Bruce G. Stewart

Related Textbook Readings

• Marieb and Hoehn (2010) Chapter 6

• Some images from your Murray State College laboratory histology studies:
  • You will be assigned microscope slide work in the laboratory.

Related Human Anatomy Coloring Book Assignments

• These will be assigned in class

Lecture Outlines

I. General Description of Skeletal System

1. The framework of bones, cartilage and other connective tissues that protects our organs and allows us to move
2. Orthopedics- the study of the skeletal system including preservation, restoration, articulations, and associated structures

II. Functions

A. Support of soft tissues of the body

B. Protection of internal organs such as the brain (cranial bones), spinal cord (vertebral column), heart and lungs (rib cage), and reproductive organs (pelvic bones)

C. Facilitation of movement by serving as points of attachment for muscle organs, by providing levers for muscles to operate, and by possessing joints to serve as fulcra

D. Storage of minerals such as calcium and phosphorus

E. Storage of blood cell producing tissues (red marrow) for hemopoiesis

F. Storage of energy rich tissues (yellow marrow)

III. Cell Types and Intercellular Matrix of Bone Tissue

Tissue types found in the skeletal system include several types of connective tissue including cartilage, bone, and dense connective tissues. Bone (=osseus) tissue is the most abundant type of tissue in the skeletal system, and we will explore its makeup first. Like other connective tissues, bone has abundant intercellular substances secreted and maintained by its cells.

A. Bone Cell Types - Four important cell types include: osteoprogenitor cells, osteoblasts, osteocytes, and osteoclasts.

• osteoprogenitor cells – unspecialized bone cells derived from the mesenchyme.They possess mitotic ability and can differentiate into osteoblasts. Osteoprogenitor cells occur in the inner lining of the periosteum (a connective tissue layer on the outer edge of the bone), the endosteum of the medullary cavity, and some canals in the bone.
• osteoblasts – bone cells that secrete the extracellular substances of bone tissue. Osteoblasts cannot reproduce themselves (lack mitotic ability). Osteoblasts are derived from osteoprogenitor cells and are typically found on the surfaces (both inner and outer) of bones. Activity of osteoblasts is stimulated by calcitonin from the thyroid gland.
• osteocytes – principle cells within the bone tissue proper. Osteoblasts become osteocytes once they are enclosed by extracellular substances. In this state, they maintain the condition of the bone.
• osteoclasts – cells descended from monocyte-like cells that can break down bone and phagocytize bone fragments. Osteoclast activity is stimulated by parathyroid hormone. Note that because of its developmental origen this cell type is more distantly related to the other bone cell types than those cells are to each other..

B. Intercellular Matrix – forms the strong structure of the tissue and houses blood vessels and bone cells

• mineral salts – primarily crystals of calcium phosphate [Ca₃(PO₄)₂-(OH₂)], some calcium carbonate (CaCO₃), and small amounts of magnesium hydroxide, fluoride, and sulfate.
• collagenous fibers – a framework of collagen fibers that make up about 33% of the bone tissue. Like steel reinforcement in concrete, these fibers provide added strength and flexibility to the bones.

IV. Histological Structure of Compact and Cancellous (Spongy) Bone

A. Histological Structure of Compact Bone

• bone tissue that is very dense with extracellular matrix and fewer spaces within the tissue. Compact bone makes up the outer layers of all bone and is especially thick in weight-bearing bones
• there are systems of canals through compact bone allow for passage of blood vessels and diffussion of nutrients, wastes, gasses, etc. Refer often to the figures in your textbook as you note these structures below:
  • perforating (=Volkmann's canals) are transverse canals that carry vessels
  • central (=Haversian) canals carry vessels longitudinally through compact bone in the center of a tissue unit called an osteon (=Haversian System)
• osteon (plural = ostea) (=Haversian System) - the name that applies to a single central canal surrounded by a distinctive ringed arrangement of bone cells and intercellular matrix
  • concentric lamellae (singular = lamella) - rings of calcified, intercellular substance architectural design encloses other structures, spaces, cells, vessels, etc.
  • lacunae (singular = lacuna) - spaces in between the lamellae that house the osteocytes
  • canaliculi (singular = canaliculus) - small canals that radiate from lacunae and contain extensions of the cytoplasm of the osteocytes. Canaliculi allow the osteocytes to reach out and touch each other. Thus, via the canaliculi, diffusion can occur cell to cell and ultimately to and from the capillary in the center of the osteon.
• interstitial lamellae - old ostea that are partly broken down but fill the spaces inbetween the "newer" ostea. To visualize this pattern, take several coins and place them on the desk touching each other; the interstitial spaces are analogous to the areas in between the coins where they do not touch

