Ch 26- Bone and Joints Flashcards
constituents of bone
- ECM -> osteoid and mineral components
- Cells -> osteocytes, osteoblasts, osteoclasts
osteocytes
- derived from osteoblasts
- have projecting dendrites for cell to cell communication
- perform mechanotransduction
osteoid ECM
- made up of type 1 collagen and osteopontin
- osteopontin- Ca homeostasis and marker for osteoblast activity
hydroxyapatite
- mineral component of ECM
- stores Ca and P
diaphysis
- shaft of bone
- made of compact tissue that encloses medullary cavity
epiphysis
- enlarged end of bone
- made of spongy tissue and articulates with neighboring bones
- covered with articular cartilage to reduce friction and absorb shock
metaphysis
- between epiphysis and diaphysis
- contains cartilage to enable bone to grow
- disappears in adulthood
periosteum
- dense layer of vascular CT enveloping bones
- not found on surfaces of joints
compact bone
- aka cortical bone
- dense bone in which bony matrix is solidly filled with organic ground substances and inorganic salts
endosteum
- covers insides of bones
- surrounds medullary cavity
medullary cavity
- central cavity of bone shafts
- where red and/or yellow marrow is stored
how much of the skeleton is replaced annually
- 10%
- regulated by cell-cell interactions and cytokines
osteoclast activation
- primary pathway= NFkB
- activated NFkB -> RANKL binding to RANK receptor
- RANK receptor located on stromal cells and osteoblasts
- also get MCSF release causing differentiation of osteoblasts to osteoclasts
osteoclast inactivation
- maturation of osteoblasts to osteoclasts is stopped by producing osteoprotegrin
- osteoproegrin is “decoy receptor” to prevent RANKL from binding to receptor
achondroplasia
- most common cause of dwarfism
- autosomal dominant
- retarded cartilage growth
- due to mutation if FGF3 causing excessive suppressed bone growth
clinical features of achrondroplasia
- shortened proximal extremities
- normal trunk length
- enlarged head with bulging forehead
- depression of bridge of nose
osteogenesis imperfecta
- type 1 collagen disease
- most common inherited disorder of CT
- affects bones*, eyes, ears, skin, teeth
- autosomal dominant
pathphysiology of osteogenesis imperfecta
- collagen subunit assembly is disturbed- defective assembly of collagen peptides
- results in too little bone and very fragile skeleton
types of osteogenesis imperfecta
- type 1- normal life span but experiences childhood fx
- type 2- fatal in uteru
osteopenia
- decreased bone mass
- bone mass < 1 or 2.5 SD
- normal bone mineral content
osteoporosis
- severe osteopenia
- bone mass < 2.5 SD
- classified as either localized or generalized
- normal bone mineral content
causes of primary generalized osteoporosis
- idiopathic
- post- menopausal*
- senile*
causes of secondary osteoporosis
- endocrine disorders
- neoplasia
- drugs- corticosteroids
- manutrition and vit C or D def
- immobilization
estrogen and osteoporosis
- estrogen required for proper functioning of osteoblasts and clasts
- decreased estrogen -> increased cytokine release
- cytokines activate osteoclasts
- called high turnover osteoporosis
low turnover osteoporosis
- age related changes
- due to accumulation of bone loss with each turn over
clinical course of osteoporosis
- depends on bones involved
- vertebral fx common
- complications of fx of femoral neck, pelvis or spine -> PE or pneumonia
endocrine disorders associated with secondary osteoporosis
- diabetes
- hyperparathyroidism
- hyper/hypothyroidism
pagets disease
- aka osteitis deformans
- increased but disordered and structurally unsound bone mass
- usually begins in late adulthood
phases of paget disease
- initial osteolytic stage
- mixed osteoclastic- osteoblastic stage
- osteosclerotic stage (silent)
pathogenesis of paget disease
- genetic and enviornmental factors
- mutations in SQSTM1 gene - increased NK-kB
- RNA virus infections -> modifies vit D sensitivity and IL-6 secretion
clinical course of paget disease
- mostly asymptomatic
- often involves axial skeleton and proximal femur
- pain localized to affected bone
- leontiasis ossea
- platybasia
- compression of posterior fossa of skull
- anterior bowing of legs
- chalk-stick fx
- compression fx of vertebra -> kyposis
- osteosarcoma and fibrosarcoma rare
leontiasis ossea
- lion face
- associated with paget disease
platybasia
- invagination of skull base
- associated with paget disease
chalk stick type fx
- occurs in long bones of lower limb in pts with paget disease
renal osteodystrophy
- skeletal changes that occur in chronic renal disease
- osteopenia/porosis
- osteomalacia
- secondary hyperparathryoidism
- growth retardation
impact of tubular dysfunction on bones
- renal tubular acidosis -> decreased pH
- dissolves the hydroxyappatite
- results in osteomalacia
