Chapter 7

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Chapter 7
Lecture
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7-1
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Bone Tissue
• Tissues and organs of the skeletal
system
• Histology of osseous tissue
• Bone development
• Physiology of osseous tissue
• Bone disorders
7-2
Bone as a Tissue
• Connective tissue with a matrix hardened
by minerals (calcium phosphate)
• Individual bones consist of bone tissue,
marrow, blood, cartilage and periosteum
• Continually remodels itself
• Functions of the skeletal system
– support, protection, movement, electrolyte
balances, acid-base balance and blood
formation
7-3
Shapes of Bones
• Long bones – levers
acted upon by
muscles
• Short bones – glide
across one another in
multiple directions
• Flat bones – protect
soft organs
7-4
General Features of Bones
• Shaft (diaphysis) = cylinder of compact bone
– marrow cavity (medullary cavity) lined with
endosteum (osteogenic cells and reticular
connective tissue)
• Enlarged ends (epiphyses)
– spongy bone covered by compact bone
– enlarged to strengthen joint and attach ligaments
• Joint surface covered with articular cartilage
• Shaft covered with periosteum
– outer fibrous layer of collagen
– inner osteogenic layer of bone forming cells
• Epiphyseal plate (growth plate)
7-5
Structure of a Long Bone
• Compact and
spongy bone
• Marrow cavity
• Articular cartilage
• Periosteum
7-6
Structure of a Flat Bone
• External and
internal surfaces
composed of
compact bone
• Middle layer is
spongy bone and
bone marrow
• Skull fracture may
leave inner layer
of compact bone
unharmed
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Cells of Osseous Tissue (1)
• Osteogenic cells in endosteum, periosteum or central
canals give rise to new osteoblasts
– arise from embryonic fibroblasts
– multiply continuously
• Osteoblasts mineralize organic matter of matrix
• Osteocytes are osteoblasts trapped in the matrix they
formed
– cells in lacunae connected by gap junctions inside canaliculi
7-8
Cells of Osseous Tissue (2)
• Osteoclasts develop in bone marrow by fusion
of 3-50 stem cells
• Reside in pits that they ate into the bone
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Matrix of Osseous Tissue
• Dry weight = 1/3 organic and 2/3 inorganic
matter
• Organic matter
– collagen, glycosaminoglycans, proteoglycans and
glycoproteins
• Inorganic matter
– 85% hydroxyapatite
– 10% calcium carbonate
– other minerals (fluoride, potassium, magnesium)
• Combination provides for strength and
resilience
– minerals resist compression; collagen resists
tension
– bone adapts by varying proportions
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Histology of Compact Bone
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Compact Bone
• Osteon = basic structural unit
– cylinders formed from layers (lamellae) of
matrix around central canal (osteonic canal)
• collagen fibers alternate between right- and lefthanded helices from lamella to lamella
– osteocytes connected to each other and their
blood supply by tiny cell processes in
canaliculi
• Perforating canals or Volkmann canals
– vascular canals perpendicularly joining
central canals
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Blood Vessels of Bone
7-13
Spongy Bone
• Spongelike appearance formed by
plates of bone called trabeculae
– spaces filled with red bone marrow
• Trabeculae have few osteons or
central canals
– no osteocyte is far from blood of bone
marrow
• Provides strength with little weight
– trabeculae develop along bone’s lines of
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stress
Spongy Bone Structure and
Stress
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Bone Marrow
• In medullary cavity (long bone) and
among trabeculae (spongy bone)
• Red marrow like thick blood
– reticular fibers and immature cells
– Hemopoietic (produces blood cells)
– in vertebrae, ribs, sternum, pelvic
girdle and proximal heads of femur
and humerus in adults
• Yellow marrow
– fatty marrow of long bones in adults
• Gelatinous marrow of old age
– yellow marrow replaced with reddish
jelly
7-16
Intramembranous Ossification
• Condensation of mesenchyme into
trabeculae
• Osteoblasts on trabeculae lay down osteoid
tissue (uncalcified bone)
• Calcium phosphate is deposited in the
matrix forming bony trabeculae of spongy
bone
• Osteoclasts create marrow cavity
• Osteoblasts form compact bone at surface
• Surface mesenchyme produces periosteum
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Intramembranous Ossification 1
• Produces flat bones of skull and clavicle.7-18
Intramembranous Ossification 2
• Note the periosteum and osteoblasts.