B. Structure of Spongy Bone (=cancellous bone)

• description - contains larger spaces and usually makes up parts of short and irregularly-shaped bones and most of epiphyses of long bones
• trabeculae (singular = trabeculum) - bony rods or thin plates that form an irregular "latticework" or framework imagine the structure of "monkey bars" in a playground where the pipe would be analogous to the trabeculae
• lacunae (with osteocytes of course!) occur within the trabeculae
• spaces in between the trabeculae contain marrow tissue with circulating blood e. blood vessels from the periosteum penetrate through a thin layer of compact bone via canals to reach the marrow cavity

V. Anatomy of a Long Bone

A. Diaphysis – shaft of a long bone

B. Epiphyses (singular = epiphysis) – certain ends of long bones (not all ends necessarily) where spongy bone is abundant along with red marrow.

C. Metaphysis - term applied sometimes to region of mature bone where the diaphysis joins the epiphysis; in growing bone this is the area of the "epiphyseal plate"; in mature bone it is also evident by the "epiphyseal line"

D. Articular cartilage – coatings of hyaline cartilage on the surface of articulating parts of the bone. This hyaline cartilage coating reduces friction in the joint.

E. Periosteum - dense, white, fibrous connective tissue covering of the bone where there is no articular cartilage. a. composed of an outer fibrous layer that supports blood vessels and nerves and an inner osteogenic layer that houses osteoprogenitor cells and osteoclasts.

F. Medullary (marrow) cavity - space in diaphysis with yellow marrow

G. Endosteum - inner lining of medullary cavity which houses osteoclasts, osteoblasts, and osteoprogenitor cells

VI. Physiology of Ossification: The Formation of Bone

A. General Formation - Ossification (=osteogenesis) begins during the 6^th to 7^th week of embryonic life.

• Two types of bone formation occur during development intramembranous ossification – within membranes endochondral ossification – within cartilage both types lead to same type of histological structure and both are the result of replacement of pre-existing connective tissue
  
• Description of Intramembranous Ossification
  
  • Types of bones formed by this method include the clavicles and most of the surface bones of the skull
  • An outline of the series of events that occur during this type of bone formation:
    1. osteoblasts cluster in fibrous membranes and form a center of ossification.
    2. osteoblasts secrete intercellular substances of collagenous fibers, and this is followed by depositions of calcium salts (calcification)
    3. after cluster is completely surrounded by the calcium matrix now forms a trabecula
    4. trabeculae interconnect and form the latticework of sponge bone
    5. their own secretions trap the osteoblasts in lacunae and they (the osteoblasts) become osteocytes
    6. spaces in between fill with red marrow
    7. surface areas of bone are reconstructed into compact bone (examine the worn femur in lab to see the spongy bone beneath the worn off surface of compact bone on the epiphysis)
• Description of Endochondral Ossification
  • occurs in the formation of most bones of the body including the bones at the base of the skull
  • growth pattern of tibia can serve as a good example (see figure in your textbook)
    1. in the beginning there is a cartilage model covered by perichondrium; except for the limited number of bones that form by intramembranous ossification, all bones of the body develop in this fashion
    2. "vascular bud" blood vessel penetrates the perichondrium about midway along the shaft
    3. osteoprogenitor cells to enlarge and form osteoblasts
    4. a periosteal collar of compact bone forms around the diaphysis (and as this continues as the next process olso occurs and the diaphysis is gets progressively thicker
    5. cartilage cells in the center of diaphysis undergo radical changes that will cause the development of a primary ossification center
       • first, hypertrophy (rapid growing) of chondrocytes (cartilage cells) occurs ---> cells increase glycogen levels and produce enzymes that catalyze future reactions
       • cartilage cells burst and spill contents into intracellar matrix of cartilage --> this produces pH increases and results in precipitation of calcium salts
       • precipitation calcium salts reduces nutrient diffusion resulting in death and degeneration of other surrounding cartilage cells
       • cavities form as chondrocytes die and degenerate, and these eventually merge forming larger cavities and ultimately the marrow cavity
       • increased development of blood vessels results in greater blood flow to inside of newly forming bone and brings in osteoprogenitor cells, osteoclasts, etc.
    6. secondary centers of ossification form in the ends of the bone as blood vessels penetrate the future epiphyses; same process occurs withing the cartilage as describe above for the diaphysis except that spongy bone will dominate the inside of the epiphyses rather than one large continuous marrow cavity
       • cartilage model grows at ends (and mostly in specific ways as will be noted shortly) blood vessels penetrate epiphyses and form secondary ossification centers makes more spongy bone ontogeny is as follows:
       • first center forms in proximal epiphysis of tibia just after birth
       • second center of tibia typically forms during 2^nd year
    7. bone tissue completely replaces cartilage except in two regions: the articular cartilage and the epiphyseal plate (the only location of lengthwise growth).
• Structure and Function of the Epiphyseal Plate (Note that figure in your textbook has slightly different terminology, which will be noted below.)
  • Growth Plate Zones

