exocrine glands are rendered unable to release their secretions, resulting in dry mouth and dry eyes. This condition may occur in isolation, or it may be associated with underlying disorders, such as rheumatoid arthritis, lupus, and scleroderma; it is also associated with the development of lymphoma. Sjögren syndrome affects women nine times more frequently than men. Currently, this disease is incurable.
Glands
During the development of certain regions of the body, epithelial cells invade the underlying connec- tive tissue, form the parenchyma (secretory units and ducts) of glands, and surround themselves with a basal lamina that they secrete. the surrounding con- nective tissue, referred to as the stroma, supports the parenchyma of the gland by providing vascular and neural supplies, and its structural elements such as capsules, which envelop the entire gland, and septa, which subdivide the gland into lobes and lobules.
the individual cells of the gland’s secretory units synthesize secretory products and store them in intra- cellular compartments known as secretory granules until the secretion is released. Depending on the gland, these secretory products may be as varied as:
• A hormone, such as insulin from the islets of langerhans;
• An enzyme, such as salivary amylase from the parotid gland, or a bicarbonate-rich fluid from Brunner’s glands of the duodenum; or
• A tear, a watery secretion from the lacrimal gland.
two principal categories of glands exist based on the manner of delivery of their secretory products:
• Exocrine glands possess ducts through which their secretory products are delivered onto an epithelial surface.
• Endocrine glands are ductless; consequently, their secretory product is delivered directly into the bloodstream or lymphatic vessels.
Frequently, cells communicate with each other by releasing cytokines, which are signaling molecules designed to act on specific cells known as target cells.
cells secreting cytokines are known as signaling cells, and their signaling molecules bind to receptors inducing these target cells to perform a specific func- tion (see chapter 2). the effects of cytokines may be classified into three categories, based on the distance between the signaling cell and the target cell:
• Autocrine: the signaling cell and the target cell are the same—the cell stimulates itself.
• Paracrine: the target cell and signaling cell are near each other, so the cytokine can diffuse to the target cell.
• Endocrine: A great enough distance separates the signaling cell from the target cell so that the cytokine has to enter the blood or lymphatic system to reach its destination.
ExocRINE GLANDS
exocrine glands may be classified by the number of cells that compose the gland:
• Unicellular—a single cell is the entire gland (e.g., goblet cell)
• Multicellular—the gland is composed of more than just a single cell (e.g., submandibular gland).
Additional classifications are based on the type of secretion the gland produces:
• Serous—watery (e.g., parotid gland)
• Mucous—viscous (e.g., minor salivary glands of the palate)
• Mixed—serous and mucous (e.g., sublingual gland)
still other classifications are based on the mechanism whereby the cells of the gland release their secretory products (Fig. 5.8):
• Merocrine—only the secretory product is released (as in the parotid gland)
• Apocrine—a small piece of the cell’s cytoplasm accompanies the secretory product (as, perhaps, in the lactating mammary gland)
• Holocrine—the entire cell dies and becomes the secretion (as in the sebaceous gland)
unicellular Exocrine Glands
the goblet cell, located in the epithelial lining of the small and large intestines and of the conducting portion of the respiratory tract, is the principal example of a unicellular exocrine gland (Fig. 5.9). the narrow base of the goblet cell, known as the stem, contacts the basal lamina. the theca, the apical portion of the cell, expanded by the numerous mucinogen-containing secretory granules, abuts the lumen of the intestine or that of the conducting portion of the respiratory sys- tem. Mucinogen, released as a result of noxious chem- ical stimulation or by neurotransmitter substances derived from the parasympathetic nervous system, is hydrated to form the viscous slippery substance known as mucin, which, when mixed with other com- ponents located in the lumen, is known as mucus.
Chapter ep ItH el Ium and glands
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Figure 5.8 Modes of glandular secretion. A, holocrine. B, Merocrine. C, Apocrine. (From Gartner LP, Hiatt JL: Color Textbook of Histology, 3rd ed. Philadelphia, Saunders, 2007, p 105.)
