The Tissue Level of Organization

4.0 Introduction

Chapter Objectives

After studying this chapter, you will be able to:

4.1 – Identify the main tissue types and discuss their roles in the human body.

4.2 – Describe the structural characteristics of the various epithelial tissues and how these characteristics enable their functions.

4.3 – Describe the structural characteristics of the various connective tissues and how these characteristics enable their functions.

4.4 – Describe the characteristics of muscle tissue and how these dictate muscle function.

4.5 – Describe the characteristics of nervous tissue and how these enable the unique functions of nervous tissue.

4.6 – Describe the process of tissue response to injury.

The cells found in the human body contain essentially the same internal structures yet they vary enormously in shape and function. The variation in cells is not randomly distributed throughout the body, rather, they occur in organized layers.  Such aggregations of cells that are similar in structure and work together to perform a specialized function are referred to as tissues.  The micrograph that opens this chapter shows the high degree of organization among different types of cells in the tissue of the cervix. You can also see how that organization breaks down when cancer takes over the regular mitotic functioning of a cell.

The human body starts as a single cell at fertilization. As this fertilized egg divides, it gives rise to trillions of cells, each built from the same blueprint, but organizing into tissues and becoming irreversibly committed to a developmental pathway.

4.1 Types of Tissues

Learning Objectives

Identify the main tissue types and discuss their roles in the human body.

By the end of this section, you will be able to:

• Identify the four primary tissue types and discuss the structure and function of each
• Describe the embryonic origin of tissue
• Identify the various types of tissue membranes and the unique qualities of each

The term tissue is used to describe a group of cells that are similar in structure and perform a specific function. Histology is the the field of study that involves the microscopic examination of tissue appearance, organization, and function.

Tissues are organized into four broad categories based on structural and functional similarities.  These categories are  epithelial, connective, muscle, and nervous.   The primary tissue types work together to contribute to the overall health and maintenance of the human body.   Thus, any disruption in the structure of a tissue can lead to injury or disease.

The Four Primary Tissue Types

Epithelial tissue refers to groups of cells that cover the exterior surfaces of the body, line internal cavities and passageways, and form certain glands. Connective tissue, as its name implies, binds the cells and organs of the body together. Muscle tissue contracts forcefully when excited, providing movement.  Nervous tissue is also excitable, allowing for the generation and propagation of electrochemical signals in the form of nerve impulses that communicate between different regions of the body (Figure 4.1.1).

An understanding of the various primary tissue types present in the human body is essential for understanding the structure and function of organs which are composed of two or more primary tissue types.  This chapter will focus on examining epithelial and connective tissues.  Muscle and nervous tissue will be discussed in detail in future chapters.

 Embryonic Origin of Tissues

The cells composing a tissue share a common embryonic origin. The zygote, or fertilized egg, is a single cell formed by the fusion of an egg and sperm cell. After fertilization, the zygote gives rise many cells to form the embryo. The first embryonic cells generated have the ability to differentiate into any type of cell in the body and, as such, are called omnipotent, meaning each has the capacity to divide, differentiate, and develop into a new organism. As cell proliferation progresses, three major cell lines are established within the embryo. Each of these lines of embryonic cells forms the distinct germ layers from which all the tissues and organs of the human body eventually form. Each germ layer is identified by its relative position: ectoderm (ecto- = “outer”), mesoderm (meso- = “middle”), and endoderm (endo- = “inner”). Figure 4.1.2 shows the types of tissues and organs associated with each of the three germ layers. Note that epithelial tissue originates in all three layers, whereas nervous tissue derives primarily from the ectoderm and muscle tissue derives from the mesoderm.

Tissue Membranes

A tissue membrane is a thin layer or sheet of cells that either covers the outside of the body (e.g., skin), lines an internal body cavity (e.g., peritoneal cavity),  lines a vessel (e.g., blood vessel),  or lines a movable joint cavity (e.g., synovial joint).   Two basic types of tissue membranes are recognized based on the primary tissue type composing each: connective tissue membranes and epithelial membranes (Figure 4.1.3).

Connective Tissue Membranes

A connective tissue membrane is built entirely of connective tissue. This type of membrane may be found encapsulating an organ, such as the kidney, or lining the cavity of a freely movable joint (e.g., shoulder).  When lining a joint, this membrane is referred to as a synovial membrane.  Cells in the inner layer of the synovial membrane release synovial fluid, a natural lubricant that enables the bones of a joint to move freely against one another with reduced friction.

Epithelial Membranes

An epithelial membrane is composed of an epithelial layer attached to a layer of connective tissue. A mucous membrane, sometimes called a mucosa, lines a body cavity or hollow passageway that is open to the external environment.  This type of membrane can be found lining portions of the digestive, respiratory, excretory, and reproductive tracts. Mucus, produced by  uniglandular cells and glandular tissue, coats the epithelial layer. The underlying connective tissue, called the lamina propria (literally “own layer”), helps support the epithelial layer.

A serous membrane lines the cavities of the body that do not open to the external environment.  Serous fluid secreted by the cells of the epithelium lubricates the membrane and reduces abrasion and friction between organs.  Serous membranes are identified according to location. Three serous membranes are found lining the thoracic cavity; two membranes that cover the lungs (pleura) and one membrane that covers the heart (pericardium). A fourth serous membrane, the peritoneum, lines the peritoneal cavity, covering the abdominal organs and forming double sheets of mesenteries that suspend many of the digestive organs.

A cutaneous membrane is a multi-layered membrane composed of epithelial and connective tissues.  The apical surface of this membrane exposed to the external environment and is covered with dead, keratinized cells that help protect the body from desiccation and pathogens.  The skin is an example of a cutaneous membrane.

Chapter Review

Aggregations of cells in the human body be classified into four types of tissues: epithelial, connective, muscle, and nervous. Epithelial tissues act as coverings, controlling the movement of materials across their surface. Connective tissue binds the various parts of the body together, providing support and protection. Muscle tissue allows the body to move and nervous tissues functions in communication.

All cells and tissues in the body derive from three germ layers: the ectoderm, mesoderm, and endoderm.

Membranes are layers of connective and epithelial tissues that line the external environment and internal body cavities of the body.  Synovial membranes are connective tissue membranes that protect and line the freely-movable joints. Epithelial membranes are composed of both epithelial tissue and connective tissue.  These membranes are found lining the external body surface (cutaneous membranes and mucous membranes) or lining the internal body cavities (serous membranes).

4.2 Epithelial Tissue

Learning Objectives

Describe the structural characteristics of the various epithelial tissues and how these characteristics enable their functions.

