Bones Flashcards

1
Q

What are the roles of bones? (5)

A
  1. Support body mass (weight bearing)
  2. facilitate movement (articulating joints)
  3. protect vital organs (CNS, thorax)
  4. site of hematopoiesis (bone marrow)
  5. calcium reservoir (& other minerals)
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2
Q

What are the similarities between cartilage and bone? (3)

A
  1. hard tissues
  2. contain living cells embedded in the matrix (lacunae)
  3. common mesenchymal progenitor cells
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3
Q

What are the differences between cartilage and bone? (3)

A
  1. bone heavily vascularized/ cartilage avascular
  2. bone access to blood vessels via canaliculi
  3. cartilage less calcified, uses long - range diffusion
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4
Q

What type of mechanical stress affects bone structure?

A
  1. compression and movement required for proper bone remodeling
  2. plasticity used by orthodontists to modify position of teeth in jaw
  3. loss of bone mass during space flight or immobilization
  4. Piezoelectric potential (-ve, bone deposition: +ve, bone reabsorption)
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5
Q

Both periosteum and endosteum contain osteogenic cells:

A
  1. cells that can divide (mesenchymal)

2. cells that can give rise to either osteoblast or chondroblast in function of environment and vascularization

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6
Q

Trabeculae (spicules)

A

network

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7
Q

Bone Matrix: Non cellular; Organic Components

A

~ 25 % of total bone mass, mostly fibrous
• Fibers: Collagen type I (90%): provide elasticity, tensile strength
• Ground substance: (amorphous)
- Glycosaminoglycans (chondroitin & keratan sulfates)
- Glycoproteins
- Osteonectin and Osteopontin: anchors minerals to collagen, initiate mineralization and promote crystal formation.
- Osteocalcin and Bone Sialoprotein: calcium binding proteins
• Osteoid: newly secreted organic matrix (not-yet fully calcified)

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8
Q

Bone Matrix: Inorganic Components

A
  • 50-70% of total bone mass
  • Provide compressive strength to bones
  • Mostly salts of calcium phosphate in amorphous or crystalline form
  • Crystals: Hydroxyapatite: Ca10(PO4)6(OH)2
  • Contain also calcium citrate, bicarbonate, fluoride
  • Water represents ~ 15 % of bone mass.
  • Hydration shell around hydroxyapatite crystals facilitate calcium exchange with fluids
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9
Q

Methods to prepare bone sections (2)

A
  1. Decalcification - flexible tissue (osteocytes in lacunae)

2. Grinding - translucent ground sections (lacunae with canaliculi)

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10
Q

Bone Cells Related to Bone Formation: (3)

A
  1. Mesenchymal osteoprogenitor: osteogenic cell
  2. Osteoblast: bone forming cells
  3. Osteocyte: terminally differentiated cells
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11
Q

Mesenchymal osteoprogenitor:

A

• Osteogenic cell (stem cells)
• Committed mesenchymal cell
• Commitment is controlled by Bone Morphogenic Proteins (BMPs), osteogenin
• Located in inner (mesenchyme/
marrow areas close to bone) and outer linings of bone
• Can self-renew or differentiate:
• Self-renewal controlled by PDGF, TGF, IGF
• Differentiation controlled by BMP, VitD3

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12
Q

Osteoblast:

A

• Bone forming cell
• Non-dividing cell
• Located on bone matrix surface
• Secrete bone matrix (osteoid, arrow)
• High secretory activity shown by abundant RER, Golgi
• Secretion activated by GH (somatotropin), sex steroids
• Deposition of osteoid (arrow) between osteoblast cell layer and existing bone
Osteoblasts secrete factors that promote osteoclast activity

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13
Q

Osteocyte:

A

• Terminally differentiated cell
• Osteoblast that became trapped in its mineralized matrix
• Located in spaces called lacunae
• Extend filopodia in canaliculi: canals connecting cells (gap junctions)
• Osteocytic osteolysis
- limited calcium release inside lacunae
- Parathyroid hormone (PTH) increase resorption (chief cells of Parathyroid gland)
- Calcitonin decrease resorption
- (parafollicular cells of Thyroid gland)

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14
Q

Osteoclast:

