Bone Pathology Flashcards
Basic Structure and Function of Bone
Cellular Components of Bone: Osteoblasts
Cellular Components of Bone: Osteoclasts
Woven or Lamellar?
Explain Endochondral Ossification
Explain Endochondral Ossification: Primary Spongiosia
Explain Itramembranous ossification
- flat bones
- formed direct from osteoblasts
- no cartilage anlagen
- enlargement- new bone on pre-exsisting surface
Roles of GH, T3, PTHrP, Int, SOX9, RUNX2, and FGF3
Remodeling
- constant turnover of bone; tightly regulated process
- ~10% of skeleton is replaced annually
- takes place at BMU
- coupled osteoblast and osteoclast activity on bone surface
- orderly sequence of osteoclast attachment, resorption, osteoblast attachment and proliferation, and matrix synthesis
- Regulated by cell-cell interaction and cytokines
Cytokines in remodeling
RANK- osteoclast precursor
RANKL- osteoblasts
OPG- “decoy” receptor; bind RANKL and prevent interaction with RANK
RANK-RANKL activate NF-kB
M-CSF produced by osteoblasts; stimulates tyrosine kinase cascade leading to osteoclast differentiation
Explain this and balance of remodeling
Bone formation and remodeling modulated by connection between RANK and WNT pathways
factors affecting balance: hormones, vit D, cytokines, growth factors
paracrine crosstalk between osteoclasts and osteoblasts: as bone is broken down substances are released that stimulate osteoblasts
peak bone mass achieved in early adulthood: by 4th decade resorption exceeds formation and steady decline in skeletal mass
Achondroplasia
most common skeletal dysplasia
autosomal dominant
retarded cartilage growth
shortened proximal extremities
enlarged head with bulging forehead
gain of function mutations in FGFR3
normally FGFR3 inhibits endochondral growth
constitutive activation = surpassed growth
approx. 90% are new mutation: almost all in paternal allele
Osteogenesis Imperfecta (OI)
Deficiencies in synthesis of type I collagen - osteoid
most common inherited disorder of connective tissue
bone and other tissue rich in collagen: joints, eyes, ears, skin, teeth
autosomal dominant mutations in a1 and a2 chains of type I collagen: effective assembly of collagen polypeptides
too little bone > extreme skeletal fragility
blue sclerae > decreased collagen (think sclerae)
hearing loss > impaired conduction
dental abnormalities > deficient dentin
Types of osteogenesis imperfect
Osteopetrosis
- AKA marble bone disease or Albers-Schonberd disease
- reduced bone resorption and diffuse, symmetric skeletal sclerosis
- Imparied formation or function of osteoclasts
- mutations interfere with acidification of osteoclast resorption pit
- i.e. CA2 required to generate protons from CO2 and H2O
- Lack of CA2 prevents acidification of resorption pit: prevents osteoclast activity
- lack medullary canal
- ends long bones are misshapen: Erlenmeyer flask deformity
- small neural foramina compress nerves
- primary spongiosia persists
- no room for marrow elements
- woven bone remains because mature trabecular cannot form
Severe Infantile form of osteopetrosis
Autosomal recessive
evident in utero or soon after birth
fracture, anemia, hydrocephaly
death early
repeated infections du etc leukopenia
Mild Adult form of Osteopetrosis
Repeated fractures
mild cranial nerve deficits
anemia
*kaplan- carbonic anhydrase deficiency
Acquired Disorder: Osteoporosis
osteopenia (decreased bone mass)
osteopenia severe enough to significantly increase risk of fracture
bone mass >2.5 STDs below mean peak bone mass
localized and generalized
senile and postmenoposal most common
normal bone but decreased in quantity (thin)
some bones more severely impacted
Senile- cortex thinned
post menopausal- trabecular plates perforated and thinned
clinical manifestations depend on involved bones
cant be reliably detected by x-rays
Best screenings for osteoporosis
Quantitative CT and DEXA scans
Osteoporosis: prevention and treatment
exercise, calcium, vitamin D, bisphophonates
Paget Disease (osteitis deformans)
increased disorder bone (uncoupling of BMU)
usually begins in late adulthood
both environmental and genetic causes
phases of Paget Disease
Initial osteolytic phase: osteoclast activity. with resorption pits: osteoclasts are giant with abundant nuclei
Mixed phase: osteoclasts persist, now with osteoblastic rimming; marrow replaced by loose connective tissue; osteoprogenitor cells and blood vessels
Sclerotic phase: mosaic pattern of lamellar bone; prominent cement lines; periosseous tissue replaced by normal marrow, thickened trabecular and soft, porous cortices.
Stage of Paget?
