Histology_Ross

Histology_Ross. into deep recesses of the adjacent extracellular space (Fig. F17.5.1). Lymphocytes within the deeply recessed extracellular space sample the luminal protein, including antigens, and thus have the opportunity to stimulate development of specific antibodies against the antigens. The destination of these exposed lympho-cytes has not yet been fully determined. Some remain within the local lymphatic tissue, but others may be des-tined for other sites in the body, such as the salivary and mammary glands. Recall that in the salivary glands, cells of the immune system (plasma cells) secrete IgA, which the glandular epithelium then converts into sIgA. Some exper-imental observations suggest that antigen contact neces-sary for the production of IgA by plasma cells occurs in the lymphatic nodules of the intestines. bb M cells lymphocytes absorptive cells lamina propria a FIGURE F17.5.1 • Diagram of M cells in a lymphatic nodule of the intestine. a. This diagram shows the relationship of the M


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Histology_Ross. of the intestines. bb M cells lymphocytes absorptive cells lamina propria a FIGURE F17.5.1 • Diagram of M cells in a lymphatic nodule of the intestine. a. This diagram shows the relationship of the M cells (microfold cells) and absorptive cells to the lymphatic nodule. The M cell is an epithelial cell that displays microfolds rather than microvilli on its apical surface. It has deep recesses within which lymphocytes come close to the lumen of the small intestine. M cells have MHC II molecules on their surface and are therefore considered antigen-presenting cells. Antigen from the intestinal lumen is presented to T lymphocytes residing within the recesses of the M cell. (Based on Owen RL, Nemanic PC, eds. Scanning Electron Microscopy. Vol II. O’Hare, IL: AMF, 1978.) b. Scanning electron micrograph of a Peyer’s patch lymphatic nodule bulging into the lumen of the ileum. Note that the area of the follicle covered by M cells is surrounded by the fingerlike projections of the intestinal


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Histology_Ross. micrograph of a Peyer’s patch lymphatic nodule bulging into the lumen of the ileum. Note that the area of the follicle covered by M cells is surrounded by the fingerlike projections of the intestinal villi. The surface of the M cells has a smooth appearance. The absence of absorptive cells and mucus-producing goblet cells in the area covered by M cells facilitates immunoreactions to antigens. 80. (Reprinted with permission from Owen RL, Johns AL. Epithelial cell specialization within human Peyer’s patches: an ultrastructural study of intestinal lymphoid follicles. Gastroenterology 1974;66:189–203.) tissue samples the antigens in the epithelial intercellular spaces. Lymphocytes and other antigen-presenting cells process the antigens and migrate to lymphatic nodules in the lamina propria where they undergo activation (see page 444), leading to antibody secretion by newly differentiated plasma cells.


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Histology_Ross. Mucosal surface is protected by immunoglobulinmediated responses.


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Histology_Ross. Mucosal surface of the gut tube is constantly challenged by the presence of ingested microorganisms (i.e., viruses, bacteria, parasites) and toxins, which after compromising the epithelial barrier may cause infections or diseases. An example of a specific defense mechanism is the immunoglobulinmediated response using IgA, IgM and IgE antibodies. Most of the plasma cells in the lamina propria of the intestine secrete dimeric dIgA antibodies rather than the more common IgG; other plasma cells produce pentameric IgM and IgE (see page 554). Dimeric dIgA is composed of two monomeric IgA subunits and a polypeptide J chain (see Fig. 16.28). Secreted dIgA molecules bind to the polymeric immunoglobulin receptor (pIgR) located at the basal domain of the epithelial cells (Fig. 17.24). The pIgR receptor is a transmembrane glycoprotein (75-kilodalton) synthesized by enterocytes and expressed on the basal plasma membrane. The pIgR–dIgA complex is then endocytosed and transported across the


Histology_Ross

Histology_Ross. receptor is a transmembrane glycoprotein (75-kilodalton) synthesized by enterocytes and expressed on the basal plasma membrane. The pIgR–dIgA complex is then endocytosed and transported across the epithelium to the apical surface of the enterocyte (this type of transport refers as transcytosis). After the pIgR–dIgA complex reach the apical surface, pIgR is proteolytically cleaved and the extracellular part of the receptor that is bound to dIgA is released into the gut lumen (see Fig. 17.24). This cleaved extracellular binding domain of the receptor is known as the secretory component (SC); secreted dIgA in association with the SC is known as secretory IgA (sIgA). The release of sIgA immunoglobulins is critical for proper immunological surveillance by the mucosal immune system. In the lumen, sIgA binds to antigens, toxins, and microorganisms. Secretory IgA prevents the attachment and invasion of viruses and bacteria into the mucosa by either inhibiting their motility, causing microbial


Histology_Ross

Histology_Ross. sIgA binds to antigens, toxins, and microorganisms. Secretory IgA prevents the attachment and invasion of viruses and bacteria into the mucosa by either inhibiting their motility, causing microbial aggregation or masking pathogen adhesion sites on the epithelial surface. For example, sIgA binds to a glycoprotein on the viral envelope of HIV virus preventing its attachment, internalization, and subsequent replication in the cell.


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Histology_Ross. Secretory IgA is the principal molecule of mucosal immunity. However, IgM molecules utilize similar pathway of the receptor-mediated transcytosis to reach the mucosal surface. Some of the IgE binds to the plasma membranes of mast cells in the lamina propria (see page 182), selectively sensitizing them to specific antigens derived from the lumen. A distinguishing characteristic of the duodenum is the presence of submucosal glands. The submucosa consists of a dense connective tissue and localized sites that contain aggregates of adipose cells. A conspicuous feature in the duodenum is the presence of submucosal glands, also called Brunner’s glands. The branched, tubular submucosal glands of the duodenum have secretory cells with characteristics of both zymogensecreting and mucus-secreting cells (Fig. 17.25).


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Histology_Ross. The branched, tubular submucosal glands of the duodenum have secretory cells with characteristics of both zymogensecreting and mucus-secreting cells (Fig. 17.25). The secretion of these glands has a pH of 8.1 to 9.3 and contains neutral and alkaline glycoproteins and bicarbonate ions. This highly alkaline secretion probably serves to protect the proximal small intestine by neutralizing the acid-containing chyme delivered to it. It also brings the intestinal contents close to the optimal pH for the pancreatic enzymes that are also delivered to the duodenum.


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Histology_Ross. FIGURE 17.24 • Diagram of immunoglobulin A (IgA) secretion and transport. A monomeric form of immunoglobulin A (IgA) is synthesized by the plasma cell. IgAs are secreted into the lamina propria in a dimeric form as dIgA. Dimeric dIgA is composed of two monomeric IgA subunits and a polypeptide J chain also produced by the plasma cell. In the lamina propria dIgA binds to the polymeric immunoglobulin receptor (pIgR) on the basal cell membrane of the enterocyte. The pIgR-IgA complex enters the cell by endocytosis and is carried out within the endocytotic vesicles to the eary endosomal compartment and then to the apical surface (a process called transcytosis). Endocytic vesicles fuse with the apical plasma membrane, the pIgR is proteolytically cleaved and dIgA is released with the extracellular portion of the pIgR receptor. This portion of the pIgR remains with the IgA dimer and become the secretory component (SC) of the secretory IgA (sIgA).


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Histology_Ross. FIGURE 17.25 • Photomicrograph of Brunner’s glands in the duodenum. This photomicrograph shows part of the duodenal wall in an H&E preparation. A distinctive feature of the duodenum is the presence of Brunner’s glands. The dashed line marks the boundary between the villi and the typical intestinal glands (crypts of Lieberkn). The latter extend to the muscularis mucosae. Under the mucosa is the submucosa, which contains Brunner’s glands. These are branched tubular glands whose secretory component consists of columnar cells. The duct of the Brunner’s gland opens into the lumen of the intestinal gland (arrow). 120.


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Histology_Ross. The muscularis externa consists of an inner layer of circularly arranged smooth muscle cells and an outer layer of longitudinally arranged smooth muscle cells. The main components of the myenteric plexus (Auerbach’s plexus) are located between these two muscle layers (Fig. 17.26). Two kinds of muscular contraction occur in the small intestine. Local contractions displace intestinal contents both proximally and distally; this type of contraction is called segmentation. These contractions primarily involve the circular muscle layer. They serve to circulate the chyme locally, mixing it with digestive juices and moving it into contact with the mucosa for absorption. Peristalsis, the second type of contraction, involves coordinated action of both circular and longitudinal muscle layers and moves the intestinal contents distally.


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Histology_Ross. The serosa of the parts of the small intestine that are located intraperitoneally in the abdominal cavity corresponds to the general description at the beginning of the chapter. Epithelial Cell Renewal in the Small Intestine All of the mature cells of the intestinal epithelium are derived from a single stem cell population.


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Histology_Ross. Epithelial Cell Renewal in the Small Intestine All of the mature cells of the intestinal epithelium are derived from a single stem cell population. Stem cells are located in the base of the intestinal gland. This intestinal stem cell niche (zone of cell replication) is restricted to the lower one half of the gland and contains highly proliferative intermediate cells (as previously explained) and cells at various stages of differentiation. A cell destined to become a goblet cell or absorptive cell usually undergoes several additional divisions after it leaves the pool of stem cells. The epithelial cells migrate upward in the intestinal gland onto the villus where they undergo apoptosis and slough off into the lumen. Autoradiographic studies have shown that the renewal time for absorptive and goblet cells in the human small intestine is 4 to 6 days.


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Histology_Ross. Enteroendocrine cells and Paneth cells are also derived from the stem cells at the base of the intestinal gland. Enteroendocrine cells appear to divide only once before differentiating. They migrate with the absorptive and goblet cells but at a slower rate. Paneth cells migrate downward and reside at the bottom of the intestinal gland. They live for approximately 4 weeks and are then replaced by differentiation of a nearby “committed” cell in the intestinal gland. Cells that are recognizable as Paneth cells no longer divide. As mentioned in the chapter on epithelial tissue (page 150) expression of the transcription factor Math1 appears to determine the fate of differentiating cells in the intestinal stem cell niche. The cells committed to the secretory lineage (i.e., they will differentiate into goblet, enteroendocrine, and Paneth cells) have increased expression of Math1. Inhibition of Math1 expression characterizes the default developmental pathway into absorptive intestinal cells


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Histology_Ross. into goblet, enteroendocrine, and Paneth cells) have increased expression of Math1. Inhibition of Math1 expression characterizes the default developmental pathway into absorptive intestinal cells (enterocytes).


