HISTOLOGY ANATOMY AND PHYSIOLOGYY
LEARN THROUGH YOUR COURSE AND FORTIFY ALL YOUR WEAKNESS WITH KNOWLEDGE
With its 50 trillion cells and thousands of organs, the human
body may seem to be a structure of forbidding complexity.
Fortunately for our health, longevity, and self-understanding, the
biologists of past generations were not discouraged by this complexity, but discovered patterns that made it more understandable.
One of these patterns is the fact that these trillions of cells belong
to only 200 different types or so, and these cells are organized into
tissues that fall into just four broad categories—epithelial, connective, nervous, and muscular tissue.
An organ is a structure with discrete boundaries that is composed of two or more of these tissue types (usually all four). Organs
derive their function not from their cells alone but from how the
cells are organized into tissues. Cells are specialized for certain
tasks—muscle contraction, defense, enzyme secretion, and so forth.
No one cell type has the mechanisms to carry out all of the body’s
vital functions. Cells work together at certain tasks and form tissues that carry out a particular function, such as nerve signaling or
nutrient digestion.
The study of tissues and how they are arranged into organs is
called histology,1 or microscopic anatomy. That is the subject of
this chapter. Here we study the four tissue classes; the variations
within each class; how to recognize tissue types microscopically
and relate their microscopic anatomy to their function; how tissues
are arranged to form an organ; and how tissues change over the life
of the individual as they grow, shrink, or change from one tissue
type to another. Histology bridges the gap between the cytology of
the preceding chapters and the organ system approach of the
chapters that follow
The Study of Tissues
Objectives
When you have completed this section, you should be able to
• name the four primary classes into which all adult tissues are
classified.
• name the three embryonic germ layers and some adult tissues
derived from each;
• visualize the three-dimensional shape of a structure from a
two-dimensional tissue section.
The Primary Tissue Classes
A tissue is a group of similar cells and cell products that
arise from the same region of the embryo and work together
to perform a specific structural or physiological role in an
organ. The four primary tissues are epithelial, connective,
nervous, and muscular tissue (table 5.1). These tissues differ from each other in the types and functions of their cells,
the characteristics of the matrix (extracellular material)
that surrounds the cells, and the relative amount of space
occupied by cells versus matrix. In muscle and epithelium, the cells are so close together that the matrix is scarcely visible, while in connective tissues, the matrix usually occupies much more space than the cells do.
The matrix is composed of fibrous proteins and,
usually, a clear gel variously known as ground substance,
tissue fluid, extracellular fluid (ECF), interstitial2 fluid,
or tissue gel. In cartilage and bone, it can be rubbery or
stony in consistency. The ground substance contains
water, gases, minerals, nutrients, wastes, and other
chemicals. In summary, a tissue is composed of cells and
matrix, and the matrix is composed of fibers and ground
substance.
Embryonic Tissues
Human development begins with a single cell, the fertilized egg, which soon divides to produce scores of identical, smaller cells. The first tissues appear when these cells
start to organize themselves into layers—first two, and
soon three strata called the primary germ layers, which
give rise to all of the body’s mature tissues. The three layers are called ectoderm, mesoderm, and endoderm. The
ectoderm3 is an outer layer that gives rise to the epidermis
and nervous system. The inner layer, the endoderm,4 gives
rise to the mucous membranes of the digestive and respiratory tracts and to the digestive glands, among other
things. Between these two is the mesoderm,5 a layer of
more loosely organized cells. Mesoderm eventually turns
to a gelatinous tissue called mesenchyme, composed of
fine, wispy collagen (protein) fibers and branching cells
called fibroblasts embedded in a gelatinous ground substance. Mesenchyme closely resembles the connective tissue layer in figure 5.11a. It gives rise to muscle, bone, and
blood, among other tissues. Most organs are composed of
tissues derived from two or more primary germ layers. The
rest of this chapter concerns the “mature” tissues that exist
from infancy through adulthood.
Interpreting Tissue Sections
Histologists use a variety of techniques for preserving, sectioning (slicing), and staining tissues to show their structural details as clearly as possible. Tissue specimens are
preserved in a fixative—a chemical such as formalin that
prevents decay. After fixation, most tissues are cut into
very thin slices called histological sections. These sections are typically only one or two cells thick, to allow the
light of a microscope to pass through and to reduce the
confusion of the image that would result from many layers
of overlapping cells. They are mounted on slides and artificially colored with histological stains to bring out detail.
If they were not stained, most tissues would appear very
pale gray. With stains that bind to different components of
a tissue, however, you may see pink cytoplasm, violet
nuclei, and blue, green, or golden brown protein fibers,
depending on the stain used.
Sectioning a tissue reduces a three-dimensional
structure to a two-dimensional slice. You must keep this
in mind and try to translate the microscopic image into a
mental image of the whole structure. Like the boiled egg
and elbow macaroni in figure 5.1, an object may look quite
different when it is cut at various levels, or planes of section. A coiled tube, such as a gland of the uterus (fig. 5.1c),
is often broken up into multiple portions since it meanders in and out of the plane of section. An experienced
viewer, however, would recognize that the separated
pieces are parts of a single tube winding its way to the
organ surface. Note that a grazing slice through a boiled egg might miss the yolk, just as a tissue section might miss
the nucleus of a cell or an egg in the ovary, even though
these structures were present.
Many anatomical structures are significantly longer
in one direction than another—the humerus and esophagus, for example. A tissue cut in the long direction is
called a longitudinal section (l.s.), and one cut perpendicular to this is a cross section (c.s. or x.s.), or transverse
section (t.s.). A section cut at an angle between a longitudinal and cross section is an oblique section. Figure 5.2
shows how certain organs look when sectioned on each of
these planes.
Epithelial Tissue
Objectives
When you have completed this section, you should be able to
• describe the properties that distinguish epithelium from
other tissue classes;
• list and classify eight types of epithelium, distinguish them
from each other, and state where each type can be found in
the body;
• explain how the structural differences between epithelia
relate to their functional differences; and
• visually recognize each epithelial type from specimens or
photographs.
Epithelial6 tissue consists of a flat sheet of closely adhering cells, one or more cells thick, with the upper surface
usually exposed to the environment or to an internal space
in the body. Epithelium covers the body surface, lines
body cavities, forms the external and internal linings of
many organs, and constitutes most gland tissue. The extracellular material is so thin it is not visible with the light
microscope, and epithelia allow no room for blood vessels. They do, however, almost always lie on a layer of
loose connective tissue and depend on its blood vessels
for nourishment and waste removal.
Between an epithelium and the underlying connective tissue is a layer called the basement membrane, usually too thin to be visible with the light microscope. It contains collagen, adhesive glycoproteins called laminin and
fibronectin, and a large protein-carbohydrate complex
called heparan sulfate. It gradually blends with collagenous and reticular fibers on the connective tissue side.
The basement membrane serves to anchor an epithelium
to the connective tissue below it. The surface of an epithelial cell that faces the basement membrane is its basal surface, and the one that faces away from the basement membrane is the apical surface.
