epithelial tissue can exist as sheets of adjoining cells covering or lining the body surface or as glands, secre- tory organs derived from epithelial cells. Most epithelia originate from ectoderm and endoderm, although mesoderm also gives rise to some epi- thelia.
• Ectoderm gives rise to the
epidermis of the skin, lining of the mouth and nasal cavity, cornea, sweat and sebaceous glands, and mammary glands.
• Endoderm gives rise to the lining of the gastrointestinal and respiratory systems and to the glands of the gastrointestinal system.
• Mesoderm gives rise to the uriniferous tubules of the kidney, the lining of the reproductive and circulatory systems, and the lining of the body cavities.
epithelium, an avascular tissue organized into sheets, receives its nutrients from the vascular supply of the adjacent connective tissue. it is composed of
closely packed cells, held together by junctional com- plexes, with little intervening extracellular space and a scant amount of extracellular matrix. the two tissues are separated from each other by the epithelially derived basal lamina.
epithelial tissue functions in:
• Protection of the tissues that it covers or lines,
• Transcellular transport of molecules across epithelial sheets,
• Secretion of various substances by glands,
• Absorption (e.g., intestinal tract and kidney tubules),
• Control of movement of ions and molecules via selective permeability, and
• Detection of sensations (e.g., taste, sight, hearing).
cLASSIfIcATIoN of EPITHELIAL MEMbRANES
the epithelium can be classified based on the number of layers of cells between the basal lamina and the free surface and the morphology of the cells. A single layer of epithelial cells is called simple epithelium, whereas two or more layers constitute a stratified epithelium. the epithelial cells abutting the free sur- face may be squamous (flat), cuboidal, or columnar, giving rise to the various types of epithelia (table 5.1 and Fig. 5.1). two additional types of epithelia are pseudostratified columnar and transitional.
KEy WoRDS
• Epithelium
• Simple epithelium
• Stratified epithelium
• Microvilli
• Junctional complex
• unicellular exocrine glands
• Multicellular exocrine glands
• Endocrine glands
Chapter ep ItH el Ium and glands
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49
Table 5.1 CLASSIFICATION OF EPITHELIA
Type Shape of Surface Cells Sample Locations Functions
Simple
simple squamous Flattened Lining: pulmonary alveoli, loop of henle, parietal layer of Bowman’s capsule, inner and middle ear, blood and lymphatic vessels, pleural and peritoneal cavities
limiting membrane, fluid transport, gaseous exchange, lubrication, reducing friction (aiding movement of viscera), lining membrane simple cuboidal cuboidal Ducts of many glands, covering of
ovary, form kidney tubules secretion, absorption, protection
simple columnar columnar Lining: oviducts, ductuli efferentes of testis, uterus, small bronchi, much of digestive tract, gallbladder, and large ducts of some glands
transportation, absorption, secretion, protection
Pseudostratified All cells rest on basal lamina, but not all reach epithelial surface; surface cells are columnar
Lining: most of trachea, primary bronchi, epididymis and ductus deferens, auditory tube, part of tympanic cavity, nasal cavity, lacrimal sac, male urethra, large excretory ducts
secretion, absorption, lubrication, protection, transportation
Stratified
stratified squamous
(nonkeratinized) Flattened (with nuclei) Lining: mouth, epiglottis, esophagus,
vocal folds, vagina Protection, secretion stratified squamous
(keratinized) Flattened (without
nuclei) epidermis of skin Protection
stratified cuboidal cuboidal Lining: ducts of sweat glands Absorption, secretion stratified columnar columnar conjunctiva of eye, some large
excretory ducts, portions of male urethra
secretion, absorption, protection
transitional Dome-shaped (relaxed),
flattened (distended) Lining: urinary tract from renal calyces
to urethra Protection, distensible
From gartner lP, hiatt Jl: color textbook of histology, 3rd ed. Philadelphia, saunders, 2007, p 86.
Figure 5.1 types of epithelia.
(From Gartner LP, Hiatt JL:
Color Textbook of Histology, 3rd ed. Philadelphia, Saunders, 2007, p 87.)
