bones joints and soft tissues (1)_compressed.pdf

BONES, JOINTS, AND SOFT TISSUE Ricamae Kessiah O. Manalo, PTRP, MD BONES  BASIC HISTOLOGY MATRIX Extracellular component of bone o Osteoid: Type 1 Collagen, GAGs, proteins, Osteopon9n / Osteocalcin): Marker of osteoblast o Minerals: Calcium hydrox...

BONES, JOINTS, AND SOFT TISSUE Ricamae Kessiah O. Manalo, PTRP, MD BONES  BASIC HISTOLOGY MATRIX Extracellular component of bone o Osteoid: Type 1 Collagen, GAGs, proteins, Osteopon9n / Osteocalcin): Marker of osteoblast o Minerals: Calcium hydroxyapa>te Types o Woven: Less structural integrity due to arrangement § Produced in fetal development or fracture repair § Always pathologic in adults o Lamellar: More structural integrity due to parallel arrangement CELLULAR COMPONENTS OF BONE DEVELOPMENTAL DISORDERS DYSOSTOSES Localized disruption of migration and condensation of mesenchyme Mutations: Homeobox genes, cytokines, cytokine receptors DYSPLASIA  FIBROBLAST GROWTH FACTOR 3 ACHONDROPLASIA Most common skeletal dysplasia and major cause of dwarfism Autosomal dominant: gain-of- func;on muta;ons in FGF3 → inhibi;on of endochondral growth Non-lethal  FIBROBLAST GROWTH FACTOR 3 THANTOPHORIC DYSPLASIA Most common lethal form of dwarfism Mutations lead to more ↑ FGF3 signaling → more severe manifestations than achondroplasia Usual cause of death: Respiratory insufficiency (underdeveloped chest cavity) TYPE I COLLAGEN OSTEOGENESIS IMPERFECTA "BRITTLE BONE DISEASE" Most common inherited disorder of connective tissue Usually, Autosomal Dominant Fundamental abnormality: Extreme skeletal fragility due to too little bone Four major types: Type 2: Most lethal o Multiple fractures in utero METABOLIC PATHWAYS OSTEOPETROSIS "MARBLE BONE DISEASE" Most are autosomal recessive o Impaired osteoclast func4on → Excessive bone forma4on § Deposited bone is woven Albers-Schönberg disease: Mild autosomal dominant form Morphology o Absence of medullary canal: Bone marrow failure with extramedullary hematopoiesis o Erlenmeyer flask deformity: Bulbous ends of long bones METABOLIC BONE DISEASE OSTEOPENIA AND OSTEOPOROSIS Osteopenia: decreased bone mass Osteoporosis: Severe osteopenia, enough to increase risk of fractures Bone resorp9on exceeds forma9on Most common forms: Senile and postmenopausal Hallmark: Histologically normal bone, but ↓ in quan9ty o Postmenopausal: bones with high surface area (cancellous part of vertebral bodies) → thinned trabecular plates → vertebral collapse o Senile: Thinned cortex with widened Haversian systems RICKETS AND OSTEOMALACIA Manifestations of Vitamin D deficiency o Rickets: Children o Osteomalacia: Adults Abnormal mineralization of bone o Decreased mineral content of bone HYPERPARATHYROIDISM Biologic effects of PTH: ↑ Ca2+ levels o Bone: Osteoclast activation → Bone resorption o Kidneys - ↑ Ca2+ tubular reabsorption - ↑ PO43- excretion (PTH = Phosphate trashing hormone) - ↑ Vitamin D synthesis → ↑ Intestinal Ca2+ absorption and ↑ Bone Ca2+ mobilization  RENAL OSTEODYSTROPHY Skeletal changes in chronic renal failure (including dialysis) o Osteopenia/osteoporosis o Osteomalacia o Secondary hyperparathyroidism o Growth retarda6on Pathophysiology o Renal tubular acidosis → Systemic acidosis → ↑ Bone demineraliza?on and osteomalacia o Poor Ca2+ reabsorp?on + Poor PO43- excre?on → ↑ PTH → ↑ Bone resorp?on o ↓ Vitamin D synthesis and dysregula?on of Ca2+- PO43-homeostasis between kidney and bone  PAGET DISEASE (OSTEITIS DEFORMANS) Increased, but disordered and structurally unsound