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Histology_Ross. The large intestine comprises the cecum with its projecting vermiform appendix, the colon, the rectum, and the anal canal. The colon is further subdivided on the basis of its anatomic location into ascending colon, transverse colon, descending colon, and sigmoid colon. The four layers characteristic of the alimentary canal are present throughout. However, several distinctive features exist at the gross level (Fig. 17.27):  Teniae coli that represent three narrowed, thickened, equally spaced bands of the outer longitudinal layer of the muscularis externa. They are primarily visible in the cecum


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Histology_Ross. FIGURE 17.26 • Electron micrograph of the myenteric (Auerbach’s) plexus. The plexus is located between the two smooth muscle (SM) layers of the muscularis externa. It consists of nerve cell bodies (CB) and an extensive network of nerve fibers (N). A satellite cell (SC), also referred to as an enteric glial cell, is seen in proximity to the neuron cell bodies. These cells have structural and chemical features in common with glial cells of the CNS. BV, blood vessel. 3,800.


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Histology_Ross. FIGURE 17.27 • Photograph of the large intestine. This photograph shows the outer (serosal) surface (left) and internal (mucosal) surface (right) of the transverse colon. On the outer surface, note the characteristic features of the large intestine: a distinctive smooth muscle band representing one of the three teniae coli (TC); haustra coli (HC), the sacculations of the colon located between the teniae; and omental appendices (OA), small peritoneal projections filled with fat. The smooth mucosal surface shows semilunar folds (arrows) formed in response to contractions of the muscularis externa. Compare the mucosal surface as shown here with that of the small intestine (Fig. 17.17).


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Histology_Ross. and colon and they are absent in the rectum, anal canal, and vermiform appendix. Haustra coli that are visible sacculations between the teniae coli on the external surface of the cecum and colon.  Omental appendices that are small fatty projections of the serosa, observed on the outer surface of the colon. The mucosa of the large intestine has a “smooth” surface; neither plicae circulares nor villi are present. It contains numerous straight tubular intestinal glands (crypts of Lieberkn) that extend through the full thickness of the mucosa (Fig. 17.28a). The glands consist of simple columnar epithelium, as does the intestinal surface from which they invaginate. Examination of the luminal surface of the large intestine at the microscopic level reveals the openings of the glands, which are arranged in an orderly pattern (Fig. 17.28b). The principal functions of the large intestine are reabsorption of electrolytes and water and elimination of undigested food and waste.


Histology_Ross

Histology_Ross. The principal functions of the large intestine are reabsorption of electrolytes and water and elimination of undigested food and waste. The primary function of the columnar absorptive cells is reabsorption of water and electrolytes. The morphology of absorptive cells is essentially identical to that of the enterocytes of the small intestine. Reabsorption is accomplished by the same Na/K-activated ATPase-driven transport system as described for the small intestine. Elimination of semisolid to solid waste materials is facilitated by the large amounts of mucus secreted by the numerous goblet cells of the intestinal glands. Goblet cells are more numerous in the large intestine than in the small intestine (see Fig. 17.28a and Plate 62, page 622). They produce mucin that is secreted continuously to lubricate the bowel, facilitating the passage of the increasingly solid contents.


Histology_Ross

Histology_Ross. The mucosal epithelium of the large intestine contains the same cell types as the small intestine except Paneth cells, which are normally absent in humans. Columnar absorptive cells predominate (4:1) over goblet cells in most of the colon, although this is not always apparent in histologic sections (see Fig. 17.28a). The ratio decreases, however, approaching 1:1, near the rectum, where the number of goblet cells increases. Although the absorptive cells secrete glycocalyx at a rapid rate (turnover time is 16 to 24 hours in humans), this layer has not been shown to contain digestive enzymes in the colon. As in the small intestine, however, Na/K-ATPase is abundant and is localized in the lateral plasma membranes of the absorptive cells. The intercellular space is often dilated, indicating active transport of fluid.


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Histology_Ross. FIGURE 17.28 • Mucosa of the large intestine. a. This photomicrograph of an H&E preparation shows the mucosa and part of the submucosa. The surface epithelium is continuous with the straight, unbranched, tubular intestinal glands (crypts of Lieberkn). The openings of the glands at the intestinal surface are identified (arrows). The epithelial cells consist principally of absorptive and goblet cells. As the absorptive cells are followed into the glands, they become fewer in number, whereas the goblet cells increase in number. The highly cellular lamina propria contains numerous lymphocytes and other cells of the immune system. b. Scanning electron micrograph of the human mucosal surface of the large intestine. The surface is divided into territories by clefts (arrows). Each territory contains 25 to 100 gland openings. 140. (Reprinted with permission from Fenoglio CM, Richart RM, Kaye GI. Comparative electron-microscopic features of normal, hyperplastic, and adenomatous human colonic


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Histology_Ross. 25 to 100 gland openings. 140. (Reprinted with permission from Fenoglio CM, Richart RM, Kaye GI. Comparative electron-microscopic features of normal, hyperplastic, and adenomatous human colonic epithelium. II. Variations in surface architecture found by scanning electron microscopy. Gastroenterology 1975;69:100–109.)


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Histology_Ross. Goblet cells may mature deep in the intestinal gland, even in the replicative zone (Fig. 17.29). They secrete mucus continuously, even to the point where they reach the luminal surface. Here, at the surface, the secretion rate exceeds the synthesis rate, and “exhausted” goblet cells appear in the epithelium. These cells are tall and thin and have a small number of mucinogen granules in the central apical cytoplasm. An infrequently observed cell type, the caveolated “tuft” cell, has also been described in the colonic epithelium; however, this cell may be a form of exhausted goblet cell. Epithelial Cell Renewal in the Large Intestine All intestinal epithelial cells in the large intestine derive from a single stem cell population.


Histology_Ross

Histology_Ross. Epithelial Cell Renewal in the Large Intestine All intestinal epithelial cells in the large intestine derive from a single stem cell population. As in the small intestine, all of the mucosal epithelial cells of the large intestine arise from stem cells located at the bottom of the intestinal gland. The lower third of the gland constitutes the intestinal stem cell niche, where newly generated cells undergo two to three more divisions as they begin their migration up to the luminal surface, where they are shed about 5 days later. The intermediate cell types found in the lower third of the intestinal gland are identical to those seen in the small intestine.


Histology_Ross

Histology_Ross. The turnover times of the epithelial cells of the large intestine are similar to those of the small intestine (i.e., about 6 days for absorptive cells and goblet cells and up to 4 weeks for enteroendocrine cells). Senile epithelial cells that reach the mucosal surface undergo apoptosis and are shed into the lumen at the midpoint between two adjacent intestinal glands.


Histology_Ross

Histology_Ross. Although the lamina propria of the large intestine contains the same basic components as the rest of the digestive tract, it demonstrates some additional structural features and greater development of some others. These include the following:  Collagen table, which represents a thick layer of collagen and proteoglycans that lies between the basal lamina of the epithelium and that of the fenestrated absorptive venous capillaries. This layer is as much as 5 m thick in the normal human colon and can be up to three times that thickness in human hyperplastic colonic polyps. The collagen table participates in regulation of water and electrolyte transport from the intercellular compartment of the epithelium to the vascular compartment.


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Histology_Ross.  Pericryptal fbroblast sheath, which constitutes a well-developed fibroblast population of regularly replicating cells. They divide immediately beneath the base of the intestinal gland, adjacent to the stem cells found in the epithelium (in both the large and small intestines). The fibroblasts then differentiate and migrate upward in parallel and synchrony with the epithelial cells. Although the ultimate fate of the pericryptal fibroblast is unknown, most FIGURE 17.29 • Electron micrograph of dividing goblet cells.


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Histology_Ross. FIGURE 17.29 • Electron micrograph of dividing goblet cells. This electron micrograph demonstrates that certain cells of the intestine continue to divide even after they have differentiated. Here, two goblet cells (GC) are shown in division. Typically, the dividing cells move away from the basal lamina toward the lumen. One of the goblet cells shows mucinogen granules (M) in its apical cytoplasm. The chromosomes (C) of the dividing cells are not surrounded by a nuclear membrane. Compare with the nuclei (N) of the nondividing intestinal epithelial cells. The lumen of the gland (L) is on the right. CT, connective tissue; E, eosinophil. 5,000.


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Histology_Ross. of these cells, after they reach the level of the luminal surface, take on the morphologic and histochemical characteristics of macrophages. Some evidence suggests that the macrophages of the core of the lamina propria in the large intestine may arise as a terminal differentiation of the pericryptal fibroblasts:  GALT, which is continuous with that of the terminal ileum. In the large intestine, GALT is more extensively developed; large lymphatic nodules distort the regular spacing of the intestinal glands and extend into the submucosa. The extensive development of the immune system in the colon probably reflects the large number and variety of microorganisms and noxious end products of metabolism normally present in the lumen.


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Histology_Ross.  Lymphatic vessels. In general, there are no lymphatic vessels in the core of lamina propria between the intestinal glands and none that extend toward the luminal surface of the large intestine. Only recently, using new very selective markers for lymphatic epithelium, researchers have found occasional small lymphatic vessels at the bases of the intestinal glands. These lymphatic vessels drain into the lymphatic network within the muscularis mucosae. The next step in lymph drainage occurs in the lymphatic plexuses in the submucosa and muscularis externa before lymph leaves the wall of the large intestine and drains into the regional lymph nodes. To understand the clinical significance of the lymphatic pattern in the large intestine, see Folder 17.6.


Histology_Ross

Histology_Ross. As noted, in the cecum and colon (the ascending, transverse, descending, and sigmoid colons), the outer layer of the muscularis externa is, in part, condensed into prominent longitudinal bands of muscle, called teniae coli, which may be seen at the gross level (see Fig. 17.27). Between these bands, the longitudinal layer forms an extremely thin sheet. In the rectum, anal canal, and vermiform appendix, the outer longitudinal layer of smooth muscle is a uniformly thick layer, as in the small intestine. Bundles of muscle from the teniae coli penetrate the inner, circular layer of muscle at irregular intervals along the length and circumference of the colon. These apparent discontinuities in the muscularis externa allow segments of the colon to contract independently, leading to the formation of haustra colli, sacculations of the colon wall.