Simple
Stratified
Squamous nonkeratinized
Keratinized Columnar
Cuboidal Transitional
(relaxed) Transitional
Transitional (distended)
Squamous Cuboidal Columnar Pseudostratified
columnar Pseudostratified
Chapter ep ItH el Ium and glands
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50 PoLARITy AND cELL SuRfAcE SPEcIALIzATIoNS epithelial cells generally possess specific regions—
domains—that impart a distinct polarity to the cell.
these domains are defined by their location at the apex or at the basolateral region of the cell. tight junctions, which are a specialization of the cell mem- brane, encircle the apex of the cell, separating the two domains from each other and imparting a polarity to the cell. each domain possesses specific modifications.
Apical Domain
the apical domain, the region of the epithelial cell facing the free surface, has an abundance of ion chan- nels, carrier proteins, h+-AtPase, aquaporins, glyco- proteins, and hydrolytic enzymes. Additionally, it serves as the region where regulated secretory prod- ucts leave the cell to enter the extracellular space.
surface modifications of the apical domain, such as microvilli and associated glycocalyx, cilia, stereocilia, and flagella, assist in performing many of the cell’s functions.
• Microvilli (Fig. 5.2) are 1- to 2-µm-long membrane-bound, finger-like projections of the apical cell surfaces of simple cuboidal and simple columnar epithelia. they represent the striated and brush borders of light microscopy and, when closely packed, may increase the surface area as much as 20-fold.
• the core of each microvillus is composed of 25 to 30 actin filaments that are held to each other by villin and fimbrin; those at the periphery of the bundle adhere to the plasmalemma via calmodulin and myosin I.
• the plus ends of the actin filaments reach the tip of the microvillus, where they are
embedded in an amorphous substance.
• the cytoplasmic ends of the actin bundle are fixed to the terminal web and composed of intermediate filaments, spectrin, actin, and other cytoskeletal components.
• the extracellular aspect of the microvillar membrane is coated with a glycocalyx whose composition depends on the location and function of the cell.
• long, nonmotile, rigid microvilli, present only in the epididymis and on the sensory hair
cells of the cochlea (inner ear), are called stereocilia. they function in increasing surface to facilitate absorption in the epididymis, whereas in the ear they assist the hair cells in signal generation.
• Cilia (Fig. 5.3) are long (7 to 10 µm in length and 0.2 µm in diameter), finger-like structures projecting from the apical domain of the cell.
they are highly conserved structures that are present in unicellular organisms, in plants, and in all members of the animal kingdom. cilia are contractile structures that allow unicellular organisms to move through water; in higher animals, where an epithelial sheet, such as that lining the respiratory tract, can have 2 billion cilia/cm2, their coordinated action can propel a fluid along an epithelial sheet.
• the core of the cilium, known as the axoneme, is a highly organized longitudinal arrangement of nine doublets surrounding two singlet microtubules, dynein, and associated elastic proteins.
• each doublet comprises a whole microtubule (subunit A), which is composed of 13 protofilaments, and a partial microtubule (subunit B), which has 10 protofilaments and shares 3 protofilaments of the whole microtubule.
• subunit A of each doublet possesses dynein arms located at prescribed intervals of 24 nm along its entire length, resembling the legs of a millipede. the free ends of these arms possess adenosine triphosphate (AtP)–dependent binding sites for subunit B.
• the elastic proteins associated with the axoneme are arranged in the following manner: the two central singlets are
surrounded by a central sheath, and a radial spoke projects toward the central sheath from each subunit A.
• Additionally, subunit A of one doublet is connected to subunit B of the adjacent doublets by a nexin bridge.
• Viewed in three dimensions, the central sheet is a cylinder around the singlets; each nexin bridge and each radial arm is a quadrilateral sheet of elastic material.
Chapter ep ItH el Ium and glands
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51
Figure 5.2 structure of a microvillus. (From Gartner LP, Hiatt JL: Color Textbook of Histology, 3rd ed. Philadelphia, Saunders, 2007, p 94.)
Villin
Actin filaments
Fimbrin
Lateral extension
Actin cortex linked by spectrin Intermediate
filaments Linkage to cell membrane Plasmalemma
Figure 5.3 structure of a cilium with its basal body. (From Gartner LP, Hiatt JL: Color Textbook of Histology, 3rd ed. Philadelphia, Saunders, 2007, p 95.)
