Bone Tissue

• Tissues and organs of �the skeletal system
• Histology of osseous �tissue
• Bone development
• Physiology of osseous �tissue
• Bone disorders

Bone as a Tissue

• Dynamic tissue that continually remodels itself
• Bones and bone tissue
• bone or osseous tissue is a connective tissue with a matrix hardened by minerals�(calcium phosphate)
• bones make up the skeletal system
• individual bones are made up of bone�tissue, marrow, cartilage & periosteum

Functions of Bone

• Supporting & protecting soft tissues
• Attachment site for muscles making movement possible
• Storage of the minerals, calcium & phosphate -- mineral homeostasis
• Blood cell production occurs in red bone marrow (hemopoiesis)
• Energy storage in yellow bone marrow

Classification of bones

• Bones are identified by:
• Shape
• Internal tissues
• Bone markings

Bone Shapes

• Long bones
• Flat bones
• Sutural bones
• Irregular bones
• Short bones
• Sesamoid bones

Shapes of Bones

Structure of a Flat Bone

• External and internal surfaces of flat bone are composed of compact bone
• Middle layer is spongy bone (diploe). No marrow cavity
• Blow to the skull may fracture outer layer and crush diploe, but not harm inner compact bone

Anatomy of a Long Bone

• Diaphysis = shaft
• Epiphysis = one end of a long bone
• Metaphysis = growth plate region
• Articular cartilage over joint surfaces acts as friction & shock absorber
• Medullary cavity = marrow cavity
• Endosteum = lining of marrow cavity
• Periosteum = tough membrane covering bone but not the cartilage
• fibrous layer = dense irregular CT
• osteogenic layer = bone cells & blood vessels that nourish or help with repairs

Long bone growth

Cells of Osseous Tissue – TTh 10

• Osteogenic cells reside in endosteum, periosteum or central canals
• arise from embryonic fibroblasts and become only source for new osteoblasts
• multiply continuously & differentiate into amitotic osteoblasts in response to stress or fractures
• Osteoblasts form and help mineralize organic matter of matrix
• Osteocytes are osteoblasts that have become trapped in the matrix they formed
• cells in lacunae connected by gap junctions inside canaliculi
• signal osteoclasts & osteoblasts about mechanical stresses

Cells of Osseous Tissue (2)

• Osteoclasts develop in bone marrow by the fusion of 3-50 of the same stem cells that give rise to monocytes found in blood
• Reside in pits called resorption bays that they have eaten into the surface of the bone

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Matrix of Osseous Tissue

• Dry weight is 1/3 organic & 2/3 inorganic matter
• Organic matter
• collagen, glycosaminoglycans, proteoglycans & glycoproteins
• Inorganic matter
• 85% hydroxyapatite (crystallized calcium phosphate salt)
• 10% calcium carbonate
• other minerals (fluoride, sulfate, potassium, magnesium)
• Combination provides for strength & resilience
• minerals resist compression; collagen resists tension
• fiberglass = glass fibers embedded in a polymer
• bone adapts to tension and compression by varying proportions �of minerals and collagen fibers

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Compact Bone

• Osteon (haversian system) = basic structural unit
• cylinders of tissue formed from layers (lamellae) of matrix arranged around central canal holding a blood vessel
• collagen fibers alternate between right- and left-handed 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
• Circumferential or outer lamellae

Histology of Compact Bone

Blood Vessels of Compact Bone

Spongy Bone

• Spongelike appearance formed by rods and 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 stress

Spongy Bone Structure and Stress

Bone Marrow

• Soft tissue that occupies the medullary cavity of a long bone or the spaces amid the trabeculae of spongy bone
• Red marrow looks like thick blood
• mesh of reticular fibers and immature cells
• hemopoietic means produces blood cells
• found 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

Intramembranous Bone Formation

• Mesenchymal cells become osteoprogenitor cells then osteoblasts.
• Osteoblasts surround themselves with matrix to become osteocytes.
• Matrix calcifies into trabeculae with spaces holding red bone marrow.
• Mesenchyme condenses as periosteum at the bone surface.
• Superficial layers of spongy bone are replaced with compact bone.

