1 12 Unit 1 Organization of the Body

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(a) Holocrine gland (b) Merocrine gland (c) Apocrine gland

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Figure 4.6 Modes of secretion in exocrine glands. (a) In holocrine glands, theentire secretory cell ruptures, releasing secretions and dead cell fragments• (b) Mero-crine glands secrete their products by exocytosis• (c) In apocrine glands, the apex ofeach secretory cell pinches off and releases its secretions.

Holocrine (h6'-luh-krin) glands accumulate theirproducts within them until the secretory cells rup-ture. (They are replaced by the division of underlyingcells.) Since holocrine gland secretions include thesynthesized product plus dead cell fragments (holos= all), you could say that their cells "die for theircause." Sebaceous (oil) glands of the skin are the onlytrue example of holocrine glands (Figure 4.6a).

Apocrine (a'-puh-krin) glands also accumulatetheir products, but in this case, accumulation occursonly at the cell apex (just beneath its free surface).Eventually, the apex of the cell pinches off (apo =from, off) and the secretion is released. The cell repairsits damage and repeats the process again and again.The mammary glands and some sweat glands releasetheir secretions by this mechanism (Figure 4.6c).

Connective tissue does much more than connectbody parts; it has many forms and many functions. Itschief subclasses are connective tissue proper, carti-lage, bone, and blood. Its major functions includebinding, support, protection, insulation, and, as blood,transportation of substances within the body. Forexample, cordlike connective tissue structures con-nect muscle to bone (tendons) and bones to bones (lig-aments), and fine, resilient connective tissue invadessoft organs and supports and binds their cells together.Bone and cartilage support and protect body organsby providing hard "underpinnings"; fat cushions,insulates, and protects body organs as well as provid-

ing reserve energy fuel.

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Common Characteristics ofConnective Tissue

Despite their multiple and varied functions in the body,connective tissues have certain common propertiesthat set them apart from other primary tissues:

Connective tissue is found everywhere in the body. Itis the most abundant and widely distributed of theprimary tissues, but its amount in particular organsvaries greatly. For example, bone and skin are madeup primarily of connective tissue, whereas the braincontains very little.

1. Common origin. All connective tissues arise frommesenchyme, an embryonic tissue derived from themesoderm germ layer, and hence have a common kin-

ship (Figure 4.7).

Connective Tissue

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Commonembryonicorigin:

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Chapter 4 Tissue: The Living Fabric 113

Fibroblast

Mesenchyme

Class ofconnectivetissueresulting:

Connective tissueproper

1. Loose connective 1. Hyalinetissue cartilage

Types: Areolar 2. FibrocartilageAdiposeReticular 3. Elastic

cartilage

2. Dense connectivetissue

Types: RegularIrregularElastic

Subclasses:

Fibrocyte

Chondroblast

Chondroeyte

Cartilage

Osteoblast

Osteocyte

Osseous (bone)

1. Compactbone

2. Spongy(cancellous)bone

Hemocytoblast

Blood cells*(and.macrophages)

Blood

*Blood cell formationand differentiation arequite complex.Details are providedin Chapter 18.

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Figure 4.7 Major classes of connective tissue. All of these classes arise from thesame common embryonic cell type (mesenchyme).

2. Degrees of vascularity. Unlike epithelium, whichis avascular, and muscle and nervous tissue, whichhave a rich vascular supply, connective tissues runthe entire gamut of vascularity. Cartilage is avascular;dense connective tissue is poorly vascularized; andthe other types have a rich supply of blood vessels.

3. Matrix. Whereas all other primary tissues are com-

posed mainly of cells, connective tissues are com-posed largely of nonliving extracellular matrix, whichseparates, often widely, the living cells of the tissue.Because of this matrix, connective tissue is able tobear weight, withstand great tension, and endureabuses, such as physical trauma and abrasion, that no

other tissue could withstand.