Histology_Ross

Histology_Ross. The muscularis externa of the large intestine produces two major types of contraction: segmentation and peristalsis. Segmentation is local and does not result in the propulsion of contents. Peristalsis results in the distal mass movement of the colonic contents. Mass peristaltic movements occur infrequently; in healthy persons, they usually occur once a day to empty the distal colon. The submucosa of the large intestine corresponds to the general description already given. Where the large intestine is directly in contact with other structures (as on much of its posterior surface), its outer layer is an adventitia; elsewhere, the outer layer is a typical serosa.


Histology_Ross

Histology_Ross. The cecum forms a blind pouch just distal to the ileocecal valve; the appendix is a thin, fingerlike extension of this pouch. The histology of the cecum closely resembles that of the rest of the colon; the appendix differs from it in having a uniform layer of longitudinal muscle in the muscularis externa (Fig. 17.30 and Plate 63, page 624). The most conspicuous feature of the appendix is the large number of lymphatic nodules that extend into the submucosa. In many adults, the normal structure of the appendix is lost, and the appendage is filled with fibrous scar tissue. Blockage of the opening between the appendix and the cecum, usually due to scarring, buildup of thick mucus, or stool that enters the lumen of the appendix from the cecum, may cause appendicitis


Histology_Ross

Histology_Ross. FIGURE 17.30 • Photomicrograph of a cross section through the vermiform appendix. The vermiform appendix displays the same four layers as those of the large intestine except that its diameter is smaller. Typically, lymphatic nodules are seen within the entire mucosa and usually extend into the submucosa. Note the distinct germinal centers within the lymphatic nodules. The muscularis externa is composed of a relatively thick circular layer and a much thinner outer longitudinal layer. The appendix is covered by a serosa that is continuous with the mesentery of the appendix (lower right). 10.  FOLDER 17.6 Clinical Correlation: The Pattern of Lymph Vessel Distribution and Diseases of the Large Intestine


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Histology_Ross. The absence of lymphatic drainage from the lamina pro-pria of the large intestine was initially discovered using stan-dard techniques of analyzing tissue samples obtained from biopsies with the light and electron microscopy. Recently, specific monoclonal antibodies D2-40 that react with a 40-kilodalton O-linked sialoglycoprotein expressed on the lym-phatic endothelium became available to study distribution of lymphatic vessels. This examination becomes important to monitor the morphologic integrity of the lamina propria in the large intestine that is associated with the absence of lymphatic vessels. For instance in a chronic superficial in-flammation of the colon and rectum known as ulcerative colitis, the formation of granulation tissue is associated with proliferation of blood and lymphatic vessels within the lamina propria. The lymphangiogenesis (the growth of lym-phatic vessels) in this disease is linked to the expression of vascular endothelial growth factors (VEGFs). The


Histology_Ross

Histology_Ross. lymphatic vessels within the lamina propria. The lymphangiogenesis (the growth of lym-phatic vessels) in this disease is linked to the expression of vascular endothelial growth factors (VEGFs). The progress of treatment in ulcerative colitis can be monitored by biop-sies, which show the disappearance of lymphatic vessels from the lamina propria. On the other hand, the increased number of lymphatic vessels in the lamina propria signals the presence of active inflammation. Discovery of the distribution of lymphatic vessels in the large intestine established the basis for the current man-agement of adenomas (adenomatous polyps of the large intestine). These are intraepithelial neoplasms located on the mass of tissue that protrudes into the lumen of the large intestine (Fig F17.6.1). The absence of lymphatic vessels from the lamina propria was important in under-standing the slow rate of metastasis from certain colon cancers. Cancers that develop in large adenomatous colonic polyps may


Histology_Ross

Histology_Ross. of lymphatic vessels from the lamina propria was important in under-standing the slow rate of metastasis from certain colon cancers. Cancers that develop in large adenomatous colonic polyps may grow extensively within the epithelium and lamina propria before they even have access to the lymphatic vessels at the level of the muscularis mucosae. Because almost 50% of all adenomatous polyps of the large intestine are located in the rectum and sigmoid colon, they can be detected with rectosigmoidoscopy. As long as the lesion is confined to the mucosa, the endo-scopic removal of such polyps is regarded as an adequate clinical treatment. However, the final therapeutic decision must be confirmed after careful microscopic examination of the resected specimen. aa b FIGURE F17.6.1 • Adenomatous polyp of the large intestine. a. This image shows a macroscopic view of the polyp (about 2 cm in diameter) that was surgically removed from the large intestine during endoscopic colonoscopy. It has


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Histology_Ross. polyp of the large intestine. a. This image shows a macroscopic view of the polyp (about 2 cm in diameter) that was surgically removed from the large intestine during endoscopic colonoscopy. It has characteristic bosselated surface (with rounded swellings) and a stalk by which attaches to the wall of the colon. b. This photomicrograph was obtained from the center of the polyp. At the tip of the polyp, note a repetitive pattern of tubules covered with the neoplastic epithelial cells that have migrated and accumulated on the intestinal surface. Stalk in the center is continuous with the submucosa of the colon. Note also the presence of a normal simple columnar epithelium of the large intestine at the base of the stalk. (Reproduced from Mitros FA, Rubin E. The Gastrointestinal Tract. In: Rubin R, Strayer DS (eds): Rubin’s Pathology: Clinicopathologic Foundations of Medicine, 5th ed. Baltimore: Lippincott Williams & Wilkins, 2008.) skin internal anal sphincter lymphatic nodules anal


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Histology_Ross. Rubin R, Strayer DS (eds): Rubin’s Pathology: Clinicopathologic Foundations of Medicine, 5th ed. Baltimore: Lippincott Williams & Wilkins, 2008.) skin internal anal sphincter lymphatic nodules anal columns external anal sphincter transverse rectal folds ampulla of rectum mucosal folds rectum anal canal perianal skin colorectal zone anal transitional zone squamous zone anal sinuses


Histology_Ross

Histology_Ross. FIGURE 17.31 • Drawing of the rectum and anal canal. The rectum and anal canal are the terminal portions of the large intestine. They are lined by the colorectal mucosa that possesses a simple columnar epithelium containing mostly goblet cells and numerous anal glands. In the anal canal the simple columnar epithelium undergoes transition into a stratified columnar (or cuboidal) epithelium and then to a stratified squamous epithelium. This transition occurs in the area referred to as the anal transitional zone, which occupies the middle third of the anal canal between the colorectal zone and the squamous zone of the perianal skin. (inﬂammation of the appendix). The appendix is also a common site for carcinoid, a type of tumor originating from enteroendocrine cells of lining mucosa (see Folder 17.3).


Histology_Ross

Histology_Ross. (inﬂammation of the appendix). The appendix is also a common site for carcinoid, a type of tumor originating from enteroendocrine cells of lining mucosa (see Folder 17.3). The rectum is the dilated distal portion of the alimentary canal. Its upper part is distinguished from the rest of the large intestine by the presence of folds called transverse rectal folds. The mucosa of the rectum is similar to that of the rest of the distal colon, having straight, tubular intestinal glands with many goblet cells.


Histology_Ross

Histology_Ross. The most distal portion of the alimentary canal is the anal canal. It has an average length of 4 cm and extends from the upper aspect of the pelvic diaphragm to the anus (Fig. 17.31). The upper part of the anal canal has longitudinal folds called anal columns. Depressions between the anal columns are called anal sinuses. The anal canal is divided into three zones according to the character of the epithelial lining:  Colorectal zone, which is found in the upper third of the anal canal and contains simple columnar epithelium with characteristics identical to that in the rectum.


Histology_Ross

Histology_Ross.  Anal transitional zone (ATZ), which occupies the middle third of the anal canal. It represents a transition between the simple columnar epithelium of the rectal mucosa and the stratified squamous epithelium of the perianal skin. The ATZ possesses a stratified columnar epithelium interposed between the simple columnar epithelium and the stratified squamous epithelium, which extends to the cutaneous zone of the anal canal (Fig. 17.32 and Plate 64, page 626).  Squamous zone, which is found in the lower third of the anal canal. This zone is lined with stratified squamous epithelium that is continuous with that of the perineal skin. In the anal canal, anal glands extend into the submucosa and even into the muscularis externa. These branched, straight tubular glands secrete mucus onto the anal surface through ducts lined with stratified columnar epithelium.


Histology_Ross

Histology_Ross. Sometimes the anal glands are surrounded by diffuse lymphatic tissue. They often lead to the formation of pathologic fistulas (a false opening between the anal canal and the perianal skin). Large apocrine glands, the circumanal glands, are found in the skin surrounding the anal orifice. In some animals, the


Histology_Ross

Histology_Ross. FIGURE 17.32 • Photomicrographs of the anal canal. a. This photomicrograph shows a longitudinal section through the wall of the anal canal. Note the three zones in the anal canal: the squamous zone (SQZ) containing stratified squamous epithelium; the anal transitional zone (ATZ) containing stratified squamous, stratified cuboidal, or columnar epithelium and simple columnar epithelium of the rectal mucosa; and the colorectal zone (CRZ) containing only simple columnar epithelium like the rest of the colon. Note the anal valve that demarcates the transition between the ATZ and SQZ. The internal anal sphincter is derived from the thickening of the circular layer of the muscularis externa. A small portion of the external anal sphincter is seen subcutaneously. 10. b. This high magnification of the area indicated by the rectangle in a shows the area of the anal transitional zone. Note the abrupt transition between stratified cuboidal and simple columnar epithelium. The simple columnar


Histology_Ross

Histology_Ross. of the area indicated by the rectangle in a shows the area of the anal transitional zone. Note the abrupt transition between stratified cuboidal and simple columnar epithelium. The simple columnar epithelium of anal glands extends into the submucosa. These straight, mucus-secreting tubular glands are surrounded by diffuse lymphatic tissue. 200.


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Histology_Ross. secretion of these glands acts as a sex attractant. Hair follicles sion). There are no teniae coli at the level of the rectum; the and sebaceous glands are also found at this site. longitudinal layer of the muscularis externa forms a uniform The submucosa of the anal columns contains the terminal sheet. The muscularis mucosae disappears at about the level ramifications of the superior rectal artery and the rectal ve-of the ATZ, where the circular layer of the muscularis ex-nous plexus. Enlargements of these submucosal veins consti-terna thickens to form the internal anal sphincter. The extute internal hemorrhoids, which are related to elevated ternal anal sphincter is formed by striated muscle of the venous pressure in the portal circulation (portal hyperten-pelvic floor. This page intentionally left blank.