Epithelia are classified into two broad categories—
simple and stratified—with four types in each category. In
a simple epithelium, every cell touches the basement
membrane, whereas in a stratified epithelium, some cells
rest on top of other cells and do not contact the basement
membrane
Simple Epithelia
Generally, a simple epithelium has only one layer of cells,
although this is a somewhat debatable point in the pseudostratified type. Three types of simple epithelia are
named for the shapes of their cells: simple squamous7
(thin scaly cells), simple cuboidal (square or round cells),
and simple columnar (tall narrow cells). In the fourth
type, pseudostratified columnar, not all cells reach the
free surface; the shorter cells are covered over by the taller
ones. This epithelium looks stratified in most tissue sections, but careful examination, especially with the electron microscope, shows that every cell reaches the basement membrane. Simple columnar and pseudostratified
columnar epithelia often produce protective mucous coatings over the mucous membranes. The mucus is secreted
by wineglass-shaped goblet cells.
Stratified Epithelia
Stratified epithelia range from 2 to 20 or more layers of
cells, with some cells resting directly on others and only
the deepest layer resting on the basement membrane.
Three of the stratified epithelia are named for the shapes
of their surface cells: stratified squamous, stratified
cuboidal, and stratified columnar epithelia. The deeper
cells, however, may be of a different shape than the surface
cells. The fourth type, transitional epithelium, was named
when it was thought to represent a transitional stage
between stratified squamous and stratified columnar
epithelium. This is now known to be untrue, but the name
has persisted.Stratified columnar epithelium is rare—seen only in
places where two other epithelial types meet, as in limited
regions of the pharynx, larynx, anal canal, and male urethra. We will not consider this type any further. The other
three types are illustrated and summarized in table 5.3.
The most widespread epithelium in the body is stratified squamous epithelium, which deserves further discussion. Its deepest layer of cells are cuboidal to columnar
and undergo continual mitosis. Their daughter cells push
toward the surface and become flatter (more squamous, or
scalelike) as they migrate farther upward, until they
finally die and flake off. Their separation from the surface
is called exfoliation, or desquamation (fig. 5.12); the study
of exfoliated cells is called exfoliate cytology. You can easily study exfoliated cells by scraping your gums with a
toothpick, smearing this material on a slide, and staining
it. A similar procedure is used in the Pap smear, an examination of exfoliated cells from the cervix for signs of uterine cancer (see chapter 28, fig. 28.5, for normal and cancerous Pap smears).
Stratified squamous epithelia are of two kinds—
keratinized and nonkeratinized. A keratinized epithelium, found on the skin surface (epidermis), is covered
with a layer of compact, dead squamous cells. These
cells are packed with the durable protein keratin and
coated with water repellent. The skin surface is therefore
relatively dry, it retards water loss from the body, and it
resists penetration by disease organisms. (Keratin is also
the protein of which animal horns are made, hence its
name.8
) The tongue, oral mucosa, esophagus, vagina, and
a few other internal membranes are covered with the
nonkeratinized type, which lacks the surface layer of
dead cells. This type provides a surface that is, again,
abrasion-resistant, but also moist and slippery. These
characteristics are well suited to resist stress produced
by the chewing and swallowing of food and by sexual
intercourse and childbirth.
Connective Tissue
Objectives
When you have completed this section, you should be able to
• describe the properties that most connective tissues have in
common;
• discuss the types of cells found in connective tissue;
• explain what the matrix of a connective tissue is and describe
its components;
• name 10 types of connective tissue, describe their cellular
components and matrix, and explain what distinguishes them
from each other; and
• visually recognize each connective tissue type from
specimens or photographs.
Overview
Connective tissue typically consists mostly of fibers and
ground substance, with widely separated cells. It is the
most abundant, widely distributed, and histologically
variable of the primary tissues. As the name implies, it
often serves to connect organs to each other—for example, the way a tendon connects muscle to bone—or serves
in other ways to support, bind, and protect organs. This
category includes fibrous tissue, fat, cartilage, bone, and
blood.
The functions of connective tissue include the
following:
• Binding of organs. Tendons bind muscle to bone,
ligaments bind one bone to another, fat holds the
kidneys and eyes in place, and fibrous tissue binds the
skin to underlying muscle.
• Support. Bones support the body, and cartilage
supports the ears, nose, trachea, and bronchi.
• Physical protection. The cranium, ribs, and sternum
protect delicate organs such as the brain, lungs, and
heart; fatty cushions around the kidneys and eyes
protect these organs.
• Immune protection. Connective tissue cells attack
foreign invaders, and connective tissue fiber forms a
“battlefield” under the skin and mucous membranes
where immune cells can be quickly mobilized against
disease agents.
• Movement. Bones provide the lever system for body
movement, cartilages are involved in movement of the
vocal cords, and cartilages on bone surfaces ease joint
movements.
• Storage. Fat is the body’s major energy reserve; bone is
a reservoir of calcium and phosphorus that can be
drawn upon when needed.
• Heat production. Brown fat generates heat in infants
and children.
• Transport. Blood transports gases, nutrients, wastes,
hormones, and blood cells.
The mesenchyme described earlier in this chapter is a
form of embryonic connective tissue. The connective
tissues present after birth fall into three broad categories: fibrous connective tissues, supportive connective
tissues (cartilage and bone), and fluid connective tissue
(blood).
Fibrous Connective Tissue
Fibrous connective tissues are the most diverse type of
connective tissue. They are also called fibroconnective tissue or connective tissue proper. Nearly all connective tissues contain fibers, but the tissues considered here are
classified together because the fibers are so conspicuous.
Fibers are, of course, just one component of the tissue,
which also includes cells and ground substance. Before
examining specific types of fibroconnective tissue, let’s
examine these components
Components of Fibrous Connective Tissue
Cells The cells of fibrous connective tissue include the
following types:
• Fibroblasts.9 These are large, flat cells that often
appear tapered at the ends and show slender, wispy
branches. They produce the fibers and ground
substance that form the matrix of the tissue.
Fibroblasts that have finished this task and become
inactive are called fibrocytes by some histologists.
• Macrophages.10 These are large phagocytic cells that
wander through the connective tissues, where they
engulf and destroy bacteria, other foreign particles,
and dead or dying cells of our own body, and activate
the immune system when they sense foreign matter
called antigens. They arise from certain white blood
cells called monocytes or from the same stem cells
that produce monocytes.
• Leukocytes,11 or white blood cells (WBCs). WBCs
travel briefly in the bloodstream, then crawl out
through the capillary walls and spend most of their
time in the connective tissues. Most of them are
neutrophils, which wander about in search of bacteria.
Our mucous membranes often exhibit dense patches
of tiny WBCs called lymphocytes, which react against
bacteria, toxins, and other foreign agents.
• Plasma cells. Certain lymphocytes turn into plasma
cells when they detect foreign agents. The plasma
cells then synthesize disease-fighting proteins called
antibodies. Plasma cells are rarely seen except in the
walls of the intestines and in inflamed tissue.
• Mast cells. These cells, found especially alongside
blood vessels, secrete a chemical called heparin that
inhibits blood clotting, and one called histamine that
increases blood flow by dilating blood vessels.