Endochondral Bone Formation (1)

• Development of Cartilage model
• Mesenchymal cells form a cartilage model of the bone during development
• Growth of Cartilage model
• in length by chondrocyte cell division and matrix formation ( interstitial growth)
• in width by formation of new matrix on the periphery by new chondroblasts from the perichondrium (appositional growth)
• cells in midregion burst and change pH triggering calcification and chondrocyte death

Endochondral Bone Formation (2)

• Development of Primary Ossification Center
• perichondrium lays down periosteal bone collar
• nutrient artery penetrates center of cartilage model
• periosteal bud brings osteoblasts and osteoclasts to center of cartilage model
• osteoblasts deposit bone matrix over calcified cartilage forming spongy bone trabeculae
• osteoclasts form medullary cavity

Endochondral Bone Formation (3)

• Development of Secondary Ossification Center
• blood vessels enter the epiphyses around time of birth
• spongy bone is formed but no medullary cavity
• Formation of Articular Cartilage
• cartilage on ends of bone remains as articular cartilage.

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The Metaphysis (Epiphyseal plate)

Secondary Ossification Center

• Begin to form in the epiphyses near time of birth
• Same stages occur as in primary ossification center
• result is center of epiphyseal cartilage being transformed into spongy bone
• Hyaline cartilage remains on joint surface as articular cartilage and at junction of diaphysis & epiphysis (epiphyseal plate)
• each side of epiphyseal plate has a metaphysis

Bone Growth in Length

• Epiphyseal plate or cartilage growth plate
• cartilage cells are produced by mitosis on epiphyseal side of plate
• cartilage cells are destroyed and replaced by bone on diaphyseal side of plate
• Between ages 18 to 25, epiphyseal plates close.
• cartilage cells stop dividing and bone replaces the cartilage (epiphyseal line)
• Growth in length stops at age 25

Zones of Growth in Epiphyseal Plate

• Zone of resting cartilage
• anchors growth plate to bone
• Zone of proliferating cartilage
• rapid cell division (stacked coins)
• Zone of hypertrophic cartilage
• cells enlarged & remain in columns
• Zone of calcified cartilage
• thin zone, cells mostly dead since matrix calcified
• osteoclasts removing matrix
• osteoblasts & capillaries move in to create bone over calcified cartilage

Epiphyseal Plates

Bone Growth in Width

• Only by appositional growth at the bone’s surface
• Periosteal cells differentiate into osteoblasts and form bony ridges and then a tunnel around periosteal blood vessel.
• Concentric lamellae fill in the tunnel to form an osteon.

Achondroplasia

• Short stature but normal-sized head and trunk
• long bones of the limbs stop growing in childhood but other bones unaffected
• Result of spontaneous mutation when DNA is replicated
• mutant allele is dominant
• Pituitary dwarf has lack of growth hormone
• short stature with normal proportions

Hormonal Abnormalities

• Oversecretion of hGH during childhood produces giantism
• Undersecretion of hGH or thyroid hormone during childhood produces short stature
• Both men or women that lack estrogen receptors on cells grow taller than normal
• estrogen responsible for closure of growth plate

Mineral Deposition

• Mineralization is crystallization process in which ions (calcium, phosphate & others) are removed from blood plasma & deposited in bone tissue
• Steps of the mineralization process
• osteoblasts produce collagen fibers that spiral along the length of the osteon in alternating directions
• fibers become encrusted with minerals hardening matrix
• ion concentration must reach the solubility product for crystal formation to occur & then positive feedback forms more
• Ectopic ossification is abnormal calcification
• may occur in lungs, brain, eyes, muscles, tendons or arteries (arteriosclerosis)

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Mineral Resorption

• Process of dissolving bone & releasing minerals into the blood
• performed by osteoclasts “ruffled border”
• hydrogen pumps in the cell membrane secrete hydrogen ions into the space between the osteoclast & the bone
• chloride ions follow by electrical attraction
• hydrochloric acid with a pH of 4 dissolves bone minerals
• an enzyme (acid phosphatase) digests the collagen
• Dental braces reposition teeth, creating greater pressure on the bone on one side of the tooth and less on the other side
• increased pressure stimulates osteoclasts; decreased pressure stimulates osteoblasts to remodel jaw bone

Functions of Calcium & Phosphate

• Phosphate is a component of DNA, RNA, ATP, phospholipids, & acid-base buffers
• Calcium is needed for communication between neurons, muscle contraction, blood clotting & exocytosis
• Calcium plasma concentration is 9.2 to 10.4 mg/dL
• 45% is as Ca+2
• Rest bound to plasma proteins & not physiologically active
• Phosphate plasma concentration is 3.5 to 4.0 mg/dL & occurs in 2 forms:
• HPO₄ ^-2 &
• H₂PO₄^-