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Histology_Ross. The esophagus is a muscular tube that conveys food and other substances from the pharynx to the stomach. The mucosa that lines the length of the esophagus has a nonkeratinized stratified squamous epithelium. The underlying lamina propria is similar to the lamina propria throughout the alimentary tract; diffuse lymphatic tissue is scattered throughout, and lymphatic nodules are present. The deep layer of the mucosa, the muscularis mucosae, is composed of longitudinally organized bundles of smooth muscle fibers. The submucosa consists of dense irregular connective tissue that contains the larger blood and lymphatic vessels, nerve fibers, and ganglion cells. The nerve fibers and ganglion cells make up the submucosal plexus (Meissner’s plexus). The muscularis externa consists of two muscle layers, an inner circular layer and an outer longitudinal layer. The upper one third of muscularis externa consists of striated muscle, a continuation of the muscle of the pharynx. Striated muscle and


Histology_Ross

Histology_Ross. an inner circular layer and an outer longitudinal layer. The upper one third of muscularis externa consists of striated muscle, a continuation of the muscle of the pharynx. Striated muscle and smooth muscle bundles are mixed and interwoven in the muscularis externa of the middle third of the esophagus. The muscularis externa of the distal one third consists only of smooth muscle, as in the rest of the digestive tract.


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Histology_Ross. Esophagus, monkey, H&E ×60; inset ×400. A cross section of the wall of the esophagus is shown here. The mucosa (Muc) consists of stratified squamous epithelium (Ep), a lamina propria (LP), and muscularis mucosae (MM ). The boundary between the epithelium and lamina propria is distinct, although uneven, as a result of the presence of numerous deep connective tissue papillae. The basal layer of the epithelium stains intensely, appearing as a dark band that is relatively conspicuous at low magnification. This is, in part, due to the cytoplasmic basophilia of the basal cells. That the basal cells are small results in a high nuclear-cytoplasmic ratio, which further intensifies the hematoxylin staining of this layer.


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Histology_Ross. The submucosa consists of irregular dense connective tissue that contains the larger blood vessels and nerves. No glands are seen in the submucosa in this figure, but they are regularly present throughout this layer and are likely to be included in a section of the wall. Whereas the boundary between the epithelium and lamina propria is striking, the boundary between the mucosa (Muc) and submucosa (SubM ) is less well marked, although it is readily discernable. The muscularis externa (ME ) shown here is composed largely of smooth muscle, but it also contains areas of striated muscle. Although the striations are not evident at this low magnification, the more densely stained eosinophilic areas (asterisks) prove to be striated muscle when observed at higher magnification. Reference to the inset, which is from an area in the lower half of the figure, substantiates this identification.


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Histology_Ross. The inset shows circularly oriented striated and smooth muscle. The striated muscle stains more intensely with eosin, but of greater significance are the distribution and number of nuclei. In the center of the inset, numerous elongated and uniformly oriented nuclei are present; this is smooth muscle (SM ). Above and below, few elongated nuclei are present; moreover, they are largely at the periphery of the bundles. This is striated muscle (StM ); the cross-striations are just perceptible in some areas. The specimen shown here is from the middle of the esophagus, where both smooth and striated muscle are present. The muscularis externa of the distal third of the esophagus would contain only smooth muscle, whereas that of the proximal third would consist of striated muscle. External to the muscularis externa is the adventitia (Adv) consisting of dense connective tissue. Mucosa, esophagus, monkey, H&E ×300.


Histology_Ross

Histology_Ross. External to the muscularis externa is the adventitia (Adv) consisting of dense connective tissue. Mucosa, esophagus, monkey, H&E ×300. As in other stratified squamous epithelia, new cells are produced in the basal layer, from which they move to the surface. During this migration, the shape and orientation of the cells change. This change in cell shape and orientation is also reflected in the appearance of the nuclei. In the deeper layers, the nuclei are spherical; in the more superficial layers, the nuclei are elongated and oriented parallel to the surface. That nuclei can be seen throughout the epithelial layer, particularly the surface cells, indicates that the epithelium is not keratinized. In some instances, the epithelium of the upper regions of the esophagus may be parakeratinized or, more rarely, keratinized.


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Histology_Ross. In some instances, the epithelium of the upper regions of the esophagus may be parakeratinized or, more rarely, keratinized. As shown in this figure, the lamina propria (LP) is a very cellular, loose connective tissue containing many lymphocytes (Lym), small blood vessels, and lymphatic vessels (LV ). The deepest part of the mucosa is the muscularis mucosae (MM ). That layer of smooth muscle defines the boundary between mucosa and submucosa. The nuclei of the smooth muscle cells of the muscularis mucosae appear spherical because the cells have been cut in cross section. KEY Adv, adventitia Ep, stratified squamous epithelium L, longitudinal layer of muscularis externa LP, lamina propria LV, lymphatic vessels Lym, lymphocytes ME, muscularis externa MM, muscularis mucosae Muc, mucosa SM, smooth muscle StM, striated muscle SubM, submucosa arrows (upper figure), lymphocytes in epithelium asterisks (lower figure), areas containing striated muscle in the muscularis externa


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Histology_Ross. PLATE 55 Esophagus And Stomach, Cardiac Region The esophagogastric junction marks a change in function from that of a conduit (esophagus) to that of a digestive organ (stomach). The epithelium of the mucosa changes from stratified squamous (protective) to a simple columnar secretory epithelium that forms mucosal glands that secrete mucinogen, digestive enzymes, and hydrochloric acid. The very cellular lamina propria is rich in diffuse lymphatic tis-sue, emphasizing the role of this layer in the immune system. Esophagogastric junction, esophagus-stomach, human, H&E ×100.


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Histology_Ross. Esophagogastric junction, esophagus-stomach, human, H&E ×100. The junction between the esophagus and stomach is shown here. The esophagus is on the right, and the cardiac region of the stomach is on the left. The large rectangle marks a representative area of the cardiac mucosa seen at higher magnification in figure below; the smaller rectangle shows part of the junction examined at higher magnification in figure on right. As noted in Plate 54, the esophagus is lined by stratifed squamous 608 epithelium (Ep) that is indented on its undersurface by deep connective tissue papillae. When these are sectioned obliquely (as five of them have been), they appear as islands of connective tissue within the thick epithelium. Under the epithelium are the lamina propria and the muscularis mucosae Cardiac region, stomach, human, H&E ×260.


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Histology_Ross. Cardiac region, stomach, human, H&E ×260. The cardiac glands and pits seen in top figure are surrounded by a very cellular lamina propria. At this higher magnification, it can be seen that many cells of the lamina propria are lymphocytes and other cells of the immune system. Large numbers of lymphocytes (L) may be localized between the smooth muscle cells of the muscularis mucosae (MM ), and thus, the muscularis mu cosae in these locations appears to be disrupted. Cardiac region, stomach, human, H&E ×440.


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Histology_Ross. Cardiac region, stomach, human, H&E ×440. The epithelium of the cardiac glands (GL ) also consists of mucous gland cells (MGC ). As seen in the photomicrograph, the nucleus of the gland cell is typically flattened; one side is adjacent to the base of the cell, while the other side is adjacent to the pale-staining cytoplasm. Again, mucus is lost during processing of the tissue, and this accounts for the pale-staining appearance of the cytoplasm. Although the cardiac glands are mostly unbranched, some branching (MM ). At the junction between the esophagus and the stomach (see also middle right figure ), the stratified squamous epithelium of the esophagus ends abruptly, and the simple columnar epithelium of the stomach surface begins.


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Histology_Ross. The surface of the stomach contains numerous and relatively deep depressions called gastric pits (P ), or foveolae, that are formed by epithelium similar to, and continuous with, that of the surface. Glands (GL ) open into the bottom of the pits; they are cardiac glands. The entire gastric mucosa contains glands. There are three types of gastric glands: cardiac, fundic, and pyloric. Cardiac glands are in the immediate vicinity of the opening of the esophagus; pyloric glands are in the funnel-shaped portion of the stomach that leads to the duodenum; and fundic glands are throughout the remainder of the stomach. PLATE 55 • E SOPHAG US AN D STOMACH, CAR DIAC R EG ION KEY D, ducts of cardiac glands Ep, epithelium GL cardiac glands L, lymphocytes LP, lamina propria MGC, mucous gland cells MM, muscularis mucosae P, gastric pits SMC, surface mucous cells arrows, intraepithelial lymphocytes


Histology_Ross

Histology_Ross. The cardiac glands (GL) are limited to a narrow region around the cardiac orifice. They are not sharply delineated from the fundic region of the stomach that contains parietal and chief cells. Thus, at the boundary, occasional parietal cells are seen in the cardiac glands. In certain animals (e.g., ruminants and pigs), the anatomy and histology of the stomach are different. In these, at least one part of the stomach is lined with stratified squamous epithelium. Esophagogastric junction, esophagus-stomach, of cells named surface mucous cells (SMC). The content of the mucous human, H&E ×440. cup is usually lost during the preparation of the tissue, and thus, the apical cup portion of the cells appears empty in routine H&E paraffin sections The columnar cells of the stomach surface and gastric pits (P ) such as the ones shown in this plate.


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Histology_Ross. produce mucus. Each surface and pit cell contains a mucous cup in its apical cytoplasm, thereby forming a glandular sheet is occasionally seen. The glands empty their secretions via ducts (D) into the bottom of the gastric pits. The cells forming the ducts are columnar, and the cytoplasm stains well with eosin. This makes it easy to distinguish the duct cells from mucous gland cells. Among the cells forming the duct portion of the gland are those that undergo mitotic division to replace both surface mucous and gland cells. Cardiac glands also contain enteroendocrine cells, but they are difficult to identify in routine H&E paraffin sections. PLATE 55 • ESOPHAGUS AND STOMACH, CARDIAC REGIONMGCMGCGLGLLPLPMMMMGLGLDD PLEpEpMMMMGLGLEp P GL MM Ep L P P PP PP PP PP DD DD DD DD DD DD GL MM SMC LP MMMMMM GL GLGLGL MGC GLGLGL LL


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Histology_Ross. PLATE 55 • ESOPHAGUS AND STOMACH, CARDIAC REGIONMGCMGCGLGLLPLPMMMMGLGLDD PLEpEpMMMMGLGLEp P GL MM Ep L P P PP PP PP PP DD DD DD DD DD DD GL MM SMC LP MMMMMM GL GLGLGL MGC GLGLGL LL The stomach is divided into three regions: the cardia, nearest the esophagus, contains cardiac glands that secrete primarily mucinogen; the pylorus, proximal to the gastrointestinal (pyloric) sphincter contains pyloric glands that secrete a mucinogen that resembles that of the sur-face mucous cells; and the fundus, the body or largest part of the stomach that contains the fundic (gastric) glands. Fundic glands contain parietal (oxyntic) cells, acidophilic cells that secrete 0.16 N HCl; and chief cells, basophilic cells that contain acidophilic secretory granules in the apical cytoplasm. The granules contain, principally, pepsinogen. The glands in all parts of the stomach contain enteroendocrine cells. Stomach, human, H&E.