Structural Elements ofConnective Tissue

In any type of connective tissue, three elements mustbe considered: ground substance, fibers, and ceils. The

ground substance and fibers make up the extracellular

matrix. (However, you should be aware that someauthors use the term matrix to indicate the groundsubstance only.) The properties of the cells and thecomposition and arrangement of extracellular matrixelements vary tremendously, giving rise to an amazingdiversity of connective tissues, each uniquely adaptedto perform its specific function in the body. For exam-

ple, the matrix can be delicate and fragile to form asoft "packing" around an organ, or it can form "ropes"

(tendons and ligaments) of incredible strength.

Ground SubstanceGround substance is an amorphous (unstructured)material that fills the space between the cells and con-tains the fibers. It is composed of interstitial fluid,

glycoproteins, and glycosaminoglycans (glY'-k6-suh-m6"-n6-glÿ-kanz") (GAGs), a diverse group of large,negatively charged polysaccharides. The long, strand-like GAGs coil, intertwine, and trap water, forming asubstance that varies from a fluid to a semistiff hydrated

gel. One type of GAG, hyaluronic (hy'-yul-yoo-rah'-nik) acid, is found in virtually all connective tissues,

1 14 Unit 1 Organization of the Body

and its relative amount helps determine the viscosityand permeability of the ground substance.

The ground substance functions as a molecular"sieve," or medium, through which nutrients and otherdissolved substances can diffuse between the bloodcapillaries and the cells. The fibers in the matrix impedediffusion somewhat and make the ground substanceless pliable.

Fibers

Three types of fibers are found in the matrix of con-nective tissue: collagen, elastic, and reticular fibers.

Of these, collagen is by far the most important andabundant.

Collagen fibers are constructed primarily of thefibrous protein collagen. Collagen molecules aresecreted into the extracellular space, where theyassemble spontaneously into fibers. Collagen fibersare extremely tough and provide high tensile strength(that is, the ability to resist longitudinal stress) to thematrix. When fresh, they have a glistening whiteappearance; they are therefore also called white fibers.

Elastic fibers are formed largely from anotherfibrous protein, elastin. Elastin has a randomly coiledstructure that allows it to stretch and recoil like a rub-ber band. The presence of elastin in the matrix givesit a rubbery, or resilient, quality. Collagen fibers, alwaysfound in the same tissue, stretch a bit and then "lock"in full extension, which limits the extent of stretchand prevents the tissue from tearing. Elastic fibers thensnap the connective tissue back to its normal lengthwhen the tension lets up. Elastic fibers are found wheregreater elasticity is needed, for example, in the skin,lungs, and blood vessel walls. Since flesh elastic fibersappear yellow, they are sometimes called yellow fibers.ÿ

Reticular fibers are believed to be fine collagen-ous fibers (with a slightly different chemistry) and arecontinuous with collagen fibers. They branch exten-sively, forming a netlike reticulum in the matrix. Theyconstruct a fine mesh around small blood vessels,

support the soft tissue of organs, and are particularlyabundant at the junction between connective tissueand other tissue types, for example, in the basement

membrane of epithelial tissues.

Cells

tissue proper: fibroblast; (2) cartilage: chondroblast(kon'-dr6-blast"); (3) bone: osteoblast (ah'-stÿ-6-blast");and (4) blood: hemocytoblast (h6"-m6-sV-t6-blast).

Once the matrix has been synthesized, the blastcells assume their less active, mature mode, indicated

by the suffix cyte (see Figure 4.7); this mode is respon-sible for maintaining the matrix in a healthy state.However, if the matrix is injured, the mature cells caneasily revert to their more active state to make repairsand regenerate the matrix. (Note that the hemocyto-blast, the stem cell of bone marrow, always remains

actively mitotic.)Additionally, connective tissue proper, especially

the loose connective tissue type called areolar, is"home" to an assortment of other cell types, such asfat cells and cells that migrate into the connective tis-sue matrix from the bloodstream. The latter includewhite blood cells (neutrophils, eosinophils, lympho-cytes) and other cell types that act in the inflammatoryand immune responses that protect the body, such asmast ceils, macrophages, and plasma cells.