A

• Bone resorbing cell
• Macrophage/monocyte lineage
- Multinucleated: fusion of monocytes promoted by Vitamin D
• Large, non-dividing, mobile
• Located on bone resorptive and free surfaces in small cavitations called Howship’s lacunae
• Ruffled border: bone resorption zone inside the Howship’s lacunae
- surrounded by a ring shaped sealing zone: clear zone
- cytoplasmic processes

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15
Q

Osteoclast function

A

Osteoclastic osteolysis = bone resorption
• Focal decalcification by acidification
(citric acid release, carbonic anhydrase)
• Extracellular digestion by hydrolytic
enzymes (collagenase, acid phosphatase,
sulfatase) for proteolysis
• Required for bone remodeling & repair (disease: osteopetrosis)
• Regulated by:
- PTH (indirect via factors from osteoblasts): increase resorption
- Calcitonin, estrogens: decreased resorption
- Critical role in calcium homeostasis

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16
Q

Periosteum: outer surfaces

A

• Tough connective tissue membrane
• Covers bone outer surface
(except articular & tendon insertion surfaces)
• Fibrous periosteum (FP):
Outer fibrous layer, highly vascularized
• Osteogenic periosteum (OP):
Inner cellular layer (osteogenic cells,osteoblasts)
• Attached to bone by collagen fiber bundles: Sharpey’s fibers
• Point of origin of Volkmann’s
canals containing blood vessels

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17
Q

Endosteum: inner surfaces

A

• Thin single cell layer
(progenitor cells, osteoblasts and osteoclasts)
• Lines bone internal surfaces (trabeculae, haversian canals)
• Important for bone nutrition and maintenance

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18
Q

Role of periosteum and endosteum in bone growth, repair and remodeling

A
  • Both contain osteogenic cells:
    • Cells that divide (mesenchymal)
    • Cells that can give rise to either
  • osteoblast or chondroblast in function of environment and vascularization
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19
Q

Mesenchymal uncommitted precursor: Vascular

A
  • osteoprogenitor
  • osteoblast
  • osteocyte
    (Intramembranous endochondral)
20
Q

Mesenchymal uncommitted precursor: Avascular

A
  • Chondroprogenitor
  • chondroblast
  • chondrocyte
    (Appositional Interstitial)
21
Q

Bone Proper; organization of collagen fibers in matrix determine the types of bone:

A

• WOVEN: Primary/immature bone
• Random disposition of collagen fibrils, amorphous calcium phosphate
• In embryonic development and during bone repair
• LAMELLAR: Secondary/mature bone
• Organized disposition of collagen fibers (lamellae), crystalline calcium phosphate
- Cancellous (spongy)
- Compact (cortical)
• Comes from remodeling of woven bone
• Adult bone

22
Q

Mature (Lamellar) Bone: Cancellous (spongy) bone

A
• Network of irregular lamellae:
	Trabeculae (spicules) 
• Large spaces filled with bone marrow:
	hematopoietic tissue
• Mostly converted to compact bone
• Exceptions: flat bones (skull diploë)
	Alveolar bone around teeth
	Short bones
	Epiphyses & Diaphysis of long bones 
• Anastomose: fusion of trabeculae trapping blood and lymphatic vessels inside canals
23
Q

Mature (Lamellar) Bone: Compact (cortical) bone

A

• Forms diaphysis of long bones
Found as thin layer around epiphyses
Forms the “tables” of skull’s flat bone
• Highly organized bone lamellae:
- Circumferential (outer and inner)
- Harversian systems (osteons)
- Interstitial (areas between osteons)
• Haversian system: Cylindrical
columns of 4-15 concentric lamellae
surrounding a canal called haversian
canal containing blood and lymphatic
vessels and nerves

24
Q

Volkmann’s canals:

A

Nutrient running at right angle to the Haversian canals; contain blood vessels and nerves of bones

25
Q

Mechanisms of Calcification - Process done by osteoblasts:

A

1- Osteoblasts secrete the new organic matrix, non-mineralized, called osteoid
2 - Osteoblasts secrete factors (alkaline phosphatase, glycoproteins such as osteonectin and osteocalcin, calcium salts…) allowing the subsequent mineralization of the matrix
3 - Osteoblasts become trapped in their own mineralized matrix: become osteocytes residing in lacunae
4 - Osteocyte keeps a limited ability to secrete and reabsorb bone in its lacuna, allowing some bone turnover to occur

