CH7 - BONE TISSUE

Osteocyte

mature bone cell formed when an osteoblast becomes surrounded by its own matrix and entrapped in a lacuna.

Intramembranous Ossification Steps

(1) Mesenchyme first condenses into a soft sheet of tissue permeated with blood vessels—the membrane to which intramembranous refers. Mesenchymal cells line up along the blood vessels, become osteoblasts, and secrete a soft collagenous osteoid tissue in the direction away from the vessel. Osteoid tissue resembles bone but is not yet calcified. (2) Calcium phosphate and other minerals crystallize on the collagen fibers of the osteoid tissue and harden the matrix. Continued osteoid deposition and mineralization squeeze the blood vessels and future bone marrow into narrower and narrower spaces. As osteoblasts become trapped in their own hardening matrix, they become osteocytes. (3) While the foregoing processes are going on, more of the mesenchyme adjacent to the developing bone condenses and forms a fibrous periosteum on each surface. The spongy bone becomes a honeycomb of slender calcified trabeculae. (4) At the surfaces, osteoblasts beneath the periosteum deposit layers of bone, fill in the spaces between trabeculae, and create a zone of compact bone on each side, as well as thickening the bone overall. This process gives rise to the sandwich like structure typical of a flat cranial bone—a layer of spongy bone between two layers of compact bone.

Metaphysis (Zones/Steps)

(1) Zone of Reserve Cartilage (2) Zone of Cell Proliferation (3) Zone of Cell Hypertrophy (4) Zone of Calcification. (5) Zone of Bone Deposition.

Healing of Fractures (1)

(1)Hematoma Formation - The hematoma is converted to granulation tissue by invasion of cells and blood capillaries

Healing of Fractures (2)

(2)Soft Callus Formation - Deposition of collagen and fibrocartilage converts granulation tissue to a soft callus.

Healing of Fractures (3)

(3)Hard Callus Formation - Osteoblasts deposit a temporary bony collar around the fracture to unite the broken pieces while ossification occurs.

Healing of Fractures (4)

(4)Bone Remodeling - Small bone fragments are removed by osteoclasts, while osteoblasts deposit spongy bone and then convert it to compact bone.

Ectopic Ossification

(Abnormal Calcification) Osseous tissue sometimes forms in the lungs, brain, eyes, muscles, tendons, arteries, and other organs

Bone Cells and Their Development.

(a) Osteogenic cells give rise to osteoblasts, which deposit matrix around themselves and transform into osteocytes. (b) Bone marrow stem cells fuse to form osteoclasts.

Trabeculae

A thin plate or layer of tissue, such as the calcified trabeculae of spongy bone

Phosphate Homeostasis

85% to 90% of phosphate is in the bones Phosphate levels are not regulated as tightly as calcium levels Calcitriol promotes its absorption by small intestine and promotes bone deposition. PTH lowers blood phosphate level by promoting its urinary excretion.

Hypocalcemia

A deficiency of calcium ions in the blood, causes excessive excitability of the nervous system and leads to muscle tremors, spasms, or tetany

(2) Zone of Cell Proliferation

A little closer to the marrow cavity, chondrocytes multiply and arrange themselves into longitudinal columns of flattened lacunae

Physiology of Osseous Tissue

A mature bone remains a metabolically active organ Involved in its own maintenance of growth and remodeling Exerts a profound influence over the rest of the body by exchanging minerals with tissue fluid Disturbance of calcium homeostasis in skeleton disrupts function of other organ systems

Bone Widening and Thickening

Appositional Growth bones increase in width throughout life Deposition of new bone at the surface Osteoblasts on deep side of periosteum deposit osteoid tissue Become trapped as tissue calcifies Lay down matrix in layers parallel to surface Forms circumferential lamellae over surface

Support (Functions of the Skeleton)

Bones of the limbs and vertebral column support the body; the mandible and maxilla support the teeth; and some viscera are supported by nearby bones.

Protection (Functions of the Skeleton)

Bones enclose and protect the brain, spinal cord, heart, lungs, pelvic viscera, and bone marrow.

Acid-Base Balance (Functions of the Skeleton)

Bone tissue buffers the blood against excessive pH changes by absorbing or releasing alkaline phosphate and carbonate salts.