bone mass Mosaic pattern of lamellar bone with cement lines “jigsaw puzzle” Clinical aspects o Primarily a disease of elderly o Most common bones: Axial skeleton, Proximal femur o Clinically, bone pain (from microfractures or nerve compression) o Complications § High-output failure: Pagetic bone as AV shunt § Most dreaded complication: Osteosarcoma and fibrosarcoma FRACTURE HEALING OSTEONECROSIS Most common causes: Trauma, Steroids Morphology o Medulla more commonly affected § No collateral circulation (unlike cortex) o Subchondral infarcts § Necrotic bone: Empty lacunae surrounded by necrotic adipocytes § Saponification: Ca2+ + Fatty acids released from adipocytes § Deposition of new bone with remaining trabeculae as scaffolding § Resorption of necrotic trabeculae by osteoclasts Sequelae: Collapse of necrotic bone, fracture, sloughing of articular cartilage OSTEOMYELITIS PYOGENIC OSTEOMYELITIS Route of infection: Hematogenous, extension, direct implantation Causative agents: o S. aureus: Most common (80-90%) o E. coli, Pseudomonas, Klebsiella: GUT infections & IV drug users o H. influenzae, GBS: Neonates o Salmonella: Sickle cell disease Location dependent on osseous vascular circulation o Neonates: Metaphyses and/or epiphyses o Older Children: Metaphyseal o Adult: Epiphyses and Subchondral regions PYOGENIC OSTEOMYELITIS Morphology o Subperiosteal abscesses o Draining sinuses: Consequence of periosteal rupture and development of so< =ssue abscesses o Sequestrum: Dead bone o Involucrum: Newly developed sleeve of bone around dead bone Clinical manifesta=ons o Systemic symptoms related to infec=on o Pain over infected bone o Radiograph: Ly=c focus with surrounding sclerosis MYCOBACTERIAL OSTEOMYELITIS More destructive and more resistant to control Involves spine in 40% of cases (Tuberculous spondylitis, Pott disease) o Kyphoscoliosis and neurologic manifestations (due to disc and vertebral destruction) TUMORS BONE-FORMING TUMORS OSTEOID OSTEOMA AND OSTEOBLASTOMA Benign tumors common in 10-20 years old Malignant transforma8on is rare Morphology o Haphazardly interconnec8ng trabeculae of woven bone WITH osteoblas8c rimming o Cytologically benign cells o Reac8ve bone surrounding the lesion OSTEOSARCOMA Bimodal age incidence o Most occur in Pelvis, Scapula, Ribs Morphology o Car6lage cap: Hyaline car6lage (disorganized growth plate-like) covered peripherally by perichondrium o Underlying bone and marrow CHONDROMA Benign tumor of hyaline cartilage that occurs in bones of endochrondral origin o Enchrondroma: Intramedullary § Most common intraosseous cartilage tumor o Juxtacortical: Bone surface Age: 20-50 years Location: Metaphysis of hand and foot bones Associations: Ollier and Maffucci syndrome o Maffucci syndrome: Spindle cell hemangiomas, and brain gliomas Enchondromatosis: Multiple enchondromas o Associated with secondary chrondrosarcomas CHONDROSARCOMA, CONVENTIONAL TYPE Second most common malignant matrix-producing tumor of bone Age: Usually a disease of elderly (>40 years) Common location: Axial skeleton (pelvis, shoulder, ribs) Morphology: Anaplastic chondrocytes with varying cellularity, atypia, and mitosis (Basis for three-tier grading) Grade is a prognostic factor TUMORS OF UNKNOWN ORIGIN  EWING SARCOMA Second most common group of bone Radiographic findings sarcomas in children o Lytic lesion with infiltrative Most common muta4on: t(11;22) margins that may involve soft tissue EWSR1-FLI1 fusion gene o Periosteal reaction: Onion-skin like deposition of the reactive bone Age: