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Musculoskeletal > Pathophysiology > Flashcards

Pathophysiology Flashcards

1
Q

osteoarthritis

A

older
NO inflammation
DEGENERATIVE: erosion of articular cartilage, osteophytes, subchondral sclerosis, alterations of the synovial membrane (can thicken) and joint capsule, eburnation (progressive thickening), Herberden nodes (increased activity at pericondrium), loose bodies/ joint mice (fragments of cartilage), cyst formation
Dx: clinical, xray, normal labs
Sx: pain gets worse with use/during the day, morning stiffness
increases mortality

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2
Q

risk factors for osteoarthritis

A
  1. age
  2. joint location
  3. obesity
  4. genetics
  5. joint malalignment
  6. trauma
  7. gender: female
  8. neuromuscular dysfunction
  9. metabolic disorders
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3
Q

morphologic changes in osteoarthritis: early vs. late

A

early: articular cartilage surface irregularity, superficial clefts, altered proteoglycan distribution
late: deepened clefts, increase surface irregularities, articular cartilage ulceration, exposed underlying bone, chondrocytes from clusters to self-repair, osteophytes

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4
Q

MMP

A

matrix metalloproteinases that degrade proteoglycans and collagen
OSTEOARTHRITIS

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5
Q

Most commonly affected joints in osteoarthritis

A

ASYMMETRIC: more LOWER

hands (DIPS and PIPS), hips, knees, spine, feet

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6
Q

Pseudogout associations

A
  1. hemochromatosis
  2. hyperPTH
  3. hypothyroidism
  4. hypophosphatasia
  5. hypomagnesemia
  6. neuropathic joints
  7. trauma
  8. age, heredity
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7
Q

First line nonopioid analgesic therapy for osteoarthritis

A

acetaminophen

max safe dose: 4g/day

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8
Q

types of intra-articular therapy for osteoarthritis

A
  1. steroids

2. hyaluronate injections

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9
Q

intra-articular steroids

A

2nd line Tx
up to every 3 mo (knee most often)
Tx: osteoarthritis pain
AE with frequent injections: infection, worsening DM, or CHF

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10
Q

hyaluronate injections

A

Tx: osteoarthritis symptom relief (improves function)
expensive
no long-term benefit
limited to KNEE

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11
Q

Surgical Tx for osteoarthritis

A

3rd line Tx

  1. arthroscopy (may reveal unsuspected focal abnormalities, results in tidal lavage, expensive, complications)
  2. osteotomy (delay need for total joint replacement)
  3. total joint replacement (when pain severe and function significantly limited)
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12
Q

anti-CCP (cyclic citrullinated peptide)

A

most sensitive and specific for RA (can be found in unaffected relatives)
produced by synovial tissue B cells
activate complement pathways, IgE ACPAs cause basophil/ mast cell degranulation
prognosis: more aggressive, accelerated atherosclerosis, risk for ischemic heart disease

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13
Q

HLA-B27

A

seronegative spondylarthropathies
MHC class I molecule that presents antigens to CD8 T cells
in psoriasis or IBD: indicates likely to develop axial (spinal) arthropathy

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14
Q

ANA

A

Ab against nucleus
most sensitive SLE: no ANA, no lupus
also: RA, scleroderma, Hashimoto’s, IPF

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15
Q

anti-dsDNA

A

high specificity for SLE

associated with: NEPHRITIS

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16
Q

anti-RNApol3Ab

A

HTN renal crisis in diffuse systemic sclerosis

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17
Q

anti-centromere

A

limited cutaneous sclerosis

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18
Q

anti-Jo1

A

Ab against histdyl-tRNA synthetase
inflammatory myopathy
associated with: arthritis in myopathies

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19
Q

anti-Mi-2

A

dermatomyositis

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20
Q

rheumatoid arthritis (RA)