Osteoblast

Bone-forming cell that arises from an osteogenic cell, deposits bone matrix, and eventually becomes an osteocyte.

The Treatment of Fractures

Closed Reduction Open Reduction Cast normally used to stabilize and immobilize healing bone Traction used to treat fractures of the femur in children Electrical stimulation accelerates repair

Calcium Homeostasis

Calcium and phosphate are used for much more than bone structure About 1,100 g calcium in adult body Hypocalcemia has a wide variety of causes, blood calcium excess Calcium homeostasis is regulated by three hormones: Calcitriol, calcitonin, and parathyroid hormone

Skeletal System (Tissues and Organs)

Composed of bones, cartilages, and ligaments; Form strong, flexible framework of the body

Irregular Bones

Elaborate shapes that do not fit into other categories

Bone Elongation (1)

Epiphyseal Plate a region of transition from cartilage to bone Functions as growth zone where the bones elongate Consists of typical hyaline cartilage in the middle With a transition zone on each side where cartilage is being replaced by bone Metaphysis is

Bone Elongation

Epiphyseal Plate a region of transition from cartilage to bone Functions as growth zone where the bones elongate Consists of typical hyaline cartilage in the middle With a transition zone on each side where cartilage is being replaced by bone Metaphysis is the zone of transition facing the marrow cavity

Short Bones

Equal in length and width, Glide across one another in multiple directions

Osteoporosis Treatments

Estrogen Replacement Therapy (ERT) slows bone resorption, but increases risk of breast cancer, stroke, and heart disease Drugs Fosamax, Actonel destroy osteoclasts PTH slows bone loss if given as daily injection Forteo (PTH derivative) increases density by 10% in 1 year Best treatment is prevention: exercise and a good bone-building diet between ages 25 and 40

Periosteum

External sheath that covers bone except where there is articular cartilage, Outer fibrous layer of collagen, Some outer fibers continuous with the tendons that attach muscle to bone, Strong attachment and continuity from muscle to tendon to bone

Yellow Marrow

Found in the medullary cavity, the hollow interior of the middle portion of short bones, mainly made up of fat cells, no longer produces blood (In cases of severe blood loss, the body can convert yellow marrow back to red marrow to increase blood cell)

Bone Marrow

General term for soft tissue that occupies the marrow cavity of a long bone and small spaces amid the trabeculae of spongy bone. Both types of bone marrow contain numerous blood vessels and capillaries. With age, more and more of it is converted to the yellow type; only around half of adult bone marrow is red.

Bone Elongation (2)

Interstitial Growth bones increase in length really a result of cartilage growth within the epiphyseal plate Epiphyses close when cartilage is gone Epiphyseal Line, Lengthwise growth is finished, Occurs at different ages in different bones

Calcitriol (1)

It increases calcium absorption by the small intestine.

Calcitriol (2)

It increases calcium resorption from the skeleton. Calcitriol binds to osteoblasts, which release another chemical messenger called RANKL. This is the ligand (L) for a receptor named RANK32 on the surfaces of osteoclast-producing stem cells. This messenger stimulates the stem cells to differentiate into osteoclasts. The new osteoclasts then liberate calcium and phosphate ions from bone.

Calcitriol (3)

It weakly promotes the reabsorption of calcium ions by the kidneys, so less calcium is lost in the urine.

Articular Cartilage

Layer of hyaline cartilage that covers the joint surface where one bone meets another, Allows joint to move more freely and relatively friction free

Movement (Functions of the Skeleton)

Limb movements, breathing, and other movements are produced by the action of muscles on the bones.

Long Bones

Longer than wide, Rigid levers acted upon by muscles

Osteoclast

Macrophage of the bone surface that dissolves the matrix and returns minerals to the extracellular fluid.