A
Disintegrating cell and its contents (secretion) New cell
B C
Secretion Intact cell
Pinched off portion of cell (secretion)
Figure 5.9 Ultrastructure of a goblet cell. (From Lentz TL: Cell Fine Structure: An Atlas of Drawings of Whole-Cell Structure.
Philadelphia, Saunders, 1971.)
Theca
Stem
Microvilli
Mucinogen droplets
Nucleus
Chapter ep ItH el Ium and glands
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60
cLINIcAL coNSIDERATIoNS
carcinoid tumors originate from DNES cells mostly in the digestive system. Before 2000, this name was applied to benign and malignant forms of DNES growths. Since that year, benign DNES growths are known as neuroendocrine tumors, but if they migrate to other parts of the body, they are called carcinoids. The following terms apply to cancers: neuroendocrine cancers (carcinomas), well differentiated (less aggressive), and poorly differentiated (more aggressive). Many physicians still prefer to use the term carcinoid for benign and well-
differentiated cancers. These DNES tumors and cancers release hormone-like substances as they grow and spread causing face flushing, wheezing, diarrhea, and rapid heartbeat; these symptoms are called carcinoid syndrome.
Additionally, these tumors and cancers can cause symptoms throughout the body.
Multicellular Exocrine Glands
secretory cells that are grouped together and orga- nized to act as secretory organs are multicellular exocrine glands. some multicellular glands display a simple structure (e.g., gastric mucosa and in the uterus), or they may be complex structures that ex- hibit assorted types of secretory units along with com pound branching (e.g., submandibular gland).
Multicellular glands are classified according to the shape and organization of their secretory units and their duct components. they may be classified as:
• Simple, where the ducts do not branch, or
• Compound, where the ducts branch.
the morphology of the secretory units on the com- pound ducts is classified as acinar (alveolar), tubular, or tubuloalveolar (Fig. 5.10).
collagenous connective tissue forms capsules that encase large multicellular glands and form strands called septa that add structural support to the gland by subdividing the gland into lobes and lobules (Fig.
5.11). nerves, blood vessels, and ducts access and exit the glands via the passageways of the septa.
Myoepithelial cells—cells of epithelial origin that possess the ability to contract—are present in major salivary glands and sweat glands, where they share the same basal lamina as the glandular acini. glan- dular acini and small ducts are wrapped by fibrillar strands of cytoplasm that extend from these myoepi- thelial cells. contractions of these cells squeeze the acini and small ducts, assisting them in delivering their secretory product.
ENDocRINE GLANDS
the endocrine glands include the suprarenal (adre- nal), thyroid, pituitary, parathyroid, ovaries, testes, placenta, and pineal glands. Because these glands are ductless, they must release their secretions (hor- mones) into the blood or into the lymphatic vessels so that they can be distributed to the target organs.
certain of these endocrine glands (e.g., the islets of langerhans of the pancreas and the interstitial cells of leydig in the testes) are simply composed of clus- ters of cells embedded within the connective tissue stroma of those organs.
hormones secreted by endocrine glands include proteins, peptides, steroids, modified amino acids, and glycoproteins (see chapter 13). endocrine secre- tory cells are arranged as cords or as follicles. cords, the most common, frequently anastomose around capillaries or blood sinusoids. their hormone, stored within the cell, is released on receiving a neural stim-
ulation or a signaling molecule. endocrine glands of the cord arrangement include the parathyroid and suprarenal glands and the anterior lobe of the pitu- itary gland. endocrine glands of the follicle arrange- ment possess follicular cells (secretory cells) that surround a depression or a cavity, and because they do not store the secretory product, they release it into the cavity where it is stored. on receiving the proper signal, the stored hormone is resorbed from the cavity by the follicular cells and then released into blood capillaries located within the associated con- nective tissue (e.g., the thyroid gland).
other glands of the body are mixed—that is, they contain exocrine and endocrine secretory units. the pancreas, ovaries, and testes each possess both kinds of glands. the exocrine portion empties its secretion into a duct, and the endocrine portion empties its secretion into the bloodstream.
