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Chapter 4
The Tissue Level of Organization
Lecture Outline
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INTRODUCTION
• A tissue is a group of similar cells that usually have a similar
embryological origin and are specialized for a particular
function.
• The nature of the extracellular material that surrounds the
connections between the cells that compose the tissue
influence the structure and properties of a specific tissue.
• Pathologists, physicians who specialize in laboratory studies
of cells and tissues, aid other physicians in making
diagnoses; they also perform autopsies.
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Chapter 4 The Tissue Level of
Organization
• Histology
– the study of tissues
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TYPES OF TISSUES AND THEIR ORIGINS
Four principal types based on function and structure
• Epithelial tissue
– covers body surfaces, lines hollow organs, body cavities,
and ducts; and forms glands.
• Connective tissue
– protects and supports the body and its organs, binds
organs together, stores energy reserves as fat, and
provides immunity.
• Muscle tissue
– is responsible for movement and generation of force.
• Nervous tissue
– initiates and transmits action potentials (nerve impulses)
that help coordinate body activities.
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Origin of Tissues
• Primary germ layers within the embryo
– endoderm
– mesoderm
– Ectoderm
• Tissue derivations
– epithelium from all 3 germ layers
– connective tissue & muscle from mesoderm
– nerve tissue from ectoderm
– Table 29.1 provides a list of structures derived
from the primary germ layers.
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DEVELOPMENT
• Normally, most cells within a tissue remain in place,
anchored to
– other cells
– a basement membranes
– connective tissues
• Exceptions include phagocytes and embryonic cells
involved in differentiation and growth.
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Biopsy
• Removal of living tissue for microscopic examination
– surgery
– needle biopsy
• Useful for diagnosis, especially cancer
• Tissue preserved, sectioned and stained before microscopic
viewing
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CELL JUNCTIONS
• Cell junctions are points of contact between adjacent
plasma membranes.
• Depending on their structure, cell junctions may serve one
of three functions.
– Some cell junctions form fluid-tight seals between cells.
– Other cell junctions anchor cells together or to
extracellular material.
– Still others act as channels, which allow ions and
molecules to pass from cell to cell within a tissue.
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CELL JUNCTIONS
• The five most
important kinds of
cell junctions are
tight junctions,
adherens
junctions,
desmosomes,
hemidesmosomes,
and gap junctions
(Figure 4.1)
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Cell Junctions
• Tight junctions
• Adherens junctions
• Gap junctions
• Desmosomes
• Hemidesmosomes
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Tight Junctions
• Watertight seal between cells
• Plasma membranes fused with
a strip of proteins
• Common between cells that line
GI and bladder
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Adherens Junctions
• Holds epithelial cells together
• Structural components
– plaque = dense layer of
proteins inside the cell
membrane
– microfilaments extend into
cytoplasm
– integral membrane proteins
connect to membrane of other
cell
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Gap Junctions
• Tiny space between plasma membranes
of 2 cells
• Crossed by protein channels called
connexons forming fluid filled tunnels
• Cell communication with ions & small
molecules
• Muscle and nerve impulses spread from
cell to cell
– heart and smooth muscle of gut
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Desmosomes
• Resists cellular separation and
cell disruption
• Similar structure to adherens
junction except intracellular
intermediate filaments cross
cytoplasm of cell
• Cellular support of cardiac
muscle
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Hemidesmosomes
• Half a desmosome
• Connect cells to extracellular
material
– basement membrane
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EPITHELIAL TISSUES
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Epithelial Tissue -- General Features
• Closely packed cells with little extracellular material
– Many cell junctions often provide secure attachment.
• Cells sit on basement membrane
– Apical (upper) free surface
– Basal surface against basement membrane
• Avascular---without blood vessels
– nutrients and wast must move by diffusion
• Good nerve supply
• Rapid cell division (high mitotic rate)
• Functions
– protection, filtration, lubrication, secretion, digestion,
absorption, transportation, excretion, sensory
reception, and reproduction.
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Basement Membrane
• Basal lamina
– from epithelial cells
– collagen fibers
• Reticular lamina
– secreted by connective tissue cells
– reticular fibers
• Functions:
– guide for cell migration during
development
– may become thickened due to
increased collagen and laminin
production
• Example: In diabetes mellitus, the
basement membrane of small blood
vessels, especially those in the retina and
kidney, thickens.
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Types of Epithelium
• Covering and lining epithelium
– epidermis of skin
– lining of blood vessels and ducts
– lining respiratory, reproductive, urinary & GI tract
• Glandular epithelium
– secreting portion of glands
– thyroid, adrenal, and sweat glands
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Classification of Epithelium
•
Classified by arrangement of cells into layers
– simple = one cell layer thick
– stratified = two or more cell layers thick
– pseudostratified = cells contact BM but all cells don’t
reach apical surface
• nuclei are located at multiple levels so it looks
multilayered
• Classified by shape of surface cells (Table 4.1)
– squamous =flat
– cuboidal = cube-shaped
– columnar = tall column
– transitional = shape varies with tissue stretching
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Epithelium
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Simple Epithelium
• Simple squamous epithelium consists of a single layer of
flat, scale-like cells (Table 4.1A)
– adapted for diffusion and filtration (found in lungs and
kidneys)
– Endothelium lines the heart and blood vessels.
– Mesothelium lines the thoracic and abdominopelvic
cavities and covers the organs within them.
• Simple cuboidal epithelium consists of a simple layer of
cube-shaped cells
– adapted for secretion and absorption (Table 4.1B).
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Simple Epithelium
• Simple columnar epithelium consists of a single layer of
rectangular cells and can exist in two forms
– Nonciliated simple columnar epithelium contains
microvilli (Figure 3.2)
• increase surface are and the rate of absorption
• goblet cells secrete mucus (Table 4.1C)
– Ciliated simple columnar epithelium contains cells with
hair-like processes called cilia (Table 4.1D)
• provides motility and helps to move fluids or particles
along a surface
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Simple Squamous Epithelium
• Single layer of flat cells
– very thin --- controls diffusion, osmosis and filtration
• blood vessel lining (endothelium) and lining of body
cavities (mesothelium)
– nuclei are centrally located
– Cells are in direct contact with each other.
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Examples of Simple Squamous
• Surface view of lining of
peritoneal cavity
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• Section of intestinal showing
serosa
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Simple Cuboidal Epithelium
• Single layer of cube-shaped cells viewed from the side
– nuclei are round and centrally located
– lines tubes of kidney
– adapted for absorption or secretion
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Example of Simple Cuboidal
• X-Sectional view of kidney tubules
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Nonciliated Simple Columnar
• Single layer rectangular cells
• Unicellular glands (goblet cells) secrete mucus
– lubricate GI, respiratory, reproductive and urinary systems
• Microvilli (non-motile, fingerlike membrane projections)
– adapted for absorption in GI tract (stomach to rectum)
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Ex. Nonciliated Simple Columnar
• Section from small intestine
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Ciliated Simple Columnar Epithelium
• Single layer rectangular cells with cilia
• Unicellular glands (goblet cells) secrete mucus
• Cilia (motile membrane extensions) move mucous
– found in respiratory system and in uterine tubes
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Ex. Ciliated Simple Columnar
• Section of uterine tube
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Pseudostratified Epithelium
• Pseudostratified epithelium (Table 4.1E) appears to have
several layers because the nuclei are at various levels.
• All cells are attached to the basement membrane but some
do not reach the apical surface.
• In pseudostratified ciliated columnar epithelium, the cells
that reach the surface either secrete mucus (goblet cells) or
bear cilia that sweep away mucus and trapped foreign
particles.
• Pseudostratified nonciliated columnar epithelium contains
no cilia or goblet cells.
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Pseudostratified Ciliated Columnar Epithelium
• Single cell layer of cells of variable height
– Nuclei are located at varying depths (appear layered.)
– Found in respiratory system, male urethra & epididymis
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Stratified Epithelium
• Epithelia have at least two layers of cells.
– more durable and protective
– name depends on the shape of the surface (apical) cells
• Stratified squamous epithelium consists of several layers of
– top layer of cells is flat
– deeper layers of cells vary cuboidal to columnar (Table
4.1F).