Osteoporosis (Estrogen)

Maintains density in both sexes; inhibits resorption by osteoclasts; Testes and adrenals produce estrogen in men; In women, rapid bone loss after menopause since ovaries cease to secrete estrogen; Common in young female athletes with low body fat causing them to stop ovulating and ovarian estrogen secretion is low

Matrix

Matrix of osseous tissue is, by dry weight, about one-third organic and two-thirds inorganic matter Organic matter synthesized by osteoblasts Collagen, carbohydrate-protein complexes, such as glycosaminoglycans, proteoglycans, and glycoproteins Inorganic matter 85% hydroxyapatite (crystallized calcium phosphate salt) 10% calcium carbonate Other minerals (fluoride, sodium, potassium, magnesium)

Endochondral Ossification (Steps)

Mesenchyme develops into a body of hyaline cartilage, covered with a fibrous perichondrium, in the location of a future bone. For a time, the perichondrium produces chondrocytes and the cartilage model grows in thickness. In a primary ossification center near the middle of this cartilage, chondrocytes begin to inflate and die, while the thin walls between them calcify. The perichondrium stops producing chondrocytes and begins producing osteoblasts. These deposit a thin collar of bone around the middle of the cartilage model, reinforcing it like a napkin ring. The former perichondrium is now considered to be a periosteum. As chondrocytes in the middle of the model die, their lacunae merge into a single cavity. Osteoclasts arrive in the blood and digest calcified tissue in the shaft, hollowing it out and creating the primary marrow cavity. Osteoblasts also arrive and deposit layers of bone lining the cavity, thickening the shaft. As the bony collar under the periosteum thickens and elongates, a wave of cartilage death progresses toward the ends of the bone. Osteoclasts in the marrow cavity follow this wave, dissolving calcified cartilage remnants and enlarging the marrow cavity of the diaphysis. The region of transition from cartilage to bone at each end of the primary marrow cavity is called a metaphysis. Soon, chondrocyte enlargement and death occur in the epiphysis of the model as well, creating a secondary ossification center. In the metacarpal bones, as illustrated in figure 7.9, this occurs in only one epiphysis. In longer bones of the arms, forearms, legs, and thighs, it occurs at both ends. The secondary ossification center hollows out by the same process as the diaphysis, generating a secondary marrow cavity in the epiphysis. This cavity expands outward from the center, in all directions. In bones with two secondary ossification centers, one center lags behind the other, so at birth there is a secondary marrow cavity at one end while chondrocyte growth has just begun at the other. The joints of the limbs are still cartilaginous at birth, much as they are in the 12-week fetus. During infancy and childhood, the epiphyses fill with spongy bone. Cartilage is then limited to the articular cartilage covering each joint surface, and to an epiphyseal plate, a thin wall of cartilage separating the primary and secondary marrow cavities at one or both ends of the bone. The plate persists through childhood and adolescence and serves as a growth zone for bone elongation. By the late teens to early twenties, all remaining cartilage in the epiphyseal plate is generally consumed and the gap between the epiphysis and diaphysis closes. The primary and secondary marrow cavities then unite into a single cavity

(4) Zone of Calcification.

Minerals are deposited in the matrix between the columns of lacunae and calcify the cartilage. These are not the permanent mineral deposits of bone, but only a temporary support for the cartilage that would otherwise soon be weakened by the breakdown of the enlarged lacuna

(3) Zone of Cell Hypertrophy

Next, the chondrocytes cease to multiply and begin to hypertrophy (enlarge), much like they do in the primary ossification center of the fetus. The walls of matrix between lacunae become very thin.

Bone Remodeling

Occurs throughout life—10% per year Repairs microfractures, releases minerals into blood, reshapes bones in response to use and disuse Remodeling is a collaborative and precise action of osteoblasts and osteoclasts Bony processes grow larger in response to mechanical stress

Bone Development

Ossification or Osteogenesis the formation of bone. In the human fetus and infant, bone develops by two methods both begin with a soft embryonic tissue called Mesenchyme : Intramembranous and Endochondral.

Solubility Product

Osteoblasts begin the process by laying down collagen fibers in a helical pattern along the length of the osteon. These fibers then become encrusted with minerals that harden the matrix. Hydroxyapatite crystals form only when the product of calcium and phosphate concentration in the tissue fluids, represented [Ca2+] ∙ [PO43-], reaches a critical value called the solubility product

PTH3

PTH binds to receptors on the osteoblasts, stimulating them to secrete RANKL, which in turn raises the osteoclast population and promotes bone resorption.

PTH4

PTH inhibits collagen synthesis by osteoblasts, thus inhibiting bone deposition.

PTH2

PTH promotes calcium reabsorption by the kidneys, so less calcium is lost in the urine.

