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CHAPTER 6 LECTURE OUTLINE

I. INTRODUCTION A. Bone is made up of several different tissues working together: bone, cartilage, dense connective tissue, epithelium, various blood forming tissues, adipose tissue, and nervous tissue. B. Each individual bone is an organ; the bones, along with their cartilages, make up the skeletal system. C. The study of bone structure and the treatment of bone disorders is referred to as osteology.

II. FUNCTIONS OF THE SKELETAL SYSTEM A. Bones support the soft tissues and provide attachment sites for muscles, thereby serving as the structural framework for the body. B. Many of the body’s internal organs are physically protected by bony coverings. C. Bones assist skeletal muscles to produce movement of body parts. D. Bones store and release several minerals, especially calcium and phosphorus, to help maintain mineral homeostasis. E. Hemopoiesis, blood cell formation, occurs in the red marrow of bones. Red bone marrow consists of developing blood cells, adipocytes, fibroblasts, and macrophages within a network of reticular fibers. F. Yellow marrow of adult bones serves as a site of triglyceride storage.

III.

STURCTURE OF BONE A. The structure of bone can be analyzed by studying a long bone (Figure 6.1a). B. A typical long bone consists of numerous parts.

1. The diaphysis is the shaft of the long bone. 2. The epiphyses are the ends of the bone that articulate with adjacent bones. 3. The metaphyses are the areas between the epiphysis and diaphysis. They include the epiphyseal plate, which is the site of bone elongation in growing bones. A layer of hyaline cartilage that allows the diaphysis of the bone to grow in length. The cartilage in the epiphyseal plate is replaced by bone; the resulting bony structure is known as the epiphyseal line. 4. Hyaline cartilage (articular cartilage) at the ends of the bones reduces friction and absorbs shock at freely moveable joints. Lack blood vessels. 5. The periosteum is a connective tissue covering of the surface of the bone which contains osteogenic cells which promotes bone growth in width, assists in fracture repair, helps nourish bone tissue, and serves as an attachment point for ligaments and tendons. It is composed of an outer fibrous layer of

dense irregular connective tissue and an inner osteogenic layer that consists of cells. The periosteum is attached to the underlying bone by perforating fibers or Sharpey’s fibers, thick bundles of collagen that extend from the periosteum into the bone extracellular matrix. 6. The space within the diaphysis is the marrow cavity, which contains yellow marrow or adipose connective tissue. 7. The endosteum is the lining of the medullary cavity. It contains a single layer of bone ‐forming cells and a small amount of connective tissue.

IV. HISTOLOGY OF BONE TISSUE A. Bone (osseous) tissue consists of widely separated cells surrounded by large amounts of matrix. B. The most abundant mineral salt is calcium phosphate It combines with another mineral salt, calcium hydroxide to form crystals of hydroxyapatite. C. There are four principal types of bone cells (Figure 6.2) 1. Osteogenic cells are unspecialized bone stem cells derived from mesenchyme, undergo cell division and develop into osteoblasts. They are found along the inner portion of the periosteum, in the endosteum, and in the canals within bone that contain blood vessels. 2. Osteoblasts are bone-building cells, promoting bone deposition. They synthesize and secrete collagen fibers and other organic components needed to build the extracellular matrix of bone tissue, and they initiate calcification. As osteoblasts surround themselves with extracellular matrix, they become trapped in their secretions and become osteocytes. 3. Osteocytes are mature bone cells (derived from osteoblasts) that maintain bone tissue. Maintain its daily metabolism, such as the exchange of nutrients and wastes with the blood.

