R/msk 4: Skeletal System

Front 1

Bone matrix composition

Back 1

20% Type I collagen and proteins
80% hydroxyapatite (CaPO4 lattice)

Front 2

Osteoblasts: origin, function

Back 2

Mesenchymal origin
Function: synthesize collagen and other matrix proteins (osteoid)

Front 3

Osteocytes: morphology and function

Back 3

Stellate with communicating pseudopodia
Function: respond to mechanical forces to initiate remodeling/repair

Front 4

Osteoclasts: origin and function

Back 4

Monocyte/macrophage lineage
Function: Seal and acidify bone (Howship's lacunae) to lead bone resporption

Front 5

Woven bone vs. Lamellar bone

Back 5

Woven: low tensile strength, formed rapidly after injury and replaced by lamellar bone

Front 6

Basic Muticellular Unit (BMU)

Back 6

Team of osteoblasts and osteoclasts that remodel trabecular bone (no net gain/loss of bone) unlike modeling (change in size and shape of bone due to unbalanced blastic/clastic activity)

Front 7

Osteoblast regulation of osteoclast activity

Back 7

RANKL expression is stimulated by PTH, PGE2, Vitamin D3 (osteoblasts), T cells
RANKL activates RANK (osteoclasts) to induce maturation
Osteogrotegerin is secreted by osteoblasts (and other cells) to compete with RANK for RANKL binding

Front 8

Osteoclast regulation of osteoblast activity

Back 8

Released cytokines from digested bone matrix (ILGF-1, TGF-B)

Front 9

Traumatic vs. pathologic fractures

Back 9

Pathologic: any bone weakened by diseases

Front 10

Phases of bone fracture (4)

Back 10

1) Fracture: hematoma, influx of angioblasts and fibroblasts
2) Inflammatory: procallus formation
3) Reparative: hard callus (woven bone and cartilage production)
4) Remodeling: callus replaced by lamellar bone

Front 11

Fracture healing is delayed by: (5)

Back 11

1) Infection
2) Instability
3) Poor bone quality
4) Sequestrum
5) Poor nutrition

Front 12

Osteomyelitis presentation in neonate, adolescent and adult.

Back 12

Neonate: extending into epiphysis
Adolescent: metaphysis
Adult: extending into epiphysis

Front 13

Treatment of osteomyelitis

Back 13

High levels of IV antibiotics; 10% require surgery to remove sequestrum (sometimes squamous cell carcinoma develops)

Front 14

Granulomatous osteomyelitis presentation

Back 14

Usually thoracic/lumbar vetebrae (Pott disease); very destructive to bone and soft tissue.
Present: pain, fever, chills, weight loss, spinal nerve compression

Front 15

Osteopetrosis

Back 15

Decreased osteoclast function, leading to thickened bones and reduced medullary cavity hematopoiesis but bones are brittle and fracture easily.
Loss of carbonic anhydrase II (loss of acidification), mutation in RANKL, etc.

Front 16

Osteogenesis Imperfecta

Back 16

Synthesis of Type I collagen is defective (brittle bones, slow healing of fractures)
Thin, blue sclera; small misshapen teeth; hearing deficits

Front 17

Osteomalacia

Back 17

Defective mineralization with widened unmineralized osteoid seams.
Usually due to vitamin D deficiency

Front 18

Rickets

Back 18

Osteomalacia in children; soft bones are prone to bending/bowing and growth plates are overgrown due to lack of mineralization

Front 19

Type I Osteoporosis

Back 19

Abrupt loss of estrogen -> inc osteoclast activity, rapid bone loss (5-10% trabecular, 2% cortical per year)

Front 20

Estrogen regulation of bone density

Back 20

1) Upregulation of Fas ligand (osteoclast apoptosis)
2) Dec osteoclast sensitivity to RANKL
3) Stim osteoblast survival

Front 21

Type II osteoporosis

Back 21

6-8% trabecular, 2-4% cortical loss/decadedue to dec osteoblast activity

Front 22

PTH regulation of bone mass

Back 22

Intermittent exposure = osteoblast stim (inc bone)
Continuous exposure = osteoclast stim (dec bone)