– basal cells replicate by mitosis
• Keratinized stratified squamous epithelium
– a tough layer of keratin (a protein resistant to friction and
repels bacteria) is deposited in the surface cells.
• Nonkeratinized epithelium remains moist.
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Stratified Epithelium
• Stratified cuboidal epithelium (Table 4.1G)
– rare tissue consisting of two or more layers of cubeshaped cells whose function is mainly protective.
• Stratified columnar epithelium (Table 4.1H) consists of
layers of cells
– top layer is columnar
– somewhat rare
– adapted for protection and secretion
• Transitional epithelium (Table 4.1I) consists of several
layers of variable shape.
– capable of stretching / permits distention of an organ
– lines the urinary bladder
– lines portions of the ureters and the urethra.
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Stratified Squamous Epithelium
• Several cell layers thick
– flat surface cells
– Keratinized = surface cells dead and filled with keratin
• skin (epidermis)
– Nonkeratinized = no keratin in moist living cells at surface
• mouth, vagina
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Papanicolaou Smear (Pap smear)
• Collect sloughed off cells of uterus and vaginal walls
• Detect cellular changes (precancerous cells)
• Recommended annually for women over 18 or if
sexually active
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Stratified Cuboidal Epithelium
• Multilayered
• Surface cells cuboidal
– rare
– sweat gland ducts
– male urethra
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Stratified Columnar Epithelium
• Multilayered
– columnar surface cells
– rare
– very large ducts
– part of male urethra
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Transitional Epithelium
• Multilayered
– surface cells varying in shape
• round to flat (if stretched)
– lines hollow organs that expand from within (urinary
bladder)
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Glandular Epithelium
• gland:
– a single cell or a mass of epithelial cells adapted for
secretion
– derived from epithelial cells that sank below the surface
during development
• Endocrine glands are ductless (Table 4.2A).
• Exocrine glands secrete their products into ducts that empty
at the surface of covering and lining epithelium or directly
onto a free surface (Table 4.2B).
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Glandular Epithelium
• Exocrine glands
– cells that secrete---sweat, ear wax, saliva, digestive
enzymes onto free surface of epithelial layer
– connected to the surface by tubes (ducts)
– unicellular glands or multicellular glands
• Endocrine glands
– secrete hormones into the bloodstream
– hormones help maintain homeostasis
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Simple Cuboidal Epithelium
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Structural Classification of Exocrine Glands
• Unicellular (single-celled) glands
– goblet cells
• Multicellular glands
– branched (compound) or unbranched (simple)
– tubular or acinar (flask-like) shape
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Examples of Simple Glands
• Unbranched ducts = simple glands
• Duct areas are blue
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Examples of Compound Glands
• Which is acinar? Which is tubular?
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Duct of Multicellular Glands
• Sweat gland duct
• Stratified cuboidal epithelium
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Exocrine Glands – Functional Classification
• Merocrine glands
– form the secretory products and discharge it by exocytosis
(Figure 4.5a).
• Apocrine glands
– accumulate secretary products at the apical surface of the
secreting cell; that portion then pinches off from the rest of
the cell to form the secretion with the remaining part of the
cell repairing itself and repeating the process (Figure 4.5b).
• Holocrine glands
– accumulate the secretory product in the cytosol
– cell dies and its products are discharged
– the discharged cell being replaced by a new one (Figure
4.5c).
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Methods of Glandular Secretion
• Merocrine -- most glands
– saliva, digestive enzymes &
watery (sudoriferous) sweat
• Apocrine
– smelly sweat
• Holocrine -- oil gland
– cells die & rupture to release
products
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CONNECTIVE TISSUE
• abundant and widely distributed
• derived from mesoderm
• derived from mesenchyme
– Immature cells have names that end in -blast( e.g.,
fibroblast, chondroblast)
– Mature cells have names that end in -cyte (e.g.,
osteocyte).
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Connective Tissues
• Cells rarely touch due to “extracellular matrix.”
• Matrix (fibers & ground substance) is secreted by cells
• Consistency varies
– liquid, gel or solid
• Good nerve & blood supply except in cartilage & tendons
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Connective Tissue Cells (Figure 4.6)
– Fibroblasts (which secrete fibers and matrix)
– Adipocytes (or fat cells, which store energy in the form of
fat)
– White blood cells (or leukocytes)
• Macrophages develop from monocytes
– engulf bacteria & debris by phagocytosis
• Plasma cells develop from B lymphocytes
– produce antibodies that fight against foreign
substances
• Mast cells produce histamine that dilate small BV
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Extracellular Matrix: Ground Substance
• Ground Substance
– glycosamino glycans (GAG’s) hyaluronic acid,
chondroitin sulfate, dermatan sulfate, and keratan sulfate
• hyaluronic acid is thick, viscous and slippery
• chondroitin sulfate is jellylike substance providing
support
• adhesion proteins (fibronectin) binds collagen fibers to
ground substance
• Chondroitin sulfate and glucosamine are used as nutritional
supplements to maintain joint cartilage. It is not known why
the supplements benefit some individuals and not others.
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• Collagen fibers
Extracellular
– composed of the protein collagen
Matrix: Fibers
– tough and resistant to stretching
(Figure 4.6).
– allow some flexibility in tissue
– bone, cartilage, tendons, and ligaments.
• Elastic fibers
– composed of the protein elastin surrounded by the
glycoprotein fibrillin
– provide strength and stretching capacity
– skin, blood vessels, and lungs.
• Reticular fibers
– composed of collagen and glycoprotein
– support in the walls of blood vessels, in spleen, in lymph
nodes
– supporting network around fat cells, nerve fibers, and
skeletal and smooth muscle fibers.
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Clinical Application: Marfan Syndrome
• Inherited disorder of fibrillin gene
• Abnormal development of elastic fibers
– Tendency to be tall with very long legs, arms, fingers and
toes
– Life-threatening weakening of aorta may lead to rupture
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Embryonic Connective Tissue
• Connective tissue that is present primarily in the embryo or
fetus is called embryonic connective tissue.
• Mesenchyme, found almost exclusively in the embryo, is the
tissue form from which all other connective tissue eventually
arises. (Table 4.3A)
• Mucous connective tissue (Wharton’s jelly) is found in the
umbilical cord of the fetus.(Table 4.3B)
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Embryonic Connective Tissue:
Mesenchyme
• Irregularly shaped cells
• semifluid ground substance with reticular fibers
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Embryonic Connective Tissue:
Mucous Connective Tissue
• Star-shaped cells in jelly-like ground substance
• Found only in umbilical cord
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Types of Mature Connective Tissue
• connective tissue proper
– loose connective tissue
• consists of all three types of fibers, several types of
cells, and a semi-fluid ground substance
– dense connective tissue
• Cartilage
– Hyaline, elastic, reticular
• bone tissue
– compact and trabecular
• Blood and Lymph
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Loose Connective Tissues
• Loosely woven fibers throughout tissues
• Sub-types of loose connective tissue
– areolar connective tissue
– adipose tissue
– reticular tissue
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Areolar Connective Tissue (Table 4.4A)
• Cell types = fibroblasts, plasma cells, macrophages, mast cells and a few
white blood cells
• All 3 types of fibers present
• Gelatinous ground substance
• It is found in the subcutaneous layer of the integument
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Areolar Connective Tissue
• Black = elastic fibers,
• Tan/Pink = collagen fibers
• Nuclei are mostly fibroblasts
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Adipose
• Adipose tissue consists of adipocytes which are specialized
for storage of triglycerides. (Table 4.4B)
– found wherever areolar connective tissue is located.
– reduces heat loss through the skin, serves as an energy
reserve, supports, protects, and generates considerable
heat to help maintain proper body temperature in
newborns (brown fat).
• Liposuction involves sucking out small amounts of adipose
tissue.
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Adipose Tissue
• Peripheral nuclei due to large fat storage droplet
• Deeper layer of skin, organ padding, yellow marrow
• Brown fat (found in infants) has more blood vessels and mitochondria
and is responsible for heat generation
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Reticular Connective Tissue
• Reticular connective tissue consists of fine interlacing
reticular fibers and reticular cells (Table 4.4C).
– forms the stroma of certain organs.
– helps to bind together the cells of smooth muscle.