Although all of these accessory cell types aredescribed in later chapters, the macrophages are sosignificant to overall body defense that they deservea brief mention here. Macrophages (ma'-kr6-fÿ"-juz)

are large, irregularly shaped cells that avidly phago-cytize both foreign matter that has managed to invadethe body and dying or dead tissue cells. They are alsocentral actors in the immune system, as you will seein Chapter 22. In connective tissues, they may be fixed(attached to the connective tissue fibers) or they maymigrate freely through the matrix. However, macro-phages are not limited to connective tissue. In fact,their body distribution is so broad and their numbersso vast that they are often referred to collectively asthe macrophage system.

Macrophages are peppered throughout loose con-nective tissue, bone marrow, lymphatic tissue, thespleen, and the mesentery that suspends the abdom-inal viscera. Those in certain sites are given specificnames; they are called histiocytes (his'-tÿ-6-sits) inloose connective tissue, Kupffer (koop'-fer) cells inthe liver, and microglial (mi"-kr6'-glÿ-ul) cells in thebrain. Although all these cells are phagocytes, somehave selective appetites. For example, the macro-phages of the spleen function primarily to engulf agingred blood cells; but they will not turn down other"delicacies" that come their way.

Each major class of connective tissue has a funda-mental cell type that exists in immature and matureforms (see Figure 4.7). The undifferentiated cells,indicated by the suffix blast (literally, "bud," or "sprout,"but meaning "forming"), are actively mitotic cells thatsecrete both the ground substance and the fibers char-acteristic of their particular matrix. The primary blastcell types by connective tissue class are (1) connective

Types of Connective Tissue

As noted, all classes of connective tissue consist ofliving cells surrounded by a matrix. Their major dif-ferences reflect cell type, fiber type, and proportionof the matrix contributed by fibers. Collectively, thesethree factors determine not only major connective tis-

sue classes, but also their subclasses and types. Theconnective tissue classes described in this section areillustrated in Figure 4.8. Additionally, since the matureconnective tissues arise from a common embryonictissue, it seems appropriate to describe this here as

well.

Chapter 4 Tissue: The Living Fabric ] 15

Embryonic Connective Tissue: Mesenchyme

Mesenchyme (meh'-zin-kim), or mesenchymal tissue,is embryonic connective tissue and represents the firstdefinitive tissue formed from the mesoderm germ layer.It arises during the early weeks of development andeventually differentiates (specializes) into all otherconnective tissues. Mesenchyme is composed of star-shaped mesenchymal cells and a fluid ground sub-stance containing fine fibrils (Figure 4.8a).

Mucous connective tissue is a temporary tissue,derived from mesenchyme and similar to it, thatappears in the fetus in very limited amounts. Whar-ton's jelly, which supports the umbilical cord, is thebest representative of this scant embryonic tissue.

and salts for surrounding body tissues. If extracellularfluids accumulate in excess, the affected areas swelland become puffy, a condition called edema.

Areolar connective tissue is soft and pliable andserves as a kind of universal packing material betweenother tissues. The most widely distributed connectivetissue in the body, it separates muscles, allowing themto move freely over one another; wraps small bloodvessels and nerves; surrounds glands; and forms thesubcutaneous tissue, which attaches the skin tounderlying structures. It is present in all mucous

membranes as the lamina propria.

Areolar Connective Tissue. Areolar (uh-rO'-uh-ler)

connective tissue has a semifluid ground substanceformed primarily of hyaluronic acid in which all threefiber types are loosely dispersed (Figure 4.8b). Fibro-blasts, flat, branching cells that appear spindle-shapedin profile, are the predominant cell type of this tissue.Numerous macrophages are also seen, but other cell

types are scattered throughout.Fat cells appear singly or in small clusters. Mast

cells are identified easily by the large, darkly stainedcytoplasmic granules that often obscure their nucleus.Mast cell granules contain (1) heparin (heh'-puh-rin),an anticoagulant that is released into the capillariesand helps prevent blood clotting, and (2) histamine(his'-tuh-mÿn), which is released during inflamma-tory reactions and makes the capillaries leaky. (Theinflammatory process is discussed in Chapter 22.)

