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Unit 3 B&L > BL 02-18-14 9-10AM OSTEOARTHRITIS-Janson_Hirsh > Flashcards

BL 02-18-14 9-10AM OSTEOARTHRITIS-Janson_Hirsh Flashcards

1
Q

Osteoarthritis (OA) defn.

A
  • Heterogeneous disorder characterized by destruction (degeneration) of articular cartilage & proliferation (hypertrophy) of contiguous bone
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2
Q

OA & other arthritises

A

= end stage of all types of arthritis

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3
Q

Clinical features of OA

A
  • localized joint tenderness
  • joint pain improved w/rest
  • stiffness <30 min, localized to involved joints
  • decreased joint mobility
  • relative preservation of function
  • hypertrophic bony spurs (osteophytes)
  • bony enlargment
  • crepitance
  • variable joint inflammation / instability
  • NO systemic involvement
  • Rarely symptomatic before age 40
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4
Q

Signs of OA - Specific pattern of deformity

A
  1. Heberden’s (DIP) & Bouchard’s (PIP) nodes - often inherited
  2. Squaring of 1st carpometacarpal joint
  3. Genu varus (bow-legged)
  4. Hallux valgus (bunion on big toe)
  5. Cervical & lumbar spine spondylosis (degenerative change)
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5
Q

Laboratory in OA - Labs in secondary OA

A
  • uric acid
  • iron, calcium. phosphate
  • ESR, CRP
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6
Q

OA Clinical Syndromes- 6 Types

A
  1. Primary generalized OA
  2. Inflammatory/erosive OA
  3. Isolated nodule OA
  4. Unifocal large joint OA
  5. Multifocal large joint OA
  6. Unifocal small joint OA
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7
Q

Laboratory in OA - Synovial fluid analysis

A

Type I fluid

  • 200-2000 WBCs
  • 25% PMNs
  • normal viscosity

Negative crystal exam

Normal glucose

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8
Q

Specific patterns of x-ray changes

A
  1. “Gull wing” changes in interphalangeal joints
  2. Medial compartment disease of the knee (wear out cartilage in knee joint)
  3. Horizontal osteophytes of spine
  4. Decreased joint space superiorly w/ relative medial preservation in hip
  5. Hallux valgus (bunion deformity of great toe) without other metatarsal disease
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9
Q

Epidemiology of OA - how common

A
  • most common arthropathy
  • advanced age is one of the strongest risk factors
  • more OA found by X-rays than is symptomatic (X-ray correlates better w/symptoms in hip OA)
  • found on autopsy in weight-bearing joints of ~100% of ppl by age 40
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10
Q

Laboratory in OA - Investigational labs

A

Cartilage degradation products in serum & joint fluid.

  • Hyaluronic acid, fragments of aggrecan
  • Type II collagen, & its breakdown products
  • Cartilage oligomeric protein
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11
Q

Radiographic evaluation

A
  1. Loss of cartilage space
  2. Bony sclerosis & eburnation (hardening of bone surfaces b/c of cartilage loss)
  3. Cystic changes of subchondral bone
  4. Osteophyte formation
  5. Altered shape of bone
  6. Joint effusion – non-inflammatory
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12
Q

Epidemiology of OA - Males vs. Females

A

Overal frequency:
45 yrs = females predominate

Women have more severe disease & increased frequency of Heberden’s/Bouchard’s nodes

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13
Q

Epidemiology of OA - Occupational risks

A
  • OA of the hips, knees, shoulders more frequent in miners
  • OA of hands more frequent in weavers
  • No increase in OA in pneumatic hammer drillers and in Finnish long distance runners
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14
Q

OA can be classified as…

A
  1. Primary, or idiopathic OA
    - no known inciting event or disease
  2. Secondary OA
    - induced by known events/disease
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15
Q

Distribution of joints involved in OA

A

Highly variable:

  • may involve 1 joint, esp. after trauma
  • may be “generalized,” affecting PIPs, DIPs, & 1st carpometacarpal (CMC) joints
  • Generally. primarily affects weight-bearing & heavily used joints
  • Tends to spare ankle, wrist, shoulder, & elbow, unless significant trauma has occurred, or metabolic / inflammatory disease present
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16
Q

Gross pathology of OA

A

Joint in OA characterized by

  • cartilage irregularities & “fissuring”
  • hypertrophy of bone adjacent to the joint
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17
Q

Microscopic pathology of OA

A

Articular cartilage surface reveals frayed & disrupted collagen fibers.