• Adipocytes (AD-ih-po-sites), or fat cells. These are
large rounded cells filled mainly with a droplet of
triglyceride, which forces the nucleus and cytoplasm
to occupy only a thin layer just beneath the plasma
membrane. They appear in small clusters in some
fibrous connective tissues. When they dominate an
area, the tissue is called adipose tissue.
Fibers Three types of protein fibers are found in fibrous
connective tissues:
• Collagenous (col-LADJ-eh-nus) fibers. These fibers,
made of collagen, are tough and flexible and resist
stretching. Collagen is about 25% of the body’s
protein, the most abundant type. It is the base of such
animal products as gelatin, leather, and glue.12 In fresh
tissue, collagenous fibers have a glistening white
appearance, as seen in tendons and some cuts of meat
(fig. 5.13); thus, they are often called white fibers. In
tissue sections, collagen forms coarse, wavy bundles,
often dyed pink, blue, or green by the most common
histological stains. Tendons, ligaments, and the deep
layer of the skin (the dermis) are made mainly of
collagen. Less visibly, collagen pervades the matrix of
cartilage and bone.
• Reticular13 fibers. These are thin collagen fibers coated
with glycoprotein. They form a spongelike framework
for such organs as the spleen and lymph nodes.
• Elastic fibers. These are thinner than collagenous
fibers, and they branch and rejoin each other along
their course. They are made of a protein called elastin,
whose coiled structure allows it to stretch and recoil
like a rubber band. Elastic fibers account for the ability
of the skin, lungs, and arteries to spring back after they
are stretched. (Elasticity is not the ability to stretch,
but the tendency to recoil when tension is released.)
Fresh elastic fibers are yellowish and therefore often
called yellow fibers.
Ground Substance Amid the cells and fibers in some tissue sections, there appears to be a lot of empty space. In
life, this space is occupied by the featureless ground substance. Ground substance usually has a gelatinous to rubbery consistency resulting from three classes of large molecules: glycosaminoglycans, proteoglycans, and adhesive
glycoproteins. It absorbs compressive forces and, like the
styrofoam packing in a shipping carton, protects the more
delicate cells from mechanical injury.
A glycosaminoglycan (GAG) (gly-COSE-ah-MEE-noGLY-can) is a long polysaccharide composed of unusual disaccharides called amino sugars and uronic acid. GAGs are
negatively charged and thus tend to attract sodium and
potassium ions, which in turn causes the GAGs to absorb
and hold water. Thus, GAGs play an important role in regulating the water and electrolyte balance of tissues. The most
abundant GAG is chondroitin (con-DRO-ih-tin) sulfate. It is
abundant in blood vessels and bones and is responsible for
the relative stiffness of cartilage. Some other GAGs that you
will read of elsewhere in this book are heparin (an anticoagulant) and hyaluronic (HY-uh-loo-RON-ic) acid. The latter is
a gigantic molecule up to 20 m long, as large as most cells.
It is a viscous, slippery substance that forms a very effective
lubricant in the joints and constitutes much of the jellylike
vitreous humor of the eyeball.
A proteoglycan is another gigantic molecule. It is
shaped somewhat like a test tube brush (fig. 5.14), with the
central core composed of protein and the bristlelike outgrowths composed of GAGs. The entire proteoglycan may be
attached to hyaluronic acid, thus forming an enormous
molecular complex. Proteoglycans form thick colloids similar to those of gravy, pudding, gelatin, and glue. This gel
slows the spread of pathogenic organisms through the tissues. Some proteoglycans are embedded in the plasma membranes of cells, attached to the cytoskeleton on the inside and
to other extracellular molecules on the outside. Thus, they
create a strong structural bond between cells and extracellular macromolecules and help to hold tissues together.
Adhesive glycoproteins are protein-carbohydrate
complexes that bind plasma membrane proteins to collagen
and proteoglycans outside the cell. They bind all the components of a tissue together and mark pathways that guide
migrating embryonic cells to their destinations in a tissue.
Types of Fibrous Connective Tissue
Fibrous connective tissue is divided into two broad categories according to the relative abundance of fiber: loose
and dense connective tissue. In loose connective tissue,
much of the space is occupied by ground substance, which
is dissolved out of the tissue during histological fixation
and leaves empty space in prepared tissue sections. The
loose connective tissues we will discuss are areolar, reticular, and adipose tissue. In dense connective tissue, fiber
occupies more space than the cells and ground substance,
and appears closely packed in tissue sections. The two
dense connective tissues we will discuss are dense regular
and dense irregular connective tissue.
Areolar14 (AIR-ee-OH-lur) tissue exhibits loosely organized fibers, abundant blood vessels, and a lot of seemingly
empty space. It possesses all six of the aforementioned cell
types. Its fibers run in random directions and are mostly collagenous, but elastic and reticular fibers are also present. Areolar tissue is highly variable in appearance. In
many serous membranes, it looks like figure 5.15, but in
the skin and mucous membranes, it is more compact (see
fig. 5.8) and sometimes difficult to distinguish from dense
irregular connective tissue. Some advice on how to tell
them apart is given after the discussion of dense irregular
connective tissue.
Areolar tissue is found in tissue sections from almost
every part of the body. It surrounds blood vessels and
nerves and penetrates with them even into the small
spaces of muscles, tendons, and other tissues. Nearly
every epithelium rests on a layer of areolar tissue, whose
blood vessels provide the epithelium with nutrition,
waste removal, and a ready supply of infection-fighting
WBCs in times of need. Because of the abundance of open,
fluid-filled space, WBCs can move about freely in areolar
tissue and can easily find and destroy pathogens.
Reticular tissue is a mesh of reticular fibers and fibroblasts. It forms the structural framework (stroma) of such
organs and tissues as the lymph nodes, spleen, thymus,
and bone marrow. The space amid the fibers is filled with
blood cells. If you imagine a kitchen sponge soaked with
blood, the sponge fibers would be analogous to the reticular tissue stroma.
Adipose tissue, or fat, is tissue in which adipocytes are
the dominant cell type. Adipocytes may also occur singly
or in small clusters in areolar tissue. Adipocytes usually
range from 70 to 120 m in diameter, but they may be five
times as large in obese people. The space between
adipocytes is occupied by areolar tissue, reticular tissue,
and blood capillaries.
Fat is the body’s primary energy reservoir. The quantity of stored triglyceride and the number of adipocytes are
quite stable in a person, but this doesn’t mean stored fat is
stagnant. New triglycerides are constantly synthesized
and stored as others are hydrolyzed and released into circulation. Thus, there is a constant turnover of stored
triglyceride, with an equilibrium between synthesis and
hydrolysis, energy storage and energy use. Adipose tissue
also provides thermal insulation, and it contributes to
body contours such as the female breasts and hips. Most
adipose tissue is a type called white fat, but fetuses,
infants, and children also have a heat-generating tissue
called brown fat, which accounts for up to 6% of an
infant’s weight. Brown fat gets its color from an unusual
abundance of blood vessels and certain enzymes in its
mitochondria. It stores lipid in the form of multiple
droplets rather than one large one. Brown fat has numerous mitochondria, but their oxidation pathway is not
linked to ATP synthesis. Therefore, when these cells oxidize fats, they release all of the energy as heat. Hibernating
animals accumulate brown fat in preparation for winter.
