Pathology Final - Bone

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  1. What are the 3 major functions of bone?
    • Mechanical - support of muscles and protection of organs
    • Metabolic – 65% mineral (storage) --> 99% of body’s calcium, 85% of phosphorus, 65% of sodium
    • Hematopoetic – Depends on patient’s age
  2. What is the general construction/composition of bone?
    • Composed of cells (osteocytes) and extracellular matrix (osteoid) impregnated with calcium and phosphate salts (hydroxyapetite)
    • Osteons (made of the above cells) form the compact bone
    • The medullary (inside) portion is mostly trabeculae, fat, hematopoietic marrow (depending on bone and age)
    • Outside portion is cancellous(cortical) bone covered by periosteum
  3. What are the different bone cells and what are their function(s)?
    • Osteoprogenitor cells – Stem cells; can produce offspring that differentiate into osteoblasts
    • Osteoblasts – Bone forming cells – Synthesize, transport, and arrange the proteins of the matrix – Have surface receptors that bind hormones, PTH, vitamin D, estrogen, cytokines, growth factors, and extracellular matrix proteins
    • Ostocytes – Osteoblasts that have been encased by matrix – Most numerous bone cell – Communicated by an intricate network of tunnels through the matrix know as caniculi
    • Osteoclasts - Responsible for bone resorption Formed from stem cells that also give rise to monocytes and macrophages Multinucleated (6-12 nuclei typically)—produce resorption pits on bone called Howship lacunae
  4. The majority of bone's organic component of the matrix is what?
    Type 1 collagen
  5. What are the two stages of bone formation?
    • Immature (woven) bone
    • Lamellar (layered) bone
  6. When does the amount of bone loss exceed bone formation?
    4th decade of life
  7. Which cell provides most of the local control of bone remodeling?
  8. When is woven bone seen in adults?
    in areas of tumor, infection, or healing (indicator of pathologic process in an adult)
  9. Lamellar bone
    replaces woven bone during growth, is deposited much more slowly, and is stronger than woven bone.
  10. What are the two mechanisms for bone growth?
    • Endochondral ossification: Longitudinal growth of long bones is based on osseous transformation of the cartilage in the growth plate
    • Intramembranous ossification: Flat bones, cranium, clavicles, Direct formation of the fibrous matrix into osteoid followed by mineralization (into hydroxyapatite), Long bones widen by this method
  11. What functions do joints serve?
    • Provides support
    • Provides structural firmness
    • Provides for movement between two or more bones
  12. What are the two types of joints?
    • Synovial (moveable diarthrodial)
    • Synarthroses (limited or no movement at all) -Interconnects bones of the head and trunk
  13. Describe the synovial joint structure
    • Enclosed in a connective tissue capsule composed of ligaments
    • Joint space lined with synovial cells secreting a lubricant
    • Joint surfaces are covered with cartilaginous caps
    • Some joints have a disk between the two cartilaginous caps called a meniscus
    • Rich supply of blood vessels and nerves
  14. Kyphosis
    forward curvature of the spine (hunch back). common in elderly
  15. Lordosis
    abnormal forward curvature of lumbar and cervical vertebrae
  16. Acondroplasia
    • Autosomal dominant genetic defect causing dwarfism (80% are new mutations however)
    • Defect of endochondral ossification – Affects long bone growth – Reduction of chondrocytes in growth plate – Short arms and legs, normal sized trunk – Enlarged head with saddle nose; small jaws
  17. Osteogenesis imperfecta
    • Group of related disorders sharing a common deficiency in type 1collagen synthesis; also called brittle bone disease
    • Varying forms with increased susceptibility to bone fractures – Range from autosomal dominant to autosomal recessive – Type II lethal – Some forms exhibit Dentinogenesis imperfecta (hereditary opalescent dentin) and blue sclera of the eye
    • Since type 1 collagen is not limited to bones patients can exhibit thin skin and defective heart valves (floppy mitral valve)
    • Multiple bone fractures are a common feature. Patients with more severe forms of the genetic problem may fracture bone just turning over in bed or sitting in a chair.