Ion Imbalances

• Changes in phosphate concentration have little effect
• Changes in calcium can be serious
• hypocalcemia is deficiency of blood calcium
• causes excessive excitability of nervous system leading to�muscle spasms, tremors or tetany
• laryngospasm may cause suffocation
• calcium normally binds to cell surface contributing to resting membrane potential
• with less calcium, sodium channels open more easily exciting neuron
• hypercalcemia
• excessive calcium binding to cell surface makes sodium channels less likely to open, depressing nervous system
• Calcium phosphate homeostasis depends on calcitriol, calcitonin & PTH

Carpopedal Spasm

• Hypocalcemia causing overexcitability of nervous system and muscle spasm of hands and feet

Calcitriol (Activated Vitamin D)

• Produced by the following process
• UV radiation penetrating the epidermis converts 7-dehydrocholesterol to previtamin D3 and then cholecalciferol (D3/calcitriol)
• liver adds OH to convert it to calcidiol
• kidney adds OH to convert calcidiol to calcitriol
• Calcitriol behaves as a hormone (blood-borne messenger)
• stimulates intestine to absorb calcium, phosphate & magnesium
• promotes urinary reabsorption of calcium ions
• promotes osteoclast activity to raise blood calcium concentration to the level needed for bone deposition
• Abnormal softness of the bones is called rickets in children and osteomalacia in adults

Calcitriol Synthesis & Action

Parathyroid Hormone

• Secreted by the parathyroid glands
• Released when calcium blood level is too low
• Functions
• stimulates osteoclast multiplication & activity
• promotes calcium resorption by the kidneys
• promotes calcitriol synthesis in the kidneys
• inhibits collagen synthesis and bone deposition by osteoblasts
• Injection of low levels of PTH can cause bone deposition

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Hormonal Control of Calcium Balance

Negative Feedback Loops in Calcium

Other Factors Affecting Bone

• 20 or more hormones, vitamins & growth factors not well understood
• Bone growth especially rapid at puberty
• hormones stimulate proliferation of osteogenic cells and chondrocytes in growth plate
• adolescent girls grow faster than boys & reach their full height earlier (estrogen has stronger effect)
• males grow for a longer time
• Growth ceases when epiphyseal plate “closes”
• anabolic steroids may cause premature closure of growth plate producing short adult stature

Fractures and Their Repair

• Stress fracture is a break caused by abnormal trauma to a bone
• car accident, fall, athletics, etc
• Pathological fracture is a break in a bone weakened by some other disease
• bone cancer or osteoporosis
• Fractures are classified by their structural characteristics -- causing a break in the skin, breaking into multiple pieces, etc
• or after a physician who first described it

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Types of Bone Fractures (Table 7.3)

Healing of Fractures

• Normally healing takes 8 - 12 weeks (longer in elderly)
• Stages of healing
• fracture hematoma (1)
• broken vessels form a blood clot
• granulation tissue (2)
• fibrous tissue formed by fibroblasts & infiltrated by capillaries
• callus formation (3)
• soft callus of fibrocartilage replaced by hard callus of bone in 6 weeks
• remodeling (4) occurs over next 6 months as spongy bone is replaced with compact bone

Healing of Fractures

Treatment of Fractures

• Closed reduction
• fragments are aligned with manipulation & casted
• Open reduction
• surgical exposure & repair with plates & screws
• Electrical stimulation can be used on fractures that take longer than 2 months to heal
• Orthopedics = prevention & correction of injuries and disorders of the bones, joints & muscles

Fractures and Their Repairs

Aging & Bone Tissue

• Bone is being built through adolescence, holds its own in young adults, but is gradually lost in aged.
• Demineralization = loss of minerals
• very rapid in women 40-45 as estrogens levels decrease
• in males, begins after age 60
• Decrease in protein synthesis
• decrease in growth hormone
• decrease in collagen production which gives bone its tensile strength
• bone becomes brittle & susceptible to fracture

Osteoporosis

• Decreased bone mass resulting in porous bones
• Those at risk
• white, thin menopausal, smoking, drinking female with family history
• athletes who are not menstruating due to decreased body fat & decreased estrogen levels
• people whose intake of calcium is too low
• Prevention or decrease in severity
• adequate diet, weight-bearing exercise, & estrogen replacement therapy (for menopausal women)
• behavior when young may be most important factor