Front 23

Causes of secondary osteoporosis

Back 23

1) Immobilization
2) Cushings, inc steroids (dec osteoblast activity or dec gut Ca absorption)
3) Inflammation (cytokines, lymphocytes)

Front 24

Pathogenesis of Paget disease

Back 24

BMU uncoupling resulting in 1) Osteoclast activity (lysis) 2) Osteoblast activity and 3) Quiescence (sclerotic, deformed bones)

Front 25

Presentation of Paget disease

Back 25

Usually asymptomatic with microfractures
Secondary joint degeneration
Spinal nerve compression, osteo/chondrosarcoma

Front 26

Features of Osteoarthritis

Back 26

F>M, inc with age
Usually DIP then knees, hips, vertebrae
No fever, malaise
Asymmetric, dec motility without ankylosis (rigidity)

Front 27

Pathogenesis of OA

Back 27

Uncontrolled loss of extracellular matrix (collagen, aggrecan) leading to fibrillation (shaggy articular surface), subchondral cysts if cracks develop and sclerosis (leading to eburnated bone)

Front 28

Characteristics of Rheumatoid Arthritis

Back 28

30-40 yo, F>M
Chronic, symmetric inflammation of joints (esp smaller joints) with joint destruction, subluxation and ankylosis

Front 29

Rheumatoid nodules: location, composition

Back 29

Under skin, in lungs, in heart; fibrinoid necrosis surrounded by epithelioid macrophages, lymphocytes,plasma cells

Front 30

Pathogenic factors of RA

Back 30

1) Hyperplastic synovial lining
2) Inflammatory infiltrate which secrete cytokines that stimulate cartilage and bone breakdown e.g. IL-1, TNFa, RANKL
3) Pannus formation, preventing cartilage access to metabolites

Front 31

Osteoma

Back 31

Middle age, F>M, skull
Benign lesion of dense homogenous bone

Front 32

Osteoid osteoma

Back 32

Young adults, M>F, cortex of long bones of legs;
Sharp nidus <2cm diameter surrounded by reactive bone
Pain relieved by NSAIDs

Front 33

Osteoblastoma

Back 33

15-45 yo, M>F, axial skeleton and extremities;
Sharp nidus >2cm, pain not relieved by NSAIDs

Front 34

Primary Osteosarcoma

Back 34

10-20 and >50 (secondary to Paget, radiation, implants)
Metaphysis of growing skeleton, around knee and hip
Malignant mesenchymal cells that produce osteoid
Painful, esp at night

Front 35

Findings of primary osteosarcoma

Back 35

Mets to lung, inc serum alkaline phosphatase, mixed radiolucency/density
Elevated periosteum, Codman's triangle, areas of hemorrhage and necrosis esp in metaphysis
Different degrees of differentiation but *must find osteoid production*

Front 36

Secondary osteosarcoma

Back 36

50-90 yo, M>F, pelvis, humerus, femur (not restricted to metaphysis)
Often high grade osteoid-producing malignancies

Front 37

Osteochondroma

Back 37

10-30 yo, M>F, metaphysis of long bones
Benign, non-painful hamartoma (lateral growth of growth plate leads to stalk of bone covered by cartilage)

Front 38

Enchondroma

Back 38

20-50 yo, metaphysis/diaphysis of long bones
Benign tumors of hyaline cartilage in medullary cavity of hands and feet (painful and can cause distortion)

Front 39

Chondrosarcoma

Back 39

40-80 yo, axial (pelvis, ribs) and humerus
Malignant but low-grade chondrocytes producing dull, aching pain and tenderness
Arising in diaphysis and filling medulla and expanding or thinning the cortex as it grows

Front 40

Giant-Cell Tumor of Bone

Back 40

20-40 yo, lytic epiphyseal tumor with club-like expansion
Locally aggressive, lesions are radiolucent "soap bubbles"
Pain and tenderness, pathological fractures

Front 41

Ewing Sarcoma

Back 41

10-20 yo, medullary cavity of long bones (cal erode into surrounding tissues)
Pain and tenderness sometimes with systemic symptoms
Gross: soft and tan; Histo: nests/sheets of small dark round cells without matrix production