  18. Osteopetrosis
    • Also called marble bone disease or Albers-Schoenberg disease
    • Multiple forms; autosomal dominant (less severe) or recessive (fatal in infancy)
    • Defective osteoclast function so lack of bone resorption
    • Bones are thick but brittle-fracture easily
    • Pain, nerve compression, deafness, blindness
  19. Osteomyelitis
    • Bacterial infection of bone
    • Can be acute or chronic
    • Most common organism is Staph aureus - Other organisms include Salmonella, TB, and Treponema pallidum, Strep, E coli - Occurs most often as a result of blood-borne spread from an infection elsewhere. - Can occurs as a consequence of bone fracture
    • Most often involves the metaphysis of bone
    • Purulent exudates may compress vasculature resulting in ischemic necrosis of bone and marrow
    • Pus can also spread along the subperiosteum and eventually perforate the soft tissue with formation of a sinus tract
    • Foci of necrotic bone (sequestra) can act as a foreign body and provide a nidus for persistent infection
    • A sleeve of new bone formation (involucrum) may surround the infected necrotic area
    • As long as pus remains, the bone will not heal properly
  20. Osteomyelitis in the jaw can begin from what sources/causes?
    • Periodontal source
    • Periapical/ pulpal source
    • Trauma
    • Post surgery
    • Hematogenous spread
    • Secondary infection of radiation field
  21. Aseptic (avascular) bone necrosis
    • Ischemic event causing a bone infarct – Caused by trauma, emboli, radiation, drugs, air emboli, microthrombi, sickle cell anemia – SYNONYM: avascular necrosis
    • Typically affects growing children, adolescents, and also the elderly. Carpal bones are frequently involved as well as the femoral head in the elderly – Ischemic fractures of the neck of the femur often in conjunction with osteonecrosis
  22. Osteoporosis
    • Multifactorial disease characterized by absolute reduction in bone mass; cortical bone thinned; trabeculae are thinner and less numerous
    • Primary osteoporosis is a disease of elderly persons
    • Several determinants of bone loss: – Initial bone mass – Diet and lifestyle – Hormones – Age-related changes in metabolism
    • Secondary osteoporosis can occur at any age and is related to identifiable causes including: – Estrogen deficiency – Physical inactivity / immobilization – Drugs (anticonvulsants/ exogenous steroids) – Calcium or vitamin C deficiency – Tumors of bone or endocrine glands (hyperthyroidism; hypo/hyperparathyroidism, hypercorticolism)
  23. Osteoporosis
    Most common in graceful slender white women of small frame Major complications of primary osteoporosis include crush fractures of the vertebral bodies and the distal end of the radius—can result in ―dowagers hump’ and loss of height up to 10% No serological abnormalities (normal calcium/ phosphorus/ alkaline phosphatase)
  24. Osteomalacia
    • Caused by Vitamin D deficiency in adults – May also be caused by hypophosphotemia
    • Inadequate mineralization of the organic bone matrix
    • Vitamin D deficiency can result from: – Inadequate intake – Inadequate exposure to sunlight – Abnormal intestinal uptake
    • Presents radiographically as increased lucency of bone
  25. Rickets (osteomalacia in children)
    • Characterized by decreased calcification and excess accumulation of osteoid, leading to increased thickness of the epiphyseal growth plates and other skeletal deformities
    • Manifestations of rickets: – Craniotabes (thinning and softening of the occipital and parietal bones) – Late closure of the fontanelles - Rachitic rosary (thickening of the costochondral junctions that resemble a string of beads) – Harrison groove depression along the line of insertion of the diaphragm into the rib cage) – Pigeon breast (protrusion of the sternum) – Decreased height
  26. Renal osteodystrophy
    • Complex bone changes associated with chronic renal failure
    • Kidney cannot excrete phosphorus—phosphate level rises—hypocalcemia---PTH stimulates bone resorption
    • Trabeculae become poorly mineralized
    • Fibrosis of marrow
  27. Paget's disease of bone
    • Also called osteitis deformans
    • Chronic (unknown etiology)
    • Irregular restructuring of bone with increase in both osteoblastic and osteoclastic activity
    • Increase in bone mass, though poorly structured
    • 50+
    • Spine, pelvis, skull, femur, and tibia typically
    • Three phases - destructive, mixed (resorption and deposition), osteosclerotic (mosaic bone)
    • Compression of cranial nerves by thickening cranial bone can lead to deafness
    • Bone pain from fractures
    • Cotton-wool appearance radiographically in late stages (sclerotic)
    • Head or jaw enlarges (hat or denture don't fit anymore)
    • Prognathism, bowed legs
  28. Stress fractures
    Fractures related to repeated minor or inapparent trauma
  29. Pathalogic fractures
    • Fractures that occur in pathologically altered bones during normal activity and seemingly unrelated to trauma