4. Osteoclasts are derived from monocytes and serve to break down, or resorb, bone tissue. They are concentrated in the endosteum. The cell releases powerful lysosomal enzymes and acids that digest the protein and mineral components of the underlying extracellular bone matrix. This breakdown of bone extracellular matrix, termed bone resorption C. The matrix of bone contains inorganic salts, primarily hydroxyapatite and some calcium carbonate, and collagen fibers. 1. These and a few other salts are deposited in a framework of collagen fibers, a process called calcification or mineralization. 2. Mineral salts confer hardness on bone while collagen fibers give bone its great tensile strength. The combination of crystallized salts and collagen fibers is responsible for the characteristics of bone. 3. The process of calcification occurs only in the presence of collagen fibers. 4. Osteoclasts secrete enzymes and acids that break down both the mineral salts and the collagen fibers of the extracellular matrix of bone. D. Depending on the size and distribution of the spaces between the hard components of bone, the regions of a bone may be categorized as compact or spongy. Some spaces serve as channels for blood vessels that supply bone cells with nutrients. Other spaces act as storage areas for red bone marrow. 1. Compact Bone a. Compact bone is arranged in units called osteons or Haversian systems (Figure 6.3a) and is found on the outside of bones. b. Osteons contain blood vessels, lymphatic vessels, nerves, and osteocytes along with the calcified matrix. c. Each osteon consists of concentric lamellae arranged around an osteonic (haversian or central) canal. Concentric lamellae are circular plates of mineralized extracellular matrix of increasing diameter, surrounding a small network of blood vessels and nerves located in the central canal d. Osteons are aligned in the same direction along lines of stress. These lines can change as the stresses on the bone changes. Between the concentric lamellae are small spaces called lacunae which contain osteocytes. Radiating in all directions from the lacunae are tiny, which are filled with extracellular fluid. Neighboring osteocytes communicate via gap junctions. e. The areas between neighboring osteons contain lamellae called interstitial lamellae. Interstitial lamellae are fragments of older osteons that have been partially destroyed during bone rebuilding or growth. Blood vessels and nerves from the periosteum penetrate the compact bone through transverse interosteonic (Volkmann’s or perforating) canals. The circumferential lamellae directly deep to the periosteum are called external circumferential lamellae. They are connected to the periosteum by

perforating (Sharpey’s) fibers. The circumferential lamellae that line the medullary cavity are called internal circumferential lamellae 2. Spongy Bone a. Spongy (cancellous) bone does not contain osteons but, instead, consists of trabeculae surrounding many red-marrow-filled spaces. Each trabecula consists of concentric lamellae, osteocytes that lie in lacunae, and canaliculi that radiate outward from the lacunae. The trabeculae of spongy bone tissue support and protect the red bone marrow. Spongy bone in the hip bones, ribs, sternum (breastbone), vertebrae, and the proximal ends of the humerus and femur is the only site where red bone marrow is stored b. It forms most of the interior structure of short, flat, and irregular bones, and the epiphyses of long bones. c. Spongy bone tissue is light and provides open spaces for the red bone marrow and, as such, is the site of hemopoiesis. d. A bone scan is a diagnostic procedure that can detect certain bone abnormalities or disorders.

V. BLOOD AND NERVE SUPPLY OF BONE A. Bone is richly supplied with blood. B. The arterial supply to bone involves several vessels. 1. The periosteal arteries pass through Volkmans’ canals to a multitude of vessels that supply the outer compact bone region. 2. The nutrient artery passes through the nutrient canal and sends branches into the central Haversian canals to provide nutrients for osteocytes.

3. The artery continues into the medullae to supply blood for the marrow and osteocells via the epiphyseal artery. Metaphyseal arteries enter the metaphyses of a long bone and, together with the nutrient artery, supply the red bone marrow and bone tissue of the metaphyses. The epiphyseal arteries enter the epiphyses of a long bone and supply the red bone marrow and bone tissue of the epiphyses. C. Veins that carry blood away from long bones are evident in three places. (Figure 6.4) 1. One or two nutrient veins follow the nutrient artery in the diaphysis. 2. Epiphyseal and metaphyseal veins accompany epiphyseal and metaphyseal arteries in the epiphysis. 3. Periosteal veins exit with their periosteal arteries in the periosteum. D. Nerves follow vessels into bone tissue and the periosteum where they sense damage and transmit pain messages.

VI. BONE FORMATION A. Bone formation is termed osteogenesis or ossification and begins when embryonic mesenchymal cells provide the template for subsequent ossification. Two types of ossification occur. 1. Intramembranous ossification is the formation of bone directly from or within fibrous connective tissue membranes. 2. Endochondral ossification is the formation of bone from hyaline cartilage models. B. Intramembranous ossification forms the flat bones of the skull, facial bones, and the mandible. 1. Development of the ossification center. An ossification center forms from mesenchymal cells to osteoprogenitor cells as they convert to osteoblasts and lay down osteoid matrix. 2. Calcification the matrix surrounds the cell and then calcifies as the osteoblast becomes an osteocyte. Calcium and other mineral salts are deposited, and the extracellular matrix hardens or calcifies (calcification). 3. Formation of trabeculae the calcifying matrix centers join to form bridges of trabeculae that constitute spongy bone with red marrow between. 4. Development of the periosteum, the periosteum first forms a collar of spongy bone that is then replaced by compact bone.