By the end of this section, you will be able to:

• Explain the general structure and function of epithelial tissue
• Distinguish between tight junctions, anchoring junctions, and gap junctions
• Distinguish between simple epithelia and stratified epithelia, as well as between squamous, cuboidal, and columnar epithelia
• Describe the structure and function of endocrine and exocrine glands

Epithelial tissue primarily appears as large sheets of cells covering all surfaces of the body exposed to the external environment and lining internal body cavities.  In addition, epithelial tissue is responsible for forming a majority of glandular tissue found in the human body.

Epithelial tissue is derived from all three major embryonic layers. The epithelial tissue composing cutaneous membranes develops from the ectoderm.  Epithelial tissue composing a majority of the mucous membranes originate in the endoderm.  Epithelial tissue that lines vessels and open spaces within the body are derived from mesoderm.  Of particular note, epithelial tissue that lines vessels in the lymphatic and cardiovascular systems is called endothelium whereas epithelial tissue that forms the serous membranes lining the true cavities is called mesothelium.

Regardless of its location and function, all epithelial tissue shares important structural features. First, epithelial tissue is highly cellular, with little or no extracellular material present between cells. Second, adjoining cells form specialized intercellular connections called cell junctions. Third, epithelial cells exhibit polarity with differences in structure and function between the exposed, or apical, facing cell surface and the basal surface closest to the underlying tissue.  Fourth, epithelial tissues are avascular;  nutrients must enter the tissue by diffusion or absorption from underlying tissues or the surface.  Last,  epithelial tissue is capable of rapidly replacing damaged and dead cells, necessary with respect to the harsh environment this tissue encounters.

Epithelial Tissue Function:

Epithelial tissues provide the body’s first line of protection from physical, chemical, and biological damage. The cells of an epithelium act as gatekeepers of the body, controlling permeability by allowing selective transfer of materials across its surface. All substances that enter the body must cross an epithelium.

Many epithelial cells are capable of secreting mucous and other specific chemical compounds onto their apical surfaces.  For example, the epithelium of the small intestine releases digestive enzymes and cells lining the respiratory tract secrete mucous that traps incoming microorganisms and particles.

The Epithelial Cell

Epithelial cells are typically characterized by unequal distribution of organelles and membrane-bound proteins between their apical and basal surfaces.  Structures found on some epithelial cells are an adaptation to specific functions.  For example, cilia are extensions of the apical cell membrane that are supported by microtubules. These extensions beat in unison, allowing for the movement of fluids and particles along the surface.  Such ciliated epithelia line the ventricles of the brain where it helps circulate cerebrospinal fluid and line the respirtatory system where it helps sweep particles of dust and pathogens up and out of the respiratory tract.

Epithelial cells in close contact with underlying connective tissues secrete glycoproteins and collagen from their basal surface which forms the basal lamina.  The basal lamina interacts with the reticular lamina secreted by the underlying connective tissue, forming a basement membrane that helps anchor the layers together.

Cells of epithelia are closely connected with limited extracellular material present. Three basic types of connections may be present: tight junctions, anchoring junctions, and gap junctions (Figure 4.2.1).

Types of Cell Junctions

Epithelial cells are held close together by cell junctions.  The three basic types of cell-to-cell junctions are tight junctions, gap junctions, and anchoring junctions.

A Tight junction restricts the movement of fluids between adjacent cells due to the presence of integral proteins that fuse together to form a firm seal.  Tight junctions are observed in the epithelium of the urinary bladder, preventing the escape of fluids comprising the urine.

An anchoring junction provides a strong yet flexible connection between epithelial cells. There are three types of anchoring junctions: desmosomes, hemidesmosomes, and adherens. Desmosomes hold neighboring cells together by way of cadherin molecules which are embedded in protein plates in the cell membranes and link together between the adjacent cells.  Hemidesmosomes, which look like half a desmosome, link cells to components in the extracellular matrix, such as the basal lamina. While similar in appearance to desmosomes, hemidesmosomes use adhesion proteins called integrins rather than cadherins. Adherens use either cadherins or integrins depending on whether they are linking to other cells or matrix. These junctions are characterized by the presence of the contractile protein actin located on the cytoplasmic surface of the cell membrane.  These junctions influence the shape and folding of the epithelial tissue.

In contrast with the tight and anchoring junctions, a gap junction forms an intercellular passageway between the membranes of adjacent cells to facilitate the movement of small molecules and ions between cells. These junctions thus allow electrical and metabolic coupling of adjacent cells.

Classification of Epithelial Tissues

Epithelial tissues are classified according to the shape of the cells composing the tissue and by the number of cell layers present in the tissue.(Figure 4.2.2) Cell shapes are classified as being either squamous (flattened and thin), cuboidal (boxy, as wide as it is tall), or columnar (rectangular, taller than it is wide). Similarly, cells in the tissue can be arranged in a single layer, which is called simple epithelium, or more than one layer, which is called stratified epithelium.  Pseudostratified (pseudo- = “false”) describes an epithelial tissue with a single layer of irregularly shaped cells that give the appearance of more than one layer.  Transitional describes a form of specialized stratified epithelium in which the shape of the cells, and the number of layers present, can vary depending on the degree of stretch within a tissue.

Epithelial tissue is classified based on the shape of the cells present and the number of cell layers present.  Figure 4.2.2 summarizes the different categories of epithelial cell tissue cells.

External Website

Summary of Epithelial Tissue Cells

Watch this video to find out more about the anatomy of epithelial tissues. Where in the body would one find non-keratinizing stratified squamous epithelium?

Simple Epithelium

The cells in a simple squamous epithelium have the appearance of thin scales. The nuclei of squamous cells  tend to appear flat, horizontal, and elliptical, mirroring the form of the cell.   Simple squamous epithelium, because of the thinness of the cells, is present where rapid passage of chemical compounds is necessary such as the lining of capillaries and the small air sacs of the lung.  This epithelial type is also found composing the mesothelium which secretes serous fluid to lubricate the internal body cavities.

In simple cuboidal epithelium, the nucleus of the box-like cells appears round and is generally located near the center of the cell. These epithelia are involved in the secretion and absorptions of molecules requiring active transport. Simple cuboidal epithelia are observed in the lining of the kidney tubules and in the ducts of glands.

In simple columnar epithelium, the nucleus of the tall column-like cells tends to be elongated and located in the basal end of the cells. Like the cuboidal epithelia, this epithelium is active in the absorption and secretion of molecules using active transport. Simple columnar epithelium forms a majority of the digestive tract and some parts of the female reproductive tract. Ciliated columnar epithelium is composed of simple columnar epithelial cells with cilia on their apical surfaces. These epithelial cells are found in the lining of the fallopian tubes where the assist in the passage of the egg, and parts of the respiratory system, where the beating of the cilia helps remove particulate matter.