Central sheath Radial spokes Nexin Plasmalemma B A
Shared heterodimers Dynein
Central microtubule pair
Peripheral microtubule doublet Plasma
membrane
Microtubule triplet
Plasma membrane
Basal body
Chapter ep ItH el Ium and glands
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52 ciliary Movement, basal body, and flagella
During ciliary movement in the presence of AtP, the dynein arms fleetingly attach to and detach from subunit B of the adjacent doublet climbing up toward the cilium tip. nexin and the radial spokes tend to restrain the climbing action, however, and the cilium bends instead.
• the bending of the cilium (a process that requires AtP) stretches the elastic proteins;
however, when the dynein arms cease their climbing action, the elastic proteins return to their normal length, and the cilium resumes its straight position (an AtP-independent process).
• Alternating these two processes in rapid
progression permits the cilia to propel substances along the epithelial surface.
the axoneme arrangement ceases at the base of the cilium where it is attached to the basal body (Fig.
5.4), a structure composed of nine triplet microtu- bules (subunits A, B, and c) with no central singlets.
the basal body resembles a centriole and develops from procentriole organizers.
• Subunits A and B of the cilium are continuous with subunits A and B of the basal body.
• Subunit C of the basal body does not continue into the cilium.
certain cells, including fibroblasts, neurons, and certain epithelial cells such as those of kidney tu- bules, may possess a single nonmotile cilium whose axoneme has no dynein arms. these are known as primary cilia, and they are believed to function as sensory organs or signal receptors.
Flagella, present only on spermatozoa in humans, are modified cilia that possess an axoneme and a robust elastic protein complex that is designed to propel the spermatozoa along the female reproduc- tive tract. Flagella are described in chapter 21.
basolateral Domain
two regions constitute the basolateral domain of epi- thelia, the lateral and basal plasma membranes. spe-
cialized junctional complexes and signal receptors, ion channels, and na+,K+-AtPase abound in these regions, which also function as sites for constitutive secretion.
Lateral Membrane Specializations
Terminal bars, as viewed by light microscopy, are sites of apparent attachment of epithelial cells that have been shown to be structures that are continuous around the circumference of the entire cell. terminal bars occupy restricted regions of the cell located in the vicinity of its apex. When examined with the electron microscope, the terminal bars were resolved to be junctional complexes that facilitate the adher- ence of contiguous cells to each other (Fig. 5.5).
three types of cell junctions constitute the terminal bar: the apicalmost zonula occludens and just basal to it, the zonula adherens, both of which are con- tinuous, beltlike junctions around the circumference of the cell, and the maculae adherentes (desmo- somes), which are spot junctions rather than con- tinuous around the cell’s perimeter. Additional types of cell junctions are located in regions of the cell other than at terminal bars and do not belong to the junctional complex. these are gap junctions, desmosomes, hemidesmosomes, and actin-linked cell-matrix adhesions. From a functional per spec- tive, there are three types of epithelial cell junc tions:
• Occluding junctions (zonulae occludentes) provide an impermeable, or selectively permeable, barrier that prevents material from traversing an epithelial membrane between adjoining cells (paracellular route).
• Anchoring junctions (zonulae adherentes, maculae adherentes, hemidesmosomes, actin- linked cell-matrix adhesions) permit epithelial cells to adhere to each other or to the basal lamina or both.
• Communicating junctions (gap junctions) permit the transcytoplasmic movement of ions and small molecules between adjacent cells, coupling them electrically and
metabolically.
Chapter ep ItH el Ium and glands
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53
Figure 5.4 structure of a cilium with its basal body. (From Gartner LP, Hiatt JL: Color Textbook of Histology, 3rd ed. Philadelphia, Saunders, 2007, p 95.)
Central sheath Radial spokes Nexin Plasmalemma BA
Shared heterodimers Dynein
Central microtubule pair Peripheral microtubule doublet Plasma
membrane
Microtubule triplet
Plasma membrane
Basal body
Figure 5.5 Junctional complexes. (From Gartner LP, Hiatt JL: Color Textbook of Histology, 3rd ed. Philadelphia, Saunders, 2007, p 97.)
Zonulae occludentes Extend along entire circumference of the cell.
Prevent material from taking paracellular route in passing from the lumen into the connective tissues.
Zonulae adherentes Basal to zonulae occludentes.
E-cadherins bind to each other in the intercellular space and to actin filaments, intracellularly.
Maculae adherentes E-cadherins are associated with the plaque; intermediate filaments form hairpin loops.
Gap junctions Communicating junctions for small molecules and ions to pass between cells.
Couple adjacent cells metabolically and electrically.
