Skeletal System Notes

Skeletal System

Skeletal Cartilages

  • The human skeleton initially consists of cartilage, which is replaced by bone, except in areas requiring flexibility.
  • Skeletal cartilage is made of resilient, molded cartilage tissue containing primarily water.
    • It contains no blood vessels or nerves.
  • Perichondrium: Dense connective tissue surrounding cartilage like a girdle.
    • Helps cartilage resist outward expansion.
    • Contains blood vessels for nutrient delivery to cartilage.
  • Cartilage is made up of chondrocytes, cells encased in small cavities (lacunae) within a jelly-like extracellular matrix.
  • Three Types of Cartilage:
    • Hyaline Cartilage: Provides support, flexibility, and resilience.
      • Most abundant type; contains collagen fibers only.
      • Located in articular (joints), costal (ribs), respiratory (larynx), and nasal cartilage (nose tip).
    • Elastic Cartilage: Similar to hyaline cartilage, but contains elastic fibers.
      • Located in the external ear and epiglottis.
    • Fibrocartilage: Contains thick collagen fibers, providing great tensile strength.
      • Located in the menisci of the knee and vertebral discs.
  • Growth of Cartilage
    • Cartilage grows in two ways:
      • Appositional Growth: Cartilage-forming cells in the perichondrium secrete matrix against the external face of existing cartilage.
        • New matrix is laid down on the surface of the cartilage.
      • Interstitial Growth: Chondrocytes within lacunae divide and secrete new matrix, expanding cartilage from within.
        • New matrix is made within the cartilage.
    • Calcification of cartilage occurs during normal bone growth in youth, but can also occur in old age.
      • Hardened cartilage is not the same as bone.

Functions of Bones

  • Seven important functions of bones:
    • Support: For the body and soft organs.
    • Protection: Protects the brain, spinal cord, and vital organs.
    • Movement: Levers for muscle action.
    • Mineral and Growth Factor Storage: Calcium and phosphorus, and a growth factors reservoir.
    • Blood Cell Formation: Hematopoiesis occurs in red marrow cavities of certain bones.
    • Triglyceride (fat) Storage: Fat, used for an energy source, is stored in bone cavities.
    • Hormone Production: Osteocalcin secreted by bones helps regulate insulin secretion, glucose levels, and metabolism.

Classification of Bones

  • 206 named bones in the human skeleton.
  • Divided into two groups based on location:
    • Axial Skeleton: Long axis of the body.
      • Skull, vertebral column, rib cage.
    • Appendicular Skeleton: Bones of the upper and lower limbs.
      • Girdles attaching limbs to the axial skeleton.
  • Bones are also classified according to one of four shapes:
    • Long Bones: Longer than they are wide.
      • Limb bones.
    • Short Bones: Cube-shaped bones (in wrist and ankle).
      • Sesamoid bones form within tendons (example: patella).
      • Vary in size and number in different individuals.
    • Flat Bones: Thin, flat, slightly curved.
      • Sternum, scapulae, ribs, most skull bones.
    • Irregular Bones: Complicated shapes.
      • Vertebrae and hip bones.