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Histology_Ross. Stomach, human, H&E. As with other parts of the gastrointestinal tract, the wall of the stomach consists of four layers: a mucosa (Muc), a submucosa (SubM ), a muscularis externa (ME ), and a serosa. The mucosa is the innermost layer and reveals three distinctive regions (arrows). The most superficial region contains the gastric pits; the middle region contains the necks of the glands, which tend to stain with eosin; and the deepest part of the mucosa stains most heavily with hema 610 toxylin. The cell types of the deep (hematoxylin-staining) portion of the fundic mucosa are considered in bottom figure. The cells of all three regions and their staining characteristics are considered in Plate 57. The inner surface of the empty stomach is thrown into long folds referred to as rugae. One such cross-sectioned fold is shown here. It consists Fundocardiac junction, stomach, human, H&E.


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Histology_Ross. Fundocardiac junction, stomach, human, H&E. This figure and figure below show the fundocardiac junction between the cardiac and fundic regions of the stomach. This junction can be identified histologically on the basis of the structure of the mucosa. The gastric pits (P ), some of which are seen opening at the surface (arrows), are similar in both regions, but the glands are different. They are composed mostly of mucus- Fundocardiac junction, stomach, human, H&E.


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Histology_Ross. Fundocardiac junction, stomach, human, H&E. This figure provides a comparison between the cardiac and fundic glands at higher magnification. The cardiac glands (CG ) consist of mucous gland cells arranged as a simple columnar epithelium; the nucleus is in the most basal part of the cell and is somewhat flattened. The cytoplasm appears as a faint network of lightly stained material. The lumina (L) of the cardiac glands are relatively wide. On the other hand, the fundic glands (FG ) (left of the dashed line) are small, and a lumen is seen readily only in certain fortuitously sectioned glands. As a consequence, most of the glands of mucosa and submucosa (asterisks). The rugae are not permanent folds; they disappear when the stomach wall is stretched, as in the distended stomach. Also evident are mamillated areas (M ), which are slight elevations of the mucosa that resemble cobblestones. The mamillated areas consist only of mucosa without submucosa.


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Histology_Ross. The submucosa and muscularis externa stain predominantly with eosin; the muscularis externa appears darker. The smooth muscle of the muscularis externa gives an appearance of being homogeneous and uniformly solid. In contrast, the submucosa, being connective tissue, may contain areas with adipocytes and contains numerous profiles of blood vessels (BV ). The serosa is so thin that it is not evident as a discrete layer at this low magnification. secreting cells and occasional enteroendocrine cells. The boundary between cardiac glands (CG ) and fundic glands (FG ) is marked by the dashed line in each figure. The full thickness of the gastric mucosa is shown here, as indicated by the presence of the muscularis mucosae (MM ) deep to the fundic glands. The muscularis mucosae under the cardiac glands is obscured by a large infiltration of lymphocytes forming a lymphatic nodule (LN ).


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Histology_Ross. appear to be cords of cells. Because this is a deep region of the fundic mucosa, most of the cells are chief cells. The basal portion of the chief cell contains the nucleus and extensive ergastoplasm, thus, its basophilia. The apical cytoplasm, normally occupied by secretory granules that were lost during the preparation of the tissue, stains poorly. Interspersed among the chief cells are parietal cells (PC). These cells typically have a round nucleus that is surrounded by eosinophilic cytoplasm. Among the cells of the lamina propria are some with pale elongate nuclei. These are smooth muscle cells (SM ) that extend into the lamina propria from the muscularis mucosae.


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Histology_Ross. KEY BV, blood vessels CG, cardiac glands FG, fundic glands L, lumen LN, lymphatic nodule M, mamillated areas ME, muscularis externa MM, muscularis mucosae Muc, mucosa P, gastric pits PC, parietal cells SM, smooth muscle cells SubM, submucosa arrows: top left figure, three differently stained regions of fundic mucosa; Top right figure, opening of gastric pits asterisks, submucosa in ruga dashed line, boundary between cardiac and fundic glands The epithelial lining of the alimentary canal is a regularly renewing epithelium; each portion has a characteristic turnover time and stem cell location. In the stomach, stem cells are located in the mucous neck. Cells that migrate upward to form the mucous cells of the gastric pit and surface have a turnover time of 3 to 5 days; cells that migrate downward to form the parietal cells, chief cells, and enteroendocrine cells of the glands have a turnover time of about 1 year. Fundic glands, stomach, monkey, H&E ×320.


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Histology_Ross. Fundic glands, stomach, monkey, H&E ×320. This figure shows an area of the fundic mucosa that includes the bottom of the gastric pits and the neck and deeper part of the fundic glands. It includes the areas marked by the arrows in top left figure of Plate 56. The surface mucous cells (SMC) of the gastric pits are readily identified because the mucous cup in the apical pole of each cell has an empty, washed-out appearance. Just below the gastric pits are the necks (N ) of the fundic glands, in which one can identify mucous neck cells (MNC ) and parietal cells (PC ). The mu612 cous neck cells produce a mucous secretion that differs from that produced by the surface mucous cells. As seen here, the mucous neck cells display a cytoplasm that is lightly stained; there are no cytoplasmic areas that stain intensely, nor is there a characteristic local absence of staining as in the mucous Submucosa, stomach, monkey, H&E ×320.


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Histology_Ross. Submucosa, stomach, monkey, H&E ×320. This figure shows the bottom of the stomach mucosa, the sub-mucosa (SubM ), and part of the muscularis externa (ME ). The muscularis mucosae (MM ) is the deepest part of the mucosa. It consists of smooth muscle cells arranged in at least two layers. As seen in the photomicrograph, the smooth muscle cells immediately adjacent to the submucosa have been sectioned longitudinally and display elongate nuclear profiles. Just above this layer, the smooth muscle cells have been cut in cross section and display rounded nuclear profiles. Gastric glands, stomach, silver stain ×160. Enteroendocrine cells constitute a class of cells that can be displayed with special histochemical or silver-staining methods but that are not readily evident in H&E sections. The distribution of cells demonstrable with special silver-staining procedures is shown here (arrows). Because of the staining procedure, Gastric glands, stomach, silver stain ×640.


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Histology_Ross. Gastric glands, stomach, silver stain ×640. At higher magnification, the argentaffn cells (arrows) are almost totally blackened by the silver staining, although a faint nucleus can be seen in some cells. The silver stains the secretory product lost during the preparation of routine sections, cup of the surface mucous cells. The mucous neck cells are also the stem cells that divide to give rise to the surface mucous cells and the gland cells. Parietal cells are distinctive primarily because of the pronounced eosinophilic staining of their cytoplasm. Their nucleus is round, like that of the chief cell, but tends to be located closer to the basal lamina of the epithelium than to the lumen of the gland because of the pearlike shape of the parietal cell.


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Histology_Ross. This figure also reveals the significant characteristics of chief cells (CC ), namely, the round nucleus in a basal location; the ergastoplasm, deeply stained with hematoxylin (particularly evident in some of the chief cells where the nucleus has not been included in the plane of the section); and the apical, slightly eosinophilic cytoplasm (normally occupied by the secretory granules). The submucosa consists of connective tissue of moderate density. Present in the submucosa are adipocytes (A), blood vessels (BV), and a group of ganglion cells (GC ). These particular cells belong to the submucosal plexus (Meissner’s plexus [MP] ). The inset shows some of the ganglion cells (GC ) at higher magnification. These are the large cell bodies of the enteric neurons. Each cell body is surrounded by satellite cells intimately apposed to the neuron cell body. The arrowheads point to the nuclei of the satellite cells.


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Histology_Ross. these cells are properly designated as argentaffn cells. The surface mucous cells (SMC) in the section mark the bottom of the gastric pits and establish the fact that the necks of the fundic glands are represented in the section. The argentaffin cells appear black in this specimen. The relatively low magnification permits the viewer to assess the frequency of distribution of these cells. and accordingly, in H&E–stained paraffin sections the argentaffin cell appears as a clear cell. The special silver staining in this figure and in figure on left shows that many of the argentaffin cells tend to be near the basal lamina and away from the lumen of the gland. KEY A, adipocytes BV, blood vessels CC, chief cells GC, ganglion cells ME, muscularis externa MM, muscularis mucosae MNC, mucous neck cells MP, Meissner’s plexus N, neck of fundic glands PC, parietal cells SMC, surface mucous cells SubM, submucosa arrows, argentaffin cells arrowheads, nuclei of satellite cells


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Histology_Ross. The gastroduodenal junction marks the entry into the absorptive portion of the alimentary canal. Thickening of the circular layer of muscularis externa at this site forms the pyloric sphincter that regulates passage of chyme from stomach to intestine. The mucous secretion of the pyloric glands helps to neutralize the chyme as it enters the intestine. Gastroduodenal junction, stomach-duodenum, monkey, H&E ×40. The gastroduodenal junction between the stomach and the duodenum is shown here. Most of the mucosa in the micro-graph belongs to the stomach; it is the pyloric mucosa (PMuc). The pyloric sphincter appears as a thickened region of smooth muscle below the pyloric mucosa. On the far right is the duodenal mucosa, the first part of the intestinal mucosa (IMuc). The area marked by the rectangle is shown at higher magnification in figure below. It provides a comparison of the two mucosal regions and also shows the submucosal 614 glands (Brunner’s glands).