26
Q

Mechanisms of Calcification - depend on factors secreted by osteoblasts in the matrix:

A
  • Alkaline phosphatase promotes accumulation of inorganic phosphate in the osteoid, this is a point of saturation where calcium phosphate precipitates
  • High affinity calcium binding proteins (osteonectin, osteocalcin)
  • Matrix vesicles containing pyrophosphate and enzymes that inhibit calcification and allow phosphate release
27
Q

Bone Remodeling:

A
  • Balance between bone deposition and resorption
  • Bone deposition : Ensure high vascularity - Trapping of new vessels during bone deposition and anastamose of trabeculae
  • Bone Resorption: Allows formation of canals/marrow cavity
  • Required to maintain shape in growing bones: skull/long bones
  • Balance deposition/resorption allows bone response to mechanical stress, adaptation to movement/strain
  • Osteons constantly remodeled
  • Help maintain calcium homeostasis (via PTH and calcitonin)
28
Q

Diseases due to unbalance between bone deposition & resorption:

A
  • Osteoporosis: resorption > deposition → bone mass loss (elderly)
  • Osteopetrosis: deposition > resorption → bone mass excess marble bone disease, due to abnormal osteoclasts
29
Q

Nutritional factors:

A

Vitamin C • deficiency: Scurvy, altered collagen formation, fragile bone, fractures
Vitamin D • deficiency: Impaired intestinal absorption of calcium
In infant, Rickets, skeletal deformities (bowing legs, knock-knee)
In adult: osteomalacia, weak bones, fractures
• excess: abnormal calcification of soft tissues, toxic
Vitamin A • deficiency: in fetus, skeletal deformity, in children, slow bone growth, small skull, CNS damage.
Childhood, premature epiphyseal closure, small stature
• excess: slow cartilage growth and accelerated ossification

30
Q

Hormonal factors:

A

Growth hormone:
• deficiency in childhood, pituitary dwarfism
• excess in childhood, gigantism
• GH excess in adult (pituitary tumor), acromegaly (enlargement of the skeleton)

Sex Steroids:
• Influence time of appearance of ossification centers during bone development and closure of epiphyses:
- Precocious (early) sexual maturity or tumor, short stature
- Delayed puberty (extreme exercise), sex hormone deficiency, tall stature

Hyperparathyroidism: excess PTH, excess bone resorption, bone mass loss, fragile bones, excess circulating calcium, deposit in soft tissue (kidney)

31
Q

Bone Growth: Reversible differentiation

A

vascular environment / growth factors

32
Q

Primary (woven/immature) bone formation: Intramembranous ossification

A

Direct; Mesenchymal Condensation & direct mineralization by osteoblasts
i.e. differentiation of mesenchymal cells into osteoblasts then osteocytes

33
Q

Primary (woven/immature) bone formation: Endochondral ossification

A

Indirect; Ossification of a preexisting cartilage model

i.e. replacement of cartilage with osteoblasts & osteocytes

34
Q

Intramembranous ossification:

A
  • Occurs in areas of vascularized mesenchyme
    • Flat bones (membrane bones)
      - Growing short bones
    • Periosteal bone collar of long bones (bone thickening)
  • Differentiation of mesenchymal precursor cells to osteoblasts, leading to bone deposition and mineralization
35
Q

Intramembranous ossifcation: sequence of events

A
  1. Mesenchymal condensations
  2. Appearance of blood vessels
  3. Differentiation into osteoblasts:
    primary ossification center
  4. Mineralization by Osteocytes
  5. Spicules/trabeculae formed
  6. Interweaving of trabeculae:
    Spongy bone & Marrow cavities
36
Q

Endochondral Ossification: short & long bones - Prenatal growth

A
  • Hyaline cartilage model (precursor, anlagen)
  • Subperiosteal bone collar around cartilage (Intramembranous) Prenatal growth
  • Primary endochondral bone (cartilage replacement)
37
Q

Endochondral Ossification: short & long bones - Postnatal growth

A

-Growth of epiphyseal plates
-Marrow cavity extends
Mature bone (compact at diaphysis/spongy at epiphysis)