Pseudostratified columnar epithelium is a type of epithelium that appears to be stratified but instead consists of a single layer of irregularly shaped and differently sized columnar cells. In pseudostratified epithelium, nuclei of neighboring cells appear at different levels rather than clustered in the basal end. The arrangement gives the appearance of stratification, but in fact, all the cells are in contact with the basal lamina, although some do not reach the apical surface. Pseudostratified columnar epithelium is found in the respiratory tract, where some of these cells have cilia.

Both simple and pseudostratified columnar epithelia are heterogeneous epithelia because they include additional types of cells interspersed among the epithelial cells. For example, a goblet cell is a mucous-secreting unicellular gland interspersed between the columnar epithelial cells of a mucous membrane (Figure 4.2.3).

Stratified Epithelium

A stratified epithelium consists of multiple stacked layers of cells. This epithelium protects against physical and chemical damage. The stratified epithelium is named by the shape of the most apical layer of cells, closest to the free space.

Stratified squamous epithelium is the most common type of stratified epithelium in the human body. The apical cells appear squamous, whereas the basal layer contains either columnar or cuboidal cells. The top layer may be covered with dead cells containing keratin. The skin is an example of a keratinized, stratified squamous epithelium. Alternatively, the lining of the oral cavity is an example of an unkeratinized, stratified squamous epithelium. Stratified cuboidal epithelium and stratified columnar epithelium can also be found in certain glands and ducts, but are relatively rare in the human body.

Another kind of stratified epithelium is transitional epithelium, so-called because of the gradual changes in the shapes and layering of the cells as the epithelium lining the expanding hollow organ is stretched.  Transitional epithelium is found only in the urinary system, specifically the ureters and urinary bladder. When the bladder is empty, this epithelium is convoluted and has cuboidal-shaped apical cells with convex, umbrella shaped,  surfaces. As the bladder fills with urine, this epithelium loses its convolutions and the apical cells transition in appearance from cuboidal to squamous. It appears thicker and more multi-layered when the bladder is empty, and more stretched out and less stratified when the bladder is full and distended.

Glandular Epithelium

A gland is a structure made up of one or more cells modified to synthesize and secrete chemical substances. Most glands consist of groups of epithelial cells. A gland can be classified as an endocrine gland, a ductless gland that releases secretions directly into surrounding tissues and fluids (endo- = “inside”), or an exocrine gland whose secretions leave through a duct that opens to the external environment (exo- = “outside”).

Endocrine Glands

The secretions of endocrine glands are called hormones. Hormones are released into the interstitial fluid, diffuse into the bloodstream, and are delivered to cells that have receptors to bind the hormones. The endocrine system a major communication system coordinating the regulation and integration of body responses.  These glands will be discussed in much greater detail in a later chapter.

Exocrine Glands

Exocrine glands release their contents through a duct or duct system that ultimately leads to the external environment. Mucous, sweat, saliva, and breast milk are all examples of secretions released by exocrine glands.

Glandular Structure

Exocrine glands are classified as either unicellular or multicellular. Unicellular glands are individual cells which are scattered throughout an epithelial lining.  Goblet cells are an example of a unicellular gland type found extensively in the mucous membranes of the small and large intestine.

Multicellular exocrine glands are composed of two or more cells which either secrete their contents directly into an inner body cavity (e.g., serous glands), or release their contents into a duct.  If there is a single duct carrying the contents to the external environment then the gland is referred to as a simple gland.  Multicellular glands that have ducts divided into one or more branches is called a compound gland (Figure 4.2.4).  In addition to the number of ducts present, multicellular glands are also classified based on the shape of the secretory portion of the gland.  Tubular glands have enlongated secretory regions (similar to a test tube in shape) while alveolar (acinar) glands have a secretory region that is spherical in shape.   Combinations of the two secretory regions are known as tubuloalveolar (tubuloacinar) glands.

Exocrine glands are classified by the arrangement of ducts emptying the gland and the shape of the secretory region.

Methods and Types of Secretion
In addition to the glandular structure, exocrine glands can be classified by their mode of secretion and the nature of the substances released (Figure 4.2.5). Merocrine secretion is the most common type of exocrine secretion. The secretions are enclosed in vesicles that move to the apical surface of the cell where the contents are released by exocytosis. For example, saliva containing the glycoprotein mucin is a merocrine secretion.  The glands that produce and secrete sweat are another example of merocrine secretion.

Apocrine secretion occurs when secretions accumulate near the apical portion of a secretory cell. That portion of the cell and its secretory contents pinch off from the cell and are released. The sweat glands of the armpit are classified as apocrine glands. Like merocrine glands, apocrine glands continue to produce and secrete their contents with little damage caused to the cell because the nucleus and golgi regions remain intact after the secretory event.

In contrast, the process of holocrine secretion involves the rupture and destruction of the entire gland cell. The cell accumulates its secretory products and releases them only when the cell bursts. New gland cells differentiate from cells in the surrounding tissue to replace those lost by secretion. The sebaceous glands that produce the oils on the skin and hair are an example of a holocrine glands (Figure 4.2.6).

Glands are also named based on the  products they produce. A serous gland produces watery, blood-plasma-like secretions rich in enzymes, whereas a mucous gland releases a more viscous product rich in the glycoprotein mucin. Both serous and mucous secretions are common in the salivary glands of the digestive system.  Such glands releasing both serous and mucous secretions are often referred to as seromucous glands.

Chapter Review

In epithelial tissue, cells are closely packed with little or no extracellular matrix except for the basal lamina that separates the epithelium from underlying tissue. The main functions of epithelia are protection from the environment, coverage, secretion and excretion, absorption, and filtration. Cells are bound together by tight junctions that form an impermeable barrier. They can also be connected by gap junctions, which allow free exchange of soluble molecules between cells, and anchoring junctions, which attach cell to cell or cell to matrix. The different types of epithelial tissues are characterized by their cellular shapes and arrangements: squamous, cuboidal, or columnar epithelia. Single cell layers form simple epithelia, whereas stacked cells form stratified epithelia. Very few capillaries penetrate these tissues.

Glands are secretory tissues and organs that are derived from epithelial tissues. Exocrine glands release their products through ducts. Endocrine glands secrete hormones directly into the interstitial fluid and blood stream. Glands are classified both according to the type of secretion and by their structure. Merocrine glands secrete products as they are synthesized. Apocrine glands release secretions by pinching off the apical portion of the cell, whereas holocrine gland cells store their secretions until they rupture and release their contents. In this case, the cell becomes part of the secretion.

4.3 Connective Tissue Supports and Protects

Learning Objectives

Describe the structural characteristics of the various connective tissues and how these characteristics enable their functions.