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Histology_Ross. Gastroduodenal junction, stomach-duodenum, monkey ×120. Examination of this region at higher magnification reveals that in addition to intestinal glands (IGl ) within the mucosa, there are glands within the duodenal submucosa. These are submucosal (Brunner’s) glands (BGl ). Some of the glandular elements (arrows) can be seen to pass from the submucosa to the mucosa, thereby interrupting the muscularis mucosae (MM ). The submucosal glands empty their secretions into the duodenal lumen by means of ducts (D). In contrast, the pyloric glands (PGl ) are relatively straight for most of their length but are coiled in the deepest part of the mucosa and are sometimes branched. They are restricted to the mucosa and empty into deep Gastroduodenal junction, stomach-duodenum, monkey ×640.


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Histology_Ross. Gastroduodenal junction, stomach-duodenum, monkey ×640. The rectangular area in figure below is considered at higher magnification here. It shows how the epithelium of the stomach differs from that of the intestine. In both cases, the epithelium is simple columnar, and the underlying lamina propria (LP ) is highly cellular because of the presence of large numbers of lymphocytes. The boundary between gastric and duodenal epithelium is marked by The submucosa of the duodenum contains submucosal (Brunner’s) glands. These are below the muscularis mucosae; therefore, this structure serves as a useful landmark in identifying the glands. In the stomach, the muscularis mucosae is readily identified as narrow bands of muscular tissue (MM ). It can be followed toward the right into the duodenum but is then interrupted in the region between the two asterisks.


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Histology_Ross. This figure also shows the thickened region of the gastric muscularis externa, where the stomach ends. This is the pyloric sphincter (PS ). Its thickness, mostly due to the amplification of the circular layer of smooth muscle of the muscularis externa, can be appreciated by comparison with the muscularis externa in the duodenum (ME ). gastric pits. The boundary between the pits and glands is, however, hard to ascertain in H&E sections.


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Histology_Ross. gastric pits. The boundary between the pits and glands is, however, hard to ascertain in H&E sections. With respect to the mucosal aspects of gastroduodenal histology, as mentioned above, the glands of the stomach empty into gastric pits. These are depressions; accordingly, when the pits are sectioned in a plane that is oblique or at right angles to the long axis of the pit, as in this figure, the pits can be recognized as being depressions because they are surrounded by lamina propria. In contrast, the inner surface of the small intestine has villi (V). These are projections into the lumen of slightly varying height. When the villus is cross-sectioned or obliquely sectioned, it is surrounded by space of the lumen, as is one of the villi shown here. In addition, the villi have lamina propria (LP ) in their core.


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Histology_Ross. the arrow. On the stomach side of the arrow, the epithelium consists of surface mucous cells (SMC). The surface cells contain an apical cup of mucous material that typically appears empty in an H&E–stained paraffin section. In contrast, the absorptive cells (AC ) of the intestine do not possess mucus in their cytoplasm. Although goblet cells are found in the intestinal epithelium and are scattered among the absorptive cells, they do not form a complete mucous sheet. The intestinal absorptive cells also possess a striated border, which is shown in Plate 60.


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Histology_Ross. PLATE 58KEY AC, absorptive cells BGl, Brunner’s glands D, ducts IGl, intestinal glands IMuc, intestinal mucosa LP, lamina propria ME, muscularis externa MM, muscularis mucosae PGl, pyloric glands PMuc, pyloric mucosa PS, pyloric sphincter SMC, surface mucous cells V, villi arrows: bottom figure, Brunner’s gland element that passes from the submucosa to the mucosa; upper right figure, boundary between gastric and duodenal epithelium asterisks, interruption in muscularis mucosae


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Histology_Ross. The small intestine is the principal site for the digestion of food and absorption of the products of digestion. It is the longest component of the alimentary canal, measuring over 6 m, and is divided into three segments: duodenum (~25 cm); jejunum (~2.5 m); and ileum (~3.5 m). The first portion, the duodenum, receives a partially digested bolus of food (chyme) from the stomach, as well as secretions from the stomach, pancreas, liver, and gallbladder that contain digestive enzymes, enzyme precursors, and other products that aid digestion and absorption. The small intestine is characterized by plicae circulares, permanent transverse folds that contain a core of submucosa, and villi, fingerlike and leaflike projections of the mucosa that extend into the lumen. Microvilli, multiple finger like extensions of the apical surface of each intesti-nal epithelial cell (enterocyte), further increase the surface for absorption of metabolites. Mucosal glands extend into the lamina propria. They


Histology_Ross

Histology_Ross. like extensions of the apical surface of each intesti-nal epithelial cell (enterocyte), further increase the surface for absorption of metabolites. Mucosal glands extend into the lamina propria. They contain the stem cells and developing cells that will ultimately migrate to the surface of the villi. In the duodenum, submucosal glands (Brunner’s glands) secrete an alkaline mucus that helps to neutralize the acidic chyme. Enterocytes not only absorb metabolites digested in the intestinal lumen but also synthesize enzymes inserted into the membrane of the mi-crovilli for terminal digestion of disaccharides and dipeptides.


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Histology_Ross. Duodenum, monkey, H&E ×120. This figure shows a segment of the duodenal wall. As in the stomach, the layers of the wall, in order from the lumen, are the mucosa (Muc), the submucosa (SubM ), the muscularis externa (ME ), and the serosa (S ). Both longitudinal (L) and circular (C ) layers of the muscularis externa can be distinguished. Although plicae circulares are found in the wall of the small intestine, including the duodenum, none is included in this photomicrograph. A distinctive feature of the intestinal mucosa is the presence of fingerlike and leaflike projections into the intestinal lumen, called villi. Most of the villi (V ) shown here display profiles that correspond to their description as fingerlike. One villus, however, displays the form of a leaflike villus (asterisk). The dashed line marks the boundary between the villi and the intestinal glands (also called crypts of Lieberkn). The latter extend as far as the muscularis mucosae (MM ).


Histology_Ross

Histology_Ross. Under the mucosa is the submucosa, containing the Brunner’s glands (BGl ). These are branched tubular or branched tubuloalveolar glands whose secretory components, shown at higher magnification in figure below, consist of columnar epithelium. A duct (D) through which the glands open into the lumen of the duodenum is shown here and, at higher magnification, in figure below, where it is marked by an arrow. Mucosa, duodenum, monkey, H&E ×240.


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Histology_Ross. Mucosa, duodenum, monkey, H&E ×240. The histologic features of the duodenal mucosa are shown at higher magnification here. Two kinds of cells can be recognized in the epithelial layer that forms the surface of the villus: enterocytes (absorptive cells) and goblet cells (GC ). Most of the cells are absorptive cells. They have a striated border that will be seen at higher magnification in Plate 60; their elongate nuclei are located in the basal half of the cell. Goblet cells are readily identified by the presence of the apical mucous cup, which appears empty. Most of the dark round nuclei also seen in the epithelial layer covering the villi belong to lymphocytes.


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Histology_Ross. The lamina propria (LP ) makes up the core of the villus. It contains large numbers of round cells whose individual identity cannot be ascertained at this magnification. Note, however, that these are mostly lymphocytes (and other cells of the immune system), which accounts for the designation of the lamina propria as diffuse lymphatic tissue. The lamina propria surrounding the intestinal glands (IGl ) similarly consists largely of lymphocytes and related cells. The lamina propria also contains components of loose connective tissue and isolated smooth muscle cells.


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Histology_Ross. The intestinal glands (IGl ) are relatively straight and tend to be dilated at their base. The bases of the intestinal crypts contain the stem cells from which all of the other cells of the intestinal epithelium arise. They also contain Paneth cells. These cells possess eosinophilic granules in their apical cytoplasm. The granules contain lysozyme, a bacteriolytic enzyme thought to play a role in regulating intestinal microbial flora. The main cell type in the intestinal crypt is a relatively undifferentiated columnar cell. These cells are shorter than the enterocytes of the villus surface; they usually undergo two mitoses before they differentiate into absorptive cells or goblet cells. Also present in the intestinal crypts are some mature goblet cells and enteroendocrine cells.


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Histology_Ross. KEY BGl, Brunner’s glands C, circular (inner) layer of muscularis externa D, duct of Brunner’s gland GC, goblet cells IGl, intestinal glands (crypts) L, longitudinal (outer) layer of muscularis externa LP, lamina propria ME, muscularis externa MM, muscularis mucosae Muc, mucosa S, serosa SubM, submucosa V, villi arrow, duct of Brunner’s gland asterisk, leaflike villus dashed line (top figure), boundary between base of villi and intestinal glands The jejunum is the principal site of absorption of nutrients in the small intestine. The villi are more finger like than leaf like and are covered largely with absorptive columnar epithelial cells (enterocytes), although goblet cells and enteroendocrine cells are also present. The stem cells for all of these cells and the Paneth cells that secrete the antibacterial enzyme lysozyme are found deep in the intestinal gland. Replicat-ing cells line the lower half of the gland. Jejunum, monkey, H&E ×22.


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Histology_Ross. Jejunum, monkey, H&E ×22. This is a longitudinal section of the jejunum, showing the permanent circular folds of the small intestine, the plicae circulares (PC ). These folds or ridges are mostly arranged with their long axis at roughly right angles to the longitudinal axis of the intestine; therefore, the plicae circulares shown here are cut in cross section. The plicae circulares consist of mucosa (Muc) as well as sub-mucosa (SubM ). The broad band of tissue external to the submucosa is the Plica circularis, jejunum, monkey, H&E ×60.


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Histology_Ross. Plica circularis, jejunum, monkey, H&E ×60. Part of the plica circularis marked by the bracket in figure above is shown at higher magnification. Note the muscularis mucosae (MM ), the intestinal glands (GI ), and the villi (V ). The boundary between the glands and villi is marked by the dashed line. Some of the glands are cut longitudinally; some are cut in cross section; most of the villi have been cut longitudinally. In conceptualizing the mucosal structure of the small intestine, it is important to recognize that the glands are epithelial depressions that project into the wall Intestinal villi, jejunum, monkey, H&E ×500.