A

30s-50s female
INFLAMMATORY, SYSTEMIC
SYMMETRIC arthritis
increases mortality
genetic (additive/multiplicative) and environmental
elevated: ESR, CRP
Ab: anti-CCP, RF
Sx: fatigue, anorexia, weight loss, weakness, general aching and stiffness, low fever
joint: morning stiffness at least 30 min, swelling, warmth, erythema
synovial fluid: exudative yellow fluid, WBC elevated, reduced viscosity
onset: one or scattered joints, often large peripheral joints (knee)
immune complexes, lysosomes, ILs, FBGF, mononuclear cells infiltrating synovial membrane (acute: PMN)

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21
Q

HLA-DR4

A

30% RA risk
binds and presents antigen to T cell
DR4 shared epitope and T cell receptor interact
selection of auto reactive T cells in thymus

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22
Q

PTPN22

A

5% RA risk

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23
Q

TNFAIP3

A

5% RA risk

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24
Q

STAT4

A

5% RA risk

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25
Q

IL2RB

A

5% RA risk

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26
Q

shared epitope hypothesis

A

RA is most strongly associated with shared epitope alleles of HLA-DRB1

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27
Q

HLA-DRB1

A

shared epitopes: RA

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28
Q

rheumatoid factor (RF)

A

IgM Ab directed against Fc portion IgG
RA: more likely to have extra-articular manifestations
Sjogren’s, MCTD, mixed cryglobulinemia
also (but not as prevalent): SLE, polymyositis, dermatomyositis
other: young, old, chronic infection, CA (B-cell), biliary cirrhosis

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29
Q

examples of antigens in RA

A

joint: type II collagen
systemic: glucose phosphate isomerase

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30
Q

role of T cells in RA

A

low levels of T cell cytokines in RA synovium
Th1: IFN-y
Th17: IL-17
suppressed Treg possible
T cells in synovial inflammation can be antigen-independent (direct cell contact with macrophages)

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31
Q

role of macrophages and fibroblasts cytokines in RA

A

abundant in RA synovium
cytokines: TNFa, IL-6, IL-15, IL-18, GM-CSF, IL-33
recruit inflammatory cells (neutrophils)
anti-inflammatory IL-1Ra and IL-10 are produced but not enough to suppress other inflammatory ones

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32
Q

What joints are involved in RA?

A

SYMMETRICAL: more UPPER extremity
wrist, MCP, PIP
other: knees, hips, ankles, elbows, shoulders
spares spine (except first 3 joints)

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33
Q

spinal cord compression

A

C1 slips forward on C2
Sx: sensory loss to catastrophic neurologic compromise to sudden death
risk with RA if cervical spine is affected

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34
Q

What deformities occur in RA?

A

wrist: volar SUBLUXATION, RADIAL rotation
MCP: ULNAR DEVIATION
PIP, DIP: SWAN NECK, BOUTONNIERE
muscle atrophy, weakened supporting structures (ligaments, joint capsules), fibrosis and tightening of tissues (lumbricals of hand)
flexion contractures in larger peripheral joints (knee, hip, elbow)

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35
Q

extra-articular RA manifestations

A
  1. skin: rheumatoid nodules
  2. vasculitis: PALPABLE PURPURA or skin ulcers
  3. keratoconjunctivitis and xerostomia (lymphocytes)
  4. episcleritis and scleritis
  5. respiratory: interstitial fibrosis, pulmonary nodules (coin lesion), pleuritis with pleural effusion
  6. cardiac: pericarditis, nodules on valves
  7. neurologic: cervical myelopathy, compressive peripheral neuropathy (carpal tunnel, ulnar tunnel), peripheral neuropathy
  8. lymphadenopathy, splenomegaly
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36
Q

Where are rheumatoid nodules found?