PTH1

PTH promotes the final step of calcitriol synthesis in the kidneys, thus enhancing the calcium-raising effect of calcitriol.

Flat Bones

Protect soft organs, Curved but wide and thin

Blood Formation (Functions of the Skeleton)

Red bone marrow is the major producer of blood cells, including cells of the immune system.

Features of Bones

Sandwich-like construction, Two layers of compact bone enclosing a middle layer of spongy bone, Both surfaces of flat bone covered with periosteum, Diploe

Calcitonin

Secreted by C cells (clear cells) of the thyroid gland when calcium concentration rises too high, Lowers blood calcium concentration in two ways Osteoclast Inhibition Osteoblast Stimulation Important in children, weak effect in adults Reduces bone loss in women during pregnancy and lactation

Parathyroid Hormone (PTH)

Secreted by the parathyroid glands (adhere to the posterior surface of thyroid gland) PTH released with low calcium blood levels PTH raises calcium blood level by four mechanisms Sporadic injection or secretion of low levels of PTH causes bone deposition, and can increase bone mass

Functions of the Skeleton (6)

Support Protection Movement Electrolyte Balance Acid-base Balance Blood Formation

Electrolyte Balance (Functions of the Skeleton)

The skeleton stores calcium and phosphate ions and releases them into the tissue fluid and blood according to the body's physiological needs.

(1) Zone of Reserve Cartilage

This region, farthest from the marrow cavity, consists of typical hyaline cartilage with resting chondrocytes, not yet showing any sign of transformation into bone.

Osteoclast Inhibition.

Within 15 minutes after it is secreted, calcitonin reduces osteoclast activity by as much as 70%, so osteoclasts liberate less calcium from the skeleton.

Osteoblast Stimulation.

Within an hour, calcitonin increases the number and activity of osteoblasts, which deposit calcium into the skeleton.

(5) Zone of Bone Deposition

Within each column, the walls between the lacunae break down and the chondrocytes die. This converts each column into a longitudinal channel (white spaces in the figure), which is immediately invaded by blood vessels and marrow from the marrow cavity. Osteoblasts line up along the walls of these channels and begin depositing concentric lamellae of matrix, while osteoclasts dissolve the temporarily calcified cartilage.

Stress Fracture

a break caused by abnormal trauma to a bone, such as fractures incurred in falls, athletics, and military combat

Pathological Fracture

a break in a bone weakened by some other disease, such as bone cancer or osteoporosis, usually caused by a stress that would not normally fracture a bone

Hypercalcemia

an excess of blood calcium, causes depression of the nervous system, emotional disturbances, muscle weakness, sluggish reflexes, and sometimes cardiac arrest

Wolff's Law Of Bone

architecture of bone determined by mechanical stresses placed on it and bones adapt to withstand those stresses

Epiphyseal Plate (Growth Plate)

area of hyaline cartilage that separates the marrow spaces of the epiphysis and diaphysis

Tendons

attach muscle to bone

Calcitriol

behaves as a hormone, acts on the bones, kidneys, and small intestine to raise blood calcium and phosphate levels and promote bone deposition. (The central panel represents the blood reservoir of calcium and shows its normal (safe) range. Calcitriol and PTH regulate calcium exchanges between the blood and the small intestine and kidneys (left). Calcitonin, calcitriol, and PTH regulate calcium exchanges between blood and bone (right).)

Osteoclasts

bone-dissolving cells on the bone surfaces. They develop from the same bone marrow stem cells that give rise to the blood cells. Thus, osteogenic cells, osteoblasts, and osteocytes all belong to one cell lineage, but osteoclasts have an independent origin (fig. 7.3). Each osteoclast is formed by the fusion of several stem cells, so osteoclasts are unusually large (up to 150 μm in diameter, visible to the naked eye). They typically have 3 or 4 nuclei, but sometimes up to 50, each contributed by one stem cell. The side of the osteoclast facing the bone surface has a ruffled border with many deep infoldings of the plasma membrane. This increases the cell surface area and thus enhances the efficiency of bone resorption. Osteoclasts often reside in pits called resorption bays (Howship14 lacunae) that they have etched into the bone surface. Bone remodeling results from the combined action of these bone-dissolving osteoclasts and bone-depositing osteoblasts.