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Histology_Ross. This figure shows portions of two adjacent villi at higher magnification. The epithelium consists chiefly of enterocytes. These are columnar absorptive cells that typically exhibit a striated border (SB), the light microscopic representation of the microvilli on the apical surface of each enterocyte. The dark band at the base of the striated border is due to the terminal web of the cell, a layer of actin filaments that extends across the apex of the cell to which the actin filaments of the cores of the microvilli attach. The nuclei of the enterocytes have essentially the same shape, orientation, and staining characteristics. Even if the cytoplasmic boundaries were not evident, the nuclei would be an indication of the columnar shape and orientation of the cells. The enterocytes rest on a basal lamina not evident in H&E–stained paraffin sections. The eosinophilic band (arrow) at the base of the cell layer, muscularis externa (ME ) and is not included in the plicae. (The serosa cannot be


Histology_Ross

Histology_Ross. lamina not evident in H&E–stained paraffin sections. The eosinophilic band (arrow) at the base of the cell layer, muscularis externa (ME ) and is not included in the plicae. (The serosa cannot be distinguished at this magnification.) Most of the villi (V ) in this specimen have been cut longitudinally, thereby revealing their full length as well as the fact that some are slightly shorter than others. The shortening is considered to be due to the contraction of smooth muscle cells in the villi. Also seen here are the lacteals (L), which in most of the villi are dilated. Lacteals are lymphatic capillaries that begin in the villi and carry certain absorbed dietary lipids and proteins from the villi to the larger lymphatic vessels of the submucosa.


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Histology_Ross. of the intestine, whereas the villi are projections that extend into the lumen. The glands are surrounded by cells of the lamina propria; the villi are surrounded by space of the intestinal lumen. The lamina propria with its lacteal occupies a central position in the villus; the lumen occupies the central position of the gland. Also note that the lumen of the gland tends to be dilated at its base. Studies of enzymatically isolated preparations of mucosa show that the bases of the glands are often divided into two to three fingerlike extensions resting on the muscularis mucosae. where one would expect a basement membrane, actually consists of flat lateral cytoplasmic processes from the enterocytes. These processes partially delimit the basal-lateral intercellular spaces (asterisks) that are dilated, as can be seen here, during active transport of absorbed substrates.


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Histology_Ross. The epithelial cells with an expanded apical cytoplasm in the form of a cup are goblet cells (GC ). In this specimen, the nucleus of almost every goblet cell is just at the base of the cup, and a thin cytoplasmic strand (not always evident) extends to the level of the basement membrane. The scattered round nuclei within the epithelium belong to lymphocytes (Ly). The lamina propria (LP ) and the lacteal (L) are located beneath the intestinal epithelium. The cells forming the lacteal are simple squamous epithelium (endothelium). Two nuclei of these cells (EC ) appear to be exposed to the lumen of the lacteal; another elongate nucleus slightly removed from the lumen belongs to a smooth muscle cell (M) accompanying the lacteals.


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Histology_Ross. KEY EC, endothelial cell GC, goblet cell GI, intestinal glands (crypts) L, lacteal LP, lamina propria Ly, lymphocytes M, smooth muscle cell ME, muscularis externa MM, muscularis mucosae Muc, mucosa PC, plicae circulares S, serosa SB, striated border SubM, submucosa V, villi arrow, basal processes of enterocytes asterisks, basal-lateral intercellular spaces dashed line, boundary between villi and intestinal glands


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Histology_Ross. The ileum is the principal site of water and electrolyte reabsorption in the small intestine. It has essentially the same histologic features as the jejunum. Some, however, are emphasized; namely, villi in the ileum are more frequently leaflike, and lymphatic tissue in the lamina propria is organized into small and large nodes that are found in great number on the antimesenteric side of the ileum. The nodes fuse to form large ac-cumulations of lymphatic tissue called Peyer’s patches. The surface epithelium of the small intestine renews itself every 5 to 6 days. The stem cells are restricted to the bottoms of the mucosal glands, and the zone of cell replication is restricted to the lower half of the gland. The cells migrate onto the villus and are lost from its tip. All of the epithelial cells, absorptive cells, and goblet cells, as well as enteroendocrine cells and Paneth cells, derive from the same stem cell population, but enteroendocrine cells migrate only slowly, and Paneth cells


Histology_Ross

Histology_Ross. absorptive cells, and goblet cells, as well as enteroendocrine cells and Paneth cells, derive from the same stem cell population, but enteroendocrine cells migrate only slowly, and Paneth cells do not migrate.


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Histology_Ross. Ileum, monkey, H&E ×20. For purposes of orientation, the submucosa (SM ) and muscularis externa (ME ) have been marked in the cross section through the ileum shown here. Just internal to the submucosa is the mucosa; external to the muscularis externa is the serosa. The mucosa reveals several longitudinally sectioned villi (V ), which have been labeled, and other unlabeled villi, which can be identified easily on the basis of their appearance as islands of tissue completely surrounded by the space of the lumen. They are, of course, not islands because this appearance is due to the plane of section that slices completely through some of the villi obliquely or in cross section, thereby isolating them from their base. Below the villi are the intestinal glands, many of which are obliquely or transversely sectioned and can be readily identified, as was done in the preceding plates, because they are totally surrounded by lamina propria.


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Histology_Ross. There are about 8 to 10 projections of tissue into the intestinal lumen that are substantially larger than the villi. These are the plicae circulares. As Aggregated lymph nodule, ileum, monkey, H&E ×100; inset ×200.


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Histology_Ross. Part of an aggregated lymph nodule and part of the overlying epithelium are shown here at higher magnification. The lymphocytes and related cells are so numerous that they virtually obscure the cells of the muscularis mucosae. Their location, however, can be estimated as being near the presumptive label (MM?? ), inasmuch as the muscularis mucosae is ordinarily adjacent to the base of the intestinal glands (Gl ). Moreover, on examination of this area at higher magnification (inset), groups of smooth muscle cells (MM ) can be seen noted above, plicae generally have circular orientation, but they may travel in a longitudinal direction for short distances and may branch. In addition, even if all the plicae are arranged in a circular manner, if the section is somewhat oblique, the plicae will be cut at an angle, as appears to be the case with several plicae in this figure. One of the distinctive features of the small intestine is the presence of single and aggregated lymph nodules in the


Histology_Ross

Histology_Ross. be cut at an angle, as appears to be the case with several plicae in this figure. One of the distinctive features of the small intestine is the presence of single and aggregated lymph nodules in the intestinal wall. Isolated nodules of lymphatic tissue are common in the proximal end of the intestinal canal. As one proceeds distally through the intestines, however, the lymph nodules occur in increasingly larger numbers. In the ileum, large aggregates of lymph nodules are regularly seen; they are referred to as Peyer’s patches. Several lymphatic nodules (LN ) forming a Peyer’s patch are shown in this figure. The nodules are partly within the mucosa of the ileum and extend into the submucosa. Although not evident in the figure, the nodules are characteristically located opposite where the mesentery connects to the intestinal tube.


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Histology_Ross. Plica circularis, ileum, monkey, H&E ×40. Sometimes, in a cross section through the intestine, a plica displays a clear cross-sectional profile such as that shown here. Note, again, that the submucosa (SM ) constitutes the core of the plica. Although many of the villi in this figure present profiles (V ) that would be expected if the villus were a fingerlike projection, others clearly do not. In particular, one villus (marked with three asterisks) shows the broad profile of a longitudinally sectioned leaf like villus. If this same villus were cut at a right angle to the plane shown here, it would appear as a finger like villus. separated by numerous lymphocytes close to the intestinal glands (Gl ). Clearly, the lymphocytes of the nodule are on both sides of the muscularis mucosae and, thus, within both the mucosa and the submucosa.


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Histology_Ross. In places, the lymph nodule is covered by the intestinal epithelium. Whereas the nature of the epithelium cannot be appreciated fully in the light microscope, electron micrographs (both scanning and transmission) have shown that among the epithelial cells are special cells, designated M cells, that sample the intestinal content (for antigen) and present this antigen to the lymphocytes in the epithelial layer. KEY Gl, intestinal glands LN, lymphatic nodules ME, muscularis externa MM, muscularis mucosae MM??, presumptive location of muscularis mucosae SM, submucosa V, villi asterisks, leaf like villus PLATE 61 • ILEUM MMMMMM??MM??GIGIMEMESMSMLNLNV LN SM ME V MEMEME SMSMSM V GI MM?? MM GIGIGI ** ** **


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Histology_Ross. PLATE 61 • ILEUM MMMMMM??MM??GIGIMEMESMSMLNLNV LN SM ME V MEMEME SMSMSM V GI MM?? MM GIGIGI ** ** ** The principal functions of the colon are reabsorption of electrolytes and water and elimination of undigested food and other waste. The mu-cosa has a smooth surface; neither plicae circulares nor villi are present. Numerous simple glands (crypts of Lieberkn) extend through the full thickness of the mucosa. The glands, as well as the surface, are lined with a simple columnar epithelium that contains goblet cells, absorp-tive cells, and enteroendocrine cells but does not normally contain Paneth cells. Here, too, stem cells are restricted to the bottoms of the glands (crypts), and the normal zone of replication extends about one third of the height of the crypt. Colon, monkey, H&E ×30.


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Histology_Ross. Colon, monkey, H&E ×30. A cross section through the large intestine is shown at low magnification. It shows the four layers that make up the wall of the colon: the mucosa (Muc), the submucosa (SubM ), the muscularis externa (ME ), and the serosa (S ). Although these layers are the same as those in the small intestine, several differences should be noted. The large intestine has no villi, nor does it have plicae circulares. On the other hand, the muscularis externa is arranged in a 622 distinctive manner, and this is evident in the photomicrograph. The longi- Mucosa, colon, monkey, H&E ×140. The mucosa, shown at higher magnification, contains straight, unbranched, tubular glands (crypts of Lieberkn) that extend to the muscularis mucosae (MM). The arrows identify the openings of some of the glands at the intestinal surface. Gener- Lamina propria, colon, monkey, H&E ×525.


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Histology_Ross. Lamina propria, colon, monkey, H&E ×525. This figure reveals the muscularis mucosae (MM) and the cells in the lamina propria (LP), many of which can be recognized as lymphocytes and plasma cells. The smooth muscle cells of the muscularis mucosae are arranged in two layers. Note that the smooth muscle cells marked by the arrowheads Intestinal glands, colon, monkey, H&E ×525.


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Histology_Ross. Intestinal glands, colon, monkey, H&E ×525. The cells that line the surface of the colon and the glands are principally absorptive cells (AC) and goblet cells (GC). The absorptive cells have a thin striated border that is evident where the arrows show the opening of the glands. Interspersed among the absorptive cells are the goblet cells (GC). As the absorptive cells are followed into the glands, they become fewer, whereas the tudinal layer (ME[l] ) is substantially thinner than the circular layer (ME[c] ) except in three locations where the longitudinal layer of smooth muscle is present as a thick band. One of these thick bands, called a tenia coli (TC ), is shown in this figure. Because the colon is cross-sectioned, the tenia coli is also cross-sectioned. The three teniae coli extend along the length of the large intestine as far as, but not into, the rectum.