impact of renal failure on bones
- decreased phosphate excretion
- causes chronic hyperphsphatemia hypocalcemia
- causes secondary hyperparahtyroidism
BMP-7 and Klotho
- normally secreted by kidneys
- play role in osteoblast activity and Ca homeostasis
pathologic fx
- involving bone weakened by a underlying disease process like a tumor
steps of healing fractures
- hematoma
- necrosis of broken bone ends
- fibroblasts invade clot
- fibroblasts secrete collagen fibers which form callus
- callus bridges broken bone ends over 2-6 weeks
- osteoblasts invade callus and convert it to bone over 3-6 weeks
osteomyelitis
- inflammation of bone secondary to infection
- most common causes= pyogenic (s. aureus) bacteria and mycobacteria
how can organisms reach bone and cause infection
- hematogenous spread
- extension from contiguous site
- direct implantation
sequestrum
- dead bone in osteomyelitis
involucrum
- newly depositied bone
- forms shell of living tissue around segment of infected bone during osteomyelitis
clinical course of osteomyelitis
- malaise, fever, chills
- leukocytosis
- pain over affected region
- destruction of discs and vertebrae -> scoliosis or kyphosis and neurological deficits
complications of osteomyelitis
- chronic osteomyelitis
- pathologic fx
- secondary amyloidosis
- endocarditis
- sepsis
- carcinoma
osteoid osteoma
- benign bone producing tumor
- < 2cm in diameter
- common in teens and 20s
- occurs in appendicular skeleton
- malignant transformation rare
osteoblastoma
- benign bone producing tumor
- > 2cm
- involves posterior spine most frequently
- malignant transformation rare
osteosarcoma
- most common primary bone tumor
- produce osteoid matrix or mineralized bone
- bimodal age distribution but most common in 20s-30s
- painful, progressively enlarging mass
- pathologic fxs
predisposing conditions for osteosarcoma
- paget disease
- bone infarcts
- prior radiation
pathogenesis of osteosarcoma
- mutation in RB
- TP53 mutations
- inactivated INK4a- encodes two tumor suppressors p16 and p14
- MDM2 and CDK4- cell cycle regulators
non-synovial joints
- solid
- provide structural integrity
- allow minimal movement
- lack joint space
- i.e. cranial sutures
synovial joints
- have joint space
- allow for wide ROM
osteoarthritis
- most common joint disease
- degeneration of cartilage -> structural/ functional failure of joints
- primary OA- aging
- secondary OA- obesity or diabetes
- joint deformity can occur but never fusion
what is the most common site for OA in women
- knees
- hands
what is the most common site of OA in men
hips
clinical features of OA
- asymptomatic until 50s
- deep, achy pain that worsens with use
- morning stiffness
- crepitus
- osteophyte formation
- limited ROM
- nerve root compression
- radicular pain
- muscle spasms or atrophy
- neurologic deficits
pathogenesis of OA
- chondrocytes get activated d/t pressure or cartilage degen -> stimulate macrophages
- macrophages release TNF alpha, IL6 and IL1
- accumulation of immune cells and more bone destruction
most common sites for OA overall
- hips
- knees
- lower lumbar and cervical vertebrae
- proximal and distal IP joints of fingers
- first CMC joints
- first TMT joints
rheumatoid arthritis
- chronic inflammatory disorder
- autoimmune
- non-suppurative, proliferative, and inflammatory synovitis
- can involve other parts of body
extra-articular involvement in RA
- skin (nodules)
- heart (MI)
- blood vessels (atherogenesis)
- lungs
clinical features of RA
- inflammation
- articular cartilage destruction
- bone erosion
- angiogenesis
- ankylosis and joint enlargement
- symmetrical joint involvment
- swollen, warm, painful joints
- morning stiffness lasts longer
swan neck deformity
- in RA
- flexion at distal IP joint
- extension and proximal IP joint
boutonniere deformity
- in RA
- extension at distal IP joint
- flexion at proximal IP joint
diagnosis of RA
- radiographic findings
- turbid synovial fluid with decreased viscosity, poor mucin clot formation, and inclusion bearing neutrophils
- RA factor and anti-CCP antibody
pathogenesis of RA
- CD4 cells initiate autoimmune response
- T cells prod cytokines that stim other inflammatory cells
- recruit and activate other immune cells -> cartilage damage
- RANKL expressed on activated t cells stimulates bone resportion
RA factor
- most pts have serum IgM or IgA antibodies that bind to Tc portion of own IgG
gout
transient attacks of acute arthritis
- initiated by crystallization of monosodium urate within and around joints
- due to hyperuricemia
hyperuricemia
plasma urate > 6.8 mg/dL
risk factors for gout
- age
- genetics
- heavy alcohol consumption
- obesity
- drugs- thiazides
- lead toxicity
morphologic changes with gout
- acute arthritis
- chronic tophaceous arthritis
- tophi in various sites
- gouty nephropathy