By the end of this section, you will be able to:

• Identify and distinguish between the different type of connective tissue: proper, supportive, and fluid – and associate each with their function and location
• Describe the common structural elements of connective tissue
• Describe how the structural properties of connective tissue relate to the unique functions of the tissue

Functions of Connective Tissues

Connective tissues perform many functions in the body, most importantly, they support and connect other tissues: from the connective tissue sheath that surrounds a muscle, to the tendons that attach muscles to bones, and to the skeleton that supports the positions of the body. Protection is another major function of connective tissue, in the form of fibrous capsules and bones that protect delicate organs. Specialized cells in connective tissue defend the body from microorganisms that enter the body. Transport of gases, nutrients, waste, and chemical messengers is ensured by specialized fluid connective tissues, such as blood and lymph. Adipose cells store surplus energy in the form of fat and contribute to the thermal insulation of the body.

Embryonic Connective Tissue

All connective tissues derive from the mesodermal layer of the embryo (see Figure 4.2.2). The first connective tissue to develop in the embryo is mesenchyme, the stem cell line from which all connective tissues are later derived. Clusters of mesenchymal cells are scattered throughout adult tissue and supply the cells needed for replacement and repair after a connective tissue injury. A second type of embryonic connective tissue forms in the umbilical cord, called mucous connective tissue or Wharton’s jelly. This tissue is no longer present after birth, leaving only scattered mesenchymal cells throughout the body.

Structural Elements of Connective Tissue

Connective tissues come in a vast variety of forms, yet they typically have in common three characteristic components: cells, large amounts of amorphous ground substance, and protein fibers. Unlike epithelial tissue, which is composed of cells closely packed together, cells of connective tissue are more widely dispersed within an extracellular matrix (ECM). The matrix plays a major role in the functioning of this tissue. The major component of the matrix is ground substance. This ground substance is usually a fluid, but it can also be mineralized and solid, as in bones.  The amount and structure of each component correlates with the function of the tissue, from the rigid ground substance in bones supporting the body to the inclusion of specialized cells; for example, a phagocytic cell that engulfs pathogens and also rids tissue of cellular debris.

Cell Types

Each class of connective tissue is formed by fundamental cell types. The cells can be found in both an active form (suffix –blast), where they are dividing and secreting the components of ground substance, and an in-active form (suffix –cyte).  The most abundant cell in connective tissue proper is the fibroblast. Polysaccharides and proteins secreted by fibroblasts combine with extra-cellular fluids to produce a viscous ground substance that, with embedded fibrous proteins and cells, forms the extra-cellular matrix. Chondroblasts and osteoblasts are the primary specialized cell type located in cartilage and bone, respectively.

Adipocytes are cells that store lipids as droplets that fill most of the cytoplasm. There are two basic types of adipocytes: white and brown. The brown adipocytes store lipids as many droplets, and have high metabolic activity. In contrast, white fat adipocytes store lipids as a single large drop and are metabolically less active. Their effectiveness at storing large amounts of fat is witnessed in obese individuals. The number and type of adipocytes depends on the tissue and location, and vary among individuals in the population.

The mesenchymal cell is a multipotent adult stem cell. These cells can differentiate into any type of connective tissue cells needed for repair and healing of damaged tissue.

The macrophage cell is a large cell derived from a monocyte, a type of blood cell, which enters the connective tissue matrix from the blood vessels. The macrophage cells are an essential component of the immune system, which is the body’s defense against potential pathogens and degraded host cells. When stimulated, macrophages release cytokines, small proteins that act as chemical messengers. Cytokines recruit other cells of the immune system to infected sites and stimulate their activities. Roaming, or free, macrophages move rapidly by amoeboid movement, engulfing infectious agents and cellular debris. In contrast, fixed macrophages are permanent residents of their tissues.

The mast cell, found in connective tissue proper, has many cytoplasmic granules. These granules contain the chemical signals histamine and heparin. When irritated or damaged, mast cells release histamine, an inflammatory mediator, which causes vasodilation and increased blood flow at a site of injury or infection, along with itching, swelling, and redness (in people with light skin), recognized as an allergic response. Mast cells are derived from hematopoietic stem cells and are part of the immune system.

Connective Tissue Fibers and Ground Substance

Three main types of fibers are secreted by fibroblasts: collagen fibers, elastic fibers, and reticular fibers. Collagen fiber is made from fibrous protein subunits linked together to form a long, straight fiber. Collagen fibers, while flexible, have great tensile strength, resist stretching, and give ligaments and tendons their characteristic resilience.

An elastic fiber contains the protein elastin along with lesser amounts of other proteins and glycoproteins. The main property of elastin is that after being stretched or compressed, it will return to its original shape. Elastic fibers are prominent in elastic tissues found in skin, the walls of large blood vessels, and in a few ligaments which support the spine.

A reticular fiber is formed from the same protein subunits as collagen fibers, however, these fibers remain narrow and are arranged in a branching network. They are found throughout the body, but are most abundant in the reticular tissue of soft organs, such as the liver and spleen, where they anchor and provide structural support to the parenchyma (the functional cells, blood vessels, and nerves of the organ).

All of these fiber types are embedded in ground substance. Secreted by fibroblasts, ground substance is made of polysaccharides, specifically hyaluronic acid, and proteins. These combine to form a proteoglycan with a protein core and polysaccharide branches. The proteoglycan attracts and traps available moisture forming the clear, viscous, colorless ground substance.

Classification of Connective Tissues

The three broad categories of connective tissue are classified according to the characteristics of their ground substance and the types of fibers found within the matrix (Table 4.1). Connective tissue proper includes loose connective tissue and dense connective tissue. Both tissues have a variety of cell types and protein fibers suspended in a viscous ground substance. Dense connective tissue is reinforced by bundles of fibers that provide tensile strength, elasticity, and protection. In loose connective tissue, the fibers are loosely organized, leaving large spaces in between. Supportive connective tissue—bone and cartilage—provide structure and strength to the body and protect soft tissues. A few distinct cell types and densely packed fibers in a matrix characterize these tissues. In bone, the matrix is rigid and described as calcified because of the deposited calcium salts. In fluid connective tissue, lymph and blood, various specialized cells circulate in a watery fluid containing salts, nutrients, and dissolved proteins.

Connective Tissue Proper

Fibroblasts are present in all connective tissue proper (Figure 4.3.1). Fibrocytes, adipocytes, and mesenchymal cells are fixed cells, which means they remain within the connective tissue. Other cells move in and out of the connective tissue in response to chemical signals. Macrophages, mast cells, lymphocytes, plasma cells, and phagocytic cells are found in connective tissue proper but are actually part of the immune system protecting the body.

Loose Connective Tissue

Loose connective tissue is found between many organs where it acts both to absorb shock and bind tissues together. It allows water, salts, and various nutrients to diffuse through to adjacent or imbedded cells and tissues.

