Orthopedic Pathology Flashcards
What what are the epiphysis and metaphysis called in immature skeletons?
epiphyseal growth plate or “physis”
growth plate cartilage is replaced by bone in skeletally mature individuals
periosteum
specialized connective fibrous tissue with osteogenic potential
covers bone but is absent in joint spaces at attachment sites of tendons or ligaments
endosteum
inner lining of diaphyis and of cancellous bone
also has osteogenic potential
intramembranous bone
arises from collagen
forms flat bones of skull and clavicles and responsible for prepubertal bone widening
enchondral bone
arises from epiphyseal cartilage (growth plate)
forms appendicular and axial skeleton and responsible for prepubertal bone lengthening
What are the zones of echondral bone formation, starting from the tip?
resting zone
zone of proliferation
zone of hypertrophy
zone of provisional calcification
primary trabeculae
resting zone
inactive chondrocytes
zone of proliferation
chondrocytes proliferate and begin to secrete cartilaginous matrix
zone of hypertrophy
chondrocytes enlarge, form columns, and secrete cartilaginous matrix
zone of provisional calcification
vitamin D causes matrix calcification and entrapped chondrocytes undergo apoptosis
primary trabeculae
scaffolds of dead cartilage form the framework on which osteoprogenitor cells (transported through newly formed vessels in the growth plate) deposit bone matrix
What diseases arise from defects in the zone of proliferation?
thanataphoric/achondroplastic dwarfism
mucopolysaccharidosis
What diseases arise from defects in the zone of provisional calcification?
Ricets/Osteomalacia
What diseases arise from defects in the primary trabeculae?
osteogenesis imperfecta/scurvy/osteopetrosis
What are the types of bone?
immature - osteoid and woven bone
mature - lamellar bone
osteoid bone
unmineralized, poorly organized immature bone matrix (Type I collagen) formed rapidly (long arrow)
ex. new bone covering lamellar/woven bone (10% of normal bone is covered by osteoid), tumor bone, rickets (osteomalacic) bone
woven bone
mineralized immature bone formed rapidly (short arrow)
high number of active osteoblasts
ex. fracture callus, sites of bone repair, periosteal reaction to infection or neoplasia
lamellar bone
mineralized mature bone formed slowly
parallel collagen type I fiber sheets/bundles (lamellae), evenly distributed osteocytes
two types - cortical (compact) bone and cancellous (spongy) bone
cortical (compact) bone
85% of lamellar bone
collagen type I first deposited in the circumferential lamellae
concentric lamellae later develop osteons that dissipate mechanical stress
cancellous (spongy) bone
15% of lamellar bone
lamella collagen type I aligned longitudinally in response to mechanical stress
formed by enchondral ossification and constantly remodeled to dissipate stress
osteoblasts
derived from mesenchymal stem cells and line surface of bone
cell surface receptors include PTH, vitamin D, estrogen, insulin-like growth factor-1 (somatomedin), and others
produce matrix proteins and type I collagen, and initiate mineralization
osteocytes
osteoblasts that are incorporated into mature bone (most common cells within bone)
cell processes communicate through canaliculi within osteon unit
important in regulating calcium and phosphate
mechanical forces cause transcriptional activation of cAMP pathways within osteocytes resulting in remodeling of bone (mechanotransduction)
produce sclerostin - protein that inhibits bone formation
osteoclasts
multinucleated cells formed from monocytic progenitor cells in response to RANK-ligand secreted from osteoblasts and bone stromal cells
responsible for bone resorption
located in “resorption pits” or Howship’s lacunae
What are the functions of osteoclasts that bind in the Howship lacunae?
acidify etracellular space resulting in release of minerals into serum and secrete digestive enzymes (cathepsisns) that dissolve organic matrix resulting in bone resorption
release growth factors and cytokines incorporated in bone that stimulate proliferation of osteoblasts
this interaction between osteoclasts and osteoblasts insures normal physiologic bone remodeling throughout life in response to mechanical stress
osteoclast “resorption pit”
forms a sealed acidified microenvironment in “resorption pits” on the surface of the bone
“ruffled” membrane contains H+ ATPase
HCl mobilizes the mineral phase and proteinase cathepsin K degrades the organic matrix
these actions release minerals and growth factors from bone
What is the process of bone remodeling in cancellous bone?
activation of osteoclasts
resorption of bone in Howship’s lacuna
“reversal” of cell type with osteoblasts
bone formation
What is the process of osteon formation in cortical bone?