    • Examples: Tumor, Paget’s disease of bone, osteoporosis
  30. What are the two types of simple fractures?
    • Complete: Single fracture through entire thickness of bone— bone is separated - Displaced fracture: fractured bone parts are out of alignment –
    • Incomplete—continuity of bone is not disrupted - Greenstick fracture - Spiral fracture
  31. Comminuted fracture
    Multiple lines of fracture and numerous fragments of bone (bone is splintered)
  32. Closed fracture
    If the overlying skin or mucosa is intact
  33. open (compound) fracture
    If the overlying skin or mucosa is disrupted
  34. Complicated fracture
    if the fracture is infected
  35. Transverse fracture
    force applied perpendicular to long axis of bone
  36. Compression fracture
    force applied in the long axis of the bone
  37. Spiral fracture
    torsional (twisting) force applied to long bone
  38. What are the stages of fracture healing?
    • Hematoma
    • Provisional callus (procallus) – Also called the inflammatory phase – Granulation tissue, newly formed cartilage and osteoid(woven bone) – Forms during the first week post fracture
    • Fibrocartilagenous callus (reparative phase) – Week two to months after trauma – New vessel ingrowth – More abundant collagen – Formation of a callus of cartilage and woven bone near fracture site
    • Fibro-osseous callus (Remodeling phase) – Can last several years – Bone is reorganized and remodeled. – Extensive osteoblast-osteoclast activity
  39. T/F Benign bone tumors are more common than malignant bone tumors?
  40. Osteochondroma (exostosis)
    • Most common Benign bone tumor
    • Presents as a slow growing bump
    • Males under age 25
    • Mushroom shaped, cartilage-capped bony projection from the bone surface
    • Lower end of femur and upper end of tibia
    • Can cause pain if nerves compressed
    • Rare malignant transformation
  41. Familial osteochondromatosis
    • -rare hereditary condition with multiple osteochondromas
    • typically involve one side of the body
    • 30% develop malignancies (chondrosarcomas)
    • Example - Maffucci syndrome
  42. Osteoma
    • Males any age
    • Tumor of dense mature bone —round to oval; sessile; slow growing
    • Occurs in skull or facial bones—often seen in paranasal sinus
    • Usually solitary except for Gardner’s syndrome which includes multiple osteomas of jaws, intestinal polyposis; skin cysts
  43. Giant cell tumor
    • Uncommon; locally aggressive benign tumor; 20s-40s
    • Large radiolucent (lytic) tumors often destroying the cortex; large multinucleated giant cells in tumor
    • Majority arise around the knee typically in metaphysis
    • Arthritis-like symptoms
    • Recurrence rate high (40-60%) after simple curettage of lesion
  44. Chondroma (endochondroma)
    • Benign tumors of hyaline cartilage
    • No age or sex preference
    • When they arise within medullary cavity they are called endochondromas
    • Usually solitary; favored locations are the short bones of the hands or the feet
  45. Osteosarcoma (osteogenic sarcoma)
    • Most common PRIMARY malignancy of bone
    • Composed of neoplastic osteoblasts Peak incidence is second decade of life (except for jaws);
    • Most osteosarcomas in adults rise from pre-existing Paget’s disease
    • 50-60% found around knee in young patients; painful enlarging mass
    • Locally invasive and metastasizes via the blood to the lungs
    • Genetic mutations are fundamental to the development of osteosarcomas. – Rb1 and p53
    • Many osteosarcomas develop at sites of the greatest bone growth where mitotic activity is at its highest
    • Most are big bulky gritty tumors which frequently destroy the overlying cortex
    • Radiographic features: – Mixed lytic and bone forming tumor – Poorly defined infiltrative margins – Sunburst periosteal reaction – AS the tumor breaks through the periosteum, the raised end of the periostium forms a triangular shadow called Codman’s triangle
  46. Chondrosarcoma
    • Production of neoplastic cartilage
    • 35-60
    • Axial skeleton (pelvis, ribs, vertebrae); rarely extremeties
    • On the basis of maturity and level of differentiation, chondrosarcomas are graded on a scale from I to III (one being the best prognosis and most differentiated)
    • The more radiolucent a chondrosarcoma is on radiographs, the more likely it is to be a high grade malignancy
  47. Multiple myeloma
    – Low back pain; bone pain – Monoclonal proliferation – Bence Jones proteinuria – Recurrent infections – Punched out radiolucencies in bone – Age 50s-60s – Renal insufficiency likely to develop – Amyloidosis in 5-10%
  48. Ewing's sarcoma
    • Tumor of the young (10-20 yrs old)
    • Malignant small round cell tumor of bone (most likely of neural origin); may metastasize early
    • Typically arises in the medullary portion of the diaphysis of long bones
    • Presents as a warm, painful, swollen, enlarging mass
    • Radiolucent tumor; Onion skin appearance to periosteum
  49. Langerhan’s cell disease
    • Group of disorders of histiocytes
    • Fits somewhere in the spectrum between benign and malignant
    • Tumor cells are CD1a positive and express HLA-DR.