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Reticular Connective Tissue
• Network of fibers & cells that produce framework of organ
• Holds organ together (liver, spleen, lymph nodes, bone marrow)
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Dense Connective Tissue
Dense connective tissue contains more
numerous, thicker, and dense fibers but
considerably fewer cells than loose
connective tissue.
Types of dense connective tissue
– dense regular connective tissue
– dense irregular connective tissue
– elastic connective tissue
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Dense Regular Connective Tissue
• Collagen fibers in parallel bundles with fibroblasts between bundles of
collagen fibers
• White, tough and pliable when unstained (forms tendons)
• Also known as white fibrous connective tissue
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Dense irregular connective tissue
• Dense irregular connective tissue contains collagen fibers
that are irregularly arranged and is found in parts of the
body where tensions are exerted in various directions (Table
4.4E).
– occurs in sheets, such as the dermis of the skin.
– found in heart valves, the perichondrium, the tissue
surrounding cartilage, and the periosteum.
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Dense Irregular Connective Tissue
• Collagen fibers are irregularly arranged (interwoven)
• Tissue can resist tension from any direction
• Very tough tissue -- white of eyeball, dermis of skin
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Elastic Connective Tissue (Table 4.4F).
• Branching elastic fibers and fibroblasts
• Can stretch & still return to original shape
• Lung tissue, vocal cords, ligament between vertebrae
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Cartilage
• Cartilage consists of a dense network of collagen fibers and
elastic fibers embedded in chondroitin sulfate.
– strength is due to its collagen fibers
– resilience is due to the chondroitin sulfate
– Chondrocytes occur with spaces called lacunae in the
matrix.
• It is surrounded by a dense irregular connective tissue
membrane called the perichondrium.
• Unlike other connective tissues, cartilage has no blood
vessels or nerves (except in the perichondrium).
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Cartilage
• The growth of cartilage is accomplished by interstitial
growth (expansion from within) and appositional growth
(from the outside).
• Types of cartilage
– hyaline cartilage
– fibrocartilage
– elastic cartilage
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Three types
• Hyaline cartilage (Table 4.4G)
of cartilage.
– most abundant, but weakest
– has fine collagen fibers embedded in a gel-type matrix
– affords flexibility and support and
– at joints, reduces friction and absorbs shock
• Fibrocartilage (Table 4.4H)
– contains bundles of collagen fibers in its matrix
– lacks perichondrium
– strongest of the three types of cartilage
• Elastic cartilage (Table 4.4J)
– contains a threadlike network of elastic fibers
– perichondrium is present
– provides strength and elasticity
– maintains the shape of certain organs
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Hyaline Cartilage
•
•
•
•
Bluish-shiny white rubbery substance
Chondrocytes sit in spaces called lacunae
No blood vessels or nerves so repair is very slow
Reduces friction at joints as articular cartilage
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Fibrocartilage
• Many more collagen fibers causes rigidity & stiffness
• Strongest type of cartilage (intervertebral discs)
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Elastic Cartilage
• Elastic fibers help maintain shape after deformations
• Ear, nose, vocal cartilages
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Growth & Repair of Cartilage
• Grows and repairs slowly because it is avascular
• Interstitial growth
– chondrocytes divide and form new matrix
– occurs in childhood and adolescence
• Appositional growth
– chondroblasts secrete matrix onto surface
– produces increase in width
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Bone (Osseous) Tissue
• Protects, provides for movement, stores minerals, site
of blood cell formation
• Bone (osseous tissue) consists of a matrix containing
mineral salts and collagenous fibers and cells called
osteocytes.
– Spongy bone
• sponge-like with spaces and trabeculae
• trabeculae = struts of bone surrounded by red
bone marrow
• no osteons (cellular organization)
– Compact bone (Table 4.4J)
• solid, dense bone
• basic unit of structure is osteon (haversian
system)
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Compact Bone: Osteon (Haversion System)
• lamellae (rings) of mineralized matrix
– calcium & phosphate---give it its hardness
– interwoven collagen fibers provide strength
• Lacunae are small spaces between lamellae that contain mature
bone cells called osteocytes.
• Canaliculi are minute canals containing processes of osteocytes
that provide routes for nutrient and waste transport.
• A central (Haversian) canal contains blood vessels and nerves.
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Liquid connective tissue
• Blood
– liquid matrix called plasma
– formed elements (Table 4.4K)
• Lymph is interstitial fluid flowing in lymph vessels.
– Contains less protein than plasma
– Move cells and substances (eg., lipids) from one part of
the body to another
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Blood
• Connective tissue with a liquid matrix (the plasma)
• Cell types include red blood cells (erythrocytes), white blood
cells (leukocytes) and cell fragments called platelets
– clotting, immune functions, transport of O2 and CO2
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MEMBRANES
Membranes are flat sheets of pliable tissue that cover or line a
part of the body.
• Epithelial membranes consist of an epithelial layer and an
underlying connective tissue layer (lamina propria)
– include mucous membranes, serous membranes, and
the cutaneous membrane or skin.
• Synovial membranes line joints and contain only connective
tissue.
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Mucous Membranes
• Mucous membranes (mucosae) line cavities that open
to the exterior (Figure 4.7a).
– mouth, stomach, vagina, urethra, etc
• Epithelial cells form a barrier to microbes
• The connective tissue layer of a mucous membrane is
called the lamina propria.
• Tight junctions between cells prevent simple diffusion of
most substances.
• Mucous is secreted from underlying glands to keep
surface moist
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Mucous Membranes
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Serous Membranes
• Simple squamous cells overlying loose CT layer
– consist of parietal and visceral layers
• Squamous cells secrete slippery fluid
• Lines a body cavity that does not open to the outside such as chest or
abdominal cavity
• Examples:
– pleura, peritoneum and pericardium
• membrane on walls of cavity = parietal layer
• membrane over organs in cavity = visceral layer
• Serous membranes may become inflamed with the buildup of serous
fluid resulting in pleurisy, peritonitis, or pericarditis.
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Serous Membranes
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Cutaneous Membranes
• Cutaneous membranes cover body surfaces and consist of
epidermis and dermis (Figure 4.7c)
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Synovial Membranes
• Line joint cavities of all freely movable joints
• Line bursae, and tendon sheaths
• No epithelial cells---just special cells that secrete slippery
synovial fluid (Figure 4.7d).
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MUSCLE TISSUE
• consists of fibers (cells) that are modified for contraction
(provide motion, maintenance of posture, and heat.)
• three types.
– Skeletal muscle tissue is attached to bones, is striated,
and is voluntary (Table 4.5A).
– Cardiac muscle tissue forms most of the heart wall, is
striated, and is usually involuntary (Table 4.5B).
– Smooth (visceral) muscle tissue is found in the walls of
hollow internal structures (blood vessels and viscera), is
nonstriated, and is usually involuntary. It provides motion
(e.g., constriction of blood vessels and airways,
propulsion of foods through the gastrointestinal tract, and
contraction of the urinary bladder and gallbadder) (Table
4.5C).
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Skeletal Muscle
• Cells are long cylinders with many peripheral nuclei
• Visible light and dark banding (looks striated)
• Voluntary (conscious control)
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Cardiac Muscle
• Cells are branched cylinders with one central nuclei
• Involuntary and striated
• Attached to and communicate with each other by intercalated discs
and desmosomes
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Smooth Muscle
• Spindle shaped cells with a single central nuclei
• Walls of hollow organs (blood vessels, GI tract, bladder)
• Involuntary and nonstriated
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NERVOUS TISSUE
• The nervous system is composed of only two principal kinds
of cells:
– neurons (nerve cells)
– neuroglia (protective and supporting cells) (Table 4.6).
• Most neurons consist of a cell body and two types of
processes called dendrites and axons.
• Neurons are sensitive to stimuli, convert stimuli into nerve
impulses, and conduct nerve impulses to other neurons,
muscle fibers, or glands.
• Neuroglia protect and support neurons (see Table 12.1) and
are often the sites of tumors of the nervous system.
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Nerve Tissue
•
•
Cell types -- nerve cells and neuroglial (supporting) cells
Nerve cell structure
– nucleus & long cell processes conduct nerve signals
• dendrite(s) --- signal travels toward the cell body
• axon ---- signal travels away from cell body
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EXCITABLE CELLS
• Neurons and muscle fibers are excitable cells
– they show electrical excitability (action potentials).