Bone Structure

  • Bones are organs because they contain different types of tissues.
  • Bone (osseous) tissue predominates, but a bone also has nervous tissue, cartilage, fibrous connective tissue, muscle cells, and epithelial cells in its blood vessels.
  • Three levels of structure:
    • Gross
    • Microscopic
    • Chemical
Gross Anatomy
  • Compact and Spongy Bone
    • Compact Bone: Dense outer layer on every bone that appears smooth and solid.
    • Spongy Bone: Made up of a honeycomb of small, needle-like or flat pieces of bone called trabeculae.
      • Open spaces between trabeculae are filled with red or yellow bone marrow.
  • Structure of Short, Irregular, and Flat Bones
    • Consist of thin plates of spongy bone (diploe) covered by compact bone.
    • Compact bone is sandwiched between connective tissue membranes.
      • Periosteum covers the outside of compact bone, and endosteum covers the inside portion of compact bone.
    • Bone marrow is scattered throughout spongy bone; there is no defined marrow cavity.
    • Hyaline cartilage covers the area of bone that is part of a movable joint.
  • Structure of Typical Long Bone
    • All long bones have a shaft (diaphysis), bone ends (epiphyses), and membranes.
      • Diaphysis: Tubular shaft that forms the long axis of the bone.
        • Consists of compact bone surrounding a central medullary cavity filled with yellow marrow in adults.
      • Epiphyses: Ends of long bones that consist of compact bone externally and spongy bone internally.
        • Articular cartilage covers articular (joint) surfaces.
      • Between the diaphysis and epiphysis is the epiphyseal line
        • Remnant of the childhood epiphyseal plate where bone growth occurs.
  • Membranes
    • Two types: periosteum and endosteum.
      • Periosteum: White, double-layered membrane that covers external surfaces except joints.
        • Fibrous layer: Outer layer consisting of dense irregular connective tissue, including Sharpey’s fibers that secure it to the bone matrix.
        • Osteogenic layer: Inner layer abutting bone contains primitive osteogenic stem cells that give rise to most bone cells.
        • Contains many nerve fibers and blood vessels that continue onto the shaft through nutrient foramen openings.
        • Anchoring points for tendons and ligaments.
      • Endosteum: Delicate connective tissue membrane covering internal bone surfaces.
        • Covers trabeculae of spongy bone.
        • Lines canals that pass through compact bone.
        • Like periosteum, contains osteogenic cells that can differentiate into other bone cells.
  • Hematopoietic Tissue in Bones
    • Red marrow is found within trabecular cavities of spongy bone and diploe of flat bones, such as the sternum.
      • In newborns, medullary cavities and all spongy bone contain red marrow.
      • In adults, red marrow is located in the heads of the femur and humerus, but the most active areas of hematopoiesis are in flat bone diploe and some irregular bones (such as the hip bone).
    • Yellow marrow can convert to red if a person becomes anemic.
  • Bone Markings
    • Sites of muscle, ligament, and tendon attachment on external surfaces.
    • Areas involved in joint formation or conduits for blood vessels and nerves.
      • Three types of markings:
        • Projection: Outward bulge of bone, due to increased stress from muscle pull or is a modification for joints.
        • Depression: Bowl- or groove-like cut-out that can serve as passageways for vessels and nerves, or plays a role in joints.
        • Opening: Hole or canal in bone that serves as passageways for blood vessels and nerves.
  • Bone Marking Examples
    • Tuberosity: Large rounded projection; may be roughened
    • Crest: Narrow ridge of bone; usually prominent
    • Trochanter: Very large, blunt, irregularly shaped process (the only examples are on the femur)
    • Line: Narrow ridge of bone; less prominent than a crest
    • Tubercle: Small rounded projection or process
    • Epicondyle: Raised area on or above a condyle
    • Spine: Sharp, slender, often pointed projection
    • Process: Any bony prominence
    • Head: Bony expansion carried on a narrow neck
    • Facet: Smooth, nearly flat articular surface
    • Condyle: Rounded articular projection
    • Ramus: Armlike bar of bone
    • Groove: Furrow
    • Fissure: Narrow, slitlike opening
    • Foramen: Round or oval opening through a bone
    • Notch: Indentation at the edge of a structure
    • Meatus: Canal-like passageway
    • Sinus: Cavity within a bone, filled with air and lined with mucous membrane
    • Fossa: Shallow, basinlike depression in a bone, often serving as an articular surface
Microscopic Anatomy of Bone
  • Cells of Bone Tissue
    • Five major cell types, each of which is a specialized form of the same basic cell type:
      • Osteogenic cells
      • Osteoblasts
      • Osteocytes
      • Bone-lining cells
      • Osteoclasts
    • Osteogenic Cells
      • Also called osteoprogenitor cells.