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Effects of Osteoporosis

Disorders of Bone Ossification

• Rickets
• calcium salts are not deposited properly
• bones of growing children are soft
• bowed legs, skull, rib cage, and pelvic deformities result
• Osteomalacia
• new adult bone produced during remodeling fails to ossify
• hip fractures are common

Chapter 8�The Skeletal System

• Overview of the skeleton
• The skull
• The vertebral column and �thoracic cage
• The pectoral girdle and �upper limb
• The pelvic girdle and �lower limb

Overview of the Skeleton

• Regions of the skeleton
• axial skeleton forms the central axis
• skull, vertebral column, ribs, sternum and sacrum
• appendicular skeleton includes the limbs & girdles
• Number of bones
• 206 in typical adult skeleton
• varies with development of sesamoid bones (patella)
• start at 270 at birth, decreases with age as bones fuse
• Surface markings defined in Table 8.2
• 4 regions of the skeleton = skull, vertebral column & thorax, upper and lower limbs and girdles

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Axial & Appendicular Skeleton

• Axial skeleton in yellow
• skull, vertebrae, sternum, ribs, sacrum & hyoid
• Appendicular skeleton in blue
• pectoral girdle
• upper extremity
• pelvic girdle
• lower extremity

Major Skull Cavities

• Cranial cavity holds brain
• Orbit contains eyeball & extraocular muscles
• Ethmoid sinus
• Nasal cavity
• Maxillary sinus
• Oral cavity

The Skull

• 22 bones joined together by sutures
• Cranial bones surround cranial cavity
• 8 bones in contact with meninges
• frontal, parietal,
• calvaria (skullcap) forms roof & walls
• Facial bones support teeth & form nasal cavity & orbit
• 14 bones with no direct contact with brain or meninges
• attachment of facial & jaw muscles

Locations of Paranasal Sinuses

• Maxillary sinus fills maxillae bone
• Other bones containing sinuses are frontal, ethmoid & sphenoid.

Frontal

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Ethmoid

Maxillary

Sphenoid

The Skull in Infancy & Childhood

• Spaces between unfused skull bones called fontanels
• filled with fibrous membrane
• allow shifting of bones during birth & growth of brain in infancy
• fuse by 2 years of age
• 2 frontal bones fuse by age six
• metopic suture
• Skull reaches adult size by 8 or 9 causing heads of children to be larger in proportion to trunk

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General Features of the Vertebral Column

• 33 vertebrae & discs of fibrocartilage between them
• Five vertebral groups
• 7 cervical in the neck
• 12 thoracic in the chest
• 5 lumbar in lower back
• 5 sacral fused into the sacrum
• 4 coccygeal fused into coccyx
• Variations in number of lumbar and sacral vertebrae

Intervertebral Discs

• Between adjacent vertebrae absorbs vertical shock
• Permit various movements of the vertebral column
• Fibrocartilagenous ring with a pulpy center

Herniated (Slipped) Disc

• Protrusion of the nucleus pulposus
• Most commonly in lumbar region
• Pressure on spinal nerves causes pain
• Surgical removal �of disc after laminectomy

Newborn Spinal Curvature

• Spine exhibits one continuous C-shaped curve
• Known as primary curvature

Adult Spinal Curvatures

• S-shaped vertebral column with 4 curvatures
• Secondary curvatures develop after birth
• lifting head as it begins to crawl develops cervical curvature
• walking upright develops lumbar curvature

Abnormal Spinal Curvatures

• Result from disease, posture, paralysis or congenital defect
• Scoliosis from lack of proper development of one vertebrae
• Kyphosis is from osteoporosis
• Lordosis is from weak abdominal muscles

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• Congenital defect of the vertebra and meningeal layers
• Leaves nervous tissue unprotected
• Can lead to paralysis
• Can be caused by genetics and folic acid deficiency (exacerbated by drinking)

Spina bifida

Arches of the Foot

• Function
• distribute body weight over foot
• yield & spring back when weight is lifted
• Longitudinal arches along each side of foot
• Transverse arch across midfoot region
• navicular, cuneiforms & bases of metatarsals

Clinical Problems

• Flatfoot
• weakened ligaments allow bones of medial arch to drop
• Clawfoot
• medial arch is too elevated
• Hip fracture
• 1/2 million/year in US
• osteoporosis
• arthroplasty

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