1. zone of reserve cartilage (first cell layer of the “growth” zone as shown in the figure in your textbook)
   • attached to the bone of the epiphysis
   • small cells that anchor the growth plate to epiphysis
   • capable of mitosis and thus produce cells for the following zone
2. zone of proliferating cartilage (rest of “growth” zone in figure in your textbook)
   • consists of slightly larger chondrocytes
   • have the appearance of being stacked in columns
   • also mitotic and maintain live chondrocytes next to those that are dying next to diaphyseal side
3. zone of hypertrophic cartilage (= “transformation” zone in your textbook)
   • larger chondrocytes also in columns
   • maturation area where rapidly growing cells begin deteriorating which is followed by calcification
4. zone of calcified matrix (= “osteogenic” zone in your textbook)
   • mostly dead cells with calcified intercellular spaces
   • invaded by osteoclasts, osteoblasts and capillaries from bone in diaphysis
   • remaining cartilage is replaced with bone
• General Patterns of Bone Growth Related to the Epiphyseal (Growth) Plate
  1. as a consequence of the structure and function of the growth plate zones, bone growth occurs on the diaphyseal side
  2. the epiphyseal plate is the only area of lengthways growth
     • functions to add bone until early adulthood
     • stimulated by human growth hormone (hGH)
     • growth usually completed by age 25 and typically earlier in females

• Growth in Diameter of Diaphysis (Shaft)
  • occurs progressively along with growth in length
  • lining of marrow cavity is destroyed by osteoclasts at a rate greater than produced by osteoblasts
  • on the outside of the bone shaft, osteoblasts produce more compact bone than osteoclasts remove
  • spongy bone forms first, then compact bone later by reconstruction
• Completion of Bone Growth
  • increased stimulation of hypertrophy of cartilage cells in the growth plate occurs due to added hormonal affects of testoterone and estrogen during puberty
  • ultimately, the rate of calcifications exceeds the ability of growth zone chondrocytes to reproduce and maintain cartilage tissue in which sufficient diffusion of nutrients can occur
  • eventually, all living cartilage cells die and are replaced by bone
  • the epiphyseal line between an epiphysis and the diaphysis of a bone is the visible remnant of the former growth plate; this is also referred to as the metaphysis

Laboratory Examination of Histological Preparations of Compact Bone, Hyaline Cartilage, Fibrocartilage, and Dense Connective Tissue

Slides will be presented to you in a laboratory session at about this point in our Notes on the Web. You must be able to recognize and name the following tissue types and specific structures:

• Ground Bone preparation of compact bone
  • ostea (singular = osteon)
  • lamellae (lamella)
  • lacunae (lacuna)
  • canaliculi (canaliculus)
  • osteocytes (or at least where they are located)
  • central canals (=Haversian canals)
  • perforating canals (Volkman's canals)
  • interstitial lamellae (an interstitial lamella)
  • capillaries (or location of capillaries)
• Hyaline Cartilage
  • lacunae (lacuna)
  • chondrocytes
  • nuclei (nucleus) of chondrocytes
  • intercellular matrix of fine collagen fibers
• Fibrocartilage
  • lacunae (lacuna)
  • chondrocytes
  • fibroblasts (or at least the nuclei of fibroblasts)
  • intercellular matrix with intermediate "smoothness" due to larger collagen fibers
• Dense Connective Tissue as illustrated by tendon long sections
  • fibroblasts (or at least the nuclei of fibroblasts)
  • intercellular matrix of clearly distinguishable coarse collagen fibers

Other structures may be added to this list during laboratory sessions, so keep abreast of activities in lab!

Video Histology Series - Bone and Related Connective Tissues
Dr. David Moran - Colorado State University

At this point we will view an excellent video histology presentation by Dr. David Moran. You can consider him to be a "visiting lecturer" throughout the semester since we will view video histology presentations by him on almost all major tissue types found in the human body systems we cover. We will always view these after we have completed our own lab exercises so that you will be better prepared to understand the presentations. Do not take these lightly since they can add a useful perspective on tissue structure, and Dr. Moran presents images taken with types of microscopes we do not have (e.g. scanning electron, transmission electron, Nomarski interference contrast, and phase contrast microscopes). He also shows images of materials prepared with different histological stains and techniques that enhance the quality of images.