Inner Osteogenic Layer

bone-forming cells, important to growth of bone and healing of fractures

Osteoblasts

bone-forming cells. They are roughly cuboidal or angular, and line up in a single layer on the bone surface under the endosteum and periosteum and resemble a cuboidal epithelium. Osteoblasts are nonmitotic, so the only way new ones can be generated is by mitosis and differentiation of osteogenic cells. They synthesize the soft organic matter of the bone matrix, which then hardens by mineral deposition. Stress and fractures stimulate osteogenic cells to multiply more rapidly and quickly generate increased numbers of osteoblasts, which reinforce or rebuild the bone. Osteoblasts also have an endocrine function: They secrete a hormone, osteocalcin, previously thought to be only a structural protein of bone. Osteocalcin stimulates insulin secretion by the pancreas, increases insulin sensitivity in adipocytes, and limits the growth of adipose tissue.

Calculus

calcified mass in an otherwise soft organ such as the lungs

Bone (Osseous Tissue)

connective tissue in which the matrix is hardened by the deposition of calcium phosphate and other minerals. The hardening process is called mineralization or calcification.

Red Marrow

consists mainly of hematopoietic tissue, form RBCs, Platelets, WBCs. Found mainly in the flat bones (such as the pelvis, sternum, cranium, ribs, vertebrae and scapulae, and in the cancellous ("spongy") material at the epiphyseal ends of long bones such as the femur and humerus production) At birth, all bone marrow is red.

Spongy (Cancellous) Bone

covered by more durable compact bone, Spongy bone in ends of long bones, and middle of nearly all others, consists of a lattice of delicate slivers of bone called spicules (rods or spines) and trabeculae

Mineral Deposition (Mineralization)

crystallization process in which calcium phosphate and other ions are taken from the blood plasma and deposited in bone tissue

Diaphysis (Shaft)

cylinder of compact bone to provide leverage

Kyphosis (Widow's Hump)

deformity of spine due to vertebral bone loss

Epiphyses

enlarged ends of a long bone (Enlarged to strengthen joint and attach ligaments and tendons)

Acid Phosphatase

enzyme secreted by osteoclasts that digests the collagen of the bone matrix (named for its ability to function in a highly acidic environment)

Cartilage

forerunner of most bones, covers many joint surfaces of mature bone

Hematopoiesis

formation of blood cells; tissue that produces blood cells

Osteocytes

former osteoblasts that have become trapped in the matrix they deposited. They reside in tiny cavities called lacunae, which are interconnected by slender channels called canaliculi. Each osteocyte has delicate cytoplasmic processes that reach into the canaliculi to contact the processes from neighboring osteocytes. Some of them also contact osteoblasts on the bone surface. Neighboring osteocytes are connected by gap junctions where their processes meet, so they can pass nutrients and chemical signals to one another and pass their metabolic wastes to the nearest blood vessel for disposal. Osteocytes have multiple functions. Some resorb bone matrix and others deposit it, so they contribute to the homeostatic maintenance of both bone density and blood concentrations of calcium and phosphate ions. Perhaps even more importantly, they are strain sensors. When a load is applied to a bone, it produces a flow in the extracellular fluid of the lacunae and canaliculi. This apparently stimulates the sensory primary cilia on the osteocytes and induces the cells to secrete signals that regulate bone remodeling—adjustments in bone shape and density to adapt to stress.

Displaced Fracture

fracture in which at least one piece is shifted out of alignment with the other

Comminuted Fracture

fracture in which in which a bone is broken into three or more pieces

Greenstick Fracture

fracture in which the bone is incompletely broken on one side but merely bent on the opposite side (the way a green twig breaks only partially and not into separate pieces)

Nondisplaced Fracture

fracture in which the bone pieces remain in proper anatomical alignment

Mesenchyme

gelatinous embryonic connective tissue derived from the mesoderm; differentiates into all permanent connective tissues and most muscle

Ligaments

hold bones together at the joints

Open Reduction

involves surgical exposure of the bone and the use of plates, screws, or pins to realign the fragments