Table 5.4 summarizes the three types of loose fibrous
connective tissues.
Think About It
Why would infants and children have more need for
brown fat than adults do? (Hint: Smaller bodies have
a higher ratio of surface area to volume than larger
bodies do.)
Dense regular connective tissue is named for two properties: (1) the collagen fibers are closely packed and leave
relatively little open space, and (2) the fibers are parallel
to each other. It is found especially in tendons and ligaments. The parallel arrangement of fibers is an adaptation
to the fact that tendons and ligaments are pulled in predictable directions. With some minor exceptions such as
blood vessels and sensory nerve fibers, the only cells in
this tissue are fibroblasts, visible by their slender, violetstaining nuclei squeezed between bundles of collagen.
This type of tissue has few blood vessels, so injured tendons and ligaments are slow to heal.
The vocal cords, suspensory ligament of the penis,
and some ligaments of the vertebral column are made of a
type of dense regular connective tissue called yellow elastic tissue. In addition to the densely packed collagen
fibers, it exhibits branching elastic fibers and more fibroblasts. The fibroblasts have larger, more conspicuous
nuclei than seen in most dense regular connective tissue.
Elastic tissue also takes the form of wavy sheets in
the walls of the large and medium arteries. When the heart
pumps blood into the arteries, these sheets enable them to
expand and relieve some of the pressure on smaller vessels downstream. When the heart relaxes, the arterial wall
springs back and keeps the blood pressure from dropping
too low between heartbeats. The importance of this elastic
tissue becomes especially clear when there is not enough
of it—for example, in Marfan syndrome (see insight 5.1,
p. 172)—or when it is stiffened by arteriosclerosis
Dense irregular connective tissue also has thick bundles
of collagen and relatively little room for cells and
ground substance, but the collagen bundles run in random directions. This arrangement enables the tissue to
resist unpredictable stresses. This tissue constitutes
most of the dermis, where it binds the skin to the underlying muscle and connective tissue. It forms a protective
capsule around organs such as the kidneys, testes, and
spleen and a tough fibrous sheath around the bones,
nerves, and most cartilages.
It is sometimes difficult to judge whether a tissue is
areolar or dense irregular. In the dermis, for example,
these tissues occur side by side, and the transition from
one to the other is not at all obvious. A relatively large
amount of clear space suggests areolar tissue, and thicker
bundles of collagen with relatively little clear space suggests dense irregular tissue.
Insight 5.1 Clinical Application
Marfan Syndrome—A Connective
Tissue Disease
Serious anatomical and functional abnormalities can result from
hereditary errors in the structure of connective tissue proteins. Marfan15 syndrome, for example, results from the mutation of a gene on
chromosome 15 that codes for a glycoprotein called fibrillin, the structural scaffold for elastic fibers. Clinical signs of Marfan syndrome
include unusually tall stature, long limbs and spidery fingers, abnormal
spinal curvature, and a protruding “pigeon breast.” Some other signs
include hyperextensible joints, hernias of the groin, and visual problems resulting from abnormally long eyeballs and deformed lenses.
More seriously, victims exhibit a weakening of the heart valves and
arterial walls. The aorta, where blood pressure is the highest, is sometimes enormously dilated close to the heart, and may suddenly rupture.
Marfan syndrome is present in about 1 out of 20,000 live births and
kills most of its victims by their mid-30s. Some authorities think that
Abraham Lincoln’s tall, gangly physique and spindly fingers were signs
of Marfan syndrome, which might have ended his life prematurely had
he not been assassinated.
15Antoine Bernard-Jean Marfan (1858–1942), French physician
Cartilage
Cartilage (table 5.6) is a supportive connective tissue
with a flexible rubbery matrix. It gives shape to the external ear, the tip of the nose, and the larynx (voicebox)—
the most easily palpated cartilages in the body. Cells
called chondroblasts16 (CON-dro-blasts) secrete the
matrix and surround themselves with it until they become
trapped in little cavities called lacunae17 (la-CUE-nee).
Once enclosed in lacunae, the cells are called chondrocytes (CON-dro-sites). Cartilage is free of blood vessels
except when transforming into bone; thus nutrition and
waste removal depend on solute diffusion through the
stiff matrix. Because this is a slow process, chondrocytes
have low rates of metabolism and cell division, and
injured cartilage heals slowly. The matrix is rich in chondroitin sulfate and contains collagen fibers that range in
thickness from invisibly fine to conspicuously coarse.
Differences in the fibers provide a basis for classifying
cartilage into three types: hyaline cartilage, elastic cartilage, and fibrocartilage.
Hyaline18 (HY-uh-lin) cartilage is named for its clear,
glassy microscopic appearance, which stems from the
usually invisible fineness of its collagen fibers. Elastic cartilage is named for its conspicuous elastic fibers, and
fibrocartilage for its coarse, readily visible bundles of collagen. Elastic cartilage and most hyaline cartilage are surrounded by a sheath of dense irregular connective tissue
called the perichondrium.19 A reserve population of
chondroblasts between the perichondrium and cartilage
contributes to cartilage growth throughout life. There is no
perichondrium around fibrocartilage.
You can feel the texture of hyaline cartilage by palpating the tip of your nose, your “Adam’s apple” at the
front of the larynx (voicebox), and periodic rings of cartilage around the trachea (windpipe) just below the larynx.
Hyaline cartilage is easily seen in many grocery items—it
is the “gristle” at the ends of pork ribs, on chicken leg and
breast bones, and at the joints of pigs’ feet, for example.
Elastic cartilage gives shape to the external ear. You can get
some idea of its springy resilience by folding your ear
down and releasing it.
Bone
The term bone refers both to organs of the body such as the
femur and mandible, composed of multiple tissue types,
and to the bone tissue, or osseous tissue, that makes up most
of the mass of bones. There are two forms of osseous tissue:
(1) Spongy bone fills the heads of the long bones. Although
it is calcified and hard, its delicate slivers and plates give it
a spongy appearance. (2) Compact (dense) bone is a more
dense calcified tissue with no spaces visible to the naked
eye. It forms the external surfaces of all bones, so spongy
bone, when present, is always covered by compact bone.
The differences between compact and spongy bone
are described in chapter 7. Here, we examine only compact
bone (table 5.7). Most specimens you study will probably be
chips of dead, dried bone ground to microscopic thinness.
In such preparations, the cells are absent but spaces reveal
their former locations. Most compact bone is arranged in
cylinders of tissue that surround central (haversian20 or
osteonic) canals, which run longitudinally through the
shafts of long bones such as the femur. Blood vessels and
nerves travel through the central canals in life. The bone
matrix is deposited in concentric lamellae, onionlike layers
around each central canal. A central canal and its surrounding lamellae are called an osteon. Tiny lacunae
between the lamellae are occupied in life by mature bone
cells, or osteocytes.21 Delicate canals called canaliculi radiate from each lacuna to its neighbors and allow the osteocytes to keep in touch with each other. The bone as a whole
is covered with a tough fibrous periosteum (PERR-ee-OSStee-um) similar to the perichondrium of cartilage.