Lecture Outlines (Continued)

VII. Bone Maintenance, Replacement and Repair

A. Remodeling – replacement of old bone by new bone

• spongy bone is transformed to compact bone by absorption next to marrow cavity and construction outside of diaphysis
• self-replacement – like skin, bone replaces itself in approximately four months (an average)
  • important that areas of mechanical stress be replace to avoid weakening due to small fractures, etc.
  • bone is replaced due to constant processes of calcium exchange with the rest of the body due to the many critical roles of calcium in physiological processes
    • blood/bone exchange is thus constant to insure that calcium ions are available for nerve cells to carry impulses, muscle myofibers to contract, and blood (vascular tissue) to perform clotting, and a host of other cellular functions in the human body
• Mechanism of Remodeling
  • osteoclasts – must act in homeostatic manner to remove both collagen fibers & calcium salts
    • too much or too little osteoclast activity results in calcium deposits, brittleness, etc.
    • osteoclasts send out cell projections that secrete enzymes from lysosomes (for digesting collagen and other proteins) and acids that dissolve calcium salts
    • osteoclasts also phagocytize whole fragments of bone matrix once it has been broken into small enough pieces
  • osteoprogenitor cells produce osteoblasts that then construct new fresh bone matrix; in the formation of ostea (Haversian systems), this occurs from the outside inward gradually forming lamellae one inside the other. Osteoblasts become trapped between the lamallae and become osteocytes

VIII. Factors that Influence Bone Growth, Remodeling, and Health (Negatively or Positively)

A. Minerals

• magnesium deficiency slows osteoclasts & also slows bone formation
  • example - hall of fame NBA basketball player, Bill Walton, had cronic ankle fracture problems until a magnesium deficiency was identified as a contributing culprit
• insufficient Ca²⁺ and/or P is a logical cause of weak bones when mineral matrix components cannot be maintained during either growth or maintenance
• insufficient Boron – boron normally aids in Ca²⁺ absorption in digestive tract, promotes better Ca²⁺ resorption, and promotes better reabsorption of Ca²⁺ by the kidneys to prevent Ca²⁺ loss in urine
• vitamin C deficiency – results in decreased production of collagen thus slows bone growth and fracture healing
• vitamin A deficiency – this results in slower growth because of roles of vitamin A in regulating activity, distribution, & coordination of osteoblasts/ osteoclasts
• vitamin B₁₂ may also play role in osteoblast activity
• Question to consider, "Are any of these problems preventable through practicing intelligent lifestyle behaviors?"

B. Hormones

• human growth hormone (hGH) produced by the pituitary gland - promotes general bone growth
• calcitonin (CT) produced by thyroid gland - accelerates calcium absorption by bone & inhibits osteoclasts
• parathormone (PTH) produced by parathyroid glands - increases number & activity of osteoclasts
• sex hormones – estrogen & testosterone - promote osteoblast activity by stimulating bone in growth. These hormones contribute to a spurt of growth during puberty. However, they also result in normal cessation of growth when degeneration of cartilage cells in epiphyseal plates results from excessive hypertrophic growth and then death as described earlier in your notes.
• other hormones such as additional thyroid hormones and insulin influence bone growth, maintenance, and general skeletal health
• Question to consider, "Are any of these problems preventable through practicing intelligent lifestyle behaviors?"

C. Exercise - Stronger and Thicker Bones

• exercise stimulates the piezoelectric effect - a physical connection between exercise and bone maintenance
  • minute currents of elasticity that stimulate formation of osteoblasts
  • stimulated by walking, running and other exercises that place healthy stress on bones
• exercise stimulates production of calcitonin by thyroid
  • this inhibits osteoclasts
• removal of mechanical stress through lack of exercise induces removal of mineral salts and collagen
• Question to consider, "Can you contribute to your own skeletal health well being through practicing intelligent lifestyle behaviors?"

D. Smoking - Don't EVEN Think that this isn't Serious!

• smoking reduces estrogen levels in women thus lowering osteoblast bone producing activity; this contributes to osteoporosis!
• smoking diminishes circulation and general health in various ways that contribute to risk of declining bone density and health
• smokers tend to be slugs when it comes to exercise; this robs them of the bone conditioning benefits of exercise as noted previously
• Click on the Van Gogh graphic (smoking skeleton) to make a required visit to study the increased risk of osteoporosis due to smoking. There will be at least one question on the exam from this page.
• Question to consider, "Do smokers contribute to their own loss of bone health by practicing this unintelligent, destructive lifestyle behavior?"