Diffuse Neuroendocrine System
endocrine cells are also scattered among the epithe- lial cells lining the digestive tract and the respiratory system. these particular endocrine cells represent the diffuse neuroendocrine system (DNES). certain paracrine and endocrine hormones are products of these Dnes cells. the Dnes designation has replaced the terms argentaffin cells, argyrophil cells, and APUD cells (see chapter 17).
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Figure 5.10 classification of multicellular exocrine glands. (From Gartner LP, Hiatt JL: Color Textbook of Histology, 3rd ed.
Philadelphia, Saunders, 2007, p 107.) Simple tubular
Secretory portion
Simple branched tubular
Compound tubular Compound acinar Compound tubuloacinar Simple coiled
tubular Simple acinar Simple branched acinar
Duct
Mixed salivary gland
Serous cell
Mucous acinus Main duct
Lobar duct Mucous cell
Serous demilunes Intralobular
duct Intralobular duct
Acinus Intercalated duct
Multicellular gland
Myoepithelial cell Striated duct Striated duct cell Intercalated
duct cell
Intercalated duct
Serous acinus
Lobule
Figure 5.11 salivary gland: its organization, secretory units, and system of ducts. (From Gartner LP, Hiatt JL: Color Textbook of Histology, 3rd ed. Philadelphia, Saunders, 2007, p 108.)
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6 coNNEcTIvE TISSuE
Connective tissue, one of the four basic tissues of the body, is derived mostly from mesoderm, and serves to connect those tissues and different types of con- nective tissues to each other. During
embryonic development, multipoten- tial mesenchymal cells of the primitive embryonic connective tissue known as mesenchyme migrate throughout the body to differentiate into mature cells of specialized connective tissue, such as tissues of cartilage, bone, and blood. Mesenchymal cells also give rise to cells of connective tissues that are not specialized—connective tissue proper, including fibroblasts, adipo- cytes, and mast cells.
the various types of connective tissues have diverse and far-ranging functions:
• cartilage, bone, tendons, ligaments, and capsules of organs provide structural support.
• Blood, lymph, and connective tissue proper act as a medium for exchange by delivering nutrients, waste products, and signaling molecules to and from cells of the body.
• certain cells that travel in the bloodstream leave the blood and enter connective tissue proper to defend and protect the body from potentially deleterious agents.
• Adipose cells store lipids and congregate to form adipose tissue serving as local storage depots of fat.
connective tissue proper is composed of extracel- lular matrix and cells, some of which function in manufacturing the matrix in which they and other cells are embedded. Depending on the function of a particular connective tissue, cells or the extracellular matrix predominates and forms the essential compo- nent. Fibers are more important than their cells, the fibroblasts, for the function of tendons and liga- ments, whereas in loose connective tissue, fibroblasts serve a more important function than do the fibers.
in other instances, such as during immunological responses, the function of the ground substance
supersedes the functions of cells and fibers because the defense of the body depends on the characteris- tics of the ground substance.
Extracellular matrix, the nonliv- ing component of connective tissue, composed of ground substance and fibers, is described in chapter 4, but its salient features are reviewed here.
ground substance is composed of:
• Glycosaminoglycans, either sulfated (e.g., keratan sulfate, heparin, chondroitin sulfates, dermatan sulfate, and heparan sulfate) or nonsulfated (e.g., hyaluronic acid).
• Proteoglycans, which, by being covalently bound to hyaluronic acid, form macromolecules of aggrecan aggregates, producing the gel state of the extracellular matrix.
