Explore bone and soft tissue pathology basics: bone composition, cells (osteoblasts, osteoclasts), development (ossification), remodeling, and fracture healing.
Got it. Here are the notes: --- BONE & JOINT PATHOLOGY — Condensed Study Notes Dr Lilian Bosire MKU Pathology --- PART 1: BASIC STRUCTURE AND FUNCTION OF BONE Composition The adult skeleton has 206 bones (~12% body weight). Functions include mechanical support, organ protection, mineral homeostasis, and hematopoiesis. Matrix (extracellular component): - Osteoid (35%) — type I collagen + glycosaminoglycans + osteopontin (osteocalcin) - Minerals (65%) — primarily hydroxyapatite [Ca10(PO4)6(OH)2]; stores 99% of body calcium and 85% of phosphorus - Serum osteopontin = marker of osteoblast activity Matrix types: - Woven bone — rapidly produced, haphazard collagen arrangement, structurally weak. Always abnormal in adults - Lamellar bone — parallel collagen fibers, strong, normal mature bone --- Bone Cells Cell Origin Function ------ --------- ---------- Osteoblast Mesenchymal Synthesizes and assembles osteoid; regulates mineralization Osteocyte Embedded osteoblast Detects mechanical forces (mechanotransduction); regulates Ca/PO4 Osteoclast Circulating monocytes Resorbs bone via acid + MMPs in a sealed resorption pit --- Development Most bones form via endochondral ossification — cartilage mold (anlage) replaced by bone: - Primary ossification center — diaphysis - Secondary ossification centers — epiphyses - Growth plates (physes) — chondrocytes proliferate, hypertrophy, then undergo apoptosis; matrix mineralizes and is replaced by bone Flat bones (e.g., cranium) form via intramembranous ossification — mesenchyme ossified directly, no cartilage intermediate. Key regulators of bone development: Factor Source Effect -------- -------- -------- Growth hormone Anterior pituitary Chondrocyte proliferation Thyroid hormone Thyroid Chondrocyte hypertrophy PTHrP Perichondrium Maintains chondrocyte proliferation Indian hedgehog (Ihh) Prehypertrophic chondrocytes Coordinates chondrocyte/osteoblast proliferation FGF-3 Mesenchymal cells Inhibits chondrocyte proliferation SOX9 Proliferating chondrocytes Chondrocyte differentiation RUNX2 Hypertrophic chondrocytes Osteoblast and terminal chondrocyte differentiation BMPs (TGF-β family) Various Diverse effects on chondrocyte proliferation/hypertrophy Wnt/β-catenin Growth plate Chondrocyte proliferation and maturation --- Remodeling and Homeostasis Approximately 10% of skeleton remodeled per year within the Basic Multicellular Unit (BMU) — coupled osteoclast and osteoblast activity. RANK/RANKL/OPG pathway: - RANK — receptor on osteoclast precursors - RANKL — expressed on osteoblasts/stromal cells; binds RANK → activates NF-κB → osteoclast generation and survival - OPG — decoy receptor secreted by osteoblasts; binds RANKL, blocking RANK activation → inhibits bone resorption - M-CSF — produced by osteoblasts; also essential for osteoclast generation - Sclerostin — produced by osteocytes; inhibits WNT/β-catenin → reduces bone formation Systemic modulators: Factor Effect on Bone -------- ---------------- PTH, IL-1, glucocorticoids Promote osteoclast differentiation → bone resorption Sex hormones, BMPs Promote OPG expression → bone deposition Estrogen, testosterone Block osteoclast activity --- PART 2: FRACTURES Types Type Description ------ ------------- Simple Skin intact Compound Bone communicates with skin surface Comminuted Bone fragmented Displaced Bone ends not aligned Stress Slowly developing; repetitive loading Greenstick Incomplete; common in infants Pathologic Through bone weakened by disease --- Fracture Healing — Stages 0–1 day: Hematoma formation — fibrin mesh seals site; platelets release PDGF, TGF-β, FGF → activate osteoprogenitor cells 0–2 weeks (Soft callus): Osteoprogenitor cells proliferate; woven bone trabeculae deposited subperiosteally; fibrocartilage and hyaline cartilage formed by chondrocytes 2–3 weeks (Bony callus): Endochondral ossification converts cartilage to bone; fracture ends bridged; callus