Perhaps the most obvious structural feature of thistissue is the loose arrangement of its fibers, whichaccount for only small portions of matrix. The rest ofthe matrix, occupied by fluid ground substance, appearsto be empty space when viewed through the micro-scope; in fact, the Latin term areola means "a smallopen space." Because of its loose and fluid nature,areolar connective tissue provides a reservoir of water

Connective tissue proper has two subclasses: the looseconnective tissues (areolar, adipose, and reticular) anddense connective tissues (dense regular, dense irreg-

ular, and elastic). Except for bone, cartilage, and blood,all mature connective tissues belong to this class.

Adipose (Fat) Tissue. Adipose (a'-dih-p6s) tissue isbasically an areolar connective tissue in which theadipocytes (a'-dih-p6-sits), commonly called fat cells,have accumulated in large numbers. A glistening oildroplet (almost pure neutral fat), which occupies mostof a fat cell's volume, compresses the nucleus and dis-places it to one side; only a thin rim of surroundingcytoplasm is seen. Since the oil-containing region looksempty, and the thin cytoplasm containing the bulgingnucleus looks like a ring with a seal, fat cells havebeen called "signet ring" cells (Figure 4.8c). Matureadipocytes are among the largest cells in the body andare fully specialized cells that are incapable of celldivision. As they take up or release fat, they becomemore plump or more wrinkled looking, respectively.

Compared to other connective tissues, adipose

tissue is very cellular; adipose cells account forapproximately 90% of the tissue mass and are packedclosely together, giving a chicken wire appearance tothe tissue. Very little matrix is seen, except for thatseparating the adipose cells into lobules (cell clusters)and permitting the passage of blood vessels and nervesto the cells. Adipose tissue is richly vascularized,indicating its high metabolic activity, and it has manyfunctions; most importantly, it acts as a storehouse ofnutrients. Without stored fat, we could not live formore than a few days without eating.

Adipose tissue may develop almost anywhereareolar tissue is plentiful, but it usually accumulatesin subcutaneous tissue, where it acts as a shock absorberand as insulation. Since fat is a poor conductor of heat,it helps prevent heat loss from the body. Other sitesof fat accumulation include genetically determined fatdepots such as the abdomen and hips, the bone mar-row, around the kidneys, and behind the eyeballs.

Some nutritionists believe that obesity in later liferesults from overfeeding during infancy and

childhood. Since unused nutrients are converted tofat for storage, excessive food intake may encouragedifferentiation of excessive numbers of fat cells, whichare capable of storing large amounts of fat throughout

Connective Tissue Proper

r

122 Unit 1 Organization of the Body

life. Fat cells may even release chemicals into the bloodthat make you hungry. Obese people have millions ofthese little "gluttons" screaming for food. Notice,however, that these theories are still controversial? •

Reticular Connective Tissue. Reticular connective tis-sue consists of a delicate network of interwoven retic-ular fibers associated with primitive reticular cells,which resemble mesenchymal cells (Figure 4.8d).Although reticular fibers are widely distributed in thebody, reticular tissue is limited to certain sites. It formsthe stroma, or internal supporting framework, of lymphnodes, the spleen, bone marrow, and the liver. Someof the reticular cells are fibroblast-like; others differ-entiate into phagocytic macrophages.

tures combine strength with elasticity. They yield eas-ily to a pulling force (or pressure) and then recoil totheir original length as soon as the tension is released.This dense, fibrous tissue is called elastic connectivetissue to distinguish it from the dense varieties in whichcollagen fibers predominate (Figure 4.8g).

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Dense Regular Connective Tissue. Dense regular con-nective tissue is one variety of the dense connectivetissues, all of which have fibers as their predominantelement. For this reason, the dense connective tissuesare often referred to as dense fibrous connective tissues.

Dense regular connective tissue contains regu-

larly arranged bundles of closely packed collagen fibersrunning in the same direction. This results in a white,flexible tissue with great resistance to pulling forces.It is found in areas where tension is always exerted ina single direction. Crowded between the collagen fibersare rows of fibroblasts that continue to form fibers andscant ground substance. As seen in Figure 4.8e, col-lagen fibers are slightly wavy. This allows the tissueto stretch somewhat, but once the fibers are straight-ened out, there is no further "give" to this tissue.