Adipose tissue consists mostly of fat storage cells, with little extracellular matrix (Figure 4.3.2). A large number of capillaries allow rapid storage and mobilization of lipid molecules. White adipose tissue is most abundant. It can appear yellow and owes its color to carotene and related pigments from plant food. White fat contributes mostly to lipid storage and can serve as insulation from cold temperatures and mechanical injuries. White adipose tissue can be found protecting the kidneys, cushioning the back of the eye, within the abdomen, and in the hypodermis. Brown adipose tissue is more common in infants, hence the term “baby fat.” In adults, there is a reduced amount of brown fat and it is found mainly in the neck and clavicular regions of the body. The many mitochondria in the cytoplasm of brown adipose tissue help explain its efficiency at metabolizing stored fat. Brown adipose tissue is thermogenic, meaning that as it breaks down fats, it releases metabolic heat, rather than producing adenosine triphosphate (ATP), a key molecule used in metabolism.

Figure 4.3.2 – Adipose Tissue: This is a loose connective tissue that consists of fat cells with little extracellular matrix. It stores fat for energy and provides insulation (LM × 800). (Micrograph provided by the Regents of University of Michigan Medical School © 2012)

Areolar tissue shows relatively little specialization and is the most widely distributed connective tissue in the body. It contains all the cell types and fibers previously described and is structured in an apparently random, web-like fashion. It fills the spaces between muscle fibers, surrounds blood and lymph vessels, and supports organs in the abdominal cavity. Areolar tissue underlies most epithelia and represents the connective tissue component of epithelial membranes.

Reticular tissue is a mesh-like, supportive framework for soft organs such as lymphatic tissue, the spleen, and the liver (Figure 4.3.3). The reticular fibers form the network onto which other cells attach. It derives its name from the Latin reticulus, which means “little net.”

Dense Connective Tissue

Dense connective tissue contains more collagen fibers than does loose connective tissue. As a consequence, it displays greater resistance to stretching and a higher tensile strength. There are three major categories of dense connective tissue: regular, irregular, and elastic. Dense regular connective tissue fibers are parallel to each other, enhancing tensile strength and resistance to stretching in the direction of the fiber orientations. Ligaments and tendons are mostly formed from dense regular connective tissue.

In dense irregular connective tissue, the arrangement of proteins fibers is irregular and lacks the uniformity seen in dense regular . This arrangement gives the tissue greater strength in all directions and less strength in any one particular direction. In some tissues, fibers crisscross and form a mesh. In other tissues, stretching in several directions is achieved by alternating layers where fibers run in the same orientation in each layer, and it is the layers themselves that are stacked at an angle. The dermis of the skin is an example of dense irregular connective tissue rich in collagen fibers.

Dense elastic tissue contains elastin fibers in addition to collagen fibers, which allows the tissue to return to its original length after stretching. Dense elastic tissues give arterial walls the strength and the ability to regain original shape after stretching (dense CT figure).

Disorders of the Connective Tissue: Tendinitis

Your opponent stands ready as you prepare to hit the serve, but you are confident that you will smash the ball past your opponent. As you toss the ball high in the air, a burning pain shoots across your wrist and you drop the tennis racket. That dull ache in the wrist that you ignored through the summer is now an unbearable pain. The game is over for now.

After examining your swollen wrist, the doctor in the emergency room announces that you have developed wrist tendinitis. She recommends icing the tender area, taking non-steroidal anti-inflammatory medication to ease the pain and to reduce swelling, and complete rest for a few weeks. She interrupts your protests that you cannot stop playing. She issues a stern warning about the risk of aggravating the condition and the possibility of surgery. She consoles you by mentioning that well known tennis players such as Venus and Serena Williams and Rafael Nadal have also suffered from tendinitis related injuries.

What is tendinitis and how did it happen? Tendinitis is the inflammation of a tendon, the thick band of fibrous connective tissue that attaches a muscle to a bone. The condition causes pain and tenderness in the area around a joint. Most often, the condition results from repetitive motions over time that strain the tendons needed to perform the tasks.

Persons whose jobs and hobbies involve performing the same movements over and over again are often at the greatest risk of tendinitis. You hear of tennis and golfer’s elbow, jumper’s knee, and swimmer’s shoulder. In all cases, overuse of the joint causes a microtrauma that initiates the inflammatory response. Tendinitis is routinely diagnosed through a clinical examination. In case of severe pain, X-rays can be examined to rule out the possibility of a bone injury. Severe cases of tendinitis can even tear loose a tendon. Surgical repair of a tendon is painful. Connective tissue in the tendon does not have abundant blood supply and heals slowly.

While older adults are at risk for tendinitis because the elasticity of tendon tissue decreases with age, active people of all ages can develop tendinitis. Young athletes, dancers, and computer operators; anyone who performs the same movements constantly is at risk for tendinitis. Although repetitive motions are unavoidable in many activities and may lead to tendinitis, precautions can be taken that can lessen the probability of developing tendinitis. For active individuals, stretches before exercising and cross training or changing exercises are recommended. For the passionate athlete, it may be time to take some lessons to improve technique. All of the preventive measures aim to increase the strength of the tendon and decrease the stress put on it. With proper rest and managed care, you will be back on the court to hit that slice-spin serve over the net.

Supportive Connective Tissues

Two major forms of supportive connective tissue, cartilage and bone, allow the body to maintain its posture and protect internal organs.

Cartilage

The distinctive appearance of cartilage is due to polysaccharides called chondroitin sulfates, which bind with ground substance proteins to form proteoglycans. Embedded within the cartilage matrix are chondrocytes, or cartilage cells, and the space they occupy are called lacunae (singular = lacuna). A layer of dense irregular connective tissue, the perichondrium, encapsulates the cartilage. Cartilaginous tissue is avascular, thus, all nutrients need to diffuse through the matrix to reach the chondrocytes. This is a factor contributing to the very slow healing of cartilaginous tissues.

The three main types of cartilage tissue are hyaline cartilage, fibrocartilage, and elastic cartilage (Figure 4.3.5 – Types of Cartilage). Hyaline cartilage, the most common type of cartilage in the body, consists of short and dispersed collagen fibers and contains large amounts of proteoglycans. Under the microscope, tissue samples appear clear. The surface of hyaline cartilage is smooth. Both strong and flexible, it is found in the rib cage and nose and covers bones where they meet to form moveable joints. It forms the template of the embryonic skeleton before bone formation. A plate of hyaline cartilage at the ends of bone allows continued growth until adulthood. Fibrocartilage is tough because it has thick bundles of collagen fibers dispersed through its matrix. The intervertebral discs are examples of fibrocartilage. Elastic cartilage contains elastic fibers as well as collagen and proteoglycans. This tissue provides support as well as elasticity. Tug gently at your ear lobes, and notice that the lobes return to their initial shape. The external ear contains elastic cartilage.

