Chapter 7 Lecture Outline See PowerPoint Image Slides for all figures and tables pre-inserted into PowerPoint without notes. 7-1 Copyright (c) The McGraw-Hill Companies, Inc. Permission required for reproduction or display. 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 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 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 7-9 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 7-10 Histology of Compact Bone 7-11 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 7-12 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 7-14 stress Spongy Bone Structure and Stress 7-15 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 7-17 Intramembranous Ossification 1 • Produces flat bones of skull and clavicle.7-18 Intramembranous Ossification 2 • Note the periosteum and osteoblasts. 7-19 Stages of Endochondral Ossification 7-20 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 7-22 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 7-25 Fetal Skeleton at 12 Weeks 7-26 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 7-27 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 7-28 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) 7-29 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 7-32 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. 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 7-37 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 7-40 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 7-42 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 7-44 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 7-46 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 7-49 Spinal Osteoporosis 7-50