A
  1. extensor surfaces of skin
  2. pleura
  3. meninges
  4. ears
    lungs, heart, tendons
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37
Q

Felty’s syndrome

A

triad

  1. splenomegaly
  2. RA
  3. leukopenia, thrombocytopenia
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38
Q

Sjogren’s syndrome

A

middle age female
Sx: keratoconjunctivitis sicca, xerostomia, parotid gland swelling, arthritis, fatigue
other glands: skin and vaginal dryness, nose, pharynx, larynx, tracheobronchial tree (hoarse, pneumonia)
Dx: anti-Ro/SS-A, anti-La/SS-B, labial salivary gland biopsy
complication: NON-HODGKIN’s LYMPHOMA
ANA, LOW C3 and C4, RF
some: leukopenia, thrombocytopenia, cryoglobulinemia, monoclonal gammopathy

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39
Q

Other organs involved in Sjogren’s

A
  1. renal: TYPE I RENAL TUBULAR ACIDOSIS, tubular interstitial nephritis, glomerulonephritis, nephrogenic diabetic insipidus
  2. GI: ESOPHAGEAL DYSFUNCTION, atrophic gastritis, biliary cirrhosis, hepatitis
  3. CNS/PNS: NEUROMYELITIS OPTICA, optic neuropathy, hemiparesis, movement disorder, cerebellar syndrome, spinal cord syndrome, progressive myelopathy, motor or sensory or autonomic neuropathy
  4. vasculitis: purpura, Raynaud’s
  5. NONHODGKIN’S LYMPHOMA, MALT
  6. PULMONARY: ILD
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40
Q

Schirmer’s test

A

filter paper to document tear flow

Dx: Sjogren’s

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41
Q

keratoconjunctivitis sicca

A

keratitis caused by decreased lacrimal secretion
Sx: dry eye, foreign body sensation, burning, photosensitivity
Dx: rose Bengal dye

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42
Q

rose Bengal dye

A

highlights epithelial lesion in eye

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43
Q

xerostomia

A

severe dry mouth
Sx: multiple dental caries, fissuring and ulceration of lips, tongue, buccal membranes, difficulty chewing/swallowing, gland enlargement (parotid or submandibular)

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44
Q

secondary Sjogren’s

A

complication of another autoimmune connective tissue disease
RA, SLE

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45
Q

What does a salivary gland look like grossly in someone with Sjogren’s?

A

enlarged, white

sometimes cysts

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46
Q

systemic lupus erythematosus (SLE)

A

african american
multi-system inflammatory disorder with flare and remission
Ab: ANA, anti-DNA, anti-Sm
genes: HLA-DR2/3, complement deficiency
need environmental exposure and genetic susceptibility
complement, immune complexes
Tx: corticosteroids, cyclophosphamide, methotrexate, mycophenolate mofetil, azathioprine, hydroxychloroquine, belimumab

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47
Q

discoid lupus erythematosus (DLE)

A

confined to skin

48
Q

drug-induced lupus erythematosus (DILE)

A

Sx: polyarthritis, fever, rash
less severe: NO nephritis (exception anti-TNFa drugs)
resolves with drug removal
Ab: anti-histone

49
Q

neonatal lupus erythematosus

A

newborns of mothers with SLE due to transfer of auto-Ab

Sx: skin rash (transient), HEART BLOCK (permanent), leukopenia

50
Q

predictors of flare in SLE

A
  1. new evidence of complement consumption
  2. rising anti-dsNDA
  3. increased ESR
  4. new lymphopenia
51
Q

SLE severity

  1. characteristics
  2. associations
A
  1. abrupt onset, increase renal, near, hematologic, serial involvement, rapid damage (irreversible organ injury)
  2. race (non-white), younger onset, MALE, low socioeconomic status
52
Q

Factors contributing to increased mortality in SLE

A
  1. early age onset, length of duration
  2. high severity at Dx
  3. non-white
  4. male
  5. low socioeconomic status
  6. poor adherence
  7. inadequate patient support system
  8. limited patient education
53
Q

leading causes of mortality in SLE

A

heart disease, malignancy, infection

54
Q

ACR criteria for classification of SLE

A

need 4/11

  1. malar rash
  2. discoid rash
  3. oral ulcers
  4. arthritis (non-erosive)
  5. serositis
  6. glomerulonephritis
  7. hematologic disorder
  8. ANA
  9. anti-dsDNA, anti-Smith, antiphospholipid
  10. neurologic
  11. photosensitivity
55
Q

anti-Smith

A

specific for SLE

56
Q

anti-RNP

A

SLE

associated with: arthritis, myositis, lung disease

57
Q

anti-Ro/SS-A

A

Sjogren’s
other: SLE
associated with: dry eyes/mouth, subacute cutaneous lupus (SCLE), neonatal lupus, photosensitivity