  • Chondrocyte cells first undergo clonal expansion (↑#) & the proteoglycan content of ECM ↓
  • Subchondral bone has ↑ density
  • Periarticular bone is hypertrophic
  • Synovium has variable findings from normal areas, to areas inflamed & w/ cellular infiltrates
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18
Q

Normal cartilage - functions

A
  • to allow joint movement w/ minimum friction

- to absorb some of the impact during normal joint loading

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19
Q

Epidemiology of OA - Sports risks

A

= in general, no increased risk (and exercise may be protective) in recreational participants.
= Chondrocytes may require some degree of mechanotransduction to maintain function

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20
Q

Epidemiology of OA - Other risks

A
  • Trauma/previous injury is associated with OA

- Obesity - best correlation with OA of the knees and hands in women

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21
Q

Collagen in cartilage

A
  • 50% of dry weight of cartilage
  • 90% of the collagen is Type II (also, IX, X, XI)
  • Forms rigid framework of articular cartilage, “holding in” hydrophilic matrix
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22
Q

Proteoglycans in cartilage

A
  • Highly charged aggregates of glycosaminoglycans
  • Bulk of ECM, contained w/in collagen fibrils
  • Major components are chondroitin sulfate & keratin sulfate
  • B/c of charge & tendency to aggregate, highly hydrophilic —> retain major component of cartilage, water
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23
Q

Matrix Proteins in cartilage

A
  • Other proteins that contribute to ECM
  • Most important proteolytic matrix metalloproteinases (MMP):
    == Collagenase
    == Gelatinase
    == Stromelysin
  • Matrix also contains lots of tissue inhibitor of metalloproteinase (TIMP) —> controls proteolytic activity of these enzymes
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24
Q

Chondrocytes in cartilage

A
  • -> Only 5% of total cartilage volume
  • Synthesize all extracellular components
  • Metabolically active
  • Receive nutrition from synovial fluid or subchondral bone by diffusion through ECM
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25
Q

Water in cartilage

A
  • Major component of cartilage

- 70% of the weight of intact cartilage

26
Q

Cartilage in OA

A

Cartilage = main focus of pathology in OA

  • Changes observed in OA cartilage represent final common pathway of abnormalities occurring in collagen, proteoglycans, matrix-proteins, & chondrocytes
  • Primarily a degenerative process, BUT inflammatory mediators plays a significant role
27
Q

Cartilage remodeling & OA

A

Cartilage normally remodels over time
Requires both:
- Destructive factors to degrade ECM components (MMPs)
- Constructive production of collage (mainly type II) & proteoglycans (aggrecan)
» Constructive factors

28
Q

Local destruction of articular cartilage in OA

A

Many factors, cytokines, & inflammatory mediators are implicated as inciting local destruction of articular cartilage:

  • focal mechanical stress
  • pro-inflammatory substances released by chondrocytes & synovium
29
Q

Focal mechanical stress involved in local destruction of articular cartilage in OA

A
  • trauma, physical forces, joint instability, defects in proprioception, metabolic abnormalities, crystal disease
  • -> can injur chondrocyte & cause degradative enzymes to be release –> collage fibrillation & matrix breakdown
  • -> Type II collagen & its degradative products can be released
30
Q

