Chapter 7 Lecture Outline See PowerPoint Image Slides for all figures and tables pre-inserted into PowerPoint without notes. Copyright (c) The McGraw-Hill Companies, Inc. Permission required for reproduction or display.

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

I. Components and Functions of the Skeletal System A. Support B. Protection C. Movement Facilitation D. Mineral Storage E. Blood Cell Production F. Energy Storage

II. Macroscopic Structure of Bones A. Two types of bone 1. compact- dense white osseous tissue 2. spongy- more loosely organized form of osseous tissue We will discuss differences between compact and spongy bone Where located Microscopic anatomy

B. Parts of a Long Bone 1. diaphysis 2. epiphysis 3. articular surfaces 4. periosteum 5. endosteum

General Features of Bones 1. Shaft (diaphysis) = cylinder of compact bone marrow cavity (medullary cavity) lined with endosteum (osteogenic cells and reticular connective tissue) 2. Enlarged ends (epiphyses) spongy bone covered by compact bone enlarged to strengthen joint and attach ligaments 3. Joint surface covered with articular cartilage 4. Shaft covered with periosteum (sheath) outer fibrous layer of collagen inner osteogenic layer of bone forming cells 5. Endosteum- lines the internal surface of the bone

Structure of a Long Bone Compact and spongy bone Marrow cavity Articular cartilage Periosteum Epiphyseal plate =growth plate

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

D. Bone Cells 1. Osteogenic cells 2. Osteoblasts 3. Osteocytes 4. Osteoclasts

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

A. Bone Matrix Matrix is 25% water, 25% proteins (mostly collagen), 50% calcium salts Calcium salts: mostly hydroxyapatite (Ca10(PO4)6(OH)2 Combination provides for strength and resilience minerals resist compression; collagen resists tension bone adapts by varying proportions

Histology of Bone

B. Compact Bone Osteon = basic structural unit= haversian system central canal =osteonic canal=haversian canal and its lamellae (cylinders formed from layers) 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

B. Compact Bone Haversian canals Volkmann canals (perforating canals) Osteon = basic structural unit= haversian system Two types of vascular channels Haversian canals Volkmann canals (perforating canals) vascular canals perpendicularly joining central canals Not all of the matrix organized into osteons Inner and outer boundaries of dense bone are organized in circumferential lamellae, run parallel to bone surface

Blood Vessels of Bone

C. Spongy Bone Spongelike appearance formed by plates of bone called trabeculae spaces filled with red bone marrow 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 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

IV. Ossification B. Endochondral Ossification Replacement of other tissues with bones A. Intramembranous Ossification -process that forms flat bones (skull, mandible) B. Endochondral Ossification -bones are formed from a hyaline cartilage model -bone tissue forms within the model -process that forms long and short bones

A. Intramembranous Ossification 1. mesenchyme (embryonic connective tissue) forms a richly vascularized layer with cell-to-cell contact 2. collagen fibers are laid down randomly forms a gel-like material 3. mesenchymal cells differentiate into osteoblasts 4. new osteoblasts continue to secrete and mineralize matrix 5. trabeculae are formed (ossification centers) becomes middle of bone 6. vascular mesenchyme condenses to form peri- and endosteum

A. Intramembranous Ossification 7. red bone marrow invades spaces between trabeculae new periosteum develops osteoblasts -these form trabeculae which grow together to form compact bone on outer surface

Intramembranous Ossification 1 Produces flat bones of skull and clavicle.

Intramembranous Ossification 2 Note the periosteum and osteoblasts.

B. Endochondral Ossification 1. Mesenchyme condenses in shape of future bone Differentiate into chondroblasts Develops perichondrium 2. Model grows as chondroblasts divide Chondroblasts hypertrophy and die Matrix becomes calcified 3. Perichondrium converts to periosteum Forms a thin periosteal collar in mid-diaphysis 4. Blood vessels invade model Carries osteoblasts, osteoclasts, and red marrow to interior of model

B. Endochondral Ossification 5. Interior osteoclasts break down calcified cartilage matrix Interior osteoblasts produce bone matrix of trabeculae, this is primary ossification center 6. Similar events begin to occur in each epiphysis These are secondary ossification centers 7. As primary ossification center enlarges, early trabeculae are removed to form medullary cavitiy This becomes populated with red marrow

Stages of Endochondral Ossification

Primary Ossification Center and Primary Marrow Cavity

Secondary Ossification Centers and Secondary Marrow Cavities

Fetal Skeleton at 12 Weeks

V. Bone Growth and Remodeling A. Interstitial growth Growth in length of bones 1. zone of cell proliferation 2. zone of cell hypertrophy 3. zone of calcification 4. zone of bone deposition B. Appositional growth Growth in diameter Occurs by subperiosteal intramembraneous ossification

Remodeling Occurs for four reasons 1. bone growth in length and width 2. changes in use of bone 3. bone tissue turnover-internal remodeling 4. plasma Ca2+ levels

V. 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

Hormonal Regulation of Bone Growth and Replacement A. Growth Hormone B. Sex steroids Bone growth especially rapid in puberty and adolescence when surges of GH, estrogen, and testosterone promote ossification C. Thyroid hormones increased GH D. Parathyroid hormones E. Calcitriol F. Calcitonin

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.

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

Calcitonin (tones down blood Ca2+ levels) 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 (PTH) 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 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

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

VII. Effect of Exercise on Bone Increased exercise causes increased mechanical stress on bone Stimulates remodeling and increased bone mass Stimulates release of calcitonin Lack of exercise causes atrophy of bone