    • Tennis racket shaped Birbeck granules under electron microscopy; "teeth floating in air" on radiographs
    • 3 different expression of the same disorder: Letterer Siewe---Acute disseminated – Hand Schuller Christian—chronic disseminated – Eosinophilic granuloma
  50. Letterer-Siewe (acute disseminated)
    • age < 2
    • punched out radiolucencies, skin lesions, pulmonary lesions, lymphadenopathy
    • rapidly fatal unless chemo (50% survival)
  51. Hand Schuller Christian (chronic disseminated LCD)
    • Children and young adults
    • Triad: (seen in a small percentage of cases) Lytic bone lesions, Exophtalmos, Diabetes insipidus
  52. Osteoarthritis
    • Degenerative joint disease
    • Progressive erosion of articular cartilage, accompnied by new bone formation subchondrally and at the margins of the affected joing
    • Not an inflammatory condition
    • Elderly, women
    • No HLA association
    • Wear and tear, mechanical trauma with some metabolic and inflammatory contributions
    • Types: Primary-unknown cause; Secondary-Occurs in joints damaged by known mechanisms (repeated stress or trauma; hormonal or metabolic problems; etc.)
    • Loss of elasticity in cartilage, fraying/fragmentation
    • Polished ivory bone appearance
    • Weight bearing joints most affected
    • Bone spurs form where ligaments attach to bone
    • Heberden nodes - distal interphalangeal joint
    • Bouchard's nodes - proximal joing
    • Pain, stiffness, crepitus, reduced mobility
  53. Rheumatoid arthritis (RA)
    • Autoimmune inflammatory joint disease
    • Rheumatoid factor present
    • Females
    • HLA-DR4 haplotype
    • Affects fingers and wrists mostly as well as knees and proximal joints
    • Pannus (granulation tissue) extends over articular cartilagefrom the edges resulting in erosion and cyst formation. Cartilage is destroyed beginning at the periphery of the joint
    • Scarring, contracture, and deformity of the joint; subluxation (partial dislocation)
    • Subcutaneous rheumatoid nodules in 1/3 of patients
    • Joint deformities in RA
    • Limitation of joint motion, joint instability, subluxation
    • Subluxation of the metacarpophalangeal joints (MCP) with ulnar deviation of the fingers
    • Swan Neck deformity of fingers
    • Boutonniere (button hole) deformity
    • Z deformity of the thumb
  54. What are some of the extra-articular manifestations of RA?
    • Pleural and pericardial effusions
    • Anemia of chronic disease
    • Vasculitis
    • Lymphadenopathy
    • Pulmonary involvement
    • Secondary reactive amyloidosis
    • Often seen with Sjogren’s syndrome
  55. Ankylosing spondylitis
    • spondyloarthropathy
    • HLA-B27 halotype
    • Rigidity of the spine due to fusion
    • Males, young adults 15-30
    • Symptoms worse in morning
    • Also associated with: – Aortic valve incompetence – Inflammatory bowel disease (Crohn’s or ulcerative colitis) – uveitis
  56. Reiter syndrome
    • Young males following intestinal infection
    • HLA-B27
    • Triad: urethritis, conjuctivitis, arthritis
    • Can't see, can't pee, can't bend at the knee.
  57. Gout
    • Uric acid crystals in joints and soft tissues
    • 90% males
    • 20-60
    • Causes: underexcretion of uric acid (most common), overproduction of uric acid
    • Intense painful inflammation (big toe most common)
    • Gouty tophi in soft tissue
    • Hypertension is common
    • May develop kidney stones
    • Lesch-Nyhart syndrome - inborn error in metabolism of purines
  58. Pseudogout
    • Like gout but affects knee and wrist mostly
    • Chondrocalcinosis
    • Calcium pyrophostphate crystals in articular cartilage and joint spaces.
    • Common in elderly
    • Can be sporadic, hyperparathyroidism, or familial (autosomal dominant)
  59. Most common malignancy of bone is?
    Metastatic disease
Card Set
Pathology Final - Bone
Pathology Final
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