Normal cartilage - characteristics

A
  • Highly hydrophilic nature of cartilage allows it to act like a sponge, with water squeezed out of cartilage during loading, followed by re-expansion during relaxation.
  • Normal cartilage is avascular, and has no nerves
31
Q

5 components of cartilage

A
  • Collagen - 50% of dry weight
  • Proteoglycans - bulk of ECM
  • Matrix Proteins
  • Chondrocytes - 5% of cartilage volume
  • Water - 70% of intact cartilage weight
32
Q

Chondrocyte/Synovium pro-inflammatory substances involved in local destruction of articular cartilage in OA

A 
Cytokines & Inflammatory mediators --> promote progression of cartilage damage
Include:
- IL-1, IL-6, IL-17, IL-18
- TNF-alpha
- Nitric oxide (NO)
- Prostaglandins (PGs)
33
Q

Interleukin-1 (IL-1) in OA

A
  • –> promotes ECM degradation & decreases new matrix formation
  • specifically, promotes degradation of type II collagen & aggrecan by stimulating chondrocytes to make MMP
  • stimulates other mediators (PGE2, NO, IL-6)
  • Plays pivotal role in sustaining inflammation & cartilage degradation
34
Q

Tumor necrosis factor α in OA

A
  • Behaves like IL-1 & works synergistically w/ it to damage cartilage
  • Stimulates production of MMPs
35
Q

Chondrocytes/Synovium also produce Inhibitor Cytokines:

A
  • IL-4, IL-10, IL-13, & IL-1 receptor antagonist (IL-1Ra)
  • -> ↓ production & activities of catabolic & proinflammatory cytokines in chondrocytes in vitro
  • –> suppress cartilage destruction in vivo
  • –> Transforming growth factor-beta (TGF-β) & insulin-like growth factor (IGF-I) implicated in maintaining cartilage by anabolic mechanism
36
Q

Other factors promoting cartilage damage in OA

A
  • Complement activation

- Adipokines

37
Q

Nitric Oxide (NO) in OA

A

Produced by endothelial cells & chondrocytes

  • -> catabolic effects on cartilage
  • -> like IL-1, increases MMP production & inhibits proteoglycan synthesis
  • as OA cartilage tries to repair itself, chondrocytes proliferate greatly
  • NO seems to induce chondrocyte apoptosis, inhibiting this reparative response
38
Q

Prostaglandins

A

= can have multiple effects on various cells in joint

Negative effects
- increased production & activation of MMPs (specifically stromelysin)

39
Q

Complement activation in pathogenesis of OA

A

High expression & activation of complement in OA pt’s synovial fluid/tissue

Membrane attack complex on chondrocytes appears critical to OA development

  • –> chondrocyte cell death or production of degradative enzymes & inflammatory mediators
  • –> cartilage loss

Released / exposed cartilage ECM components may trigger complement cascade

40
Q

Adipokines in OA

A
  • cytokines mainly produced by adipose tissue
  • may be linked to development of OA
  • Obesity associated w/systemic low-grade inflam.
  • ↑ Risk of hand OA in obese individuals (not explained by overloading of the joints)
41
Q

Cartilage component levels during development of OA

A

Initially, water content increases in cartilage

  • – Collagen-proteoglycan network weakens
  • – Collagen fibers become weaker w/ looser “weave”

Proteoglycan content begins to decrease (in advanced OA, may be 50% or less of normal)
—> accompanied by increase in degradative enzymes

Chondrocytes initially increase in number, then in later stages of OA die

42
Q

Development of OA on Gross morphologic level

A
  • Cartilage surface becomes disrupted & fragmented with pits & ulcers.
  • Bone may develop bare areas.
  • Bone responds by making osteophytes, which may be capped by fibrocartilage
  • Bone reparative processes may cause formation of type I collagen
43
Q

Etiology of OA

A
  • Unknown

- Several predisposing factors IDed

44
Q

Genetic predisposing factors for OA

A
  • Some forms of OA have genetic predisposition
  • Recently demonstrated that point mutations in type II collagen gene can result in accelerated familial OA & chondrodysplasia.
  • –> accounts for only a tiny % of cases of OA
45
Q