      • Mitotically active stem cells in the periosteum and endosteum.
      • When stimulated, they differentiate into osteoblasts or bone-lining cells.
      • Some remain as osteogenic stem cells.
    • Osteoblasts
      • Bone-forming cells that secrete unmineralized bone matrix called osteoid.
        • Osteoid is made up of collagen and calcium-binding proteins.
        • Collagen makes up 90% of bone protein.
      • Osteoblasts are actively mitotic.
    • Osteocytes
      • Mature bone cells in lacunae that no longer divide.
      • Maintain bone matrix and act as stress or strain sensors.
        • Respond to mechanical stimuli such as increased force on bone or weightlessness.
        • Communicate information to osteoblasts and osteoclasts (cells that destroy bone) so bone remodeling can occur.
    • Bone-Lining Cells
      • Flat cells on bone surfaces believed to also help maintain the matrix (along with osteocytes).
        • On external bone surfaces, lining cells are called periosteal cells.
        • On internal surfaces, they are called endosteal cells.
    • Osteoclasts
      • Derived from the same hematopoietic stem cells that become macrophages.
      • Giant, multinucleate cells function in bone resorption (breakdown of bone).
        • When active, cells are located in depressions called resorption bays.
        • Cells have ruffled borders that serve to increase surface area for enzyme degradation of bone.
        • Also helps seal off the area from the surrounding matrix.
  • Compact Bone
    • Also called lamellar bone.
    • Consists of:
      • Osteon (Haversian system)
      • Canals and canaliculi
      • Interstitial and circumferential lamellae
    • Osteon (Haversian System)
      • An osteon is the structural unit of compact bone.
      • Consists of an elongated cylinder that runs parallel to the long axis of the bone.
        • Acts as tiny weight-bearing pillars.
      • An osteon cylinder consists of several rings of bone matrix called lamellae.
        • Lamellae contain collagen fibers that run in different directions in adjacent rings.
        • Withstands stress and resists twisting.
        • Bone salts are found between collagen fibers.
    • Canals and Canaliculi
      • The central (Haversian) canal runs through the core of the osteon.
        • Contains blood vessels and nerve fibers.
      • Perforating (Volkmann’s) canals: canals lined with endosteum that occur at right angles to the central canal.
        • Connect blood vessels and nerves of the periosteum, medullary cavity, and central canal.
      • Lacunae: Small cavities that contain osteocytes.
      • Canaliculi: Hairlike canals that connect lacunae to each other and to the central canal.
        • Osteoblasts that secrete bone matrix maintain contact with each other and osteocytes via cell projections with gap junctions.
        • When the matrix hardens and cells are trapped the canaliculi form,
        • Allow communication between all osteocytes of the osteon and permit nutrients and wastes to be relayed from one cell to another.
    • Interstitial and Circumferential Lamellae
      • Interstitial Lamellae
        • Lamellae that are not part of the osteon.
        • Some fill gaps between forming osteons; others are remnants of osteons cut by bone remodeling.
      • Circumferential Lamellae
        • Just deep to the periosteum, but superficial to the endosteum, these layers of lamellae extend around the entire surface of the diaphysis.
        • Help long bone resist twisting.
  • Spongy Bone
    • Appears poorly organized but is actually organized along lines of stress to help bone resist any stress.
    • Trabeculae, like cables on a suspension bridge, confer strength to the bone.
      • No osteons are present, but trabeculae do contain irregularly arranged lamellae and osteocytes interconnected by canaliculi.
      • Capillaries in the endosteum supply nutrients.
Chemical Composition of Bone
  • Bone is made up of both organic and inorganic components.
    • Organic Components
      • Include osteogenic cells, osteoblasts, osteocytes, bone-lining cells, osteoclasts, and osteoid.
      • Osteoid, which makes up one-third of the organic bone matrix, is secreted by osteoblasts.
        • Consists of ground substance and collagen fibers, which contribute to high tensile strength and flexibility of bone.
      • Resilience of bone is due to sacrificial bonds in or between collagen molecules that stretch and break to dissipate energy and prevent fractures.
        • If there is no additional trauma, the bonds re-form.
    • Inorganic Components
      • Hydroxyapatites (mineral salts)
        • Make up 65% of bone by mass.
        • Consist mainly of tiny calcium phosphate crystals in and around collagen fibers.
        • Responsible for hardness and resistance to compression.
      • Bone is half as strong as steel in resisting compression and as strong as steel in resisting tension.
      • Lasts long after death because of mineral composition.
      • Can reveal information about ancient people.