About a third of the dry weight of bone is composed
of collagen fibers and chondroitin sulfate; two-thirds consists of minerals (mainly calcium salts) deposited around
the collagen fibers.
Blood
Blood (table 5.8) is a fluid connective tissue that travels
through tubular vessels. Its primary function is to transport
cells and dissolved matter from place to place. Blood consists of a ground substance called plasma and of cells and
cell fragments collectively called formed elements. Erythrocytes22 (eh-RITH-ro-sites), or red blood cells, are the most
abundant formed elements. In stained blood films, they
look like pink discs with a thin, pale center. They have no
nuclei. Erythrocytes transport oxygen and carbon dioxide.
Leukocytes, or white blood cells, serve various roles in
defense against infection and other diseases. They travel
from one organ to another in the bloodstream and lymph
but spend most of their lives in the connective tissues.
Leukocytes are somewhat larger than erythrocytes and have
conspicuous nuclei that usually appear violet in stained
preparations. There are five kinds, distinguished partly by
variations in nuclear shape: neutrophils, eosinophils,
basophils, lymphocytes, and monocytes. Their individual
characteristics are considered in detail in chapter 18.
Platelets are small cell fragments scattered amid the blood
cells. They are involved in clotting and other mechanisms
for minimizing blood loss, and in secreting growth factors
that promote blood vessel growth and maintenance.
Nervous and Muscular Tissue—
Excitable Tissues
Objectives
When you have completed this section, you should be able to
• explain what distinguishes excitable tissues from other tissues;
• name the cell types that compose nervous tissue;
• identify the major parts of a nerve cell;
• visually recognize nervous tissue from specimens or
photographs;
• name the three kinds of muscular tissue and describe the
differences between them; and
• visually identify any type of muscular tissue from specimens
or photographs.
Excitability is a characteristic of all living cells, but it is
developed to its highest degree in nervous and muscular
tissue, which are therefore described as excitable tissues.
The basis for their excitation is an electrical charge difference (voltage) called the membrane potential, which
occurs across the plasma membranes of all cells. Nervous
and muscular tissues respond quickly to outside stimuli
by means of changes in membrane potential. In nerve
cells, these changes result in the rapid transmission of signals to other cells. In muscle cells, they result in contraction, or shortening of the cell.
Nervous Tissue
Nervous tissue (table 5.9) consists of neurons (NOORons), or nerve cells, and a much greater number of neuroglia (noo-ROG-lee-uh), or glial (GLEE-ul) cells, which
protect and assist the neurons. Neurons are specialized to
detect stimuli, respond quickly, and transmit coded
information rapidly to other cells. Each neuron has a
prominent soma, or cell body, that houses the nucleus and
most other organelles. This is the cell’s center of genetic
control and protein synthesis. Somas are usually round,
ovoid, or stellate in shape. Extending from the soma,
there are usually multiple short, branched processes
called dendrites23 that receive signals from other cells
and transmit messages to the soma, and a single, much
longer axon, or nerve fiber, that sends outgoing signals to
other cells. Some axons are more than a meter long and
extend from the brainstem to the foot. Nervous tissue is
found in the brain, spinal cord, nerves, and ganglia,
which are knotlike swellings in nerves. Local variations
in the structure of nervous tissue are described in chapters 12 to 16.
Muscular Tissue
Muscular tissue consists of elongated cells that are specialized to respond to stimulation by contracting; thus, its
primary job is to exert physical force on other tissues and
organs—for example, when a skeletal muscle pulls on a
bone, the heart contracts and expels blood, or the bladder
contracts and expels urine. Not only do movements of the
body and its limbs depend on muscle, but so do such processes as digestion, waste elimination, breathing,
speech, and blood circulation. The muscles are also an
important source of body heat. The word muscle means
“little mouse,” apparently referring to the appearance of
rippling muscles under the skin. There are three histological types of muscle—skeletal, cardiac, and smooth—which differ in appearance,
physiology, and function (table 5.10). Skeletal muscle
consists of long, cylindrical cells called muscle fibers.
Most of it is attached to bones, but there are exceptions in
the tongue, upper esophagus, some facial muscles, and
some sphincter24 (SFINK-tur) muscles (ringlike or cufflike muscles that open and close body passages). Each cell
contains multiple nuclei adjacent to the plasma membrane. Skeletal muscle is described as striated and voluntary. The first term refers to alternating light and dark
bands, or striations (stry-AY-shuns), created by the overlapping pattern of cytoplasmic protein filaments that
cause muscle contraction. The second term, voluntary,
refers to the fact that we usually have conscious control
over skeletal muscle.
Cardiac muscle is essentially limited to the heart,
though it extends slightly into the nearby blood vessels. It,
too, is striated, but it differs from skeletal muscle in its
other features. Its cells are much shorter, so they are commonly called myocytes25 rather than fibers. The myocytes
are branched and contain only one nucleus, which is
located near the center. A light-staining region of glycogen
often surrounds the nucleus. Cardiac myocytes are joined
end to end by junctions called intercalated26 (in-TURkuh-LAY-ted) discs. Electrical connections at these junctions enable a wave of excitation to travel rapidly from cell
to cell, and mechanical connections keep the myocytes
from pulling apart when the heart contracts. The electrical
junctions allow all the myocytes of a heart chamber to be
stimulated, and contract, almost simultaneously. Intercalated discs appear as dark transverse lines separating each
myocyte from the next. They may be only faintly visible,
however, unless the tissue has been specially stained for
them. Cardiac muscle is considered involuntary because it
is not usually under conscious control; it contracts even if
all nerve connections to it are severed.
Smooth muscle lacks striations and is involuntary.
Smooth muscle cells are fusiform (thick in the middle and
tapered at the ends) and relatively short. They have only
one, centrally placed nucleus. Small amounts of smooth
muscle are found in the iris of the eye and in the skin, but
most of it, called visceral muscle, forms layers in the walls
of the digestive, respiratory, and urinary tracts, blood vessels, the uterus, and other viscera. In locations such as the
esophagus and small intestine, smooth muscle forms adjacent layers, with the cells of one layer encircling the organ
and the cells of the other layer running longitudinally.
When the circular smooth muscle contracts, it may propel
contents such as food through the organ. When the longitudinal layer contracts, it makes the organ shorter and thicker. By regulating the diameter of blood vessels,
smooth muscle is very important in controlling blood
pressure and flow. Both smooth and skeletal muscle form
sphincters that control the emptying of the bladder and
rectum
Intercellular Junctions, Glands,
and Membranes
Objectives
When you have completed this section, you should be able
• describe the junctions that hold cells and tissues together;
• describe or define different types of glands;
• describe the typical anatomy of a gland;
• name and compare different modes of glandular secretion;
• describe the way tissues are organized to form the body’s
membranes; and
• name and describe the major types of membranes in the body.