• Action potentials will be discussed further in Chapters 10
and 12.
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TISSUE REPAIR: RESTORE HOMEOSTASIS
• Tissue repair is the process that replaces worn out,
damaged, or dead cells.
• Each of the four classes of tissues has a different capacity
to replenish its parenchymal cells.
– Epithelial cells are replaced by the division of stem cells
or by division of undifferentiated cells.
– Some connective tissues such as bone has a continuous
capacity for renewal whereas cartilage replenishes cells
less readily.
– Muscle cells have a poor capacity for renewal.
– Nervous tissue has the poorest capacity for renewal
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Tissue Repair: Restoring Homeostasis
• Worn-out, damaged tissue must be replaced
• Fibrosis is the process of scar formation.
– If the injury is extensive granulation tissue (actively
growing connective tissue) is formed.
• Adhesions, which sometimes result from scar tissue
formation, cause abnormal joining of adjacent tissues,
particularly in the abdomen and sites of previous surgery.
These can cause problems such as intestinal obstruction.
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Tissue Engineering
• New tissues grown in the laboratory (skin & cartilage)
• Scaffolding of cartilage fibers is substrate for cell
growth in culture
• Research in progress
– insulin-producing cells (pancreas)
– dopamine-producing cells (brain)
– bone, tendon, heart valves, intestines & bone
marrow
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Conditions Affecting Tissue Repair
• Nutrition
– adequate protein for structural components
– vitamin C for production of collagen and new blood vessels
• Proper blood circulation
– delivers O2 & nutrients & removes fluids & bacteria
• With aging
– collagen fibers change in quality
– elastin fibers fragment and abnormally bond to calcium
– cell division and protein synthesis are slowed
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DISORDERS: HOMEOSTATIC IMBALANCES
• Disorders of epithelial tissues are mainly specific to
individual organs, such as skin cancer which involves the
epidermis or peptic ulcer disease which involves the
epithelial lining of the stomach or small intestine.
• The most prevalent disorders of connective tissue are
autoimmune disorders which are diseases in which
antibodies produced by the immune system fail to
distinguish what is foreign from what is self and attacks the
body’s own tissues.
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Sjogren’s Syndrome
• Autoimmune disorder producing exocrine gland
inflammation
• Dryness of mouth and eyes
• 20 % of older adults show some signs
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Systemic Lupus Erythematosus (SLE)
•
•
•
•
•
•
Autoimmune disorder -- causes unknown
Chronic inflammation of connective tissue
Nonwhite women during childbearing years
Females 9:1 (1 in 2000 individuals)
Painful joints, ulcers, loss of hair, fever
Life-threatening if inflammation occurs in major organs -- liver, kidney, heart, brain, etc.
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end
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Chapter 5
The Integumentary System
Lecture Outline
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INTRODUCTION
• The skin and its accessory structures make up the
integumentary system.
• The integumentary system functions to guard the body’s
physical and biochemical integrity, maintain a constant body
temperature, and provide sensory information about the
surrounding environment.
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Chapter 5
The Integumentary System
• Skin and its accessory
structures
– structure
– function
– growth and repair
– development
– aging
– disorders
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General Anatomy
• A large organ composed of all
4 tissue types
• 22 square feet
• 1-2 mm thick
• Weight 10 lbs.
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STRUCTURE OF THE SKIN (Figure 5.1)
• The superficial portion of the skin is
the epidermis and is composed of
epithelial tissue.
• The deeper layer of the skin is the
dermis and is primarily composed of
connective tissue.
• Deep to the dermis is the
subcutaneous layer or hypodermis.
(not a part of the skin)
– It consists of areolar and adipose
tissue.
– fat storage, an area for blood
vessel passage, and an area of
pressure-sensing nerve endings.
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Overview of Epidermis
• Stratified squamous epithelium
– avascular (contains no blood vessels)
– 4 types of cells
– 5 distinct strata (layers) of cells
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Four Principle Cells of the Epidermis – Figure 5.2
• keratinocytes (Figure 5.2a)
– produce the protein keratin, which helps protect the
skin and underlying tissue from heat, microbes, and
chemicals, and lamellar granules, which release a
waterproof sealant
• melanocytes (Figure 5.2b)
– produce the pigment melanin which contributes to skin
color and absorbs damaging ultraviolet (UV) light
• Langerhans cells (Figure 5.2c)
– derived from bone marrow
– participate in immune response
• Merkel cells (Figure 5.2d)
– contact a sensory structure called a tactile (Merkel) disc
and function in the sensation of touch
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Layers of the Epidermis
• There are four or five layers of the epidermis, depending
upon the degree of friction and mechanical pressure applied
to the skin.
• From deepest to most superficial the layers of the epidermis
are (Figures 5.3 a and b).
– stratum basale (stratum germinativum)
– stratum spinosum
– stratum granulosum
– stratum lucidum (only in palms and soles)
– stratum corneum
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Layers (Strata) of the Epidermis
•
•
•
•
•
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Stratum corneum
Stratum lucidum
Stratum granulosum
Stratum spinosum
Stratum basale
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Stratum Basale (stratum germinativum)
• Deepest single layer of epidermis
– merkel cells, melanocytes,
keratinocytes & stem cells
that divide repeatedly
– keratinocytes have a
cytoskeleton of tonofilaments
– Cells attached to each other &
to basement membrane by
desmosomes & hemidesmosomes
• When the germinal portion of the
epidermis is destroyed, new skin
cannot regenerate with a skin
graft.
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Stratum Spinosum (Figure 5.2a)
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• provides strength and
flexibility to the skin
– 8 to 10 cell layers are
held together by
desmosomes.
– During slide preparation,
cells shrink and appear
spiny (where attached to
other cells by
desmosomes.)
• Melanin is taken in by
keratinocytes (by
phagocytosis) from nearby
melanocytes.
115
Stratum Granulosum
• transition between the
deeper, metabolically active
strata and the dead cells of
the more superficial strata
• 3-5 layers of flat dying cells
that show nuclear
degeneration
– example of apoptosis
• Contain lamellar granules
that release lipid that repels
water
• Contain dark-staining
keratohyalin granules
– keratohyalin converts
tonofilaments into keratin
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Stratum Lucidum
• present only in the fingers tips,
palms of the hands, and soles
of the feet.
• Three to five layers of clear,
flat, dead cells
• Contains precursor of keratin
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Stratum Corneum
• 25 to 30 layers of flat dead cells
filled with keratin and
surrounded by lipids
– continuously shed
• Barrier to light, heat, water,
chemicals & bacteria
• Lamellar granules in this layer
make it water-repellent.
• Constant exposure to friction
will cause this layer to increase
in depth with the formation of a
callus, an abnormal thickening
of the epidermis.
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Keratinization and Growth of the Epidermis
• Stem cells divide to produce keratinocytes
• As keratinocytes are pushed up towards the surface, they fill
with keratin
– Keratinization is replacement of cell contents with the
protein keratin; occurs as cells move to the skin surface
over 2-4 weeks.
• Epidermal growth factor (EGF) and other hormone-like
proteins play a role in epidermal growth.
• Table 5.1 presents a summary of the features of the
epidermal strata.
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Clinical Application
• Psoriasis is a chronic skin disorder characterized by a more rapid
division and movement of keratinocytes through the epidermal strata .
– cells shed in 7 to 10 days as flaky silvery scales
– abnormal keratin produced
• Skin Grafts
– New skin can not regenerate if stratum basale and its stem cells are
destroyed
– autograft: covering of wound with piece of healthy skin from self
– isograft is from twin
– autologous skin
• transplantation of patient’s skin after it has grown in culture
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Dermis (Figure 5.1)
• Connective tissue layer composed of collagen & elastic
fibers, fibroblasts, macrophages & fat cells
• Contains hair follicles, glands, nerves & blood vessels
• Two major regions of dermis
– papillary region
– reticular region
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Dermis - Papillary Region
• Top 20% of dermis
• areolar connective tissue containing fine elastic fibers, corpuscles of
touch (Meissner’s corpuscles), adipose cells, hair follicles, sebaceous
glands, sudoriferous glands
– The collagen and elastic fibers provide strength, extensibility (ability
to stretch), and elasticity (ability to return to original shape after
stretching) to skin.