osteons form in response to stress
first osteoclastic resorption (“cutting cones”)
osteon then filled with bone produced by osteoblasts in a concentric fashion
osteocytes (most common cellular element) within rings of the osteon communicate through dendritic processes and regulate bone remodeling and mineral stores
What are the primary causes of acute osteomyelitis?
primarily caused by bacterial infection resulting from:
1) hematogenous spread
2) contiguous spread from adjacent extra-osseous site
3) direct inoculation of organism into bone
4) ischemia (vascular insufficiency)
**Staphyloccocus aureus is the most common
infection localizes in the vascularized regions of bone, can seed periosteal tissue through the Volkman canals
What are the histological features of acute osteomyelitis?
microscopically, acute inflammatory cells are ultimately associated with non-viable bone (sequestrum)
periosteum/endosteum responds by forming new bone (involucrum) around the dead, infected bone
managed by surgery and a long course of antibiotics
categories of bone diseases
abnormal matrix
too little matrix
too little mineralization
too much bone resorption
too little bone resorption
What are the types of osteogenesis imperfecta? What is the cause?
four distinct phenotypic and genetic groups
autosomal recessive form is most severe and lethal in perinatal period
caused by defect in syhtnesis of Type I collagen - abnormal type I collagen results in more serious disease than decreased synthesis of collagen
What are the physical outcomes of osteogenesis imperfect?
affects bone (fractures that resolve with excess callus formation)
dentin of teeth (dentinogenesis imperfecta)
eyes (thin sclera allow visualization of choroidal vasculature resulting in blue sclera)
ligaments (joint laxity and early osteoarthritis)
and ossicles of the ear (hearing defects).
What are the histological features of osteogenesis imperfecta?
cartilaginous columns are not converted to bone
medullary cavity containing thin trabecular bone and marrow fibrosis
osteoporosis
Definition: Bone that is histologically normal but decreased in quantity. Clinically defined as ≥ 1 atraumatic fractures or low bone mineral density on bone density scan (dual-energy x-ray absorptiometry). Process can be-
- ) Localized-immobility (Sudeck’s atrophy), inflammation
- ) Generalized -Senile & postmenopausal osteoporosis are the two most common forms of the disorder. Osteoporosis also occurs with endocrinopathies, type 1 diabetes mellitus, scurvy, OI, drugs (corticosteroids), ¯Vitamin D, and space travel.
pathogenesis of senile and postmenapausal osteoporosis
Depends upon initial bone density and subsequent loss of bone that occurs with age
Bone mass peaks in early adulthood (75% dependent on genetics & 25% function of environment)
With aging, osteoblasts lose their ability to form new bone and growth factors lose potency
Bone loss is further accentuated by activation of osteoclasts
postmenopausal osteoporosis
after menopause, estrogen deficiency up-regulates osteoclastogenic factors IL-1, IL-6, & TNF-a and decreases OPG resulting in osteoclastogenesis
up to 2% cortical and 9% cancellous bone lost per year
affects bones with large surface area (ie., vertebral body) (right). Fractures of vertebra and wrist
high-turnover osteoporosis-activity of osteoclasts>osteoblasts
senile osteoporosis
men and women > 80 years of age
caused by:
1) osteoblasts have decreased reproductive and biosynthetic potential with age
2) growth factors in matrix less potent
thin cortex leads to fractures involve hip and vertebra
low-turnover osteoporosis (decreased activity of osteoblasts, normally active osteoclasts)
vitamin D deficiency (RIckets/Osteomalacia)
Increased PTH (due to decreased serum calcium) and decreased serum phosphate stimulate Vitamin D synthesis by 1-hydroxylation of 25-hydroxycholecalciferol in kidney
Vitamin D, in turn, suppresses PTH gene expression and PTH secretion from parathyroid gland
Hypovitaminosis D is presently considered a pandemic problem. 25% of elderly individuals suffer mild osteomalacia due to lack of sun exposure and ↓ calcium and magnesium intake.
What are the results of vitamin D deficiency?
inability to calcify the zone of hypertrophy in developing growth plate (so chondrocytes do not die and are not replaced by bone)
inability to calcify osteoid formed throughout life during remodeling process
What is the role of vitamin D?