Bone

Bone is the hardest connective tissue. It provides protection to internal organs and supports the body. Bone’s rigid extracellular matrix contains mostly collagen fibers embedded in a mineralized ground substance containing hydroxyapatite, a form of calcium phosphate. Both components of the matrix, organic and inorganic, contribute to the unusual properties of bone. Without collagen, bones would be brittle and shatter easily. Without mineral crystals, bones would flex and provide little support. Osteoblasts are the active bone forming cells, producing the organic part of the extracellular matrix. The mature bone cells, osteocytes, are located within lacunae.  Bone is a highly vascularized tissue. Unlike cartilage, bone tissue can recover from injuries in a relatively short time.

The histology of a cross sectional view of compact bone shows a typical arrangement of osteocytes in concentric circles around a central canal. This structural unit of compact bone is called the osteon. There is no such structural unit in cancellous bone, or spongy bone, which looks like a sponge under the microscope and contains empty spaces between trabeculae. It is lighter than compact bone and found in the interior of bones and at the end of long bones. Compact bone is solid and has greater structural strength.

Fluid Connective Tissue

Blood and lymph are fluid connective tissues. Cells circulate in a liquid extracellular matrix. The formed elements circulating in blood are all derived from hematopoietic stem cells located in bone marrow (Figure 4.3.6 – Blood: A Fluid Connective Tissue). Erythrocytes, red blood cells, transport oxygen and carbon dioxide. Leukocytes, white blood cells, are responsible for defending against potentially harmful microorganisms or molecules. Platelets are cell fragments involved in blood clotting. Some white blood cells have the ability to cross the endothelial layer that lines blood vessels and enter adjacent tissues. Nutrients, salts, and wastes are dissolved in the liquid matrix and transported through the body.

Lymph contains a liquid matrix and white blood cells. Lymphatic capillaries are highly permeable, allowing larger molecules and excess fluid from interstitial spaces to enter the lymphatic vessels. Lymph vessels return molecules and fluid to the venous blood that could not otherwise directly enter the bloodstream. In this way, specialized lymphatic capillaries transport absorbed fats away from the intestine and deliver these molecules to the blood.

Chapter Review

Connective tissue is a heterogeneous tissue with many cell shapes and tissue architecture. Structurally, all connective tissues contain cells that are embedded in an extracellular matrix stabilized by proteins. The chemical nature and physical layout of the extracellular matrix and proteins vary enormously among tissues, reflecting the variety of functions that connective tissue fulfills in the body. Connective tissues separate and cushion organs, protecting them from shifting or traumatic injuries. Connective tissues also provide support and assist movement, store and transport energy molecules, protect against infections, and contribute to temperature homeostasis.

Many different cells contribute to the formation of connective tissues. They originate in the mesodermal germ layer and differentiate from mesenchyme and hematopoietic tissue in the bone marrow. Fibroblasts are the most abundant and secrete many protein fibers, adipocytes specialize in fat storage, hematopoietic cells from the bone marrow give rise to all the blood cells, chondrocytes form cartilage, and osteocytes form bone. The extracellular matrix contains fluid, proteins, polysaccharide derivatives, and, in the case of bone, mineral crystals. Protein fibers fall into three major groups: collagen fibers (which are thick, strong, flexible, and resist stretch), reticular fibers (which are thin and form a supportive mesh, and elastin (fibers that are thin and elastic).

The major types of connective tissue are connective tissue proper, supportive tissue, and fluid tissue. Loose connective tissue proper includes adipose tissue, areolar tissue, and reticular tissue. These serve to hold organs and other tissues in place and, in the case of adipose tissue, isolate and store energy reserves. The matrix is the most abundant feature for loose tissue although adipose tissue does not have much extracellular matrix. Dense connective tissue proper is richer in fibers and may be regular, with fibers oriented in parallel as in ligaments and tendons,  irregular, with fibers oriented in several directions, or elastic, with a large amount of the protein elastin embedded within the fibers. Organ capsules (collagenous type) and walls of arteries (elastic type) contain dense, irregular connective tissue. Cartilage and bone are supportive tissue. Cartilage contains chondrocytes and is somewhat flexible. Hyaline cartilage is smooth and clear, covers joints, and is found in the growing portion of bones. Fibrocartilage is tough because of extra collagen fibers and forms, among other things, the intervertebral discs. Elastic cartilage can stretch and recoil to its original shape because of its high content of elastic fibers.  Bones are made of a rigid, mineralized matrix containing calcium salts, crystals, and osteocytes lodged in lacunae. Bone tissue is highly vascularized. Cancellous bone is spongy and less solid than compact bone. Fluid tissue, for example blood and lymph, is characterized by a liquid matrix and no supporting fibers.

4.4 Muscle Tissue

Learning Objectives

Describe the characteristics of muscle tissue and how these dictate muscle function.

By the end of this section, you will be able to:

• Identify the three types of muscle tissue
• Compare and contrast the functions of each muscle tissue type

Muscle tissue is characterized by properties that allow movement. Muscle cells are excitable; they respond to a stimulus. They are contractile, meaning they can shorten and generate a pulling force. When attached between two movable objects, such as two bones, contraction of the muscles cause the bones to move. Some muscle movement is voluntary, which means it is under conscious control. For example, a person decides to open a book and read a chapter on anatomy. Other movements are involuntary, meaning they are not under conscious control, such as the contraction of your pupil in bright light. Muscle tissue is classified into three types according to structure and function: skeletal, cardiac, and smooth (Table 4.2).

Skeletal muscle is attached to bones and its contraction makes possible locomotion, facial expressions, posture, and other voluntary movements of the body. Forty percent of your body mass is made up of skeletal muscle. Skeletal muscles generate heat as a byproduct of their contraction and thus participate in thermal homeostasis. Shivering is an involuntary contraction of skeletal muscles in response to lower than normal body temperature. The muscle cell, or myocyte, develops from myoblasts derived from the mesoderm. Myocytes and their numbers remain relatively constant throughout life. Skeletal muscle tissue is arranged in bundles surrounded by connective tissue. Under the light microscope, muscle cells appear striated with many nuclei squeezed along the membranes. The striation is due to the regular alternation of the contractile proteins actin and myosin, along with the structural proteins that couple the contractile proteins to connective tissues. The cells are multinucleated as a result of the fusion of the many myoblasts that fuse to form each long muscle fiber.

Cardiac muscle forms the contractile walls of the heart. The cells of cardiac muscle, known as cardiomyocytes, also appear striated under the microscope. Unlike skeletal muscle fibers, cardiomyocytes are single cells with a single centrally located nucleus. A principal characteristic of cardiomyocytes is that they contract on their own intrinsic rhythm without external stimulation. Cardiomyocytes attach to one another with specialized cell junctions called intercalated discs. Intercalated discs have both anchoring junctions and gap junctions. Attached cells form long, branching cardiac muscle fibers that act as a syncytium, allowing the cells to synchronize their actions. The cardiac muscle pumps blood through the body and is under involuntary control.

