Musculoskeletal Disorders Flashcards
What are osteoblasts?
Bone forming cells, have role in mineralization, produce type I collagen, key role in osteoclast differentiation
What are osteocytes?
Differentiated osteoblasts (hardened from minerals, surrounded in osteoid), become buried in matrix, coordinate bone remodelling
What are osteoclasts?
Bone resorptive cells, large and multinucleated, contains lysosomes filled with hydrolytic enzymes
What are the stages of bone remodelling?
Activation, resorption, reversal, formation, quiescence
What are the key steps in bone remodelling?
Begins with osteoclasts, resorb mineral component of matrix and secrete protease to digest protein matrix, osteoblasts migrate to resorbed surface and lay down new bone (protein matrix and then becomes mineralized), osteoblasts become buried and becomes osteocytes
What is RANK?
Receptor activated nuclear factor Kappa-B, expressed on surface of osteoclasts and osteoclast precursors
What is RANKL?
Ligand for RANK, plays key role in osteoclast formation/function/survival
What happens when RANKL binds to RANK?
Osteoclast differentiation as well as bone resorption
What serves to prevent resorption caused by the RANK/RANKL pathway?
OPG (osteoprotegeren) which prevents the binding of RANKL to RANK, produced by osteoblasts
What decreases the production of OPG?
Glucocorticoids and proinflammatory cytokines (TNF-a, IL-1)
What are some of the key players in bone health?
Proinflammatory cytokines (IL-1, TNF-a), vit D, nutrients, parathyroid hormone, sex hormones (estrogen), glucocorticoids
What is the action of parathyroid hormone?
Acts on kidney to resorb calcium from renal tubules to increase amount in blood, increase Vit D consumption, increases bone resorption
What is the role of estrogen in bone health?
Inhibits bone resorption, blocks IL-6 and IL-6 is potent stimulator of resorption. Also protects bone from resorption effects of PTH
What are some necessary nutrients for bone health?
Calcium, vit D, protein, Vit K, folate and B12
What is osteoporosis?
Metabolic bone disease, decreased bone mass (bone mineral score of less than -2.5 on DEXA scan), bone formation not equal to bone resorption
What are some signs of osteoporosis?
Usually considered to be silent, first sign is often a fracture
What is sarcopenia?
Gradual and generalized loss of skeletal muscle mass and strength with risk of adverse outcomes. Neurogenic, metabolic, and morphologic changes
What is a challenge with sarcopenia?
Hard to tell whether just normal aging process or abnormal
What is the most movable and complex joint?
Synovial joint
What is the composure of a synovial joint?
Fibrous joint capsule, synovial membrane, joint cavity (space), synovial fluid, articular cartilage (covers the bony surface)
What is arthritis?
Common alteration in the articular system, characterized by inflammation, cartilage destruction, bony spurs and sclerotic lesions
What are three key types of arthritis?
Rheumatoid arthritis (inflammatory), osteoarthritis (hypertrophic), gout (metabolic)
What occurs in osteoarthritis?
Disruption of integrity of collagen network, catabolism of cartilage, primary lesion appears on cartilage
What occurs as a result of catabolism of cartilage?
Breakdown of cartilage into the synovial fluid, initiates an inflammatory response by synoviocytes, results in lesions on the cartilage
What occurs in osteoarthritis as result of activation of inflammation?
Activated synovial macrophages that cause synovitis, cytokines released into synovial fluid, ROS and proteinases
What are some clinical manifestations of osteoarthritis?
Occurs later in life, slow onset, joints ache and are tender with little swelling, often begins on one side of body and usually localized to one set of joints, morning stiffness <1 hour and returns with activity
What is rheumatoid arthritis?
Autoimmune condition, synovial membrane inflammation with systemic signs, ATROPHIC
What occurs in the inflammatory response in rheumatoid arthritis?
Antibodies against self-antigens and inflammatory cytokines in synovial membrane, inflammatory cytokines convert the synovium into thick, abnormal layer (pannus), cells in the synovial membrane hypertrophy and proliferate, RANKL activated
What are rheumatoid factors?
Normal antibodies that turn into autoantibodies and attack the host tissues, bind with self-antigens in the blood and synovial membrane and form immune complexes
What are some clinical manifestations of rheumatoid arthritis?
Begins anytime, more rapid progression, joints painful/stiff/swollen, affects small and large joints on both sides of body (symmetrical), morning stiffness >1 hour, systemic symptoms
What are some risks for gout?
Metabolic syndrome, poor lifestyle, excessive alcohol, hyperlipidemia, urate-elevating medications, history of urolithiasis, CKD/renal disease
What characterizes gout?
Excess burden of uric acid