Intercellular Junctions
Most cells, with the exception of blood and metastatic
cancer cells, must be anchored to each other and to the
matrix if they are to grow and divide normally. The connections between one cell and another are called intercellular junctions. These attachments enable the cells to
resist stress and communicate with each other. Without
them, cardiac muscle cells would pull apart when they
contracted, and every swallow of food would scrape away
the lining of your esophagus. The principal types of intercellular junctions are
Tight Junctions
A tight junction completely encircles an epithelial cell
near its apex and joins it tightly to the neighboring cells,
like the plastic harness on a six-pack of soda cans. Proteins
in the membranes of two adjacent cells form a zipperlike pattern of complementary grooves and ridges. This seals
off the intercellular space and makes it difficult for some
substances to pass between the cells. In the stomach and
intestines, tight junctions prevent digestive juices from
seeping between epithelial cells and digesting the underlying connective tissue. They also help to prevent intestinal bacteria from invading the tissues, and they ensure
that most digested nutrients pass through the epithelial
cells and not between them.
Desmosomes
If a tight junction is like a zipper, a desmosome27 (DEZmo-some) is more like the snap on a pair of jeans, a patch
that holds cells together and enables a tissue to resist
mechanical stress, but does not totally encircle a cell.
Desmosomes are common in the epidermis, cardiac muscle, and cervix of the uterus. The neighboring cells are
separated by a small gap, which is spanned by a fine mesh
of glycoprotein filaments. These filaments terminate in a
thickened protein plaque at the surface of each cell. On
the cytoplasmic side of each plaque, intermediate filaments from the cytoskeleton approach and penetrate the
plaque, turn like a J, and return a short distance back into
the cytoplasm. Each cell contributes half of the complete
desmosome. The basal cells of epithelial tissue have
hemidesmosomes—half-desmosomes that anchor them to
the underlying basement membrane.
Gap (Communicating) Junctions
A gap junction is formed by a ringlike connexon, which
consists of six transmembrane proteins surrounding a
water-filled channel. Ions, glucose, amino acids, and
other small solutes can pass directly from the cytoplasm
of one cell into the next through these channels. In the
embryo, nutrients pass from cell to cell through gap
junctions until the circulatory system forms and takes
over the role of nutrient distribution. Gap junctions are
found in the intercalated discs of cardiac muscle and
between the cells of some smooth muscle. The flow of
ions through these junctions allows electrical excitation
to pass directly from cell to cell so that the cells contract
in near-unison. Gap junctions are absent from skeletal
muscle.
Insight 5.2 Clinical Application
Pemphigus Vulgaris—
An Autoimmune Disease
The immune system normally produces defensive antibodies that
selectively attack foreign substances and leave the normal tissues of
our bodies alone. But in a family of disorders called autoimmune diseases, antibodies fail to distinguish our own cells and tissues from foreign ones. Such misguided antibodies, called autoantibodies, thus
launch destructive attacks on our own bodies. (Autoimmune diseases
are discussed in more detail in chapter 21.) One such disease is pemphigus vulgaris28 (PEM-fih-gus vul-GAIR-iss), a disorder in which
autoantibodies attack the proteins of the desmosomes in the skin and
mucous membranes. This breaks down the attachments between
epithelial cells and causes widespread blistering of the skin and oral
mucosa, loss of tissue fluid, and sometimes death. The condition can be
controlled with drugs that suppress the immune system, but such drugs
reduce the patient’s immune defenses against other diseases.
28pemphigus blistering vulgaris common
Glands
A gland is a cell or organ that secretes substances for use
elsewhere in the body or releases them for elimination
from the body. The gland product may be something synthesized by the gland cells (such as digestive enzymes) or
something removed from the tissues and modified by the
gland (such as urine). Glands are composed predominantly of epithelial tissue.
Endocrine and Exocrine Glands
Glands are broadly classified as endocrine or exocrine.
They originate as invaginations of a surface epithelium. In
exocrine29 (EC-so-crin) glands, they usually maintain
their contact with the surface by way of a duct, an epithelial tube that conveys their secretion to the surface. The
secretion may be released to the body surface, as in the
case of sweat, mammary, and tear glands, but more often it
is released into the cavity (lumen) of another organ such
as the mouth or intestine. Endocrine30 (EN-doe-crin)
glands lose their contact with the surface and have no
ducts. They do, however, have a high density of blood capillaries and secrete their products directly into the blood.
The secretions of endocrine glands, called hormones,
function as chemical messengers to stimulate cells elsewhere in the body. Endocrine glands are the subject of
chapter 17 and are not further considered here.
The exocrine-endocrine distinction is not always
clear. The liver is an exocrine gland that secretes one of its products, bile, through a system of ducts but secretes hormones, albumin, and other products directly into the
bloodstream. Several glands have both exocrine and
endocrine components, such as the pancreas, testis, ovary,
and kidney. And nearly all of the viscera have at least
some cells that secrete hormones, even though most of
these organs are not usually thought of as glands (for
example, the brain and heart).
Unicellular glands are exocrine cells found in an
epithelium that is predominantly nonsecretory. For example, the respiratory tract, which is lined mainly by ciliated
cells, also has a liberal scattering of nonciliated, mucussecreting goblet cells
Exocrine Gland Structure
Figure 5.30 shows a generalized multicellular exocrine
gland—a structural arrangement found in such organs as
the mammary gland, pancreas, and salivary glands. Most
glands are enclosed in a fibrous capsule. The capsule often
gives off extensions called septa, or trabeculae (trah-BECyou-lee), that divide the interior of the gland into compartments called lobes, which are visible to the naked eye.
Finer connective tissue septa may further subdivide each
lobe into microscopic lobules (LOB-yools). Blood vessels,
nerves, and the gland’s own ducts generally travel through these septa. The connective tissue framework of the gland,
called its stroma, supports and organizes the glandular tissue. The cells that perform the tasks of synthesis and
secretion are collectively called the parenchyma (pa-RENkih-muh). This is typically simple cuboidal or simple
columnar epithelium.
Exocrine glands are classified as simple if they have
a single unbranched duct and compound if they have a
branched duct. If the duct and secretory portion are of uniform diameter, the gland is called tubular. If the secretory
cells form a dilated sac, the gland is called acinar and the
sac is an acinus31 (ASS-ih-nus), or alveolus32 (AL-vee-OHlus). A gland with secretory cells in both the tubular and
acinar portions is called a tubuloacinar gland
Types of Secretions
Glands are classified not only by their structure but also by
the nature of their secretions. Serous (SEER-us) glands
produce relatively thin, watery fluids such as perspiration, milk, tears, and digestive juices. Mucous glands,
found in the tongue and roof of the mouth among other
places, secrete a glycoprotein called mucin (MEW-sin).
After it is secreted, mucin absorbs water and forms the
sticky product mucus. (Note that mucus, the secretion, is
spelled differently from mucous, the adjective form of the
word.) Mixed glands, such as the two pairs of salivary
glands in the chin, contain both serous and mucous cells
and produce a mixture of the two types of secretions. Cytogenic33 glands release whole cells. The only examples of
these are the testes and ovaries, which produce sperm and
egg cells.
of Secretion
Glands are classified as merocrine or holocrine depending
on how they produce their secretions. Merocrine34 (MERRoh-crin) glands, also called eccrine35 (EC-rin) glands, have
vesicles that release their secretion by exocytosis, as
described in chapter 3 (fig. 5.32a). These include the tear
glands, pancreas, gastric glands, and many others. In
holocrine36 glands, cells accumulate a product and then
the entire cell disintegrates, so the secretion is a mixture of
cell fragments and the substance the cell had synthesized
prior to its disintegration (fig. 5.32b). The oil-producing
glands of the scalp are an example. Holocrine secretions
tend to be thicker than merocrine secretions.Some glands, such as the axillary (armpit) sweat
glands and mammary glands, are named apocrine37 glands
from a former belief that the secretion was composed of bits
of apical cytoplasm that broke away from the cell surface.