Metabolic abnormalities in cartilage as predisposing factors for OA

A

Several metabolic diseases are associated w/ accelerated OA (mechanism unknown):

  • hemochromatosis
  • Wilson’s disease
  • ochronosis

Direct chondrocyte toxicity + deposition of calcium pyrophosphate crystals in ECM may contribute to the disease process

46
Q

Trama as predisposing factor in OA

A

In the form of:

  • mechanical instability
  • mechanical incongruity
  • excessive load (obesity)
  • denervation (loss of normal pain feedback)

Disruption of normal joint mechanics cause rapid development of OA

Postulated that trauma –> chondrocyte injury –> imbalance between anabolic & catabolic products of these cells (mechanotransduction) –> ECM degradation & eventual OA

47
Q

IL-17 in OA

A
  • produced by Th17 T-cells

- increases expression of IL-1

48
Q

IL-18 in OA

A
  • produced by macrophages

- induces IL-1 & TNF α production

49
Q

Age as predisposing factor in OA

A
  • 75% of persons over age 70 have OA
  • uncommon under age 40
  • May in part be associated w/age-related ↓# of chondrocyte in articular cartilage
50
Q

Inflammatory joint disease as predisposing factor in OA

A
  • Cartilage damage initiated by other processes may also result in development of secondary OA
    <— RA, crystals, or infection
51
Q

Types of treatment targets in OA

A
  1. Biomechanical or biochemical targets?
  2. Primary prevention? (reduce risk factors like obesity & repetitive activities)
  3. Secondary prevention? (prevent progression with disease modifying OA drugs - DMOADs)
  4. Tertiary treatment? (treat consequences of OA)
52
Q

Obesity as predisposing factor in OA

A
  • related to knee and hip OA, as well as to hand OA
53
Q

Timing of Dx in OA

A
  • B/c OA is defined by symptoms & radiographic changes, Dx not made clinically until very late (many years) after initiation of disease.
54
Q

Psychosocial variables in OA

A
  • Degree of pain perception (psychosocial) disproportionate to degree of true OA involvement
55
Q

Intra-articular agents for OA

A
  • Corticosteroids

- Hyaluronic acid to OA knee pain

56
Q

Nutraceuticals for OA

A
  • Most commonly glucosamine & chondroitin sulfate

Glucosamine = aminosaccharide component of glycosaminoglycans, hyaluronan, keratan sulfate & heparin sulfate

57
Q

Physical modalities to prevent rapid cartilage loss

A
  • ↓ Weight, if obese
  • Modify activities & occupation
  • ↓ Weight bearing load (canes, crutches)
  • Assistive devices
  • Physical therapy - gait instruction, strengthening
  • Exercise may…
  • –> improve general health
  • –> modify risk factors in disease progression
  • –> ↑ ROM & flexibility
  • –> ↑ Endurance & Strength
  • –> ↓ Fall risk
  • –> May even be chondroprotective
58
Q

Types of Medication for OA

A
  • Topical agents
  • Nonopioid analgesics (e.g., acetaminophen)
  • Anti-inflammatory agents such as NSAIDs
  • Opioid analgesics
  • Nutraceuticals & alternative therapies
  • Intra-articular agents
  • Adjunctive therapy such as muscle relaxants
59
Q

Surgery types for OA

A
  • arthroscopic
  • reparative
  • reconstructive
  • total joint replacement
60
Q

Alternative therapies for OA

A 
Used by over 80% of patients w/ OA
Some have been formally studied w/out proven benefit, including:
- Leech therapy
- S-adenosylmethionine (SAMe)
- Ginger extract
- Avocado/Soybean Unsaponifiables
- Acupuncture
- Electromagnetic fields
- Magnets

Unit 3 B&L (18 decks)

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