C. Endochondral ossification involves replacement of cartilage by bone and forms most of the bones of the body. 1. The first step in endochondral ossification is the development of the cartilage model. Mesenchyme to crowd together in the general shape of the future bone, and then develop into chondroblasts. Secrete cartilage extracellular matrix, producing a cartilage model. Perichondrium develops. 2.

Growth of the cartilage model, the cartilage model grows in length by continual cell division of chondrocyte. Interstitial (endogenous) growth results in an increase in length. Appositional (exogenous) growth meaning growth at the outer surface.

3. Development of the primary ossification center, primary ossification center develops in the diaphysis. Cartilage is being removed and replaced by bone. Once the perichondrium starts to form bone, it is known as the periosteum. Primary ossification center, a region where bone tissue will

replace most of the cartilage. Osteoblasts then begin to deposit bone extracellular matrix over the remnants of calcified cartilage, forming spongy bone trabeculae. 4. The formation of a medullary cavity, osteoclasts break down some of the newly formed spongy bone trabeculae. This activity leaves a cavity, the medullary (marrow) cavity. 5.

Development of secondary ossification centers in the epiphysis. The secondary ossification centers spongy bone remains in the interior of the epiphyses and secondary ossification proceeds outward from the center of the epiphysis toward the outer surface of the bone.

6. Formation of articular cartilage and the epiphyseal plate, the hyaline cartilage that covers the epiphyses becomes the articular cartilage. D. Growth in Length 1. To understand how a bone grows in length, one needs to know details of the epiphyseal or growth plate. 2. The epiphyseal plate consists of four zones 3.

Zone of resting cartilage consists of small chondrocytes and does not function in bone growth. They anchor the epiphyseal plate to the epiphysis of the bone.

4. Zone of proliferation cartilage consists of large chondrocytes that undergo interstitial growth as they divide and secrete extracellular matrix. To replace those that die at the diaphyseal side of the epiphyseal plate. 5.

Zone of hypertrophic cartilage consists of large, maturing chondrocytes arranged in columns.

6. Zone of calcified cartilage consists of chondrocytes that are dead because the extracellular matrix around them has calcified. Osteoclasts dissolve the calcified cartilage. The osteoblasts lay down bone extracellular matrix, replacing the calcified cartilage by the process of endochondral ossification. 7. The activity of the epiphyseal plate is the only means by which the diaphysis can increase in length. 8. When the epiphyseal plate closes, is replaced by bone, the epiphyseal line appears and indicates the bone has completed its growth in length.

E. Growth in Thickness 1. Bone can grow in thickness or diameter only by appositional growth at the periosteum 2. Bone grows in diameter as a result of interstitial and appositional addition of new bone tissue by osteoblasts around the outer surface of the bone and to a lesser extent internal bone dissolution by osteoclasts in the bone cavity. F. Bone Remodeling 1. Remodeling is the ongoing replacement of old bone tissue by new bone tissue. 2. involves bone resorption, the removal of minerals and collagen fibers from bone by osteoclasts, and bone deposition, the addition of minerals and collagen fibers to bone by osteoblasts. 3. Old bone is constantly destroyed by osteoclasts, whereas new bone is constructed by osteoblasts. 4. Bone resorption, an osteoclast attaches tightly to the bone surface at the endosteum or periosteum and forms a leakproof seal. The enzymes digest collagen fibers and other organic substances while the acids dissolve the bone minerals. Several osteoclasts carve out a small tunnel in the old bone. The degraded bone proteins and extracellular matrix minerals, mainly calcium and phosphorus, enter an osteoclast by endocytosis, 5. Clinical Connection: Remodeling and Orthodontics- Braces are artificial stress, osteoclasts and osteoblasts remodel the sockets so that the teeth align properly. 6. Clinical Connection: Paget’s Disease- is an excessive proliferation of osteoclasts so that bone resorption occurs faster than bone deposition. If too much mineral material is deposited in the bone,

