Porth's Essentials of Pathophysiology, 4e

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Disorders of the Skeletal System: Metabolic and Rheumatic Disorders

C h a p t e r 4 4

interleukin (IL)-1 and TNF (Fig. 44-11). These chemi- cal messengers stimulate the production and release of proteases (enzymes) that are destructive to joint struc- tures. The resulting damage predisposes the chondro- cytes to additional injury and impairs their ability to maintain cartilage synthesis and repair the damage. The combined effects of inadequate repair mechanisms and imbalances between the proteases and their inhibitors contribute further to disease progression. The earliest structural changes in OA include enlargement and reorganization of the chondrocytes in the superficial part of the articular cartilage. 3,4 This is accompanied by edematous changes in the cartilaginous matrix, principally the intermediate layer. The cartilage loses its smooth aspect and surface cracks or micro- fractures occur, allowing synovial fluid to enter and widen the crack. As the crack deepens, vertical clefts form and eventually extend through the full thickness of the articular surface and into the subchondral bone. Portions of the articular cartilage eventually become completely eroded and the exposed surface of the sub- chondral bone becomes thickened and polished to an ivory-like consistency (eburnation). Fragments of car- tilage and bone often become dislodged, creating free- floating osteocartilaginous bodies (“joint mice”) that enter the joint cavity. Synovial fluid may leak though the defects in the residual cartilage to form cysts within the bone (Fig. 44-12). As the disease progresses, the under- lying subchondral bone becomes sclerotic and thickened in response to increased pressure on the surface of the joint, rendering it less effective as a shock absorber. Sclerosis, or formation of new bone and cysts, usually occurs at the joint margins, forming abnormal bony out- growths called osteophytes, or spurs (see Fig. 44-12). As the joint begins to lose its integrity, there is trauma to the synovial membrane, which results in nonspecific inflam- mation. Compared with RA, however, the inflammatory

the mechanical stress. 3 Thus, the subchondral bone pro- tects the overlying articular cartilage, providing it with a pliable bed and absorbing the energy of the force (Fig. 44-10). Articular cartilage has two major components: an extracellular matrix, which is rich in proteoglycan and collagen fibers, and a limited number of chondro- cytes, which produce the matrix. Popularly known as wear-and-tear arthritis, OA is characterized by significant changes in both the com- position and mechanical properties of cartilage. 3,4 The articular cartilage injury is thought to result from chondrocyte injury and release of cytokines such as B FIGURE 44-10. (A) A joint normally undergoes deformation of the articular cartilage and the subchondral bone when carrying a load.This maximizes the contact area and spreads the force of the load. (B) If the joint does not deform with a load, the stresses are concentrated and the joint breaks down. A

Aging Mechanical stress

Chondrocyte response

Bone cysts

Osteophyte

Release of cytokines (e.g., TNF, IL-1)

Production, release of protease enzymes

Loss of smooth cartilage surface

Development of surface cracks

Destruction of joint structures

Destruction of subchondral bone

Erosion of cartilage and bone

Joint space narrows

Osteophyte formation

FIGURE 44-12. Joint changes in osteoarthritis.The left side denotes early changes and joint space narrowing with cartilage breakdown.The right side shows more severe disease progression with lost cartilage and osteophyte formation.

FIGURE 44-11. Disease process in osteoarthritis.