Osteoarthritis Flashcards
Health/function of joint depends on
- Anatomy (mechanics)
- Energy efficient motion
- Shock absorption - Physiology (biology)
- Balance of anabolic/catabolic proc
- Regulation of inflammation
- Response to dz and infection
Articular cartilage components (hyaline cartilage)
- Chondrocytes-1-2% total cartilage volume
2. Extracellular matrix-70% water, 30% dry weight
Extracellular matrix
- 70% water
- 30% dry weight
- 50% collagen (mostly type II)
- 35% proteoglycans
- 10% glycoprotein
- 5% mineral, lipids, other
Chondrocytes
- synthesize, organize, regulate composition of extracellular matrix
- Detect and respond to mechanical stimuli
Collagen fibrils
- 90-95% type II collagen
- Slow turnover
- Framework for organizatino of other matrix molecules/chondrocytes
Proteoglycans
Glycosaminoglycans (GAGs) attached to protein core
- Aggrecan
- 85% proteoglycan content of ECM
- Core protein interacts with hyaluronan
- neg charged glycosaminoglycans
- Condroitin sulfate
- Keratin sulfate
- Resists compressive forces (high density neg charge attracts water to separate molecules) - Small proteoglycans
- bind growth factors, regulate collagen synthesis
Cartilage nutrition
Nutrition and waste removal through synovial fluid
-applied load compresses cartilage squeezes things out
Collagen resists osmotic pressure exerted by proteoglycans resulting in
positive cartilage swelling pressure
Cartilage layers
- Superficial (tangential)
- chondrocytes and collagen arranged parallel to joint surface
- Most dense zone of collagen and cells - Intermediate (transitional)
- larger ovoid chondrocytes
- collagen fibers oblique to surface
- many branching fibers - Deep (radiate)
- largest chondrocytes arranged perpendicular to surface and arranged in columns
- collagen fibers oriented perpendicular to surface - Calcified cartilage
Two other important cartilage structures
- Tidemark
- junction of calcified and noncalcified cartilage - Subchondral bone
- supports cartilage
- determines shape and congruity of joint surface
Synovial membrane
- Subintimal layer
2. Intimal layer
Subintimal layer of synovial membrane
- fibrous and fatty tissue
- abundant vascular and nerve supply
Intimal layer of synovial membrane
- 1 to 4 synoviocytes thick, no basement membrane to allow passage of plasma and production synovial fluid
- Type A synoviocytes-phagocytes
- Type B synoviocytes-secrete protein
- Type C synoviocytes-intermediary between A and B
Type B synoviocytes
- Synovial fluid components
- hyaluronan, lubricin, collagen - Inflammatory and catabolic cytokines
- interleukins, prostaglandins, pro-matrix metalloproteinases
Synovial fluid
- Ultrafiltrate of plasma (low protein < 2 g/dL)
- Low cellularity (< 500 cells/uL) 90% monos
- Inflammation alters permeability
- Hyaluranon
Hyaluranon
- Large molecule
- Responsible for synovial fluid viscosity
- High affinity for water
- Molecules entangle, provides joint fluid viscosity
Subchondral bone
- Dense, like cortical bone in diaphysis of long bones
- Haversian canals run parallel to joint surface
- Supports cartilage
Ligaments/tendons/muscle
Regulate range of motion and provide stability
Joint capsule
- Fibrous, poorly cellular
- Composed of collagen, proteoglycan, noncollagenous proteins and water
- Lined by synovial membrane
- regulates range of motion and stabilizes
Vascular supply
- Substantial to synovial membrane
- None to cartilage
Innervation
- Proprioceptive and nociceptive fibers
- Nerve fibers terminate in joint capsule, ligaments, menisci
- No ennervation in articular cartilage
Matrix Metalloproteinases (MMPS)
- Articular cartilage/extracellular matrix degradation
- Released in latent form, must be activated
Aggrecanases
ADAMTS4 and ADAMTS5
-A Disintegrin And Metalloprotease with ThromboSpondin motifs
Cytokines
- Soluble peptides produced by cells (endocrine/paracrine/autocrine fashion)
- Proinflammatory cytokines
- IL-1a and b, TNF-a - Proteoglycan synthesis inhibition
- IL-1a and b stim production of MMPs by chondrocytes and synoviocytes - Inhibited by IL-1 receptor antagonist protein (IRAP)
Prostaglandins
- PGE2
- Causes proteoglycan depletion from cartilage matrix
- softening of cartilage - Enhances pain perception
- Production stimulated by IL-1
Oxygen derived free radicals
- Produced by neutrophils and macrophages
2. Cleaves proteoglycan, collagen, and hyaluranon molecules
Consequences of inflammatory mediator production
- biochemical damage to articular cartilage
- Accelerated degradation articular cartilage collagen and proteoglycan
- Inability of chondrocytes to replace collagen and proteoglycans
- Weakened articular cartilage can’t resist loading and shear stress
- Development gross cartilaginous lesions
- Wear particles causes continued damage and further mediator production
Intrinsic mech cartilage repair
- inc metabolic activity of chondrocytes
- increased cell division
- synthesis proteoglycans and collagen
Extrinsic mech cartilage repair
- Mesenchymal elements subchondral bone produce connective tissue
- fibrocartilage, not type II collagen
Matrix flow cartilage repair
- Cartilage produced at periphery of lesion
- Wave-like lips of cartilage migrate towards center of defect
- very limited movement
Partial thickness lesions
- Calcified cartilage layer not breached
- Minimal to no inflammatory response
- some intrinsic repair
- pre-existing cartilage superior to repair cartilage
Full thickness lesions
- Injury through to subchondral bone with exposure
- penetration of SC bone causes inflammatory repsonse
- formation of granulation tissue
- fibroblasts recruited and produce collagen
- fibrous tissue undergoes chondrification to produce fibrocartilage (inferior to type II)
Osteochondral defect
Injury extends into or beyond subchondral bone
Osteoarthritis definition
Chronic degeneration of joint tissues/articular cartilage, w/ irreversible changes to joint.
OA occurs due to
cumulative effects of joint tissue over time, or single major trauma
Altered mechanics of injury produce change in
biology (catabolism>anabolism) of joint which further degrades mechanical properties of joint.
Tissue changes contributing to or resulting from OA
- Synovitis
- Capsulitis
- Ligamentous damage
- primary cartilage damage
Diagnosis of OA
- PE
- Local anesthesia
- Rads
- U/S
- Nuclear Scintigraphy
- Computed tomography
- MRI
- Synovial fluid analysis
Treatment of OA
- REST
- SX
- arthroscopy
- arthrodesis
- facilitated ankylosis - Medical therapy
- NSAIDS
- Corticosteroids
- Dz modifiers
- Biologics
- Complementaries