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Stages of Endochondral
Ossification
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Endochondral Ossification 1
• Bone develops from pre-existing model
– perichondrium and hyaline cartilage
• Most bones develop this process
• Formation of primary ossification center
and marrow cavity in shaft of model
– bony collar developed by osteoblasts
– chondrocytes swell and die
– stem cells give rise to osteoblasts and
clasts
– bone laid down and marrow cavity created7-21
Primary Ossification Center and
Primary Marrow Cavity
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Endochondral Ossification 2
• Secondary ossification centers and
marrow cavities form in ends of bone
– same process
• Cartilage remains as articular cartilage
and epiphyseal (growth) plates
– growth plates provide for increase in
length of bone during childhood and
adolescence
– by early twenties, growth plates are gone
and primary and secondary marrow
cavities united
7-23
Secondary Ossification Centers
and Secondary Marrow Cavities
7-24
The Metaphysis
– Zone of reserve cartilage = hyaline cartilage
– Zone of proliferation
• chondrocytes multiply forming columns of flat
lacunae
– Zone of hypertrophy = cell enlargement
– Zone of calcification
• mineralization of matrix
– Zone of bone deposition
• chondrocytes die and columns fill with
osteoblasts
• osteons formed and spongy bone is created
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Fetal Skeleton at 12 Weeks
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Bone Growth and Remodeling
• Bones increase in length
– interstitial growth of epiphyseal plate
– epiphyseal line is left behind when cartilage gone
• Bones increase in width = appositional growth
– osteoblasts lay down matrix in layers on outer
surface and osteoclasts dissolve bone on inner
surface
• Bones remodeled throughout life
– Wolff’s law of bone = architecture of bone
determined by mechanical stresses
• action of osteoblasts and osteoclasts
– greater density and mass of bone in athletes or
manual worker is an adaptation to stress
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Dwarfism
• Achondroplastic
– long bones stop
growing in childhood
• normal torso, short limbs
– spontaneous mutation
during DNA replication
– failure of cartilage
growth
• Pituitary
– lack of growth hormone
– normal proportions with
short stature
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Mineral Deposition
• Mineralization is crystallization process
– osteoblasts produce collagen fibers spiraled
the length of the osteon
– minerals cover the fibers and harden the
matrix
• ions (calcium and phosphate and from blood
plasma) are deposited along the fibers
• ion concentration must reach the solubility product
for crystal formation to occur
• Abnormal calcification (ectopic)
– may occur in lungs, brain, eyes, muscles,
tendons or arteries (arteriosclerosis)
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Mineral Resorption from Bone
• Bone dissolved and minerals released into
blood
– performed by osteoclasts “ruffled border”
– hydrogen pumps in membrane secrete hydrogen into
space between the osteoclast and bone surface
– chloride ions follow by electrical attraction
– hydrochloric acid (pH 4) dissolves bone minerals
– enzyme (acid phosphatase) digests the collagen
• Dental braces reposition teeth and remodel
bone
– create more pressure on one side of the tooth
– stimulates osteoclasts to remove bone
– decreased pressure stimulates osteoblasts
7-30
Calcium and Phosphate
• Phosphate is component of DNA, RNA,
ATP, phospholipids, and pH buffers
– ~750 g in adult skeleton
– plasma concentration is ~ 4.0 mg/dL
– 2 plasma forms: HPO4 -2 and H2PO4-
• Calcium needed in neurons, muscle
contraction, blood clotting and exocytosis
– ~1100g in adult skeleton
– plasma concentration is ~ 10 mg/dL
7-31
Ion Imbalances
• Changes in phosphate levels = little effect
• Changes in calcium can be serious
– hypocalcemia is deficiency of blood calcium
• causes excitability of nervous system if too low
– muscle spasms, tremors or tetany ~6 mg/dL
– laryngospasm and suffocation ~4 mg/dL
• with less calcium, sodium channels open more easily,
sodium enters cell and excites neuron
– hypercalcemia is excess of blood calcium
• binding to cell surface makes sodium channels less likely to
open, depressing nervous system
– muscle weakness and sluggish reflexes, cardiac arrest ~12
mg/dL
• Calcium phosphate homeostasis depends on
calcitriol, calcitonin and PTH hormone
regulation
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Carpopedal Spasm
• Hypocalcemia demonstrated by muscle spasm
of hands and feet.