Osteoporosis

most common bone disease, severe loss of bone density, bones lose mass and become brittle due to loss of organic matrix and minerals, affects spongy bone the most since it is the most metabolically active, subject to pathological fractures of hip, wrist, and vertebral column Kyphosis (Widow's Hump) Complications of loss of mobility are pneumonia and thrombosis

Perforating (Sharpey) Fibers

other outer fibers that penetrate into the bone matrix

Calcitriol Functions

principal function of calcitriol is to raise the blood calcium concentration (does this in three ways); also necessary for bone deposition (without it, calcium and phosphate levels in the blood are too low for normal deposition, the result is a softness of the bones called rickets in children and osteomalacia in adults)

Compact (Dense) Bone

outer shell of long bone onion-like Concentric Lamellae layers of matrix concentrically arranged around a Central (Haversian) Canal and connected with each other by Canaliculi. A Central Canal and its Lamellae constitute an Osteon (Haversian System)—the basic structural unit of compact bone. In longitudinal views and three-dimensional reconstructions, we can see that an Osteon is actually a cylinder of tissue surrounding a central canal. Along their length, central canals are joined by transverse or diagonal passages called Perforating (Volkmann) Canals. The central and perforating canals are lined with endosteum. Collagen Fibers "corkscrew" down the matrix of a given lamella in a helical arrangement like the threads of a screw. The helices coil in one direction in one lamella and in the opposite direction in the next lamella This enhances the strength of bone on the same principle as plywood, made of thin layers of wood with the grain running in different directions from one layer to the next. In areas where the bone must resist tension (bending), the helix is loosely coiled like the threads on a wood screw and the fibers are more stretched out on the longitudinal axis of the bone. In weight-bearing areas, where the bone must resist compression, the helix is more tightly coiled like the closely spaced threads on a bolt, and the fibers are more nearly transverse. The skeleton receives about half a liter of blood per minute. Blood vessels, along with nerves, enter the bone tissue through Nutrient Foramina on the surface. These foramina open into the perforating canals that cross the matrix and feed into the central canals. The innermost osteocytes around each central canal receive nutrients from these blood vessels and pass them along through their gap junctions to neighboring osteocytes. They also receive wastes from their neighbors and convey them to the central canal for removal by the bloodstream. Thus, the cytoplasmic processes of the osteocytes maintain a two-way flow of nutrients and wastes between the central canal and the outermost cells of the osteon. Not all of the matrix is organized into osteons. The inner and outer boundaries of dense bone are arranged in circumferential lamellae that run parallel to the bone surface. Between osteons, we can find irregular regions called interstitial lamellae, the remains of old osteons that broke down as the bone grew and remodeled itself

Closed Reduction

procedure in which the bone fragments are manipulated into their normal positions without surgery

Endochondral Ossification

process in which a bone develops from a preexisting model composed of hyaline cartilage. It begins around the sixth week of fetal development and continues into a person's 20s. Most bones of the body develop in this way, including the vertebrae, ribs, sternum, scapula, pelvic girdle, and bones of the limbs.

Intramembranous Ossification

produces the flat bones of the skull and most of the clavicle (collarbone), important role in the lifelong thickening, strengthening, and remodeling of the long bones discussed next. Throughout the skeleton, it is the method of depositing new tissue on the bone surface even past the age where the bones can no longer grow in length.

Spicules

skeletal fibers composed of flexible protein and mineralized particles

Medullary Cavity (Marrow Cavity)

space in the diaphysis of a long bone that contains bone marrow

Diploe

spongy layer in the cranium, Absorbs shock, Marrow spaces lined with endosteum

Osteogenic Cells

stem cells that develop from embryonic mesenchymal cells and then give rise to most other bone cell types. They are found in the endosteum and inner layer of the periosteum. They multiply continually, and some go on to become the osteoblasts described next.

Osteon

structural unit of compact bone consisting of a central canal surrounded by concentric cylindrical lamellae of matrix

Tetany

the inability of the muscle to relax

Mineral Resorption

the process of dissolving bone and releasing minerals into the blood, releases minerals into the blood and makes them available for other uses, carried out by osteoclasts (have surface receptors for calcium and respond to falling levels of calcium in the tissue fluid)

Metaphysis

the zone of transition facing the marrow cavity

Endosteum

thin layer of reticular connective tissue lining marrow cavity, has cells that dissolve osseous tissue and others that deposit it