Closer study showed this to be untrue; these glands are primarily merocrine in their mode of secretion. These glands
are nevertheless different from other merocrine glands in
function and histological appearance, and they are still
referred to as apocrine glands even though their mode of
secretion is not unique
Membranes
In atlas A, the major cavities of the body were described,
as well as some of the membranes that line them and cover
their viscera. We now consider some histological aspects
of the major body membranes.
The largest membrane of the body is the cutaneous
(cue-TAY-nee-us) membrane—or more simply, the skin
(detailed in chapter 6). It consists of a stratified squamous
epithelium (epidermis) resting on a layer of connective tissue (dermis). Unlike the other membranes to be considered, it is relatively dry. It retards dehydration of the body
and provides an inhospitable environment for the growth
of infectious organisms.
The two principal kinds of internal membranes are
mucous and serous membranes. A mucous membrane
(mucosa) (fig. 5.33), lines passageways that open to the
exterior environment: the digestive, respiratory, urinary,
and reproductive tracts. A mucosa consists of two to three
layers: (1) an epithelium, (2) an areolar connective tissue
layer called the lamina propria38 (LAM-ih-nuh PRO-preeuh), and sometimes, (3) a layer of smooth muscle called
the muscularis (MUSK-you-LAIR-iss) mucosae. Mucous
membranes have absorptive, secretory, and protective
functions. They are often covered with mucus secreted by
goblet cells, multicellular mucous glands, or both. The
mucus traps bacteria and foreign particles, which keeps
them from invading the tissues and aids in their removal
from the body. The epithelium of a mucous membrane
may also include absorptive, ciliated, and other types of
cells.
A serous membrane (serosa) is composed of a simple
squamous epithelium resting on a thin layer of areolar
connective tissue. Serous membranes produce watery
serous (SEER-us) fluid, which arises from the blood and
derives its name from the fact that it is similar to blood
serum in composition. Serous membranes line the insides
of some body cavities and form a smooth outer surface on
some of the viscera, such as the digestive tract. The pleurae, pericardium, and peritoneum described in atlas A are
serous membranes.
The circulatory system is lined with a simple squamous epithelium called endothelium, derived from mesoderm. The endothelium rests on a thin layer of areolar tissue, which often rests in turn on an elastic sheet.
Collectively, these tissues make up a membrane called the
tunica interna of the blood vessels and endocardium of the heart. The simple squamous epithelium that lines the
pleural, pericardial, and peritoneal cavities is called
mesothelium.
Some joints of the skeletal system are lined by
fibrous synovial (sih-NO-vee-ul) membranes, made only
of connective tissue. These membranes span the gap from
one bone to the next and secrete slippery synovial fluid
(rich in hyaluronic acid) into the joint.
Tissue Growth, Development,
Death, and Repair
Objectives
When you have completed this section, you should be able to
• name and describe the ways that a tissue can change from
one type to another;
• name and describe the modes of tissue growth
• name and describe the modes and causes of tissue shrinkage
and death; and
• name and describe the ways the body repairs damaged
tissues.
Changes in Tissue Type
You have studied the form and function of more than two
dozen discrete types of human tissue in this chapter. You
should not leave this subject, however, with the impression
that once these tissue types are established in the adult, they
never change. Tissues are, in fact, capable of changing from
one type to another within certain limits. Most obviously,
unspecialized tissues of the embryo develop into more
diverse and specialized types of mature tissue—mesenchyme to muscle, for example. This development of a
more specialized form and function is called differentiation.
Epithelia often exhibit metaplasia,39 a change from
one type of mature tissue to another. For example, the
vagina of a young girl is lined with a simple cuboidal
epithelium. At puberty, it changes to a stratified squamous
epithelium, better adapted to the future demands of intercourse and childbirth. The nasal cavity is lined with ciliated pseudostratified columnar epithelium. However, if
we block one nostril and breathe through the other one for
several days, the epithelium in the unblocked passage
changes to stratified squamous. In smokers, the pseudostratified columnar epithelium of the bronchi may transform into a stratified squamous epithelium.
Think About It
What functions of a pseudostratified columnar
epithelium could not be served by a stratified
squamous epithelium? In light of this, what might be
some consequences of bronchial metaplasia in heavy
smokers?
Tissue Growth
Tissues grow either because their cells increase in number
or because the existing cells grow larger. Most embryonic
and childhood growth occurs by hyperplasia40 (HY-purPLAY-zhuh), tissue growth through cell multiplication.
Exercised muscles grow, however, through hypertrophy41
(hy-PUR-truh-fee), the enlargement of preexisting cells.
Neoplasia42 (NEE-oh-PLAY-zhuh) is the development of a
tumor (neoplasm)—whether benign or malignant—composed of abnormal, nonfunctional tissue.
Tissue Shrinkage and Death
The shrinkage of a tissue through a loss in cell size or number is called atrophy43 (AT-ruh-fee). Atrophy results from
both normal aging (senile atrophy) and lack of use of an
organ (disuse atrophy). Muscles that are not exercised
exhibit disuse atrophy as their cells become smaller. This
was a serious problem for the first astronauts who participated in prolonged microgravity space flights. Upon
return to normal gravity, they were sometimes too weak
from muscular atrophy to walk. Space stations and shuttles now include exercise equipment to maintain the
crews’ muscular condition. Disuse atrophy also occurs
when a limb is immobilized, as in a cast.
Necrosis44 (neh-CRO-sis) is the premature, pathological death of tissue due to trauma, toxins, infection, and so
forth. Gangrene is any tissue necrosis resulting from an
insufficient blood supply. Gas gangrene is necrosis of a wound resulting from infection with certain bacteria.
Infarction is the sudden death of tissue, such as heart
muscle (myocardial infarction), which occurs when its
blood supply is cut off. A decubitus ulcer (bed sore) is tissue necrosis that occurs when immobilized persons, such
as those confined to a hospital bed or wheelchair, are
unable to move, and continual pressure on the skin cuts
off blood flow to an area. Cells dying by necrosis usually
swell, exhibit blebbing (bubbling) of their plasma membranes, and then rupture. The cell contents released into
the tissues trigger an inflammatory response in which
macrophages phagocytize the cellular debris.
Apoptosis45 (AP-oh-TOE-sis), or programmed cell
death, is the normal death of cells that have completed
their function and best serve the body by dying and getting
out of the way. Cells undergoing apoptosis shrink and are
quickly phagocytized by macrophages and other cells. The
cell contents never escape the cell, so there is no inflammatory response. Although billions of cells die every hour
by apoptosis, they are engulfed so quickly that they are
almost never seen except within macrophages. For this
reason, apoptosis was not discovered until recently.