• Finger like projections are called dermal papillae
– anchors epidermis to dermis
– contains capillaries that feed epidermis
– contains Meissner’s corpuscles (touch) & free nerve endings for
sensations of heat, cold, pain, tickle, and itch
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Dermis - Reticular Region
•
•
•
•
Dense irregular connective tissue
Contains interlacing collagen and elastic fibers
Packed with oil glands, sweat gland ducts, fat & hair follicles
Provides strength, extensibility & elasticity to skin
– stretch marks are dermal tears from extreme stretching
• Epidermal ridges form in fetus as epidermis conforms to
dermal papillae
– fingerprints are left by sweat glands open on ridges
– increase grip of hand
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Dermis -- Structure
• Epidermal ridges increase friction for better grasping ability
and provide the basis for fingerprints and footprints. The
ridges typically reflect contours of the underlying dermis.
• Lines of cleavage in the skin indicate the predominant
direction of the underlying collagen fibers. Knowledge of
these lines is especially important to plastic surgeons.
• Table 5.2 presents a comparison of the structural features of
the papillary and reticular regions of the dermis.
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Tattoos
• Tattooing is a permanent coloration of the skin in which a
foreign pigment is injected into the dermis.
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Basis of Skin Color
• The color of skin and mucous membranes can provide clues
for diagnosing certain problems, such as
– Jaundice
• yellowish color to skin and whites of eyes
• buildup of yellow bilirubin in blood from liver disease
– Cyanosis
• bluish color to nail beds and skin
• hemoglobin depleted of oxygen looks purple-blue
– Erythema
• redness of skin due to enlargement of capillaries in
dermis
• during inflammation, infection, allergy or burns
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Skin Color Pigments
• Melanin produced in epidermis by melanocytes
– melanocytes convert tyrosine to melanin
• UV in sunlight increases melanin production
– same number of melanocytes in everyone, but differing amounts of
pigment produced
– results vary from yellow to tan to black color
• Clinical observations
– freckles or liver spots = melanocytes in a patch
– albinism = inherited lack of tyrosinase; no pigment
– vitiligo = autoimmune loss of melanocytes in areas of the skin
produces white patches
• The wide variety of colors in skin is due to three pigments - melanin,
carotene, and hemoglobin (in blood in capillaries) - in the dermis.
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Skin Color Pigments
•
•
Carotene in dermis
– yellow-orange pigment (precursor of vitamin A)
– found in stratum corneum & dermis
Hemoglobin
– red, oxygen-carrying pigment in blood cells
– if other pigments are not present, epidermis is
translucent so pinkness will be evident
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Accessory Structures of Skin
• develop from the
embryonic epidermis
• Cells sink inward during
development to form:
– hair
– oil glands
– sweat glands
– nails
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HAIR
• Hairs, or pili, are present on most skin surfaces
except the palms, palmar surfaces of the digits,
soles, and plantar surfaces of the digits.
• Hair consists of
– a shaft above the surface (Figure 5.5a)
– a root that penetrates the dermis and
subcutaneous layer (Figure 5.5c,d)
– the cuticle (Figure 5.5b), and
– a hair follicle (Figure 5.5c,d).
• New hairs develop from cell division of the matrix in
the bulb.
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Structure of Hair
• Shaft -- visible
– medulla, cortex & cuticle
– CS round in straight hair
– CS oval in wavy hair
• Root -- below the surface
• Follicle surrounds root
– external root sheath
– internal root sheath
– base of follicle is bulb
• blood vessels
• germinal cell layer
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Structure of Hair
• Shaft -- visible
– medulla, cortex & cuticle
– CS round in straight hair
– CS oval in wavy hair
• Root -- below the surface
• Follicle surrounds root
– external root sheath
– internal root sheath
– base of follicle is bulb
• blood vessels
• germinal cell layer
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Structure of Hair
• Shaft -- visible
– medulla, cortex & cuticle
– CS round in straight hair
– CS oval in wavy hair
• Root -- below the surface
• Follicle surrounds root
– external root sheath
– internal root sheath
– base of follicle is bulb
• blood vessels
• germinal cell layer
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Hair Related Structures
•
Arrector pili
– smooth muscle in
dermis contracts with
cold or fear.
– forms goosebumps as
hair is pulled vertically
• Hair root plexus
– detect hair movement
• sebaceous (oil) glands
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Types of hair
•
•
•
•
Lanugo is a fine, nonpigmented hair that covers the fetus.
Vellus hair is a short, fine hair that replaces lanugo
Course pigmented hair appears in response to androgens
Hair that appears in response to androgens and hair of the
head, eyelashes and eyebrows is known as terminal hair.
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Hair removal
• Depilatories dissolve the protein in the hair shaft
• Electrolysis uses an electric current to destroy the hair
matrix.
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Hair Growth
• The hair growth cycle consists of a growing stage and a resting stage.
– Growth cycle = growth stage & resting stage
• Growth stage
– lasts for 2 to 6 years
– matrix cells at base of hair root producing length
• Resting stage
– lasts for 3 months
– matrix cells inactive & follicle atrophies
– Old hair falls out as growth stage begins again
• normal hair loss is 70 to 100 hairs per day
• Both rate of growth and the replacement cycle can be altered by
illness, diet, high fever, surgery, blood loss, severe emotional stress,
and gender.
• Chemotherapeutic agents affect the rapidly dividing matrix hair cells
resulting in hair loss.
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Hair Color
• Hair color is due primarily to the amount and type of
melanin.
• Graying of hair occurs because of a progressive decline in
tyrosinase.
– Dark hair contains true melanin
– Blond and red hair contain melanin with iron and sulfur
added
– Graying hair is result of decline in melanin production
– White hair has air bubbles in the medullary shaft
• Hormones influence the growth and loss of hair (Clinical
applications).
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Functions of Hair
• Prevents heat loss
• Decreases sunburn
• Eyelashes help protect eyes
• Touch receptors (hair root
plexus) senses light touch
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Glands of the Skin
• Specialized exocrine glands found in
dermis
• Sebaceous (oil) glands
• Sudiferous (sweat) glands
• Ceruminous (wax) glands
• Mammary (milk) glands
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Sebaceous (oil) glands
• Sebaceous (oil) glands are usually connected to hair
follicles; they are absent in the palms and soles
(Figures 5.1 and 5.6a).
• Secretory portion of gland is located in the dermis
– produce sebum
• contains cholesterol, proteins, fats & salts
• moistens hairs
• waterproofs and softens the skin
• inhibits growth of bacteria & fungi (ringworm)
• Acne
– bacterial inflammation of glands
– secretions are stimulated by hormones at puberty
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Sudoriferous (sweat) glands
Eccrine sweat glands have an extensive distribution most areas of skin
– secretory portion is in dermis with duct to surface
– ducts terminate at pores at the surface of the epidermis (Figure
5.6b).
– regulate body temperature through evaporation (perspiration)
– help eliminate wastes such as urea.
Apocrine sweat glands are limited in distribution to the skin of the axilla,
pubis, and areolae; their duct open into hair follicles (Figure 5.6c).
– secretory portion in dermis
– duct that opens onto hair follicle
– secretions are more viscous
• Table 5.3 compares eccrine and apocrine sweat glands.
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Ceruminous Glands
• Ceruminous glands are modified sudoriferous glands that
produce a waxy substance called cerumen.
– found in the external auditory meatus
– contains secretions of oil and wax glands
– barrier for entrance of foreign bodies
• An abnormal amount of cerumen in the external auditory
meatus or canal can result in impaction and prevent sound
waves from reaching the ear drum (Clinical Application).
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Structure of Nails (Figure 5.7)
• Tightly packed keratinized cells
• Nail body
– visible portion pink due to underlying
capillaries
– free edge appears white
• Nail root
– buried under skin layers
– lunula is white due to thickened
stratum basale
• Eponychium (cuticle)
– stratum corneum layer
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Nail Growth
• Nail matrix is below
nail root -- produces
growth
• Cells transformed into
tightly packed
keratinized cells
• 1 mm per week
• Certain nail conditions
may indicate disease
(Figure 5.8)
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TYPES OF SKIN
• Thin skin
– covers all parts of the body except for the palms and
palmar surfaces of the digits and toes.
– lacks epidermal ridges
– has a sparser distribution of sensory receptors than thick
skin.