58
Q

anti-La/SS-B

A

Sjogren’s
other: SLE
associated with: dry eyes/mouth, subacute cutaneous lupus (SCLE), neonatal lupus, photosensitivity

59
Q

antiphospholipid antibodies (aPLs)

A

B2-glycoprotein I, anticardiolipin
SLE, RA, increase age
associated with: clotting
determine through: IgG or IgM in serum or coagulation assay (lupus anticoagulant test)

60
Q

SLE Sx: musculoskeletal

A

arthralgia
arthritis: symmetric/asymmetric, can be deforming, non-erosive
myalgia, myositis, weakness

61
Q

SLE Sx: serositis

A
  1. pleura: pleuritic chest pain, pleural effusion
  2. pericardium: chest pain, pericardial effusion
  3. peritoneal cavity: abdominal pain, fluid accumulation
62
Q

SLE Sx: renal

A

ANTI-DNA antibodies
significant morbidity and mortality
any renal structure can be affected: glomerulus, tubules, interstitium, vasculature
immune complexes: in situ and in circulation
other: aggregates of Ig, complement, and MAC

63
Q

SLE Sx: hematologic

A 
all cell lines
RBC: hemolytic anemia, anemia of chronic disease
WBC: leukopenia, lymphopenia
Platelet: thrombocytopenia
lymphadenopathy
64
Q

SLE Sx: neuropsychiatric

A

psychiatric: depression, psychosis, cognitive abnormalities
brain: seizure, stroke, movement disorder
spinal cord: transverse myelitis, MS-like disease, peripheral neuropathy

65
Q

SLE Sx: GI

A

less common
abdominal pain: serositis, vasculitis, bowel perforation, peritonitis
liver disease: autoimmune hepatitis, liver enzyme elevation

66
Q

SLE obstetrical problems

A

fertility normal
small for gestational age, fetal loss (antiphospholipid), neonatal lupus
beware of teratogenic drugs: methotrexate

67
Q

SLE Sx: cardiovascular

A
  1. pericarditis
  2. myocarditis
  3. endocarditis (valves: Libman-Sacks)
  4. coronary artery disease (lupus, medications, inflammation)
  5. peripheral vascular disease (vasculitis, Raynaud’s phenomenon)
68
Q

drugs that cause lupus

A 
hydralazine
procainamide
isoniazid
hydantoins
chloropromazine
methyldopa
penicillamine
minocycline
anti-TNF
IFNa
other: dietary, smoking, Vit. D deficiency
69
Q

antiphospholipid syndrome

A

most common: stroke (arterial)
other: DVT, miscarriages after 10 weeks
Dx: clinical event plus persistently positive aPLs (12 weeks apart)

70
Q

class I lupus nephritis

A

normal histology

71
Q

class II lupus nephritis

A

mesangial proliferation

72
Q

class III lupus nephritis

A

focal proliferative GN (

73
Q

class IV lupus nephritis

A

diffuse proliferative ( > 50% of glomeruli)

74
Q

class V lupus nephritis

A

membranous pattern

75
Q

class VI lupus nephritis

A

advanced sclerosing glomerulopathy

76
Q

systemic sclerosis

A

AA, female
Sx: Raynaud’s, microvasculature, renal, GI, pulmonary
major mortality and morbidity: PAH, ILD

77
Q

pathogenesis of systemic sclerosis

A

fibroblasts: fibrosis
endothelial cells: obliteration of small arteries
B cells: Ab production
T cells: cellular infiltration, cytokines, GF dysregulation
monocytes: transdifferentiation to fibroblasts when exposed to IFNy

78
Q

SS Sx: microvasculature/vasculature

A 
increased endothelial cell apoptosis, up regulation MHC class II and ICAM-1
platelets aggregate: microthrombi, digital artery occlusion
intimal proliferation (thickening) with narrowing of lumen, adventitial fibrosis, telangiectasis of vasa vasorum
79
Q

Raynaud’s phenomenon

A

episodic attacks of vasoconstriction in blood vessels in extremities due to cold/stress
pale: lack of blood flow
blue: vessels dilate to keep blood in tissue
red: flow returns, reactive hyperemia
primary or associated with: SSc, lupus, RA, polymyositis, MCTD (reconsider if not present), etc.