Bone Development

  • Ossification (osteogenesis) is the process of bone tissue formation.
    • The formation of a bony skeleton begins in month 2 of development.
    • Postnatal bone growth occurs until early adulthood.
    • Bone remodeling and repair are lifelong.
Formation of the Bony Skeleton
  • Up to about week 8, fibrous membranes and hyaline cartilage of the fetal skeleton are replaced with bone tissue.
    • Endochondral Ossification
      • Bone forms by replacing hyaline cartilage.
      • Bones are called cartilage (endochondral) bones.
      • Forms most of the skeleton.
    • Intramembranous Ossification
      • Bone develops from a fibrous membrane.
      • Bones are called membrane bones.
  • Endochondral Ossification
    • Forms essentially all bones inferior to the base of the skull, except clavicles.
    • Begins late in month 2 of development.
    • Uses previously formed hyaline cartilage models.
    • Requires breakdown of hyaline cartilage prior to ossification.
    • Begins at the primary ossification center in the center of the shaft.
      • Blood vessels infiltrate the perichondrium, converting it to periosteum.
      • Mesenchymal cells specialize into osteoblasts.
    • Five Main Steps in the Process of Ossification:
      • A bone collar forms around the diaphysis of the cartilage model.
      • Central cartilage in the diaphysis calcifies, then develops cavities.
      • The periosteal bud invades the cavities, leading to the formation of spongy bone.
        • The bud is made up of blood vessels, nerves, red marrow, osteogenic cells, and osteoclasts.
      • The diaphysis elongates, and a medullary cavity forms.
        • Secondary ossification centers appear in the epiphyses.
      • The epiphyses ossify.
        • Hyaline cartilage remains only in epiphyseal plates and articular cartilages.
  • Intramembranous Ossification: Begins within fibrous connective tissue membranes formed by mesenchymal cells.
    • Forms the frontal, parietal, occipital, temporal, and clavicle bones.
    • Four Major Steps Involved:
      • Ossification centers are formed when mesenchymal cells cluster and become osteoblasts.
      • Osteoid is secreted, then calcified.
      • Woven bone is formed when osteoid is laid down around blood vessels, resulting in trabeculae.
        • The outer layer of woven bone forms the periosteum.
      • Lamellar bone replaces woven bone, and red marrow appears.
Postnatal Bone Growth
  • Long bones grow lengthwise by interstitial (longitudinal) growth of the epiphyseal plate.
  • Bones increase in thickness through appositional growth.
  • Bones stop growing during adolescence.
    • Some facial bones continue to grow slowly throughout life.
  • Growth in Length of Long Bones
    • Interstitial growth requires the presence of epiphyseal cartilage in the epiphyseal plate.
    • The epiphyseal plate maintains constant thickness.
      • The rate of cartilage growth on one side is balanced by bone replacement on the other.
    • The epiphyseal plate consists of five zones:
      • Resting (quiescent) zone
      • Proliferation (growth) zone
      • Hypertrophic zone
      • Calcification zone
      • Ossification (osteogenic) zone
    • Zones of the Epiphyseal Plate
      • Resting (Quiescent) Zone: Area of cartilage on the epiphyseal side of the epiphyseal plate that is relatively inactive.
      • Proliferation (Growth) Zone: Area of cartilage on the diaphysis side of the epiphyseal plate that is rapidly dividing.
        • New cells formed move upward, pushing the epiphysis away from the diaphysis, causing lengthening.
      • Hypertrophic Zone: Area with older chondrocytes closer to the diaphysis.
        • Cartilage lacunae enlarge and erode, forming interconnecting spaces.
      • Calcification Zone: Surrounding cartilage matrix calcifies; chondrocytes die and deteriorate.
      • Ossification Zone: Chondrocyte deterioration leaves long spicules of calcified cartilage at the epiphysis-diaphysis junction.
        • Spicules are then eroded by osteoclasts and are covered with new bone by osteoblasts.
        • Ultimately replaced with spongy bone.
        • The medullary cavity enlarges as spicules are eroded.
    • Near the end of adolescence, chondroblasts divide less often.
    • The epiphyseal plate thins, then is replaced by bone.
    • Epiphyseal Plate Closure: Occurs when the epiphysis and diaphysis fuse.
      • Bone lengthening ceases.
        • Females: occurs around 18 years of age.
        • Males: occurs around 21 years of age.
  • Growth in Width (Thickness)
    • Growing bones widen as they lengthen through appositional growth.
      • Can occur throughout life.
    • Bones thicken in response to increased stress from muscle activity or added weight.
    • Osteoblasts beneath the periosteum secrete bone matrix on the external bone.
    • Osteoclasts remove bone on the endosteal surface.
    • There is usually more building up than breaking down, which leads to thicker, stronger bone that is not too heavy.
  • Hormonal Regulation of Bone Growth
    • Growth Hormone: The most important hormone in stimulating epiphyseal plate activity in infancy and childhood.
    • Thyroid Hormone: Modulates the activity of growth hormone, ensuring proper proportions.
    • Testosterone (males) and Estrogens (females) at Puberty: Promote adolescent growth spurts.
      • End growth by inducing epiphyseal plate closure.
    • Excesses or deficits of any hormones cause abnormal skeletal growth.