E. Aging

• loss of Ca and decrease in protein formation is correlated with aging
• some of loss is result of natural aging processes and/or disease; some is result of unintelligent lifestyle behaviors
• Ca loss in females
  • begins after age 30 and accelerates age 40-45 as estrogen decreases
  • as much as 30% can be lost by age 70
• males - begins Ca loss around age 60
• premature abandonment of exercise results in decreased ability to make bone matrix
  • this contributes to bone brittleness which is NOT necesarilly atributable to aging alone; that is, older people who exercise or are significantly more active are more likely to have stronger bones that same-age people who are sedentary
  • our society tends to exist in denial about the lifestyle components of our conditions
• Questions to consider, "Has your own level of activity decreased as you have gotten older?" "Is there any way you could improve your exercise patterns in order to save your own skeleton?"

IX. Some Homeostatic Imbalances

A. Osteoporosis – age-correlated disorder with lifestyle contributors (like smoking, poor nutrition, and lack of exercise).

• characterized by decreased bone mass, increase likelihood of fracture, and slower healing of injuries.
  • affects older more than younger
  • affects whites more than blacks
  • affects women earliler and more frequently than men
• contributing factors
  • in women a contributing cause is decreased levels of estrogens (which recall stimulate osteoblast activity)
  • smoking (decreases blood estrogen levels, reduces likelihood of beneficial exercise, and degrads general health)
  • pregnancy and nursing (note importance of proper diet and lifestyle behaviors)
  • prolonged cortisone treatment
  • high thyroid hormone levels
  • various deficiencies
  • lack of exercise
• treatments and prevention
  • prevention! start early in life with healthy habits that reduce risk factors. don't smoke!
  • supplements like anabolic steroids, calcitonin, calcium, sodium fluoride, and others depending on specifics of health issues of the individual

B. Rickets – vitamin D deficiency in children

• epiphyseal cartilage cells continue to be produced but don’t degenerate
• bones stay soft and do not ossify
• weight bearing bones deform

C. Osteomalacia – vitamin D deficiency in adults

• causes demineralization and softening of bones
• similar symptoms as in rickets, but develops in adults later in life

D. Paget’s disease – overactive osteoclasts & osteoblasts a. causes irregular thickening & softening of bones

E. Osteomyelitis – infectious diseases of bone

• a common one is caused by infection with resistant strains of Staphylococcus aureus
• can get in via blood, fractures, etc.
• treated with massive amounts of antibiotics; very difficult to defeat

F. Fractures

• types - learn the following types from you textbook
  • comminuted
  • compression
  • spiral
  • epiphyseal
  • depressed
  • greenstick
• repair - a process that is divided into some distinctive stages
  • formation of the fracture hematoma - blood clotting around fracture that occurs about six to eight hours after injury; surrounding cells tend to die due to blockage of nutrients
  • formation of callus - initial weak bony bridge across fracture that forms from osteoblast activity working through the protein fibers of the fracture hematoma
    • external callus – formed by bones cells associated with the periosteum
    • internal callus – fromed by bone cells associated with the endosteum and marrow
    • about 48 hours after fracture the repair begins in ernest as cells of osteogenic layer of periosteum and cells of endosteum and marrow form new trabeculae (external and internal calli respectively) which connect weakly by the end of the first week.
    • next several days – bone fragments collared and then the external callus is reinforced by more trabeculae joining pieces
    • remodeling of calli restores the compact bone on the outer portions while maintaining the spongy bone core - this varies in time, but four to six weeks is a general time for many bone
  • Repair of bones is radically affected by certain lifestyle behaviors like smoking and poor nutrition.

Reminder about Textbook Study

As with other topics, your textbook has excellent presentations of the materials on the skeletal system. While you should focus on the specific material in the Notes on the Web, you should always use your textbook as a resource for illustrations and for understanding content that your notes cover. Plus, in these particular notes, you are assigned some material directly from your text (bone break types).

As with all materials throughout the semester, you will have opportunities to ask questions or ask that any relevant material from your assignments be discussed in class.

Related Internet Resources

• Osteoporosis and Bone Physiology by Susan Ott, MD., Associate Professor, Department of Medicine, University of Washington. This site covers a variety of bone disease and prevention issues. The earlier link to the smoking/osteoporosis page is found in this web site.