Smooth muscle tissue contraction is responsible for involuntary movements in the internal organs. It forms the contractile component of the digestive, urinary, and reproductive systems as well as the airways and blood vessels. Each cell is spindle shaped with a single nucleus and no visible striations (Figure 4.4.1 – Muscle Tissue).

Chapter Review

The three types of muscle cells are skeletal, cardiac, and smooth. Their morphologies match their specific functions in the body. Skeletal muscle is voluntary and responds to conscious stimuli. The cells are striated and multinucleated appearing as long, unbranched cylinders. Cardiac muscle is involuntary and found only in the heart. Each cell is striated with a single nucleus and they attach to one another to form long fibers. Cells are attached to one another at intercalated disks. The cells are interconnected physically and electrochemically to act as a syncytium. Cardiac muscle cells contract autonomously and involuntarily. Smooth muscle is involuntary. Each cell is a spindle-shaped fiber and contains a single nucleus. No striations are evident because the actin and myosin filaments do not align in the cytoplasm.

4.5 Nervous Tissue

Learning Objectives

Describe the characteristics of nervous tissue and how these enable the unique functions of nervous tissue.

By the end of this section, you will be able to:

• Identify the classes of cells that make up nervous tissue
• Describe the characteristics of nervous tissue

Nervous tissue is characterized as being excitable and capable of sending and receiving electrochemical signals that provide the body with information. Two main classes of cells make up nervous tissue: the neuron and neuroglia (Figure 4.5.1 The Neuron). Neurons propagate information via electrochemical impulses, called action potentials, which are biochemically linked to the release of chemical signals. Neuroglia play an essential role in supporting neurons.

Neurons display distinctive morphology, well suited to their role as conducting cells, with three main parts. The cell body includes most of the cytoplasm, organelles, and nucleus. Dendrites, which receive input from other neurons, branch off the cell body and appear as thin extensions. A long axon extends from the cell body and may be wrapped in an insulating layer known as myelin, which is formed by accessory cells. Axons transmit electrical signals traveling away from the cell body. The synapse is the gap between nerve cells, or between a nerve cell and its target. The signal is transmitted across the synapse by chemical compounds known as neurotransmitters. Neurons categorized as multipolar neurons have several dendrites and a single prominent axon. Bipolar neurons possess a single dendrite and axon with the cell body, while unipolar neurons have only a single process extending out from the cell body, which divides into a functional dendrite and into a functional axon. When a neuron is sufficiently stimulated, it generates an action potential that propagates down the axon towards the synapse. If enough neurotransmitters are released at the synapse to stimulate the next neuron (or muscle, or gland), a response is generated.

The second class of neural cells are the neuroglia or glial cells, which have been characterized as having a simple support role. The word “glia” comes from the Greek word for glue. Recent research is shedding light on the more complex role of neuroglia in the function of the brain and nervous system. Astrocyte cells, named for their distinctive star shape, are abundant in the central nervous system. The astrocytes have many functions, including regulation of ion concentration in the intercellular space, uptake and/or breakdown of some neurotransmitters, and formation of the blood-brain barrier, the membrane that separates the circulatory system from the brain. Microglia protect the nervous system against infection and are related to macrophages. Oligodendrocyte cells produce myelin in the central nervous system (brain and spinal cord) while the Schwann cell produces myelin in the peripheral nervous system (Figure 4.5.2 Nervous Tissue).

Chapter Review

The most prominent cell of the nervous tissue, the neuron, is characterized mainly by its ability to receive stimuli and respond by generating an electrical signal, known as an action potential, which can travel rapidly over great distances in the body. A typical neuron displays a distinctive morphology: a large cell body branches out into short extensions called dendrites, which receive chemical signals from other neurons, and a long tail called an axon, which relays signals away from the cell to other neurons, muscles, or glands. Many axons are wrapped by a myelin sheath, a lipid derivative that acts as an insulator and facilitates the transmission of the action potential. Other cells in the nervous tissue, the neuroglia, include the astrocytes, microglia, oligodendrocytes, and Schwann cells.

4.6 Tissue Injury and Aging

Learning Objectives

Describe the process of tissue response to injury.

By the end of this section, you will be able to:

• Identify the cardinal signs of inflammation
• List the body’s response to tissue injury
• Explain the process of tissue repair
• Discuss the progressive impact of aging on tissue
• Describe cancerous mutations’ effect on tissue

Tissues of all types are vulnerable to injury and, inevitably, aging. In the former case, understanding how tissues respond to damage can guide strategies to aid repair. In the latter case, understanding the impact of aging can help in the search for ways to diminish its effects.

Tissue Injury and Repair

Inflammation is the standard, initial response of the body to injury. Whether biological, chemical, physical, or radiation burns, all injuries lead to the same sequence of physiological events. Inflammation limits the extent of injury, partially or fully eliminates the cause of injury, and initiates repair and regeneration of damaged tissue. Necrosis, or accidental cell death, causes inflammation. Apoptosis is programmed cell death, a normal step-by-step process that destroys cells no longer needed by the body. By mechanisms still under investigation, apoptosis does not initiate the inflammatory response. Acute inflammation resolves over time by the healing of tissue. If inflammation persists, it becomes chronic and leads to diseased conditions. Arthritis and tuberculosis are examples of chronic inflammation. The suffix “-itis” denotes inflammation of a specific organ or type. For example, peritonitis is the inflammation of the peritoneum, and meningitis refers to the inflammation of the meninges, the tough membranes that surround the central nervous system.

The four cardinal signs of inflammation—redness (at least for people with light colored skin), swelling, pain, and local heat—were first recorded in antiquity. Cornelius Celsus is credited with documenting these signs during the days of the Roman Empire, as early as the first century AD. A fifth sign, loss of function, may also accompany inflammation.

Upon tissue injury, damaged cells release inflammatory chemical signals that evoke local vasodilation, the widening of the blood vessels. Increased blood flow can change the color of the integument and result in a localized temperature increase. In response to injury, mast cells present in tissue degranulate, releasing the potent vasodilator histamine. Increased blood flow and inflammatory mediators recruit white blood cells to the site of inflammation. The endothelium lining the local blood vessel becomes “leaky” under the influence of histamine and other inflammatory mediators allowing neutrophils, macrophages, and fluid to move from the blood into the interstitial tissue spaces. The excess liquid in tissue causes swelling, properly called edema. The swollen tissues stimulate mechanical receptors, which can cause the perception of pain. Prostaglandins released from injured cells also activate pain pathways. Non-steroidal anti-inflammatory drugs (NSAIDs) reduce perceived pain because they inhibit the synthesis of prostaglandins. High levels of NSAIDs reduce inflammation. Antihistamines decrease allergies by blocking histamine receptors and as a result, the histamine response.

