukocytoclastic vasculitis

47
Q

Giant cell arteritis

A

Large-vessel vasculitis

temporal arteries or vessels originating from aortic arch → Temporal headache, scalp tenderness, visual loss

48
Q

Takayasu’s arteritis

A

large-vessel vasculitis

49
Q

ANCA positive vasculitis

A
  • Granulomatosis with polyangiitis (GPA)
  • Eosinophilic granulomatosis with polyangiitis
  • Microscopic polyangiitis (MPA)
50
Q

Granulomatosis with polyangiitis (GPA)

A

Effects upper respiratory tract, lungs, kidneys

Associated with serum cytoplasmic-ANCA (c-ANCA)

51
Q

Microscopic polyangiitis (MPA) are positive for serum ____________

A

Serum perinuclear-ANCA (p-ANCA)

52
Q

Clinical features of vasculitis

A
  • Skin lesions, palpable purpura
  • Fever, anorexia, weight loss, weakness, fatigue
  • MSK symptoms: arthralgias, arthritis myalgias, peripheral neuropathy
  • Inflammatory infiltration into nerve and nerve blood supply → neuropathy (Mononeuritis multiplex)
  • Glomerulonephritis (IC deposition in glomeruli) → protein in urine
53
Q

Lab findings of vasculitis (8)

A
  • Anemia, thrombocytosis
  • Low albumin
  • Elevated ESR and CRP
  • Polyclonal gammopathy
  • Elevated liver enzymes (AST, ALT)
  • Low complement (consumed by immune complex formation, classical complement pathway)
  • Cryoglobulins
  • Detection of serum autoantibodies (RF, ANA, ANCA)
54
Q

Different immunopathogenic mechanisms that mediate vasculitis (5)

A

1) Immune Complexes
2) Anti-neutrophil Cytoplasmic Antibodies (ANCA)
3) Anti-endothelial antibodies
4) T cell dependent mediated endothelial cell injury
5) Infection of endothelial cells

55
Q

Immune complex mechanisms of vasculitis

A

Deposition of circulating ICs at the vascular endothelium → activation of complement and attraction of PMNs

  • Deposition in skin, kidneys, nerves, etc.
  • Results in decreased complement levels
  • Antigen can be: drugs, bugs, connective tissue disease, malignancy
56
Q

mechanism of ANCA in vasculitis

A

ANCA = abs to antigens found in the cytoplasm of neutrophils

Inflammatory cytokines → activated PMNs that express PR3 or MPO on cell surface

ANCA binds neutrophil surface → further neutrophil activation and binding to vascular endothelial cells → vascular damage

-Role in amplifying inflammatory vascular response

57
Q

Types of ANCA (2)

A

1) cytoplasmic-ANCA

2) perinuclear-ANCA

58
Q

c-ANCA

stains what?
associated with what disease?

A

cytoplasmic staining, binds proteinase 3 (PR3) in primary granules of PMNs

→ Granulomatosis with polyangiitis (GPA)

Effects Lung, kidney, mononeuritis

59
Q

p-ANCA

stains what?
associated with what disease?

A

perinuclear staining, binds MPO in primary granule of PMN

→ Microscopic polyangiitis (MPA)
Effects Kidney

60
Q

Clinical features of Polymyositis and Dermatomyositis (4)

A

1) Chronic muscle weakness (symmetric proximal muscle weakness, problem standing, climbing stairs, etc.)
* *WEAKNESS MORE THAN PAIN**

2) Inflammation of muscle tissues by chronic inflammatory cells
3) Skin disease
4) Constitutional symptoms

61
Q

Lab findings of Polymyositis and Dermatomyositis

A

1) Elevated muscle enzymes (CPK, aldolase, AST, ALT, LDH)
2) Autoantibodies (ANAs, MSA, MAA)
3) Elevated ESR
4) EMG findings (myopathic findings)
5) MRI findings (muscle inflammation, edema, fibrosis, calcinosis)

62
Q

EMG findings of PM/DM (3)

A

myopathic findings

1) Decreased amplitude of motor unit APs
2) Spontaneous fibrillations
3) Increased insertional activity

63
Q

Anti-synthetase Syndrome

  • type of antibody?
  • presentation
A

Anti-synthase abs: directed against Anti-histidyl-tRNA synthetase (aminoacyl-tRNA synthetase)

-anti-Jo-1 antibody

PM or DM presenting with **Interstitial lung disease (very SOB, new onset cough)

NOT PATHOLOGIC OR MYOTOXIC ANTIBODIES

64
Q

Biopsy findings in PM

A

PM → CD8+ T cells, macrophages

*CTL mediated muscle injury

65
Q

Biopsy findings in DM

A

DM → CD4+ T cells, B cells, macrophages, dendritic cells)
Concentrated in perivascular regions of muscle

*Complement mediated vasculopathy

66
Q

Polymyositis

Distribution?
Inflammatory infiltrate?
Rash?

A

Endomysial distribution of inflammatory cells surrounding and invading muscle fibers (more generalized inflammation)

CD8+ T cells

No rashes

67
Q

Dermatomyositis

Distribution?
Inflammatory infiltrate?
Rash?

A

Perivascular and perifascicular inflammatory infiltrate

CD4+ T cells

Skin RASHES present

Rashes = Gottron’s, Heliotrope, Shawl, Gun Holster

More atrophy of muscles

68
Q

PM and DM may be triggered by…

A

Viral infections

  • Disease pattern is seasonal
  • Elevated IFN
69
Q

Ankylosing Spondylitis

Onset?