Apparently every cell has a built-in “suicide program” that enables the body to dispose of it when necessary. In some cases, a receptor protein in the plasma membrane called Fas binds to an extracellular suicide signal.
Fas then activates intracellular enzymes that destroy the
cell, including an endonuclease that chops up its DNA
and a protease that destroys cellular proteins. In other
cases, cells seem to undergo apoptosis automatically if
they stop receiving growth factors from other cells. For
example, in embryonic development we produce about
twice as many neurons as we need. Those that make connections with target cells survive, while the excess 50%
die for lack of nerve growth factor. Apoptosis also “dissolves” the webbing between the fingers and toes during
embryonic development; it frees the earlobe from the side
of the head in people with the genotype for detached earlobes (see chapter 4); and it causes shrinkage of the uterus
after pregnancy and of the breasts after lactation ceases.
Tissue Repair
Damaged tissues can be repaired in two ways: regeneration or fibrosis. Regeneration is the replacement of dead or
damaged cells by the same type of cells as before. Regeneration restores normal function to the organ. Most skin
injuries (cuts, scrapes, and minor burns) heal by regeneration. The liver also regenerates remarkably well. Fibrosis
is the replacement of damaged tissue with scar tissue,
composed mainly of collagen produced by fibroblasts.
Scar tissue helps to hold an organ together, but it does not
restore normal function. Examples include the healing of severe cuts and burns, the healing of muscle injuries, and
scarring of the lungs in tuberculosis
Insight 5.3 Clinical Application
Keloids
In some people, especially dark-skinned adults, healing skin wounds
exhibit excessive fibrosis, producing raised, shiny scars called keloids
(fig. 5.35). Keloids extend beyond the boundaries of the original wound
and tend to return even if they are surgically removed. Keloids may
result from the excessive secretion of a fibroblast-stimulating growth
factor by macrophages and platelets. They occur most often on the
upper trunk and earlobes. Some tribespeople practice scarification—
scratching or cutting the skin to induce keloid formation as a way of
decorating the body
1. Severed blood vessels bleed into the cut. Mast cells
and cells damaged by the cut release histamine,
which dilates blood vessels, increases blood flow to
the area, and makes blood capillaries more
permeable. Blood plasma seeps into the wound,
carrying antibodies, clotting proteins, and blood
cells.
2. A blood clot forms in the tissue, loosely knitting the
edges of the cut together and interfering with the
spread of pathogens from the site of injury into
healthy tissues. The surface of the blood clot dries
and hardens in the air, forming a scab that
temporarily seals the wound and blocks infection.Beneath the scab, macrophages begin to clean up
tissue debris by phagocytizing and digesting it.
3. New blood capillaries sprout from nearby vessels
and grow into the wound. The deeper portions of
the clot become infiltrated by capillaries and
fibroblasts and transform into a soft mass called
granulation tissue. Macrophages remove the blood
clot while fibroblasts deposit new collagen to
replace it. This fibroblastic (reconstructive) phase of
repair begins 3 to 4 days after the injury and lasts
up to 2 weeks.
4. Surface epithelial cells around the wound multiply
and migrate into the wounded area, beneath the
scab. The scab loosens and eventually falls off, and
the epithelium grows thicker. Thus, the epithelium
regenerates while the underlying connective tissue
undergoes fibrosis, or scarring. Capillaries
withdraw from the area as fibrosis progresses. The
scar tissue may or may not show through the
epithelium, depending on the severity of the
wound. The wound may exhibit a depressed area at
first, but this is often filled in by continued fibrosis
and remodeling from below, until the scar becomes
unnoticeable. This remodeling (maturation) phase
of tissue repair begins several weeks after injury
and may last as long as 2 years
Insight 5.4 Clinical Application
The Stem Cell Controversy
One of the most controversial scientific issues at the dawn of the
twenty-first century has been stem cell research. At least 18 countries
have recently debated or enacted laws to regulate stem cell research,
with politicians, scientists, bioethicists, and religious leaders joining in
the debate, and legions of lay citizens contributing their opinions to
newspaper editorial pages. What are stem cells and why is this subject
so controversial?
Stem cells are immature cells with the ability to develop into one
or more types of mature, functional cells. Adult stem (AS) cells sparsely
populate most of the body’s organs and retain the ability to differentiate into mature, functional cells. When an adult stem cell divides, one
daughter cell remains a stem cell and the other differentiates into a
mature tissue cell. The latter replaces a cell lost to damage or to normal cellular turnover. Some stem cells are unipotent, able to develop
into only one mature cell type, such as sperm or epidermal squamous
cells. Others are multipotent, able to produce multiple mature cell
types, as when bone marrow stem cells differentiate into red and white
blood cells.
Not surprisingly, biologists see stem cells as a possible treatment for
diseases that result from the loss of functional cells. Skin and bone
marrow stem cells have been used in therapy for many years. Scientists
hope that with a little coaxing, stem cells might replace cardiac muscle damaged by heart attack; restore function to an injured spinal cord;
cure parkinsonism by replacing lost brain cells; or cure diabetes mellitus by replacing lost insulin-secreting cells. But adult stem cells have
limited developmental potential, and probably cannot make all the cell
types needed to treat a broad range of degenerative diseases. In addition, they are present in very small numbers, and difficult to harvest
and culture in the quantities needed for therapy.
Embryonic stem (ES) cells, however, may hold greater potential. ES
cells harvested from week-old human embryos composed of 100 to
150 cells are pluripotent—able to develop into any type of embryonic
or adult cell. New laboratory methods have made ES cells easier to culture than AS cells and have greatly accelerated stem cell research in
recent years.
The road to therapy with ES cells remains full of technical, ethical, and legal speed bumps. Will ES cells be rejected by the recipient’s
immune system? Can the ES cells or the growth media in which they
are cultured introduce viruses or other pathogens into the recipient?
How can the ES cells be made to lodge and grow in the right place in
the patient’s body? Could they grow into tumors instead of healthy
tissue? Can ES cell therapy ever be economical enough to be affordable to any but the very rich? Scientists can scarcely begin to tackle
these problems, however, unless and until a bioethical question is
resolved: Can we balance the benefits of stem cell therapy against
the destruction of early human embryos from which the ES cells are
harvested?
Where do these embryos come from? Most are donated by couples
using in vitro fertilization (IVF) to conceive a child. IVF entails collecting numerous eggs from the prospective mother, fertilizing them
in glassware with the father’s sperm, letting them develop into
embryos (technically, pre-embryos) of about 8 to 16 cells, and then
transplanting some of these into the mother’s uterus (see Insight
29.4). To overcome the low odds of success, excess embryos are
always produced and some are always left over. The excess embryos
are often destroyed, but many couples choose instead to donate
them for research that may ultimately benefit other patients. It
would seem sensible to use the embryos for beneficial purposes
rather than to simply destroy and discard them. Opponents of stem
cell research argue, however, that potential medical benefits cannot
justify the destruction of a human embryo. Understandably, this has
aroused an intense debate that is likely to restrain stem cell research
for some time to come.