After containment of an injury, the tissue repair phase starts with removal of toxins and waste products. Clotting (coagulation) reduces blood loss from damaged blood vessels and forms a network of fibrin proteins that trap blood cells and bind the edges of the wound together. A scab forms when the clot dries, reducing the risk of infection. Sometimes a mixture of dead leukocytes and fluid called pus accumulates in the wound. As healing progresses, fibroblasts from the surrounding connective tissues replace the collagen and extracellular material lost by the injury. Angiogenesis, the growth of new blood vessels, results in vascularization of the new tissue known as granulation tissue. The clot retracts pulling the edges of the wound together, and it slowly dissolves as the tissue is repaired. When a large amount of granulation tissue forms and capillaries disappear, a pale scar is often visible in the healed area. A primary union describes the healing of a wound where the edges are close together. When there is a gaping wound, it takes longer to refill the area with cells and collagen. The process called secondary union occurs as the edges of the wound are pulled together by what is called wound contraction. When a wound is more than one quarter of an inch deep, sutures (stitches) are recommended to promote a primary union and avoid the formation of a disfiguring scar. Regeneration is the addition of new cells of the same type as the ones that were injured (Figure 4.6.1 – Tissue Healing).

Tissue and Aging

According to poet Ralph Waldo Emerson, “The surest poison is time.” In fact, biology confirms that many functions of the body decline with age. All the cells, tissues, and organs are affected by senescence, with noticeable variability between individuals owing to different genetic makeup and lifestyles. The outward signs of aging are easily recognizable. The skin and other tissues become thinner and drier, reducing their elasticity, contributing to wrinkles and high blood pressure. Hair turns gray because follicles produce less melanin, the brown pigment of hair and the iris of the eye. The face looks flabby because elastic and collagen fibers decrease in connective tissue and muscle tone is lost. Glasses and hearing aids may become parts of life as the senses slowly deteriorate, all due to reduced elasticity. Overall height decreases as the bones lose calcium and other minerals. With age, fluid decreases in the fibrous cartilage disks intercalated between the vertebrae in the spine. Joints lose cartilage and stiffen. Many tissues, including those in muscles, lose mass through a process called atrophy. Lumps and rigidity become more widespread. As a consequence, the passageways, blood vessels, and airways become more rigid. The brain and spinal cord lose mass. Nerves do not transmit impulses with the same speed and frequency as in the past. Some loss of thought, clarity, and memory can accompany aging. More severe problems are not necessarily associated with the aging process and may be symptoms of an underlying illness.

As exterior signs of aging increase, so do the interior signs, which are not as noticeable. The incidence of heart diseases, respiratory syndromes, and type 2 diabetes increases with age, though these are not necessarily age-dependent effects. Wound healing is slower in the elderly, accompanied by a higher frequency of infection as the capacity of the immune system to fend off pathogens declines.

Aging is also apparent at the cellular level because all cells experience changes with aging. Telomeres, regions of the chromosomes necessary for cell division, shorten each time cells divide. As they do, cells are less able to divide and regenerate. Because of alterations in cell membranes, transport of oxygen and nutrients into the cell and removal of carbon dioxide and waste products from the cell are not as efficient in the elderly. Cells may begin to function abnormally, which may lead to diseases associated with aging, including arthritis, memory issues, and some cancers.

The progressive impact of aging on the body varies considerably among individuals. However, studies indicate that exercise and healthy lifestyle choices can slow down the deterioration of the body that comes with old age.

Homeostatic Imbalances: Tissues and Cancer

Cancer is a generic term for many diseases in which cells escape regulatory signals. Uncontrolled growth, invasion into adjacent tissues, and colonization of other organs, if not treated early enough, are its hallmarks. Health suffers when tumors “rob” blood supply from the “normal” organs.

A mutation is defined as a permanent change in the DNA of a cell. Epigenetic modifications, changes that do not affect the code of the DNA but alter how the DNA is decoded, are also known to generate abnormal cells. Alterations in the genetic material may be caused by environmental agents, infectious agents, or errors in the replication of DNA that accumulate with age. Many mutations do not cause any noticeable change in the functions of a cell, however, if the modification affects key proteins that have an impact on the cell’s ability to proliferate in an orderly fashion, the cell starts to divide abnormally. As changes in cells accumulate, they lose their ability to form regular tissues. A tumor, a mass of cells displaying abnormal architecture, forms in the tissue. Many tumors are benign, meaning they do not metastasize nor cause disease. A tumor becomes malignant, or cancerous, when it breaches the confines of its tissue, promotes angiogenesis, attracts the growth of capillaries, and metastasizes to other organs (Figure 4.6.2 Development of Cancer). The specific names of cancers reflect the tissue of origin. Cancers derived from epithelial cells are referred to as carcinomas. Cancer in myeloid tissue or blood cells form myelomas. Leukemias are cancers of white blood cells, whereas sarcomas derive from connective tissue. Cells in tumors differ both in structure and function. Some cells, called cancer stem cells, appear to be a subtype of cell responsible for uncontrolled growth. Recent research shows that contrary to what was previously assumed, tumors are not disorganized masses of cells, but have their own structures.

Cancer treatments vary depending on the disease’s type and stage. Traditional approaches, including surgery, radiation, chemotherapy, and hormonal therapy. The aim is to remove or kill rapidly dividing cancer cells, but these strategies have their limitations. Depending on a tumor’s location, for example, cancer surgeons may be unable to remove it. Radiation and chemotherapy are difficult, and it is often impossible to target only the cancer cells. The treatments inevitably destroy healthy tissue as well. To address this, researchers are working on pharmaceuticals that can target specific proteins implicated in cancer-associated molecular pathways.

Chapter Review

Inflammation is the classic response of the body to injury and follows a common sequence of events. The area is red, feels warm to the touch, swells, and is painful. Injured cells, mast cells, and resident macrophages release chemical signals that cause vasodilation and fluid leakage in the surrounding tissue. The repair phase includes blood clotting, followed by regeneration of tissue as fibroblasts deposit collagen. Some tissues regenerate more readily than others. Epithelial and connective tissues replace damaged or dead cells from a supply of adult stem cells. Muscle and nervous tissues undergo either slow regeneration or do not repair at all.

Age affects all the tissues and organs of the body. Damaged cells do not regenerate as rapidly as in younger people. Perception of sensation and effectiveness of response are lost in the nervous system. Muscles atrophy, and bones lose mass and become brittle. Collagen decreases in some connective tissue, and joints stiffen.