the surplus may form thick bumps, called spurs. The newly formed bone, especially that of the pelvis, limbs, lower vertebrae, and skull, becomes enlarged, hard, and brittle and fractures easily. G. Factors Affecting Bone remodeling and growth 1. Adequate dietary intake of minerals and vitamins is necessary for growth and maintenance of bone. a. Calcium and phosphorus are needed for bone growth in large concentrations, with other minerals needed in smaller amounts. b. Vitamins C, K, B12, and A are needed for bone growth. 2. The most important hormones for stimulation of bone growth during childhood are the insulin-like growth factors (IGFs), which are stimulated by human growth hormone (hGH). 3. IGFs stimulate osteoblasts, promote cell division at the epiphyseal plate and in the periosteum, and enhance synthesis of the proteins needed to build new bone. IGFs are produced in response to the secretion of growth hormone (GH) from the anterior lobe of the pituitary gland. Thyroid hormones (T3 and T4) from the thyroid gland also promote bone growth by stimulating osteoblasts. Hormone insulin from the pancreas promotes bone growth by increasing the synthesis of bone proteins. 2. At puberty, the sex hormones (estrogen and testosterone) stimulate sudden growth and modifications of the skeleton to create the male and female forms. 3. Clinical Connection: Hormonal abnormalities can affect growth in height. Oversecretion of growth hormone (GH) during childhood produces giantism. Achondroplasia an inherited condition in which the conversion of hyaline cartilage to bone is abnormal and the long bones of the limbs stop growing in childhood. H. Fracture and Repair of Bone 1. A fracture is any break in a bone 2. A stress fracture is a series of microscopic fissures in bone that forms without any evidence of injury to other tissues. 3. Fracture repair involves formation of a clot called a fracture hematoma, organization of the fracture hematoma into granulation tissue called a procallus (subsequently transformed into a fibrocartilaginous [soft] callus), conversion of the fibrocartilaginous callus into the spongy bone of a bony (hard) callus, and, finally, remodeling of the callus to nearly original form. 4. Treatments for fractures include the anatomic realignment of the bone fragments, immobilization to maintain realignment, and restoration of function. 5. Open compound Fracture- The broken ends of the bone protrude through the skin. Conversely, a closed (simple) fracture does not break the skin. 6. Comminuted fracture- The bone is splintered, crushed, or broken into pieces at the site of impact, and smaller bone fragments lie between the two main fragments

7. Greenstick fracture- A partial fracture in which one side of the bone is broken and the other side bends; similar to the way a green twig breaks on one side while the other side stays whole, but bends; occurs only in children, whose bones are not fully ossified and contain more organic material than inorganic material. 8. Impacted Fracture- One end of the fractured bone is forcefully driven into the interior of the other. 9. Pott fracture- Fracture of the distal end of the lateral leg bone (fibula), with serious injury of the distal tibial articulation. 10. Colles fracture- Fracture of the distal end of the lateral forearm bone (radius) in which the distal fragment is displaced posteriorly. 11. Clinical Connection: Treatments for Fractures- Reduction, is commonly referred to as setting a fracture. In closed reduction, the fractured ends of a bone are brought into alignment by manual manipulation, and the skin remains intact. In open reduction, the fractured ends of a bone are brought into alignment by a surgical procedure

VII.

BONE’S ROLE IN CALCIUM HOMEOSTASIS

A. Bone is the major reservoir for calcium ions (Ca 2+) in the body; the blood level calcium ions (Ca 2+) are very closely regulated. One way to maintain the level of calcium in the blood is to control the

rates of calcium resorption from bone into blood and of calcium deposition from blood into bone. Both nerve and muscle cells depend on a stable level of calcium ions (Ca2+). Blood clotting also requires Ca2+ and enzymes require Ca2+ as a cofactor. The blood plasma level of Ca2+ is very closely regulated between 9 and 11 mg/100 mL. B. An important hormone regulating Ca2+ exchange between bone and blood is parathyroid hormone (PTH), secreted by the parathyroid gland. It increases blood calcium ion levels. C. PTH secretion operates via a negative feedback system. If some stimulus causes the blood Ca2+ level to decrease, parathyroid gland cells (receptors) detect this change and increase their production of cyclic AMP. The gene for PTH within the nucleus of a parathyroid gland cell (the control center) detects the intracellular increase in cyclic AMP (the input). As a result, more PTH (the output) is released into the blood. The presence of higher levels of PTH increases the number and activity of osteoclasts (effectors), which step up the pace of bone resorption. The resulting release of Ca2+ from bone into blood returns the blood Ca2+ level to normal. PTH also acts on the kidneys (effectors) to decrease loss of Ca2+ in the urine, so more is retained in the blood. D. PTH stimulates formation of calcitriol (the active form of vitamin D), a hormone that promotes absorption of calcium from foods in the gastrointestinal tract into the blood E. Another hormone that contributes to the homeostasis of blood Ca 2+ is calcitonin (CT). It is secreted by the thyroid gland and decreases blood ...