• Thick skin (0.6 to 4.5 mm)
– covers the palms, palmar surfaces of the digits, and
soles
– features a stratum lucidum and thick epidermal ridges
– lacks hair follicles, arrector pili muscles, and sebaceous
glands, and has more sweat glands than thin skin.
• Table 5.4 summarizes the fractures of thin and thick skin.
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FUNCTIONS OF SKIN -- thermoregulation
• Perspiration & its evaporation
– lowers body temperature
– flow of blood in the dermis is adjusted
• Exercise
– in moderate exercise, more blood brought to surface
helps lower temperature
– with extreme exercise, blood is shunted to muscles and
body temperature rises
• Shivering and constriction of surface vessels
– raise internal body temperature as needed
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FUNCTIONS OF SKIN
• blood reservoir
– extensive network of blood vessels
• protection - physical, chemical and biological barriers
– tight cell junctions prevent bacterial invasion
– lipids released retard evaporation
– pigment protects somewhat against UV light
– Langerhans cells alert immune system
• cutaneous sensations
– touch, pressure, vibration, tickle, heat, cold, and pain
arise in the skin
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FUNCTIONS OF SKIN
• Synthesis of Vitamin D
– activation of a precursor molecule in the skin by UV light
– enzymes in the liver and kidneys modify the activated
molecule to produce calcitriol, the most active form of
vitamin D.
– necessary vitamin for absorption of calcium from food in
the gastrointestinal tract
• excretion
– 400 mL of water/day, small amounts salt, CO2, ammonia
and urea
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Transdermal Drug Administration
• method of drug passage across the epidermis and into the
blood vessels of the dermis
– drug absorption is most rapid in areas where skin is thin
(scrotum, face and scalp)
• Examples:
– nitroglycerin (prevention of chest pain from coronary
artery disease)
– scopolamine ( motion sickness)
– estradiol (estrogen replacement therapy)
– nicotine (stop smoking alternative)
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MAINTAINING HOMEOSTASIS: SKIN WOUND
HEALING
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Epidermal Wound Healing
•
•
•
•
Abrasion or minor burn
Basal cells migrate across the wound (Figure 5.9a)
Contact inhibition with other cells stops migration
Epidermal growth factor stimulates basal cells to
divide and replace the ones that have moved into the
wound (Figure 5.9b).
• Full thickness of epidermis results from further cell
division
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Deep Wound Healing
• When an injury extends to tissues deep to the epidermis, the repair process
is more complex than epidermal healing, and scar formation results.
• Healing occurs in 4 phases
– inflammatory phase has clot unite wound edges and WBCs arrive from
dilated and more permeable blood vessels
– migratory phase begins the regrowth of epithelial cells and the formation
of scar tissue by the fibroblasts
– proliferative phase is a completion of tissue formation
– maturation phase sees the scab fall off
• Scar formation
– hypertrophic scar remains within the boundaries of the original wound
– keloid scar extends into previously normal tissue
• collagen fibers are very dense and fewer blood vessels are present
so the tissue is lighter in color
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Deep Wound Healing
• Phases of Deep Wound Healing
– During the inflammatory phase, a blood clot unites the
wound edges, epithelial cells migrate across the wound,
vasodilatation and increased permeability of blood
vessels deliver phagocytes, and fibroblasts form (Figure
5.9c).
– During the migratory phase, epithelial cells beneath the
scab bridge the wound, fibroblasts begin scar tissue, and
damaged blood vessels begin to grow. During this phase,
tissue filling the wound is called granulation tissue.
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Phases of Deep Wound Healing
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Deep Wound Healing
• Phases of Deep Wound Healing
– During the proliferative phase, the events of the
migratory phase intensify.
– During the maturation phase, the scab sloughs off, the
epidermis is restored to normal thickness, collagen fibers
become more organized, fibroblasts begin to disappear,
and blood vessels are restored to normal (Figure 5.9).
– Scar tissue formation (fibrosis) can occur in deep wound
healing.
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DEVELOPMENT OF THE INTEGUMENTARY
SYSTEM
• Epidermis develops from ectodermal germ layer
– Hair, nails, and skin glands are epidermal derivatives
(Figure 5.10a).
– The connective tissue and blood vessels associated with
the gland develop from mesoderm.
• Dermis develops from mesenchymal mesodermal germ
layer cells
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Development of the Skin
•
•
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Timing
– at 8 weeks, fetal “skin” is
simple cuboidal
– nails begin to form at 10
weeks, but do not reach
the fingertip until the 9th
month
– dermis forms from
mesoderm by 11 weeks
– by 16 weeks, all layers of
the epidermis are present
– oil and sweat glands form
in 4th and 5th month
– by 6th months, delicate
fetal hair (lanugo) has
formed
Slippery coating of oil and
sloughed off skin called vernix
caseosa is present at birth
158
Age Related Structural Changes
•
•
•
•
•
Collagen fibers decrease in number & stiffen
Elastic fibers become less elastic
Fibroblasts decrease in number
decrease in number of melanocytes (gray hair, blotching)
decrease in Langerhans cells (decreased immune
responsiveness)
• reduced number and less-efficient phagocytes
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AGING AND THE INTEGUMENTARY SYSTEM
• Most of the changes occur in the dermis
– wrinkling, slower growth of hair and nails
– dryness and cracking due to sebaceous gland atrophy
– Walls of blood vessels in dermis thicken so decreased
nutrient availability leads to thinner skin as
subcutaneous fat is lost.
• anti-aging treatments
– microdermabrasion, chemical peel, laser resurfacing,
dermal fillers, Botuliism toxin injection, and non surgical
face lifts.
– Sun screens and sun blocks help to minimize
photodamage from ultraviolet exposure
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Photodamage
•
•
•
•
Ultraviolet light (UVA and UVB) both damage the skin
Acute overexposure causes sunburn
DNA damage in epidermal cells can lead to skin cancer
UVA produces oxygen free radicals that damage collagen
and elastic fibers and lead to wrinkling of the skin
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DISORDERS: HOMEOSTATIC IMBALANCES
• Skin cancer can be caused by excessive exposure to
sunlight.
• Among the risk factors for skin cancer are skin type, sun
exposure, family history, age, and immunologic status.
– The three most common forms are
– basal cell carcinoma,
– squamous cell carcinoma, and
– malignant melanoma.
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Skin Cancer
• 1 million cases diagnosed per year
• 3 common forms of skin cancer
– basal cell carcinoma (rarely metastasize)
– squamous cell carcinoma (may metastasize)
– malignant melanomas (metastasize rapidly)
• most common cancer in young women
• arise from melanocytes ----life threatening
• key to treatment is early detection watch for
changes in symmetry, border, color and size
• risks factors include-- skin color, sun exposure,
family history, age and immunological status
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Burns
• Tissue damage from excessive heat, electricity,
radioactivity, or corrosive chemicals that destroys
(denatures) proteins in the exposed cells is called a burn.
• Generally, the systemic effects of a burn are a greater threat
to life than are the local effects.
• The seriousness of a burn is determined by its depth,
extent, and area involved, as well as the person’s age and
general health. When the burn area exceeds 70%, over half
of the victims die.
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Burns
• Destruction of proteins of the skin
– chemicals, electricity, heat
• Problems that result
– shock due to water, plasma and plasma
protein loss
– circulatory & kidney problems from loss of
plasma
– bacterial infection
• Two methods for determining the extent of a burn
are the rule of nines and the Lund-Bowder
method (Figure 5.13).
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Burns
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Types of Burns
• First-degree
– only epidermis (sunburn)
• Second-degree burn
– destroys entire epidermis & part of dermis
– fluid-filled blisters separate epidermis & dermis
– epidermal derivatives are not damaged
– heals without grafting in 3 to 4 weeks & may scar
• Third-degree or full-thickness
– destroy epidermis, dermis & epidermal derivatives
– damaged area is numb due to loss of sensory nerves
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Burns
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Pressure Sores
• Pressure ulcers, also known as decubitus ulcers
– caused by a constant deficiency of blood to
tissues overlying a bony projection that has
been subjected to prolonged pressure
– typically occur between bony projection and
hard object such as a bed, cast, or splint
– the deficiency of blood flow results in tissue
ulceration.