Vitamin D increases calcium and phosphate absorption from the intestine
During enchondral bone formation, it is required for the calcification of cartilaginous matrix that surrounds chondrocytes in the Zone of Provisional Calcification of the growth plate (rickets)
In adults, required for calcification of osteoid (osteomalacia)
pathological findings in Rickets (osteomalacia)
In children (Vitamin D deficiency), growth plate becomes widened with cartilage (“metaphyseal flare”)
Cartilage matrix (star) and newly formed osteoid (right lower) do not calcify. (normal growth plate on left)
What are the important features of osteomalacia?
osteomalacia in adults is usually due to chronic renal failure (renal osteodystrophy) caused by-
1) Decreased serum calcium, phosphate retention and decreased synthesis of Vitamin D (due to loss of kidney mass).
2) Decreased serum calcium leads to increased PTH (“secondary” hyperparathyroidism)
Osteomalacia results in long bone ”insufficiency” fractures on Xray and bone pain.
What are the histological features of osteomalacia?
Osteomalacia in adults is usually due to chronic renal failure (renal osteodystrophy)
osteomalacic bone shows excess osteoid (LEFT, calcium stains black; RIGHT, trichrome stain with red osteoid).
What are the clinical findings of hyperparathyroidism?
(GI tract) moans, bones,(renal) stones, and psychiatric overtones
What is the pathogenesis of hyperparathyroidism?
primary (most commonly, adenoma and less often, primary chief cell hyperplasia) and secondary causes (most often in response to chronic renal failure)
increased PTH results in osteoclastogenesis
affects cortical > cancellous bone (bone loss in fingers & clavicles by Xray)
What are the histological findings of hyperparathyroidism
microscopically, aggregates of activated osteoclasts form “cutting cones” that resorb bone
“dissecting osteitis” - railroad track appearance of bony trabeculi due to central resorption by osteoclasts (leads to loss of bone-osteoporosis)
subperiosteal cortical bone resorption by osteoclasts
severe disease (most often occurring in secondary hyperparathyroidism) causes fractures that result in hemorrhage, cyst formation,& fibrosis (“osteitis fibrosa cystica” or “brown tumor of bone”)
enlarged Haversian canals
dissecting osteitis
result of hyperparathyroidism
aggregates of activated osteoclasts form a “cutting cone” along the longitudinal axis of a trabecula
brown tumor of bone “osteitis fibrosa cystica”
spindled stromal cells, osteoclasts, foci of hemorrhage, and hemosiderin deposits (arrow)
What is the definition of Paget’s disease of bone
“Collage of matrix madness” due to dyssynchrony of osteoclastic/osteoblastic activity Older population; European Caucasians
What are the types of Paget’s disease of bone, and what are the phenotypic manifestations?
Polyostotic (85%) > monostotic (15%)
femur or axial skeleton involved in 80% of cases
Results in “chalk stick” fractures, cranial/spinal nerve deficits, high-output cardiac failure (↑ marrow vascularity), & rarely, sarcomatous transformation (mostly, craniofacial and axial bones)
What are the three phases of Paget’s disease of bone?
Marked bone resorption followed by rapid new bone formation:
1) osteolytic - numerous, enlarged osteoclasts >100 nuclei per cell and highly vascular marrow
2) “mixed” osteoblastic/osteolytic
3) sclerotic - thickened bone exhibiting a haphazard arrangement of cement lines
What are the histologic findings of Paget’s disease of bone?
abnormally large osteoclasts with >100 nuclei per cell, thickened bone with hapazard cement lines
What is the pathogenesis of Paget’s disease of bone?
Pathogenesis involves viral and genetic interactions: Mutated p62, a key regulator of RANKL/NFKB
mediated osteoclastogenesis, sensitizes osteoclast precursors to RANKL, while paramyxovirus stimulates osteoclastogenesis resulting in an increased number of multinucleated osteoclasts with enhanced resorption capacity
What are the radiographic and histologic findings of Paget’s Disease?
radiograph shows characteristic tapering lytic process in the distal femur (top,left)
highly vascularized stroma occasionally results in high-output cardiac failure (top, right)
enlarged osteoclasts active during the early osteolytic phase of the disease (bottom, left; arrows)
osteosclerotic phase of disease is characterized by thickened bone with a haphazard (mosaic) pattern of cement lines (bottom, right)
What are the characteristics of osteopetrosis?
absent or defective osteoclast activity (in most cases, osteoclasts fail to acidify “resorption” pits)
failure of bone remodeling resulting in abnormally thickened bone
What are the clinical features of osteopetrosis?
fractures (no osteon formation)
anemia/thrombocytopenia/infections
deforming extramedullary hematopoiesis
cranial nerve defects