80
Q

nailfold capillary pattern

A

indicates the development of a secondary CT disease (ex: SSc) in a Raynaud’s patient

81
Q

types of scleroderma

A 
localized scleroderma (small area): morphea, linear scleroderma
systemic scleroderma: limited, diffuse, sine
82
Q

limited scleroderma

A

face, distal extremities
Ab: anti-centromere
Sx: severe digital ischemia, calcinosis
PAH more likely than in diffuse

83
Q

diffuse scleroderma

A

all skin

Ab: anti-topoisomerase 1 (Scl70)

84
Q

anti-centromere

A

LIMITED SCLERODERMA

clinical: severe digital ischemia, PAH, sicca syndrome, calcinosis

85
Q

anti-topoisomerase1 (Scl70)

A

DIFFUSE SCLERODERMA

clinical: pulmonary fibrosis, cardiac involvement

86
Q

PM/Scl

A

antigens
overlap of LIMITED/DIFFUSE Scleroderma
clinical: myositis, pulmonary fibrosis, acro-osteolysis

87
Q

anti-U1-RNP

A

MCTD
overlap of limited/diffuse scleroderma
clinical: SLE, inflammatory arthritis, pulmonary fibrosis
lack of: severe renal or CNS involvement

88
Q

scleroderma renal crisis (SRC)

A

life-threatening
risk factors: corticosteroids, anti-RNA polymerase III Ab
Tx: angiotensin converting enzyme inhibitors
other associations: new anemia or cardiac events, anti polymerase I Ab, NSAIDS, cyclosporine

89
Q

anti-RNA polymerase III

A

SCLERODERMA RENAL CRISIS

90
Q

SSc Sx: GI

A

gut dysmotility universal

upper: more common
lower: poor prognosis

91
Q

SSc Sx: pulmonary

A

pleurisy, pleural effusion, pleural scarring, aspiration pneumonia, malignancy, ILD, PAH

92
Q

localized scleroderma

A

children

nonsystematic skin disease

93
Q

plaque morphea

A

localized scleroderma

isolated circular patch of thickened skin

94
Q

generalized morphea

A

localized scleroderma

multiple lesions involving extensive areas of skin and can occasionally coalesce, mimicking systemic sclerosis

95
Q

keloid morphea

A

localized scleroderma

nodular form resembling keloids

96
Q

bullous morphea

A

localized scleroderma

subepithelial bullae

97
Q

linear scleroderma

A

localized scleroderma

linear streak that crosses dermatomes and is associated with atrophy of muscle

98
Q

en coupe de sabre

A

linear scleroderma underlying bone and rarely the brain

99
Q

mixed connective tissue disease (MCTD)

A

sequential overlap of lupus, scleroderma, inflammatory myositis over mo. to yrs
Ab: U1-RNP
Sx: Raynaud’s in ALL, membranous glomerulonephritis, pulmonary HTN

100
Q

What is the most common cause of death in MCTD?

A

pulmonary HTN

need echo to screen for abnormal P2

101
Q

ankylosing spondylitis (AS)

A 
adolescence - 35 yrs, male
TNFa excess
insidious onset
Sx: chronic low back pain, back stiffness (limited RoM), ascends spine, worse in morning and improve, sacroiliac tenderness, loss of lumbar lordosis and thoracic/cervical kyphosis
abnormal SCHOBER's test (
102
Q

enteropathic arthritis

A

inflammatory bowel disease-associated arthropathy: Crohn’s, ulcerative colitis, Whipple’s disease
peripheral: parallels GI
axial: does not parallel GI (B27 associated)
Tx: NSAIDS (can cause IBD flare)