• Preventable with proper care
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Chapter 6
The Skeletal System: Bone Tissue
Lecture Outline
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INTRODUCTION
• 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.
• Each individual bone is an organ; the bones, along with their
cartilages, make up the skeletal system.
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Chapter 6
The Skeletal System:Bone Tissue
• Dynamic and ever-changing throughout life
• Skeleton composed of many different tissues
– cartilage, bone tissue, epithelium, nerve, blood forming tissue,
adipose, and dense connective tissue
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Functions of Bone
• Supporting & protecting soft tissues
• Attachment site for muscles making movement
possible
• Storage of the minerals, calcium & phosphate -mineral homeostasis
• Blood cell production occurs in red bone
marrow (hemopoiesis)
• Energy storage in yellow bone marrow
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Anatomy of a Long
Bone
• diaphysis = shaft
• epiphysis = one end of a
long bone
• metaphyses are the
areas between the
epiphysis and diaphysis
and include the
epiphyseal plate in
growing bones.
• Articular cartilage over
joint surfaces acts as
friction reducer & shock
absorber
• Medullary cavity =
marrow cavity
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Anatomy of a Long
Bone
• Endosteum = lining of
marrow cavity
• Periosteum = tough
membrane covering bone
but not the cartilage
– fibrous layer = dense
irregular CT
– osteogenic layer =
bone cells & blood
vessels that nourish
or help with repairs
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Histology of Bone
• A type of connective tissue as
seen by widely spaced cells
separated by matrix
• Matrix of 25% water, 25%
collagen fibers & 50%
crystalized mineral salts
• 4 types of cells in bone tissue
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HISTOLOGY OF BONE TISSUE
• Bone (osseous) tissue consists of widely separated cells
surrounded by large amounts of matrix.
• The matrix of bone contains inorganic salts, primarily
hydroxyapatite and some calcium carbonate, and collagen
fibers.
• These and a few other salts are deposited in a framework of
collagen fibers, a process called calcification or
mineralization.
– The process of calcification occurs only in the presence
of collagen fibers.
– Mineral salts confer hardness on bone while collagen
fibers give bone its great tensile strength.
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bone cells.(Figure 6.2)
1. Osteogenic cells undergo cell division and develop into
osteoblasts.
2. Osteoblasts are bone-building cells.
3. Osteocytes are mature bone cells and the principal cells of
bone tissue.
4. Osteoclasts are derived from monocytes and serve to
break down bone tissue.
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Cells of Bone
• Osteoprogenitor cells ---- undifferentiated cells
– can divide to replace themselves & can become osteoblasts
– found in inner layer of periosteum and endosteum
• Osteoblasts--form matrix & collagen fibers but can’t divide
• Osteocytes ---mature cells that no longer secrete matrix
• Osteoclasts---- huge cells from fused monocytes (WBC)
– function in bone resorption at surfaces such as endosteum
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Cells of
Bone
Osteoblasts
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Osteocytes
Osteoclasts
181
Matrix of Bone
• Inorganic mineral salts provide bone’s hardness
– hydroxyapatite (calcium phosphate) & calcium carbonate
• Organic collagen fibers provide bone’s flexibility
– their tensile strength resists being stretched or torn
– remove minerals with acid & rubbery structure results
• Bone is not completely solid since it has small spaces for
vessels and red bone marrow
– spongy bone has many such spaces
– compact bone has very few such spaces
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Compact Bone
• Compact bone is arranged in units called osteons or
Haversian systems (Figure 6.3a).
• Osteons contain blood vessels, lymphatic vessels, nerves,
and osteocytes along with the calcified matrix.
• Osteons are aligned in the same direction along lines of
stress. These lines can slowly change as the stresses on
the bone changes.
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Compact or
Dense Bone
• Looks like solid hard layer of bone
• Makes up the shaft of long bones and the external layer
of all bones
• Resists stresses produced by weight and movement
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Histology of Compact Bone
• Osteon is concentric rings (lamellae) of calcified matrix
surrounding a vertically oriented blood vessel
• Osteocytes are found in spaces called lacunae
• Osteocytes communicate through canaliculi filled with
extracellular fluid that connect one cell to the next cell
• Interstitial lamellae represent older osteons that have been
partially removed during tissue remodeling
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Spongy Bone
• Spongy (cancellous) bone does not contain osteons. It
consists of trabeculae surrounding many red marrow filled
spaces (Figure 6.3b).
• It forms most of the structure of short, flat, and irregular
bones, and the epiphyses of long bones.
• Spongy bone tissue is light and supports and protects the
red bone marrow.
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The Trabeculae of Spongy Bone
• Latticework of thin plates of bone called trabeculae oriented along lines
of stress
• Spaces in between these struts are filled with red marrow where blood
cells develop
• Found in ends of long bones and inside flat bones such as the
hipbones, sternum, sides of skull, and ribs.
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Blood and Nerve Supply of Bone
• Periosteal arteries
– supply periosteum
• Nutrient arteries
– enter through nutrient
foramen
– supplies compact bone of
diaphysis & red marrow
• Metaphyseal & epiphyseal aa.
– supply red marrow & bone
tissue of epiphyses
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BONE FORMATION
• All embryonic connective tissue begins as mesenchyme.
• Bone formation is termed osteogenesis or ossification and
begins when mesenchymal cells provide the template for
subsequent ossification.
• Two types of ossification occur.
– Intramembranous ossification is the formation of bone
directly from or within fibrous connective tissue
membranes.
– Endochondrial ossification is the formation of bone from
hyaline cartilage models.
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Intramembranous
• Intramembranous ossification forms the flat bones of the
skull and the mandible (Figure 6.5).
– An ossification center forms from mesenchymal cells as
they convert to osteoblasts and lay down osteoid matrix.
– The matrix surrounds the cell and then calcifies as the
osteoblast becomes an osteocyte.
– The calcifying matrix centers join to form bridges of
trabeculae that constitute spongy bone with red marrow
between.
– On the periphery the mesenchyme condenses and
develops into the periosteum.
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Intramembranous Bone
Formation
• Mesenchymal cells become osteoprogenitor cells then
osteoblasts.
• Osteoblasts surround themselves with matrix to
become osteocytes.
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• Matrix calcifies into trabeculae with
spaces holding red bone marrow.
• Mesenchyme condenses as
periosteum at the bone surface.
• Superficial layers of spongy bone
are replaced with compact bone.
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Intramembranous Bone
Formation (cont.)
192
Intramembranous
Bone Formation
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Endochondrial
• Endochondrial ossification involves replacement of cartilage
by bone and forms most of the bones of the body (Figure
6.6).
• The first step in endochondrial ossification is the
development of the cartilage model.
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Endochondral Bone Formation
• Development of Cartilage model
– Mesenchymal cells form a
cartilage model of the bone during
development
• Growth of Cartilage model
– in length by chondrocyte cell
division and matrix formation (
interstitial growth)
– in width by formation of new matrix
on the periphery by new
chondroblasts from the
perichondrium (appositional
growth)
– cells in midregion burst and
change pH triggering calcification
and chondrocyte death
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Endochondral Bone Formation
• Development of Primary
Ossification Center
– perichondrium lays down
periosteal bone collar
– nutrient artery penetrates
center of cartilage model
– periosteal bud brings
osteoblasts and osteoclasts
to center of cartilage model
– osteoblasts deposit bone
matrix over calcified cartilage
forming spongy bone
trabeculae
– osteoclasts form medullary
cavity
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Endochondral Bone Formation
• Development of Secondary Ossification Center
– blood vessels enter the epiphyses around time of birth
– spongy bone is formed but no medullary cavity
• Formation of Articular Cartilage
– cartilage on ends of bone remains as articular cartilage.
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Bone Scan
• Radioactive tracer is given intravenously
• Amount of uptake is related to amount of blood flow to
the bone
• “Hot spots” are areas of increased metabolic activity that
may indicate cancer, abnormal healing or growth
• “Cold spots” indicate decreased metabolism of
decalcified bone, fracture or bone infection
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BONE GROWTH
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Growth in Length
• To understand how a bone grows in length, one needs to
know details of the epiphyseal or growth plate (Figure 6.7).