• some adhesive glycoproteins, such as
fibronectin, which is dispersed throughout the extracellular matrices, and laminin, which is also widespread as it is localized in the basal lamina.
others, such as chondronectin, are located in cartilage, and osteonectin is located in bone.
Fibers, also nonliving substances, are of two types:
• Collagen fibers are of 25 different types depending on the amino acid sequence of their three alpha chains, but only 6 are of major importance for the purpose of this textbook (table 6.1). Most collagen fibers have great tensile strength. glycine, proline, hydroxyproline, and hydroxylysine are the most common amino acids of collagen.
• elastin and microfibrils compose elastic fibers.
the amorphous protein elastin, composed mostly of glycine and proline, is responsible for their elasticity (e.g., elastic fibers may be stretched 150% of their length), whereas microfibrils are responsible for their stability.
elastin also contains a high concentration of lysine, responsible for the formation of desmosine bonds that are elastic and deformable.
KEy WoRDS
• Extracellular matrix
• cells of connective tissue
• Lipid storage by fat cells
• Inflammatory response
• connective tissue types
Chapter Conne Ct Ive tI ssue
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63
cLINIcAL coNSIDERATIoNS
ehlers-Danlos syndrome is a group of rare genetic disorders affecting humans caused by defective collagen synthesis. Symptoms vary widely based on the type of Ehlers-Danlos syndrome the patient has. In each case, the symptoms are ultimately due to faulty or reduced amounts of collagen, the most common of which include unstable joints that are easily dislocated and hypermobile because of overstretchable ligaments that are composed of defective collagen. Some forms affect the skin, and others affect the walls of blood vessels. The severity of the syndromes of this incurable disease can vary from mild to life-threatening.
Marfan syndrome is an autosomal dominant disorder in which the elastic tissue is weakened because of a mutation in the fibrillin gene. This disorder affects the elastic fibers of the cardiovascular, ocular, and skeletal systems.
Individuals with Marfan syndrome are unusually tall, with very long arms, fingers, legs, feet, and toes. Cardiovascular problems are life-threatening and include valvular problems and dilation of the ascending aorta. Ocular disorders include myopia and detached lens. Skeletal disorders include abnormally weak periosteum because of defects in the elastic fibers being unable to provide an appositional force in bone development.
Table 6.1 MAJOR TYPES AND CHARACTERISTICS OF COLLAGEN
Molecular Type Molecular
Formula Synthesizing Cells Function Location in Body
I (fibril-forming); most common of all collagens
[α(i)]2α2(i) Fibroblasts, osteoblasts, odontoblasts, cementoblasts
Resists tension Dermis, tendon, ligaments, capsules of organs, bone, dentin, cementum II (fibril-forming) [α1(ii)]3 chondroblasts Resists pressure hyaline cartilage,
elastic cartilage III (fibril-forming); also
known as reticular fibers; highly glycosylated
[α1(iii)]3 Fibroblasts, reticular cells, smooth muscle cells, hepatocytes
Forms structural framework of spleen, liver, lymph nodes, smooth muscle, adipose tissue
lymphatic system, spleen, liver, cardiovascular system, lung, skin IV (network-forming);
do not display 67-nm periodicity, and alpha chains retain propeptides
[α1(iV)]2α2(iV) epithelial cells, muscle
cells, schwann cells Forms meshwork of lamina densa of basal lamina to provide support and filtration
Basal lamina
V (fibril-forming) [α1(V)]2α2(V) Fibroblasts,
mesenchymal cells Associated with type i collagen, also with placental ground substance
Dermis, tendon, ligaments, capsules of organs, bone, cementum, placenta VII (network-forming);
form dimers that assemble into anchoring fibrils
[α1(Vii)]3 epidermal cells Forms anchoring fibrils that fasten lamina densa to underlying lamina reticularis
Junction of epidermis and dermis
From gartner lP, hiatt Jl: color textbook of histology, 3rd ed. Philadelphia, saunders, 2007, p 76.