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Chapter 7 Lecture Outline

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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

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 7-3 formation

Shapes of Bones
• Long bones – levers acted upon by muscles • Short bones – glide across one another in multiple directions • Flat bones – protect soft organs

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)

Structure of a Long Bone
• Compact and spongy bone • Marrow cavity • Articular cartilage • Periosteum


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 7-7

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

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

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


Histology of Compact Bone


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

Blood Vessels of Bone


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 7-14 stress

Spongy Bone Structure and Stress


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

• •

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 7-17

Intramembranous Ossification 1

• Produces flat bones of skull and clavicle. 7-18

Intramembranous Ossification 2

• Note the periosteum and osteoblasts.


Stages of Endochondral Ossification


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 7-21 – bone laid down and marrow cavity created

Primary Ossification Center and Primary Marrow Cavity


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

Secondary Ossification Centers and Secondary Marrow Cavities


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

Fetal Skeleton at 12 Weeks


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


• 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

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)

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


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

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


Carpopedal Spasm

• Hypocalcemia demonstrated by muscle spasm of hands and feet. 7-33

Hormonal Control of Calcium Balance

• Calcitriol, PTH and calcitonin maintain normal blood calcium concentration.


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


Calcitriol Synthesis and Action


• 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


Correction for Hypercalcemia


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


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

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

Types of Bone Fractures


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

Healing of Fractures 2


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 7-46

Fractures and Their Repairs


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

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

Spinal Osteoporosis