With its enormous tensile strength, dense regularconnective tissue forms the tendons, cords that attachmuscles to bones, and flat, sheetlike tendons calledaponeuroses (a"-p6-noo-r6'-s6s), which attach mus-

cles to other muscles or to bones. Dense regular con-nective tissue also forms the ligaments that bind bonestogether at joints. Ligaments contain more elastic fibersthan do tendons and thus are slightly more stretchy.

Dense Irregular Connective Tissue. Dense irregularconnective tissue has the same structural elements asthe regular variety, but the collagen fibers are inter-woven and arranged irregularly, that is, they run inmore than one plane (Figure 4.8f). This type of tissueusually forms sheets in body areas where tension isexerted from many different directions. It is found inthe skin as the dermis, and it forms the fibrous cap-sules of some organs (testes, lymph nodes, and liver)and the fibrous coverings of bones, cartilages, andnerves. It is also the basis of most fasciae (fash'-e-ah),

glistening white sheets that surround the muscles.

Elastic Connective Tissue. The vocal cords and someligaments, such as the ligamenta flava (lih-guh-men'-tuh flÿ'-vuh) connecting adjacent vertebrae, are com-posed almost entirely of elastin fibers. These struc-

Hyaline Cartilage. Hyaline (hV-uh-lin) cartilage, orgristle, is very resistant to wear and tear. Although itcontains large amounts of collagen fibers, they are notapparent and the matrix appears amorphous and glassywhite (Figure 4.8h).

The most widely distributed cartilage type in thebody, hyaline cartilage provides firm support with somepliability. It covers the ends of long bones as articu-lar cartilage, providing springy pads that absorbcompression stresses at joints. Hyaline cartilage alsosupports the tip of the nose, connects the ribs to thesternum, and forms most of the larynx and supportingcartilages of the trachea and bronchial tubes. Most of

CartilageCartilage (kar'-tih-lij) has qualities intermediatebetween dense connective tissue and bone; it is toughand yet flexible, providing a resilient rigidity to thestructures it supports (see the box on p. 128). Cartilageis avascular and devoid of nerve fibers. Its groundsubstance consists of large amounts of the GAG chon-droitin sulfate, as well as hyaluronic acid bound toproteins. The ground substance is heavily investedwith firmly bound collagen fibers and, in some cases,reticular or elastic fibers. As a result, the matrix isusually quite firm.

Chondroblasts produce the matrix and are thepredominant cell type in cartilage. Their mature forms,chondrocytes, are found singly or in small groupswithin cavities called lacunae (]uh-koo'-n0). The rigidnature of the cartilage matrix prevents the cells frombecoming widely separated. The surfaces of most car-tilage structures are surrounded by a well-vascular-ized dense irregular connective tissue membrane calleda perichondrium (payr"-ih-kon'-dr0-um) (peri =

around; chondro = cartilage), from which the nutrientsdiffuse through the matrix to the chondrocytes. Thismode of nutrient delivery limits cartilage thickness.

Cartilages heal slowly when injured--a phenom-enon excruciatingly familiar to those experienc-

ing sports injuries. During later life, cartilages tend tocalcify or even ossify (become bony). In such cases,the chondrocytes are poorly nourished and die. •

There are three varieties of cartilage: hyaline car-tilage, fibrocartilage, and elastic cartilage.

Chapter 4 Tissue: The Living Fabric 123

the embryonic skeleton is formed of hyaline cartilagebefore bone is formed. Hyaline cartilage persists dur-ing childhood as the epiphyseal (eh-pih"-fih-sÿ'-ul)plates, actively growing regions near the end of longbones that provide for continued growth in length.

