BL 02-18-14 9-10AM OSTEOARTHRITIS-Janson_Hirsh Flashcards
(60 cards)
1
Q
Osteoarthritis (OA) defn.
A
- Heterogeneous disorder characterized by destruction (degeneration) of articular cartilage & proliferation (hypertrophy) of contiguous bone
2
Q
OA & other arthritises
A
= end stage of all types of arthritis
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
4
Q
Signs of OA - Specific pattern of deformity
A
- Heberden’s (DIP) & Bouchard’s (PIP) nodes - often inherited
- Squaring of 1st carpometacarpal joint
- Genu varus (bow-legged)
- Hallux valgus (bunion on big toe)
- Cervical & lumbar spine spondylosis (degenerative change)
5
Q
Laboratory in OA - Labs in secondary OA
A
- uric acid
- iron, calcium. phosphate
- ESR, CRP
6
Q
OA Clinical Syndromes- 6 Types
A
- Primary generalized OA
- Inflammatory/erosive OA
- Isolated nodule OA
- Unifocal large joint OA
- Multifocal large joint OA
- Unifocal small joint OA
7
Q
Laboratory in OA - Synovial fluid analysis
A
Type I fluid
- 200-2000 WBCs
- 25% PMNs
- normal viscosity
Negative crystal exam
Normal glucose
8
Q
Specific patterns of x-ray changes
A
- “Gull wing” changes in interphalangeal joints
- Medial compartment disease of the knee (wear out cartilage in knee joint)
- Horizontal osteophytes of spine
- Decreased joint space superiorly w/ relative medial preservation in hip
- Hallux valgus (bunion deformity of great toe) without other metatarsal disease
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
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
11
Q
Radiographic evaluation
A
- Loss of cartilage space
- Bony sclerosis & eburnation (hardening of bone surfaces b/c of cartilage loss)
- Cystic changes of subchondral bone
- Osteophyte formation
- Altered shape of bone
- Joint effusion – non-inflammatory
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
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
14
Q
OA can be classified as…
A
- Primary, or idiopathic OA
- no known inciting event or disease - Secondary OA
- induced by known events/disease
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
16
Q
Gross pathology of OA
A
Joint in OA characterized by
- cartilage irregularities & “fissuring”
- hypertrophy of bone adjacent to the joint
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
18
Q
Normal cartilage - functions
A
- to allow joint movement w/ minimum friction
- to absorb some of the impact during normal joint loading
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
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
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
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
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
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
25
Water in cartilage
- Major component of cartilage
| - 70% of the weight of intact cartilage
26
Cartilage in OA
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
Cartilage remodeling & OA
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
Local destruction of articular cartilage in OA
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
Focal mechanical stress involved in local destruction of articular cartilage in OA
- 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
Normal cartilage - characteristics
- 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
5 components of cartilage
- Collagen - 50% of dry weight
- Proteoglycans - bulk of ECM
- Matrix Proteins
- Chondrocytes - 5% of cartilage volume
- Water - 70% of intact cartilage weight
32
Chondrocyte/Synovium pro-inflammatory substances involved in local destruction of articular cartilage in OA
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Cytokines & Inflammatory mediators --> promote progression of cartilage damage
Include:
- IL-1, IL-6, IL-17, IL-18
- TNF-alpha
- Nitric oxide (NO)
- Prostaglandins (PGs)
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33
Interleukin-1 (IL-1) in OA
- --> 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
Tumor necrosis factor α in OA
- Behaves like IL-1 & works synergistically w/ it to damage cartilage
- Stimulates production of MMPs
35
Chondrocytes/Synovium also produce Inhibitor Cytokines:
- 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
Other factors promoting cartilage damage in OA
- Complement activation
| - Adipokines
37
Nitric Oxide (NO) in OA
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
Prostaglandins
= can have multiple effects on various cells in joint
Negative effects
- increased production & activation of MMPs (specifically stromelysin)
39
Complement activation in pathogenesis of OA
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
Adipokines in OA
- 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
Cartilage component levels during development of OA
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
Development of OA on Gross morphologic level
- 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
Etiology of OA
- Unknown
| - Several predisposing factors IDed
44
Genetic predisposing factors for OA
- 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
Metabolic abnormalities in cartilage as predisposing factors for OA
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
Trama as predisposing factor in OA
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
IL-17 in OA
- produced by Th17 T-cells
| - increases expression of IL-1
48
IL-18 in OA
- produced by macrophages
| - induces IL-1 & TNF α production
49
Age as predisposing factor in OA
- 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
Inflammatory joint disease as predisposing factor in OA
- Cartilage damage initiated by other processes may also result in development of secondary OA
<--- RA, crystals, or infection
51
Types of treatment targets in OA
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
Obesity as predisposing factor in OA
- related to knee and hip OA, as well as to hand OA
53
Timing of Dx in OA
- B/c OA is defined by symptoms & radiographic changes, Dx not made clinically until very late (many years) after initiation of disease.
54
Psychosocial variables in OA
- Degree of pain perception (psychosocial) disproportionate to degree of true OA involvement
55
Intra-articular agents for OA
- Corticosteroids
| - Hyaluronic acid to OA knee pain
56
Nutraceuticals for OA
- Most commonly glucosamine & chondroitin sulfate
Glucosamine = aminosaccharide component of glycosaminoglycans, hyaluronan, keratan sulfate & heparin sulfate
57
Physical modalities to prevent rapid cartilage loss
- ↓ 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
Types of Medication for OA
- 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
Surgery types for OA
- arthroscopic
- reparative
- reconstructive
- total joint replacement
60
Alternative therapies for OA
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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
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