Hemidesmosomes Attach epithelial cells to underlying basal lamina.
Strands of transmembrane proteins Extracellular space Adjacent plasma membranes
Extracellular space
Actin filaments Intermediate
filaments
Plaque
Desmogleins
Adjacent plasma membranes Extracellular space
Connexons
Integrins (transmembrane receptor proteins)
Chapter ep ItH el Ium and glands
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54 Zonulae occludentes (tight junctions), the most apical component of the junctional complex, are formed by the fusion of the outer leaflets of adjacent cell membranes (Fig. 5.6). the fusion extends along the entire circumference of epithelial cells and, when viewed with freeze fracture electron microscopy, fusion strands, linear arrangements of transmem- brane proteins, are evident on the P-face, and con- comitant linear grooves are noted on the e-face.
• Depending on the integrity of the tight junction, several instances of fusion may be present, resembling a diverging system of fusion strands, so that some zonulae occludentes are more leaky, having fewer fusion strands, or less leaky, possessing more fusion strands.
• these transmembrane proteins are present in the membranes of both cells, and they contact each other, in a calcium-independent manner, in the extracellular space, obliterating that space. there are three types of transmembrane proteins present in tight junctions:
• Claudins are the most important of the three components; this protein blocks the
extracellular space when two cells contact one another.
• Tricellulin, instead of claudin, is present in regions where three cells contact each other.
• Occludins are the third type of protein; their function is not understood.
• tight junctions are reinforced by the other two components of the junctional complex, zonulae adherentes and maculae adherentes.
• three cytoplasmic scaffolding proteins—tight junction proteins (zonula occludens) Zo1, Zo2, and Zo3—ensure the proper alignment of the claudins, occludins, and tricellulins of cells facing each other, but the mechanism of their actions is not understood.
• Attached to the Zo1 protein is another complex of molecules, afadin-nectin complex, which is believed to meet its counterpart from the adjoining cell and reinforce the adherence of the claudins to each other.
tight junctions limit or prevent paracellular move- ment of material across the epithelial sheet, and pre- vent the migration of integral proteins between the apical and basolateral domains of the cell mem- brane.
Zonulae adherentes, similar to zonulae occlu- dentes, are beltlike junctions that encircle the cell
(see Fig. 5.6). these adhesion junctions rely on cal- cium-dependent transmembrane linker proteins, cadherins, to hold adjacent cells to one another.
the calcium-sensitive moiety of cadherins is extra- cellularly located and is a flexible, hingelike struc- ture.
• in the presence of ca++, the hinge region is unable to flex, and as it extends, it contacts and binds to the extended moiety of the cadherin of the adjacent cell, but the two membranes cannot be more than 15 to 20 nm apart. the intracellular moieties of cadherins are affixed to actin filament bundles that course parallel to the cell membrane.
• the links to the actin filaments occur via catenins, vinculin, and α-actinin. in this fashion, the transmembrane linker cadherins attach the cytoskeleton of one cell to the cytoskeleton of its neighboring cell. As in the zonulae occludentes, an afadin-nectin complex reinforces this adhesion junction.
• Adherens junctions may also be ribbonlike attachments, as in capillary endothelia, where they do not encircle the perimeter of the cell;
here these junctions are known as fasciae adherentes.
other weldlike cell junctions, known as desmo- somes (approximately 400 × 250 × 10 nm), appear to be haphazardly located on the basolateral plasma- lemmae of cells of simple epithelia and on the adja- cent cell membranes of stratified squamous epithelia, such as that of the epidermis (see Fig. 5.6). each half of a desmosome pairs up on the intracellular surfaces of the membranes of adjoining epithelial cells.
• Desmoplakins and pakoglobins function as attachment proteins composing each plaque.
• cytokeratin filaments (intermediate filaments) are thought to reduce the shearing forces on the cell as they penetrate the plaque and turn back on themselves to reenter the cytoplasm.
• the intercellular space between opposing desmosome plaques (approximately 30 nm in width) contains filamentous ca++-dependent transmembrane linker proteins of the cadherin family, desmoglein and desmocollin.
• if ca++ is present, the transmembrane linker proteins of each cell form a bond with each other. When calcium is unavailable, the bond is broken, and the two halves of the desmosome are unable to maintain their firm contact, and the cells become detached from each other.
Lateral Membrane Specializations (cont.)