Pain - when, where, what kind, what makes it better?

A

1) Onset YOUNG (16-40yrs)
2) Axial
3) Morning stiffness
4) improved with exercise
5) Effects Sacroilitis, entheses

70
Q

Lab findings in Ankylosing Spondylitis

elevated _______
no _____ or ______

A

Elevated ESR
no RF, no ANA (seronegative)
(NO ANTIBODIES)

71
Q

Xray findings in Ankylosing Spondylitis (3)

A
  • Spinal fusion (bambooing of spine)
  • peripheral arthritis involving large joints
  • asymmetric distribution
72
Q

Ankylosing Spondylitis, reactive arthritis, psoriatic arthritis all associated with what risk allele?

A

HLA-B27

73
Q

HLA-B27 people are genetically susceptible to develop disease when exposed to _________ such as ____________

A

environmental trigger

salmonella, shigella, yersinia, campylobacter, chlamydia* can induce reactive arthritis in 20% of B27+ individuals

74
Q

HLA-B27 theories (4)

A

1) Arthritogenic peptide hypothesis
2) Molecular mimicry
3) Free heavy chain hypothesis
4) Unfolded protein hypothesis

75
Q

Arthritogenic peptide hypothesis

A

specific microbial peptides bind HLA-B27 → present to CD8+ CTLs*

76
Q

Molecular Mimicry

A

autoreactivity to self antigens due to similarity between epitopes on antigen and HLA-B27 molecule

77
Q

Free heavy chain hypothesis

A

formation of stable homodimers of HLA-B27 heavy chains* without antigen in a cell

→ activate NK cells* via interaction with Killer Cell Immunoglobulin-like Receptor (KIR)*

78
Q

Unfolded protein hypothesis

A

HLA-B27 has propensity to misfold in ER → unfolded protein stress response → inflammatory cytokines* (IL-23) → upregulate Th17*

79
Q

Seronegative spondyloarthropathies pathology (2)

Synovium has increased ________ (cyotkine)

A

Enthesis: inflammation of ligament, tendon, and fibrous structures as they insert into bone

Synovium has increased TNFa

No RF or ANA antibodies

80
Q

Types of spondyloarthropathy (4)

A

1) Ankylosing Spondyloarthritis
2) Psoriatic arthritis
3) IBD (Crohn’s, UC)
4) Reactive Arthritis (STDs, Cdiff, etc.)

81
Q

RA vs. Spondylo

1) symmetric or asymmetric?
2) peripheral or axial?
3) big or small joints?
4) antibodies?
5) where does it occur?
6) gender?

A

RA:

1) symmetric
2) peripheral
3) small joints
4) RF+, CCP+
5) synovitis
6) female 2:1

Spondylo:

1) asymmetric
2) axial
3) BIG joints
4) no abs (seronegative)
5) occurs at entheses
6) male

82
Q

Systemic Lupus Erythematosus Symptoms and clinical features (6)

A
  • Malar rash
  • Discoid rash
  • photosensitivity
  • arthritis
  • 9:1 females (young)
  • affects kidneys (Type III immune complex deposition or type II ab against specific cell/tissue
83
Q

Organ specific immunity

A

Immune response against single/restricted set of autoantigens within a given organ → autoimmune destruction of only those organs

84
Q

Systemic Autoimmunity

A

Immune response against multiple auto-antigens → disease affects multiple organs with immune complexes and direct immune attack

e.g. SLE

85
Q

Genetics of SLE

A

Multigenic disease with a major MHC contribution

-HLA-DR3, C4 Null Alleles

86
Q

Pathophysiology theories of SLE (5)

A

1) Sex hormones (disease accelerating effect of estrogen, protective effect of androgens)
2) Sun exposure
3) Type II antibody-mediated disease
4) Type III immune complex disease
5) BOTH innate and adaptive immune systems involved

87
Q

SLE has antibodies to…

A

nuclear component (ANA) –> markers of disease, causes of tissue damage (LUMPY BUMPY)

-anti-dsDNA antibodies

> 95% of SLE patients have ANA, but ANA is NOT specific to SLE

88
Q

T cell involvement in pathogenesis of SLE (2)

A

Recognition of self as foreign –> T AND B cell response

Antibody responses towards autoantigen are antigen driven and require CD4+ T cells

Loss of T cell tolerance for self –> activation of autoreactive B cells

89
Q

Antiphospholipid antibodies act to increase ___________

A

clotting

90
Q

Vasculitis T cell mediated endothelial injury

A

HLA-DR4 and giant cell arteritis; suggests ANTIGEN-DRIVEN vascular inflammation

91
Q

The worst symptoms of PM and DM is ________ and it occurs in 60% of patients.

A

Interstitial lung disease

92
Q

Reactive arthritis often occurs with a history of __________

A

infectious diarrhea or urethritis

93
Q

Reactive arthritis is asymmetric, oligoarticular and _________ arthritis. Can include _________ and _________

A

Lower extremity

Dactylitis (sausage fingers)
Reiter’s Syndrome (can’t see, can’t pee, can’t climb a tree)

94
Q

Chance of developing AS:

______ if HLA-B27 +
______ if HLA-B27 + and 1st degree relative with AS

A

2%

20%

Blood and Lymph (9 decks)

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