Stage 3: sclerotic phase
Clinical findings and treatment of Paget disease
variable
majority of patients asymptomatic; incidental radiographic finding
most symptoms are mild; readily created with calcitonin and bisphophonates
Hyperparathyroidsim
osteoclast activation - increased bone resorption and calcium mobilization; due to increased RANKL expression. on osteoblasts
increased calcium resorption by renal tubules
increased urinary excretion of phosphates
increased synthesis of active vitamin D by kidneys; calcium absorption from the gut; induces RANKL on osteoblasts thus mobilizing bone calcium
Hyperparathyroidism associated disorders
Osteoporosis: generalized; phalanges, vertebrae, proximal femur
dissecting osteitis - osteoclasts tunnel through trabecular; marrow spaces replaced by fibrovascular tissue
brown tumor- bone loss leads to micro fractures and secondary hemorrhage; influx of macrophages and fibrous tissue; can undergo cystic degeneration
osteitis fibrosa cystica- hallmark of severe hyperparathyroidism; increased bone cell activity; peritrabecular fibrosis; cystic brown tumors
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brown tumor and osteitis fibrous cystica caused by hyperparathyroidism
Secondary response to hyperparathyroidism
chronic hypocalcemia
compensatory overactivity of parathyroids, increased PTH
renal failure most common cause; inadequate vitamin D sythesiss; affects Gi calcium absorption
decreasing bone mass leads to more susceptible to fractures, bone deformation, and joint problems
treatment: decreased PTH levels reverses bone changes
Renal Osteodystrophy and mechanisms of skeletal deformities
skeletal changes in chronic renal disease
mechanisms of skeletal deformities with renal disease
- tubular dysfunction- renal tubular acidosis; low pH dissolves hydroxyapatite and demineralizes and osteomalacia
- generalized renal failure- affects glomerular and tubular function; reduced phosphate excretion; chronic hyperphosphatemia; hypocalcemia; secondary hyperparathyroidism
- decreased production of secreted factors- involves BMP-7, FGF23, Klotho; results in osteopenia and osteomalacia
3 main types of Renal Osteodystrohpy
High turnover- increased bone resorption and formation
low turnover (aplastic)- little osteoblastic and osteoclastic activity; osteomalacia less commonly
mixed pattern
Osteocnecrosis
infarction of bone and marrow
medullary cavity or medulla and cortex
usually due to fractures or steroids
all cause vascular insufficiency by: mechanical injury; thromboembolism; external pressure, venous occlusion.
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Osteonecrosis:
•Medullary infarcts – geographic•Cortex not affected•Collateral blood flow•In subchondral infarcts – wedge shaped necrosis•Overlying articular cartilage viable•Supplied by synovial fluid
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Osteonecrosis:
•Empty lacunae surrounded by necrotic adipocytes•Healing response – osteoclasts resorb necrotic trabeculae•Remaining trabeculae act as scaffolding for new bone•With subchondral infarcts the pace of replacement is too slow•à Collapse of the necrotic bone and distortion, fracture, and sloughing of articular cartilage
Osteonecrosis symptoms
•Symptoms depend on location & extent of infarction•Subchondral – pain with activity initially•Constant later•Collapse à severe secondary arthritis•Medullary – small & clinically silent•Exceptions Gaucher disease & sickle cell anemia
Osteomyelitis
- Inflammation of bone & marrow•Secondary to infection
- Pyogenic bacteria & mycobacteria most common
- Infection through: hematogenous spread, extension from contiguous site, direct implantation
- Staphylococcus aureus 80%-90% of culture positive cases
Infections pathogens of osteomyelitis
- GU infections & IV drug users – E. coli, Pseudomonas, Klebsiella•Neonates – H. influenzae and Group B strep
- Sickle cell patients – Salmonella
- Mixed infections – direct spread/inoculation•50% - no organism isolated
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Osteomyelitis:
- Acute – bacterial proliferation
- Neutrophils•Necrosis of bone marrow
- Subperiosteal abscess may form•Lifting of periosteum à impaired blood supply ànecrosis
- Dead bone = sequestrum - surrounded by involucrum
- Ruptured periosteum can drain to skin
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Osteomyelitis
- After a week, chronic inflammatory cells release cytokines causing
- Osteoclastic bone resorption
- Ingrowth of fibrous tissue
- Deposition of reactive bone
- Involucrum – shell of living tissue around infected bone
disease and treatment?
Osteomyelitis
- May manifest as acute systemic illness or minimal subtle symptoms
- Characteristic radiographic finding
s•Lytic bone destruction with surrounding sclerosis
- Tx: antibiotics & surgical drainage
- Up to 25% persist as chronic infection
- Causes•Delay in diagnosis•Extensive bone necrosis•Inadequate therapy•Weakened immune system•Spontaneous acute flare-ups
- Complications: pathologic fracture, secondary amyloidosis, endocarditis, sepsis, malignancy
Mycobacterial osteomyelitis
•1-3% of patients with TB have osseous involvement•Infection may persist for years•Localized pain, low grade fevers, chills, weight loss•Usually solitary•Caseating granulomata•Destructive & treatment resistant than pyogenic
•Pott disease – tubercular spondylitis•Multiple vertebrae•Extends into soft tissue•Permanent compression fractures•Scoliosis or kyphosis•Neurologic defects due to spinal cord & nerve compression•Other complications•Arthritis, sinus tract, abscess, amyloidosis
Skeletal Syphilis and types
- Treponema pallidum (spirochete)•Congenital syphilis – lesions appear around 5th month of gestation•Areas of active endochondral ossification & periosteum
- “Saber shin” – massive reactive periosteal bone deposition
- Acquired syphilis – tertiary stage•Nose, palate, skull, extremities
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Skeletal syphilis