38
Q

Step 1: Prenatal growth, hyaline cartilage model & subperiosteal bone collar

A
  • Embryonic mesenchymal condensation
  • Differentiate into chondroblasts
  • Small hyaline cartilage model (anlagen)
  • Capillaries penetrate perichondrium at mid-portion of cartilage model, mesenchymal cells become osteogenic, periosteum
  • Formation of subperiosteal bone collar by intramembranous ossification (i.e. mesenchyme differentiates into osteoblasts)
39
Q

Step 2: Prenatal growth, cartilage degeneration & primary ossification center

A
  • Chondrocytes in midregion of cartilage proliferate in long stacks, hypertrophy, matrix calcifies, cartilage degenerates, forms calcified trabeculae & spaces
  • Blood vessels from periosteal bud (cluster of blood vessels and perivascular tissue from periosteum) enter calcified cartilage, bringing osteoprogenitor cells, osteoclasts and bone marrow stem cells
  • Endochondral ossification (cartilage replacement) with osteoprogenitors, osteoblasts.
    Primary bone formed on calcified cartilage remnants & bone marrow formation (D):
    Primary ossification center (diaphyseal)
40
Q

Step 3: Postnatal growth, formation of secondary ossification centers

A
  • Formation of a secondary (epiphyseal) ossification center in one of the epiphysis (E) following same mechanism as for primary center (invasion by epiphyseal artery, primary bone & marrow formation)
  • Diaphysis: bone collar grows toward epiphyses, Spongy bone formed in center, Marrow cavity enlarges
    -Epiphysis: growth of epiphyseal growth plate, bone growth in length until adulthood. Regulated by GH/IGF1 (somatomedins)
    5 distinct zones in epiphyseal cartilage

-Spongy bone replaces woven bone at the
first epiphysis. Articular cartilage remains around the epiphysis
Second secondary ossification center starts at second epiphysis

41
Q

Step 4: Postnatal growth until adulthood: growth plate closure

A
  • The first epiphysis matures (G): growth plate closes and progressively disappears (16-20 y.)
  • The only remaining cartilage in the epiphysis is the articular cartilage
  • Growth of second epiphyseal plate
  • Expansion of central marrow cavity
  • Bone collar becomes compact boneAdult bone (H):
  • Epiphyseal cartilage plate no longer present
  • Compact bone at diaphysis
  • Spongy bone at epiphysis
  • Marrow space contains yellow (adipose) marrow
  • Periosteum surrounds shaft (no at articular joint)
  • Articular cartilage without perichondrium
42
Q

Bone growth & remodeling of long bone

A
  • Epiphyseal plate provide growth in length

- Epiphyseal spicules get incorporated into diaphysis

43
Q

Unstable/mobile fractures repaired by endochondral ossification:

A

Fracture, interruption of blood supply, necrosis & blood clot

↓ oxygen supply, macrophages/fibroblasts, fibrous tissue

Periosteal osteoprogenitors become chondrogenic

Cartilage bridge formed at site (callus) as early as 4 days after break

Blood vessels reappear, osteogenic potential

Primary bone forms as early as 2 weeks after break, then secondary bone

mechanical stress & muscular activity necessary to restore bone shape

44
Q

Fractures in non-weight bearing bones or hair line fracture can be repaired directly by

A

intramembranous ossification

45
Q

Joints : arthroses

A

Synarthrose: permit little or no movement

  • Syndesmosis (fibrous joints): joined by dense connective tissue (cranial sutures in young)
  • Synostose: immobilized, fused bones (old skull bones)
  • Synchondrose (primary cartilaginous joint): bones joined by hyaline cartilage (rib/sternum)
  • Symphysis (secondary cartilaginous joint): bones joined by fibrocartilage (pubic symphysis, intervertebral discs)
46
Q

Diarthrose (synovial/articular joint)

A
  • movable joints between long bones
    - articular cartilage (no perichondrium)
    - Synovial fluid
    - Capsule (2 layers)
    outer membrane: fibrous
    inner membrane: synovial membrane
    A cell: Phagocytic
    B cell: secrete synovial fluid
  • Reinforced by ligaments
  • Stabilized by muscles and tendons
  • Ligaments and tendons attached to bone by Sharpey’s fibers