• The epiphyseal plate consists of four zones: (Figure 6.7b)
– zone of resting cartilage,
– zone of proliferation cartilage,
– zone of hypertrophic cartilage, and
– zone of calcified cartilage The activity of the epiphyseal
plate is the only means by which the diaphysis can
increase in length.
• When the epiphyseal plate closes, is replaced by bone, the
epiphyseal line appears and indicates the bone has
completed its growth in length.
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Bone Growth in Length
• Epiphyseal plate or cartilage growth
plate
– cartilage cells are produced by
mitosis on epiphyseal side of plate
– cartilage cells are destroyed and
replaced by bone on diaphyseal
side of plate
• Between ages 18 to 25, epiphyseal
plates close.
– cartilage cells stop dividing and
bone replaces the cartilage
(epiphyseal line)
• Growth in length stops at age 25
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• Zone of resting cartilage
– anchors growth plate to bone
• Zone of proliferating cartilage
– rapid cell division (stacked
coins)
• Zone of hypertrophic cartilage
– cells enlarged & remain in
columns
• Zone of calcified cartilage
– thin zone, cells mostly dead
since matrix calcified
– osteoclasts removing matrix
– osteoblasts & capillaries move
in to create bone over calcified
cartilage
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Zones of Growth in
Epiphyseal Plate
202
Growth in Thickness
• Bone can grow in thickness or diameter only by appositional
growth (Figure 6.8).
• The steps in thes process are:
– Periosteal cells differentiate into osteoblasts which
secrete collagen fibers and organic molecules to form the
matrix.
– Ridges fuse and the periosteum becomes the
endosteum.
– New concentric lamellae are formed.
– Osetoblasts under the peritsteum form new
circumferential lamellae.
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Bone Growth in Width
• Only by appositional growth at the bone’s surface
• Periosteal cells differentiate into osteoblasts and form bony ridges and
then a tunnel around periosteal blood vessel.
• Concentric lamellae fill in the tunnel to form an osteon.
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Factors Affecting Bone Growth
• Nutrition
– adequate levels of minerals and vitamins
• calcium and phosphorus for bone growth
• vitamin C for collagen formation
• vitamins K and B12 for protein synthesis
• Sufficient levels of specific hormones
– during childhood need insulinlike growth factor
• promotes cell division at epiphyseal plate
• need hGH (growth), thyroid (T3 &T4) and insulin
– sex steroids at puberty
– At puberty the sex hormones, estrogen and
testosterone, stimulate sudden growth and modifications
of the skeleton to create the male and female forms.
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Hormonal Abnormalities
• Oversecretion of hGH during childhood produces giantism
• Undersecretion of hGH or thyroid hormone during childhood
produces short stature
• Both men or women that lack estrogen receptors on cells
grow taller than normal
– estrogen is responsible for closure of growth plate
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BONES AND HOMEOSTASIS
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Bone Remodeling
• Remodeling is the ongoing replacement of old bone tissue
by new bone tissue.
– Old bone is constantly destroyed by osteoclasts,
whereas new bone is constructed by osteoblasts.
– In orthodontics teeth are moved by brraces. This places
stress on bone in the sockets causing osteoclasts and
osteablasts to remodel the sockets so that the teeth can
be properly aligned (Figure 6.2)
– Several hormones and calcitrol control bone growth and
bone remodeling (Figure 6.11)
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Bone Remodeling
• Ongoing since osteoclasts carve out small tunnels and
osteoblasts rebuild osteons.
– osteoclasts form leak-proof seal around cell edges
– secrete enzymes and acids beneath themselves
– release calcium and phosphorus into interstitial fluid
– osteoblasts take over bone rebuilding
• Continual redistribution of bone matrix along lines of
mechanical stress
– distal femur is fully remodeled every 4 months
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Fracture and Repair of Bone
A fracture is any break in a bone.
• Fracture repair (Figure 6.10)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.
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Fracture & Repair of Bone
• Healing is faster in bone than in
cartilage due to lack of blood
vessels in cartilage
• Healing of bone is still slow
process due to vessel damage
• Clinical treatment
– closed reduction = restore
pieces to normal position by
manipulation
– open reduction = realignment
during surgery
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Fractures
• Named for shape or position of fracture line
• Common types of fracture
– greenstick -- partial fracture
– impacted -- one side of fracture driven into the
interior of other side
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Fractures
• Named for shape or position of fracture line
• Common types of fracture
– closed -- no break in skin
– open fracture --skin broken
– comminuted -- broken ends of bones are
fragmented
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Fractures
• Named for shape or position of fracture line
• Common types of fracture
– Pott’s -- distal fibular fracture
– Colles’s -- distal radial fracture
– stress fracture -- microscopic fissures from
repeated strenuous activities
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Repair of a
Fracture
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Repair of a Fracture
• Formation of fracture hematoma
– damaged blood vessels produce clot in 6-8 hours, bone cells die
– inflammation brings in phagocytic cells for clean-up duty
– new capillaries grow into damaged area
• Formation of fibrocartilagenous callus formation
– fibroblasts invade the procallus & lay down collagen fibers
– chondroblasts produce fibrocartilage to span the broken ends of the
bone
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Repair of a Fracture
• Formation of bony callus
– osteoblasts secrete spongy bone that joins 2 broken ends of
bone
– lasts 3-4 months
• Bone remodeling
– compact bone replaces the spongy in the bony callus
– surface is remodeled back to normal shape
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Calcium Homeostasis & Bone Tissue
• Skeleton is a reservoir of Calcium & Phosphate
• Calcium ions involved with many body systems
– nerve & muscle cell function
– blood clotting
– enzyme function in many biochemical reactions
• Small changes in blood levels of Ca+2 can be deadly
(plasma level maintained 9-11mg/100mL)
– cardiac arrest if too high
– respiratory arrest if too low
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Hormonal Influences
• Parathyroid hormone (PTH) is secreted if
Ca+2 levels falls
– PTH gene is turned on & more PTH is
secreted from gland
– osteoclast activity increased, kidney
retains Ca+2 and produces calcitriol
• Calcitonin hormone is secreted from
parafollicular cells in thyroid if Ca+2 blood
levels get too high
– inhibits osteoclast activity
– increases bone formation by
osteoblasts
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EXERCISE AND BONE TISSUE
• Within limits, bone has the ability to alter its strength in
response to mechanical stress by increasing deposition of
mineral salts and production of collagen fibers.
– Removal of mechanical stress leads to weakening of
bone through demineralization (loss of bone minerals)
and collagen reduction.
• reduced activity while in a cast
• astronauts in weightless environment
• bedridden person
– Weight-bearing activities, such as walking or moderate
weightlifting, help build and retain bone mass.
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Development of Bone Tissue
• Both types of bone formation begin
with mesenchymal cells
• Mesenchymal cells transform into
chondroblasts which form cartilage
OR
• Mesenchymal cells become
osteoblasts which form bone
Mesenchymal Cells
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Developmental Anatomy
5th Week =limb bud appears as
mesoderm covered with ectoderm
6th Week = constriction produces
hand or foot plate
and skeleton now totally
cartilaginous
7th Week = endochondral ossification
begins
8th Week = upper & lower limbs
appropriately named
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AGING AND BONE TISSUE
• Of two principal effects of aging on bone, the first is the loss
of calcium and other minerals from bone matrix
(demineralization), which may result in osteoporosis.
– very rapid in women 40-45 as estrogens levels decrease
– in males, begins after age 60
• The second principal effect of aging on the skeletal system
is a decreased rate of protein synthesis
– decrease in collagen production which gives bone its
tensile strength
– decrease in growth hormone
– bone becomes brittle & susceptible to fracture
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Osteoporosis
• Decreased bone mass resulting in porous bones
• Those at risk
– white, thin menopausal, smoking, drinking female with family
history
– athletes who are not menstruating due to decreased body fat
& decreased estrogen levels
– people allergic to milk or with eating disorders whose intake
of calcium is too low
• Prevention or decrease in severity
– adequate diet, weight-bearing exercise, & estrogen
replacement therapy (for menopausal women)
– behavior when young may be most important factor
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Disorders of Bone Ossification
• Rickets
• calcium salts are not deposited properly
• bones of growing children are soft
• bowed legs, skull, rib cage, and pelvic deformities
result
• Osteomalacia
• new adult bone produced during remodeling fails
to ossify
• hip fractures are common
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