103
Q

Reactive arthritis (Reiter’s syndrome)

A

inflammatory arthritis after INFECTION
triad: ARTHRITIS, URETHRITIS (sterile, mucopurulent discharge), CONJUNCTIVITIS, oral ulcers, circinate balanitis (penis ulcer), onycholysis, keratoderma blennorrhagica
GI: Salmonella, Campylobacter, Yersinia, Shigella, C. difficile
GU/resp: chlamydia
common in: HIV/AIDS (more severe and resistant to Tx)
lab: ESR, CRP, culture is usually neg.
OBSERVE: lasts months
recurrence common

104
Q

psoriatic arthritis

A 
progressive disease
CD8 cells
synovium: increase vascularity, neutrophils, CD3 T cell (correlate with Tx response)
elevated ESR: poor prognosis
Tx: TNF inhibitors (infliximab)
severe: think HIV
other Sx: conjunctivitis, iritis
105
Q

juvenile chronic arthritis

A

?

106
Q

Juvenile-onset ankylosing spondylitis

A

?

107
Q

list of spondyloarthropathies

A
  1. ankylosing spondylitis
  2. enteropathic arthritis
  3. reactive arthritis
  4. psoriatic arthritis
  5. undifferentiated spondylarthropathies
  6. juvenile chronic arthritis and juvenile-onset ankylosing spondylitis
108
Q

common features of spondylarthropathies

A
  1. RF NEGATIVE
  2. HLA-B27
  3. AXIAL skeleton
  4. large joint asymmetric oligoarthritis: LOWER extremities
  5. familial
  6. enthesitis, dactylitis
109
Q

x ray findings on ankylosing spondylitis

A

spinal osteopenia, bony ankylosis, vertebral fractures, atlantoaxial/ atlantoocipital subluxation, upward subluxation of axis

110
Q

What is more likely to occur if a patient has peripheral joint involvement in ankylosing spondylitis?

A

aortic regurgitation, heart block

111
Q

Tx for ankylosing spondylitis

A

NSAIDs
then as time progresses: sulfasalazine, local corticosteroids, TNF blockers, surger
always: analgesics, exercise, PT

112
Q

immunopathology of psoriatic arthritis

A

elevated immunoglobulins
T cells: HLA-DR, receptors for IL-2 and adhesion molecules, secrete IL-6
fibroblasts: IL-1B, IL-6, PDGF
synovium: TNFa, IL-1, IL-6, IL-8, IL-18
serum: IL-10, IL-13, IFNa, VEGF, FBGF, IL-18

113
Q

IL-18

A

PsA
stimulates angiogenesis
upregulates chemokines on synovial fibroblasts
increases mononuclear cell recruitment

114
Q

Patterns of PsA

A
  1. polyarticular pattern: > 4 joints, RA-like
  2. oligoarticular: 4 joints or less, asymmetric
  3. DIP involvement pattern
  4. arthritis Mutilans (severe)
  5. axial development (B27+: sacroiliitis and spondylitis)
115
Q

Tx of enteropathic arthritis: ulcerative colitis vs. Crohn’s

A

NSAIDS
UC: sulfasalazine
CD: adalimumab
both: glucosteroids, azathioprine, methotrexate, infliximab

116
Q

arthritis of celiac disease

A

GLUTEN
T cell: HLA-DQ2/8
Sx: fatigue, headache, arthralgias (axial or peripheral)
associated with development: T1DM, anemia, osteoporosis, neuropathies, joint symptoms
Dx: small bowel biopsy, IgA anti tissue transglutaninase and IgA antiedomysial Ab
Tx: eliminate gluten

117
Q

Diffuse idiopathic skeletal hyperostosis (DISH)

A

calcification and ossification most common on the right side of the spine (NOT inflammatory)
MELTED CANDLE WAX
left side in people with: dextrocardia, situs inversus
descending thoracic aorta prevents manifestationf of DISH on one side of the spine

Musculoskeletal (13 decks)

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