Bone Remodeling

  • About 5–7% of bone mass is recycled each week.
    • Spongy bone is replaced approximately every 3-4 years.
    • Compact bone is replaced approximately every 10 years.
  • Bone remodeling consists of both bone deposit and bone resorption.
    • Occurs at the surfaces of both the periosteum and endosteum.
    • Remodeling units: packets of adjacent osteoblasts and osteoclasts coordinate the remodeling process.
  • Bone Deposit
    • New bone matrix is deposited by osteoblasts.
    • Osteoid Seam: A band of unmineralized bone matrix that marks the area of new matrix.
    • Calcification Front: An abrupt transition zone between the osteoid seam and older mineralized bone.
    • Triggers for deposit not confirmed but may include:
      • Mechanical signals
      • Increased concentration of calcium and phosphate ions for hydroxyapatite formation.
      • Matrix proteins that bind and concentrate calcium.
      • An appropriate amount of the enzyme alkaline phosphatase for mineralization.
  • Bone Resorption
    • Resorption is a function of osteoclasts.
    • Dig depressions or grooves as they break down the matrix.
    • Secrete lysosomal enzymes and protons (H+H^+) that digest the matrix.
      • Acidity converts calcium salts to soluble forms.
    • Osteoclasts also phagocytize demineralized matrix and dead osteocytes.
      • Digested products are transcytosed across the cell and released into interstitial fluid and then into the blood.
    • Once resorption is complete, osteoclasts undergo apoptosis.
    • Osteoclast activation involves PTH (parathyroid hormone) and immune T cell proteins.
Control of Remodeling
  • Remodeling occurs continuously but is regulated by genetic factors and two control loops:
    • Hormonal controls
    • Response to mechanical stress
  • Hormonal Controls
    • Negative feedback loop that controls blood Ca2+Ca^{2+} levels.
    • Calcium functions in many processes, such as nerve transmission, muscle contraction, blood coagulation, gland and nerve secretions, as well as cell division.
    • 99% of 1200–1400 gms of calcium are found in bone.
    • Intestinal absorption of Ca2+Ca^{2+} requires vitamin D.
    • Parathyroid Hormone (PTH): Produced by the parathyroid glands in response to low blood calcium levels.
      • Stimulates osteoclasts to resorb bone.
      • Calcium is released into the blood, raising levels.
      • PTH secretion stops when homeostatic calcium levels are reached.
    • Calcitonin: Produced by parafollicular cells of the thyroid gland in response to high levels of blood calcium levels.
      • Effects are negligible, but at high pharmacological doses, it can lower blood calcium levels temporarily.
    • Other Hormones Play a Role in Bone Density and Turnover
      • Leptin
        *Hormone released by adipose tissue
        *May play a role in bone density regulation by inhibiting osteoblasts
      • Serotonin
        *Neurotransmitter regulates mood and sleep; also interferes with osteoblast activity
        *Most serotonin made in gut
        *Secreted into blood after a meal
        *May inhibit bone turnover after a meal, so bone calcium is locked in when new calcium is flooding into bloodstream
  • Response to Mechanical Stress
    • Bones reflect the stresses they encounter.
      • Bones are stressed when weight bears on them or muscles pull on them.
    • Wolff’s Law: Bones grow or remodel in response to demands placed on them.
      • Stress is usually off-center, so bones tend to bend.
        • Bending compresses one side and stretches the other side.
        • The diaphysis is thickest where bending stresses are greatest.
        • Bone can be hollow because compression and tension cancel each other out in the center of the bone.
    • Wolff’s law also explains:
      • Handedness (right- or left-handed) results in thicker and stronger bones of the corresponding upper limb.
      • Curved bones are thickest where most likely to buckle.
      • Trabeculae form trusses along lines of stress.
      • Large, bony projections occur where heavy, active muscles attach.
        • Weightlifters have enormous thickenings at the muscle attachment sites of the most used muscles.
      • Bones of fetuses and bedridden people are featureless because of a lack of stress on the bones.
    • Mechanical stress causes remodeling by producing electrical signals when bone is deformed.
      • Compressed and stretched regions are oppositely charged.
      • Compression/tension changes fluid flow within canaliculi, which may also stimulate remodeling.
    • Hormonal controls determine whether and when remodeling occurs in response to changing blood calcium levels, but mechanical stress determines where it occurs.