Fibrocartilage. The coarse collagenic fibers of fibro-cartilage are arranged in thin, roughly parallel bun-dles that give the matrix a grainy fibrous appearance.The chrondrocytes are seen squeezed between the col-

lagen bundles (Figure 4.8i). Fibrocartilage looks quitesimilar to dense regular connective tissue. Because itis compressible and resists tension well, fibrocartilageis found where strong support and the ability to with-stand heavy pressure are required. For example, theintervertebral discs, which provide resilient cushionsbetween the bony vertebrae, and the spongy cartilagesof the knee are fibrocartilage structures.

soluble protein molecules that only become visibleduring blood clotting. Still, we must recognize thatblood is quite atypical as connective tissues go. Bloodacts as the transport vehicle for the cardiovascularsystem, carrying nutrients, wastes, respiratory gases,and many other substances throughout the body. Bloodis considered in detail in Chapter 18.

Muscle Tissue

Elastic Cartilage. Histologically, elastic cartilageresembles hyaline cartilage (Figure 4.8j). However,elastic cartilage contains more elastin fibers than othercartilage varieties, which gives this tissue a yellowcolor in the fresh state. It is found where strength andexceptional ability to stretch are needed. Elastic car-tilage forms the "skeletons" of the auditory tubes, theexternal ear, and the epiglottis. The epiglottis is theflap that covers the opening to the respiratory pas-sageway when we swallow, preventing food or fluidsfrom entering the lungs.

Because of its hardness, bone, or osseous (ah'-sÿ-us)

tissue, has an exceptional ability to support and pro-tect softer tissues. Bones of the skeleton also providecavities for fat storage and synthesis of blood cells.The matrix of bone is similar to that of cartilage, butit is harder and more rigid because bone matrix hasfar more collagen fibers and deposits of inorganic cal-cium salts (bone salts).

Osteoblasts produce the organic portion of thematrix; then, bone salts are deposited on and betweenthe fibers. Mature bone cells, or osteocytes, reside inthe lacunae within the matrix they have made (Figure4.8k). Unlike cartilage, the next firmest connective tis-sue, bone is very well supplied by blood vessels, whichinvade the bone tissue. We will consider the structureand metabolism of bone further in Chapter 6.

Blood or vascular tissue is considered a connectivetissue because it has living cells, called formed ele-ments or blood cells, surrounded by a fluid matrixcalled plasma (Figure 4.81). The "fibers" of blood are

Blood

Bone (Osseous Tissue)

Muscle tissues are highly cellular, well-vascularizedtissues that are responsible for most types of bodymovement. Among the most important characteristicsof muscle cells are their elongated shape, whichenhances their shortening (contraction) function, andtheir possession of specialized myof!laments, com-posed of the contractile proteins actin and myosin (mi'-6-sin). There are three types of muscle tissue: skeletal,cardiac, and smooth.

Skeletal muscle is packaged by connective tissuesheets into organs called skeletal muscles that areattached to the bones of the skeleton; these musclesform the flesh of the body. As the muscles contract,they pull on bones or skin, causing gross body move-ments or facial expressions. Skeletal muscle cells arelong, cylindrical cells that contain many nuclei. Theirobvious banded, or striated, appearance reflects thealignment of their myofibrils (Figure 4.9a).

Cardiac muscle makes up the walls of the heart;it is found nowhere else in the body. Its contractionspropel blood through the blood vessels to all parts ofthe body. Like skeletal muscle ceils, cardiac musclecells are striated. However, they differ structurally inthat (1) they are uninucleate cells and (2) they arebranching cells that fit together tightly at unique junc-tions called intercalated (in-ter'-kuh-lÿ"-tid) discs(Figure 4.9b).

Smooth muscle is so named because no externallyvisible striations can be seen. Individual smooth mus-cle cells are spindle-shaped and contain one centrallylocated nucleus (Figure 4.9c). Smooth muscle occursin the walls of hollow organs (digestive and urinarytract organs, uterus, and blood vessels). It generallyacts to propel substances through the organ by alter-nately contracting and relaxing.

Since skeletal muscle contraction is under ourconscious control, skeletal muscle is often called vol-

untary muscle, while the other two types are calledinvoluntary muscle. Skeletal and smooth muscle aredescribed in detail in Chapter 9; cardiac muscle isdiscussed in Chapter 19.