Chapter ep ItH el Ium and glands
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55
Figure 5.6 Junctional complexes. (From Gartner LP, Hiatt JL: Color Textbook of Histology, 3rd ed. Philadelphia, Saunders, 2007, p 97.)
Zonulae occludentes Extend along entire circumference of the cell.
Prevent material from taking paracellular route in passing from the lumen into the connective tissues.
Zonulae adherentes Basal to zonulae occludentes.
E-cadherins bind to each other in the intercellular space and to actin filaments, intracellularly.
Maculae adherentes E-cadherins are associated with the plaque; intermedi- ate filaments form hairpin loops.
Gap junctions
Communicating junctions for small molecules and ions to pass between cells. Couple adjacent cells metabolically and electrically.
Hemidesmosomes Attach epithelial cells to underlying basal lamina.
Strands of transmembrane proteins Extracellular space
Adjacent plasma membranes Extracellular space
Actin filaments
Intermediate filaments
Plaque
Desmogleins
Adjacent plasma membranes Extracellular space
Connexons
Integrins (transmembrane receptor proteins)
cLINIcAL coNSIDERATIoNS
Pemphigus vulgaris is an autoimmune disease of the skin in which antibodies are produced against desmosomal proteins. Antibodies bind to the desmosomal proteins disturbing cell adhesion. This disturbance leads to blistering of the epidermis causing loss of tissue fluids. If this condition is left untreated, death occurs.
Systemic steroids and immunosuppressants are used to control this disease.
Chapter ep ItH el Ium and glands
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56 Gap JunctionS
the most abundant of the junctional complexes, gap junctions, are present in most epithelial tissues and neurons and in cardiac and smooth muscle cells. gap junctions are sites of intercellular communication because they permit small molecules to pass through the narrow (2 to 4 nm) wide intercellular space.
these gap junctions couple cells chemically and elec- trically to each other, facilitating intercellular com- munications in adult and embryonic tissues.
• six connexins, transmembrane channel–forming proteins, gather to form aqueous channels, known as connexons, in the cell membrane (Fig. 5.7).
• the number of connexons that are present in a gap junction varies from a few to several thousands.
• connexons of one side of the gap junction that are in register with connexons on the opposing side of the gap junction bind to each other forming a hydrophilic communication channel, 1.5 to 2 nm in diameter, through which molecules less than 1 kDa in size can pass between adjoining cells.
• Although the manner in which passage of material through gap junctions is not understood, it is known that an increase in cytosolic ca++ concentrations or a decrease in cytosolic ph closes gap junctions, whereas gap junctions open if the cytoplasmic ph is high, or ca++ concentration is low.
Basal Surface Specializations
Basal lamina, cell membrane plications, and hemides- mosomes are the three principal specializations of the basal surfaces of epithelial cells (see Fig. 5.7).
hemidesmosomes, located on the basal surface of the cell, contribute to anchoring the basal plasma membrane to the underlying basal lamina.
• the basal lamina, a product of the epithelium located at the interface between the epithelium
and the underlying connective tissue, was discussed in chapter 4.
• Basal plasma membrane enfoldings of epithelial cells, especially those concerned with ion transport, increase plasmalemma surface area and compartmentalize the basal cytoplasm into mitochondria-housing segments. the presence of mitochondria coupled with the plicated plasma membrane makes the cell appear striated when viewed by light microscopy.
• Hemidesmosomes appear to be half of a desmosome and are located on the basal plasma membrane. they assist in the attachment of the basal plasmalemma to the basal lamina, facilitating the anchoring of the cell to the underlying connective tissue.
• located on the cytoplasmic side of the plasma membrane, hemidesmosomes display
attachment plaques composed of desmoplakins, plectin, and other minor proteins, into which the terminal ends of keratin intermediate filaments
(tonofilaments) are embedded.
• Transmembrane linker proteins, which are integrins, a family of extracellular matrix receptors, penetrate the plaque on the cytoplasmic side and pass through the cell membrane; their extracellular moiety binds to laminin and type IV collagen present in the basal lamina.
Renewal of Epithelial cells
there is a high replacement rate for cells of an epi- thelium, but this rate is faster in some organs, as in the lining of the gastrointestinal tract, and slower in other regions, as in the epidermis of skin. the renewal rate for a particular organ is generally constant, however. in the event that numerous cells are lost because of infection or injury, mitotic activity is increased to restore the cell population to normal levels.