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Hormonal Control of Calcium
Balance
• Calcitriol, PTH and calcitonin maintain
normal blood calcium concentration.
7-34
Calcitriol (Activated Vitamin D)
• Produced by the following process
– UV radiation and epidermal keratinocytes convert
steroid derivative to cholecalciferol - D3
– liver converts it to calcidiol
– kidney converts that to calcitriol (vitamin D)
• Calcitriol behaves as a hormone that raises
blood calcium concentration
– increases intestinal absorption and absorption from
the skeleton
– increases stem cell differentiation into osteoclasts
– promotes urinary reabsorption of calcium ions
• Abnormal softness (rickets) in children and
(osteomalacia) in adults without vitamin D
7-35
Calcitriol Synthesis and
Action
7-36
Calcitonin
• Secreted (C cells of thyroid gland) when
calcium concentration rises too high
• Functions
– reduces osteoclast activity as much as 70%
– increases the number and activity of
osteoblasts
• Important in children, little effect in adults
– osteoclasts more active in children
– deficiency does not cause disease in adults
• Reduces bone loss in osteoporosis
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Correction for Hypercalcemia
7-38
Parathyroid Hormone
• Glands on posterior surface of thyroid
• Released with low calcium blood levels
• Function = raise calcium blood level
– causes osteoblasts to release osteoclast-stimulating
factor (RANKL) increasing osteoclast population
– promotes calcium resorption by the kidneys
– promotes calcitriol synthesis in the kidneys
– inhibits collagen synthesis and bone deposition by
osteoblasts
• Sporatic injection of low levels of PTH causes
7-39
bone deposition
Correction for Hypocalcemia
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Other Factors Affecting Bone
• Hormones, vitamins and growth factors
• Growth rapid at puberty
– hormones stimulate osteogenic cells, chondrocytes
and matrix deposition in growth plate
– girls grow faster than boys and reach full height
earlier (estrogen stronger effect)
– males grow for a longer time and taller
• Growth stops (epiphyseal plate “closes”)
– teenage use of anabolic steroids = premature closure
of growth plate and short adult stature
7-41
Fractures and Their Repair
• Stress fracture caused by trauma
– car accident, fall, athletics, etc
• Pathological fracture in bone weakened
by disease
– bone cancer or osteoporosis
• Fractures classified by structural
characteristics
– break in the skin
– multiple pieces
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Types of Bone Fractures
7-43
Healing of Fractures 1
• Normally 8 - 12 weeks (longer in elderly)
• Stages of healing
– fracture hematoma (1) - clot forms, then
osteogenic cells form granulation tissue
– soft callus (2)
• fibroblasts produce fibers and fibrocartilage
– hard callus (3)
• osteoblasts produce a bony collar in 6 weeks
– remodeling (4) in 3 to 4 months
• spongy bone replaced by compact bone
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Healing of Fractures 2
7-45
Treatment of Fractures
• Closed reduction
– fragments are aligned with manipulation and casted
• Open reduction
– surgical exposure and repair with plates and screws
• Traction risks long-term confinement to bed
• Electrical stimulation used on fractures
– if 2 months necessary for healing
• Orthopedics = prevention and correction of
injuries and disorders of the bones, joints and
muscles
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Fractures and Their Repairs
7-47
Osteoporosis 1
• Bones lose mass and become brittle (loss
of organic matrix and minerals)
– risk of fracture of hip, wrist and vertebral
column
– complications (pneumonia and blood
clotting)
• Postmenopausal white women at greatest
risk
– by age 70, average loss is 30% of bone mass
– black women rarely suffer symptoms
7-48
Osteoporosis 2
• Estrogen maintains density in both sexes
(inhibits resorption)
– testes and adrenals produce estrogen in men
– rapid loss after menopause, if body fat too low or
with disuse during immobilizaton
• Treatment
– ERT slows bone resorption, but increases risk
breast cancer, stroke and heart disease
– PTH slows bone loss if given daily injection
• Forteo increases density by 10% in 1 year
• may promote bone cancer
– best treatment is prevention -- exercise and
calcium intake (1000 mg/day) between ages 25
and 40
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Spinal Osteoporosis
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