stiffens; weight bearing possible 3 weeks–months: Remodeling — woven bone replaced by lamellar bone; medullary cavity restored; excess callus resorbed Near-perfect union is the norm in children. In older adults, surgical immobilization often required. Complications of poor healing: - Inadequate immobilization → delayed union or nonunion - Nonunion → pseudoarthrosis (false joint with synovial-like lining) - Open fractures → infection - Malnutrition, skeletal dysplasia --- PART 3: OSTEONECROSIS (AVASCULAR NECROSIS) Infarction of bone and marrow. Can be medullary or subchondral. Common causes: Fractures, corticosteroid use, alcohol abuse, sickle cell crisis, bisphosphonate therapy, radiation, Gaucher disease, dysbarism Morphology: - Medullary infarcts — geographic; trabecular bone + marrow necrosis; collateral flow limits cortical involvement - Subchondral infarcts — wedge/triangular shape; overlying cartilage survives (nourished by synovial fluid); dead bone shows empty lacunae + necrotic adipocytes; calcium soaps form from released fatty acids Outcome: Subchondral infarcts collapse → secondary osteoarthritis. Medullary infarcts often clinically silent. --- PART 4: OSTEOMYELITIS Inflammation of bone and marrow, virtually always infectious. Pyogenic Osteomyelitis Organism: S. aureus in 80–90% of culture-positive cases. Bacterial cell wall proteins bind bone matrix collagen to facilitate adherence. Other organisms: - Neonates — H. influenzae, group B streptococci - Sickle cell disease — Salmonella - IV drug users / UTI — E. coli, Pseudomonas, Klebsiella - ~50% culture-negative Routes of infection: Hematogenous spread (most common in children), contiguous extension, direct inoculation Age-related bone distribution: - Neonates — metaphysis + epiphysis (vessels cross growth plate) - Older children — metaphysis - Adults — epiphysis and subchondral regions (after growth plate closure) Morphology: Acute phase: Neutrophil infiltration → bone and marrow necrosis within 48 hours → bacteria spread via Haversian canals to periosteum → subperiosteal abscess → periosteal lifting → impaired blood supply → more necrosis Chronic phase: Dead bone = sequestrum . Reactive new bone shell around sequestrum = involucrum . Sinus tracts may form to skin. Clinical features: Fever, chills, leukocytosis, intense bone pain. Radiology: lytic focus surrounded by sclerosis. Diagnosis: blood culture + bone biopsy. Treatment: antibiotics + surgical drainage. Chronic osteomyelitis occurs in 5–25% — associated with delayed diagnosis, extensive necrosis, or poor host defenses. Complications include pathologic fracture, amyloidosis, endocarditis, sepsis. --- Mycobacterial Osteomyelitis (Pott Disease) - More destructive and resistant to control than pyogenic - Hematogenous origin from visceral TB (usually pulmonary) - 40% of cases involve the spine (Pott disease) — infection crosses intervertebral discs, destroys vertebrae + soft tissue → compression fractures → scoliosis, kyphosis, neurologic deficits - Histology: granulomatous inflammation with caseous necrosis - Complications: TB arthritis, psoas abscess, sinus tracts, amyloidosis --- PART 5: INFECTIOUS ARTHRITIS Suppurative (Bacterial) Arthritis Route: Mainly hematogenous. In neonates, may spread from adjacent epiphyseal osteomyelitis. Organisms by age: Age Group Organism ----------- ---------- knee ankle) - Granulomas with caseous necrosis in synovium; pannus erodes cartilage and bone margins - End result: fibrous ankylosis and obliteration of joint space --- Viral Arthritis Caused by alphavirus, parvovirus B19, rubella, EBV, hepatitis B and C. Mechanism: direct viral infection of joint or autoimmune reaction. Ranges from acute to subacute. --- Lyme Arthritis Causative agent: Borrelia burgdorferi (spirochete), transmitted by Ixodes ticks Three clinical stages: 1. Early localized — skin infection (erythema migrans) 2. Early disseminated — cranial nerves, heart, meninges 3. Late disseminated — arthritis (occurs months after infection if untreated) - Arthritis currently shoulder elbow ankle) - Spir