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Histology_Ross. The submucosa consists of a rather dense irregular connective tissue. It contains the larger blood vessels (BV ) and areas of adipose tissue (see A in figure below). ally, the lumen of the glands is narrow except in the deepest part of the gland, where it is often slightly dilated (asterisks, lower left figure). Between the glands (Gl) is a lamina propria (LP) that contains considerable numbers of lymphocytes and other cells of the immune system. Two rectangles mark areas of the mucosa that are examined at higher magnification in figures below. show rounded nuclei; however, other smooth muscle cells appear as more or less rounded eosinophilic areas. These smooth muscle cells have been cut in cross section. Just above these cross-sectioned smooth muscle cells are others that have been cut longitudinally; they display elongate nuclei and elongate strands of eosinophilic cytoplasm.


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Histology_Ross. goblet cells increase in number. Other cells in the gland are enteroendocrine cells, not easily identified in routine H&E–stained paraffin sections, and, in the deep part of the gland, undifferentiated cells of the replicative zone, derived from the stem cells in the base of the crypt. The undifferentiated cells are readily identified if they are undergoing division, by virtue of the mitotic figures (M) they display (see figure on left). KEY A, adipose tissue AC, absorptive cells BV, blood vessels GC, goblet cells GI, intestinal glands LP, lamina propria M, mitotic figures ME, muscularis externa ME(c), circular layer of muscularis externa ME(l), longitudinal layer of muscularis externa MM, muscularis mucosae Muc, mucosa S, serosa SubM, submucosa TC, tenia coli arrowheads, smooth muscle cells showing rounded nuclei arrows, opening of intestinal glands asterisks, lumen of intestinal glands


Histology_Ross

Histology_Ross. The appendix (vermiform appendix) is typically described as a wormor fingerlike structure [L. vermis, worm; forma, form]. It arises from the cecum (the first segment of the large intestine; the others, in order, are the ascending, transverse, and descending colon; the sigmoid colon; the rectum; and the anal canal) and forms a blind-ending tube ranging from 2.5 cm to as much as 13 cm in length (average length of ~8 cm). Because it is a blind-ended pouch, intestinal contents may be trapped or sequestered in the appendix, often leading to inflammation and in-fection. In infants and children it is both relatively and absolutely longer than in adults and contains numerous lymphatic nodules, suggesting that it has an immunologic role. Recent evidence indicates that it (and the cecum and terminal ileum) may be the “bursa equivalent” in mam-mals, i.e., the portion of the immature immune system in which potential B lymphocytes achieve immunocompetence (equivalent to the bursa of Fabricius in


Histology_Ross

Histology_Ross. ileum) may be the “bursa equivalent” in mam-mals, i.e., the portion of the immature immune system in which potential B lymphocytes achieve immunocompetence (equivalent to the bursa of Fabricius in birds). The wall of the appendix is much like that of the small intestine, having a complete longitudinal layer of muscularis externa, but it lacks both plicae circulares and villi. Thus, the mucosa is similar to that of the colon, having simple glands. Even this resemblance is often obliterated, however, by the large number and size of the lymphatic nodules that usually fuse and extend into the submucosa. In later life, the amount of lymphatic tissue in the appendix regresses, and there is a consequent reduction in size. In many adults, the normal structure is lost, and the appendage is filled with fibrous scar tissue.


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Histology_Ross. Appendix, human, H&E ×25. mucosa (Muc), submucosa (Subm), muscularis externa (ME ), and serosa (S ) are identified. Cross section of an appendix from a preadolescent, showing the various structures composing its wall. The lumen (L), Appendix, human, H&E ×80; inset ×200.


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Histology_Ross. Appendix, human, H&E ×80; inset ×200. This micrograph is a higher magnification of the boxed area in figure above. It reveals the straight tubular glands (Gl ) that extend to the muscularis mucosae. Below is the submucosa (Subm) in which the lymphatic nodules (LN ) and considerable diffuse lymphatic tissue are present. Note the distinct germinal centers (GC ) of the lymph nodules and the cap region (Cap) that faces the lumen. The more superficial part of the submucosa blends and merges with the mucosal lamina propria because of the numerous lymphocytes in these two sites. The deeper part of the submucosa is relatively de void of lymphocyte infiltration and contains the large blood vessels (BV ) and nerves. The muscularis externa (ME ) is composed of a relatively thick circular layer and a much thinner outer longitudinal layer. The serosa (S ) is only partially included in this micrograph.


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Histology_Ross. The inset is a higher magnification of the rectangular area in lower figure. Note that the epithelium of the glands in the appendix is similar to that of the large intestine. Most of the epithelial cells contain mucin; hence, the light appearance of the apical cytoplasm. The lamina propria, as noted, is heavily infiltrated with lymphocytes, and the muscularis mucosae at the base of the glands is difficult to recognize (arrows). KEY BV, blood vessel Cap, cap of lymphatic nodule GC, germinal center Cl, gland L, lumen LN, lymphatic nodule ME, muscularis externa Muc, mucosa S, serosa Subm, submucosa arrows, muscularis mucosae at base of glands


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Histology_Ross. At the anal canal, there is a transition from the simple columnar epithelium of the intestinal mucosa to the keratinized stratified squamous ep-ithelium of the skin. Between these two distinctly different epithelia there is a narrow region (anal transitional zone) where the epithelium is first stratified columnar (or stratified cuboidal) and then nonkeratinized stratified squamous. At the level of the anal canal, the muscularis mucosae disappears. At the same level, the circular layer of the muscularis externa thickens to become the internal anal sphincter. The external anal sphincter is formed by the striated muscles of the pelvic floor. Anal canal, human, H&E ×40.


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Histology_Ross. Anal canal, human, H&E ×40. A view of the anal canal is shown at low magnification. Mucosa characteristic of the large intestine (colorectal zone) is seen on the upper left of the micrograph. This region is the upper part of the anal canal, and the intestinal glands are the same as those present in the colon. The muscularis mucosae (MM ) is readily identified as the narrow band of tissue under the glands. Both the intestinal glands and the muscularis mucosae terminate within626 the left rectangular area of the field, and here, at the diamond, there is the first major change in the epithelium. This area called the anal transitional zone is examined at higher magnification in bottom left figure. The right rectangular area includes the stratified squamous epithelium (StS ) of the Anal transitional zone, anal canal, human, H&E ×160; inset ×300.


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Histology_Ross. Anal transitional zone, anal canal, human, H&E ×160; inset ×300. The junction between the simple columnar (SC ) and the stratified (ST ) epithelium called the anal transitional zone is marked with the diamond. The simple columnar epithelium of the upper part of the anal canal contains numerous goblet cells, and as in the mucosa of the colon, this epithelium is continuous with skin in the squamous zone of the anal canal and is examined at higher magnification in bottom right figure. Between the two diamonds in the rectangular areas shown is epithelium of the lower part of the anal canal. Under this epithelium, there is a lymphatic nodule that has a well-formed germinal center. Isolated lymphatic nodules under mucous membranes should not be construed to have fixed locations. Rather, they may or may not be present, according to local demands.


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Histology_Ross. Also, at this low magnification, note the internal anal sphincter muscle (IAS ), i.e., the thickened, most distal portion of the circular layer of smooth muscle of the muscularis externa. Under the skin on the right is the subcutaneous part of the external anal sphincter muscle (EAS ). It is composed of striated muscle fibers, which are seen in cross section. the epithelium of the intestinal glands (IG ). These glands continue to about the same point as the muscularis mucosae (MM ). Characteristically, the lamina propria contains large numbers of lymphocytes (Lym), particularly so in the region marked. A higher magnification of the stratified columnar epithelium (StCol ) and stratified cuboidal epithelium (StC ) found in the transition zone is shown in the inset. Squamous zone, anal canal, human, H&E ×160.


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Histology_Ross. Squamous zone, anal canal, human, H&E ×160. The final change in epithelial type that occurs at the squamous zone of the anal canal is shown here. On the right is the stratified squamous epithelium of skin (StS(k)). The keratinized nature of the surface is apparent. On the other hand, the stratified squamous epithelium (StS ) below the level of the diamond is not keratinized, and nucleated cells can be seen all the way to the surface. Again, numerous lymphocytes (Lym) are in the underlying connective tissue, and many have migrated into the epithelium in the nonkeratinized area.


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Histology_Ross. KEY EAS, external anal sphincter IAS, internal anal sphincter IG, intestinal glands LN, lymphatic nodules Lym, lymphocytes MM, muscularis mucosae SC, simple columnar epithelium ST, stratified epithelium StC, stratified cuboidal epithelium StCol, stratified columnar epithelium StS, stratified squamous epithelium StS(k), stratified squamous epithelium (keratinized) arrow, termination of muscularis mucosae diamonds, junctions between epithelial types Digestive System III: Liver, Gallbladder, and Pancreas


Histology_Ross

Histology_Ross. Digestive System III: Liver, Gallbladder, and Pancreas LIVER / 628 Overview / 628 Liver Physiology / 629 Blood Supply to the Liver / 631 Structural Organization of the Liver / 632 Liver Lobules / 633 Blood Vessels of the Parenchyma / 636 Perisinusoidal Space (Space of Disse) / 636 Lymphatic Pathway / 638 Hepatocytes / 639 Biliary Tree / 641 GALLBLADDER / 643 PANCREAS / 647 Overview / 647 Exocrine Pancreas / 647 Duct System of the Exocrine Pancreas / 649 Endocrine Pancreas / 649 Functions of Pancreatic Hormones / 651 Regulation of Islet Activity / 653 Folder 18.1 Clinical Correlation: Lipoproteins / 630 Folder 18.2 Clinical Correlation: Congestive Heart Failure and Liver Necrosis / 635 Folder 18.3 Insulin Production and Alzheimer’s Disease / 655 Folder 18.4 Functional Considerations: Insulin Synthesis, an Example of Posttranslational Processing / 655


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Histology_Ross. The liver is the largest mass of glandular tissue in the body and the largest internal organ, weighing approximately 1,500 g and accounting for nearly 2.5% of adult body weight. It is located in the upper right and partially in the upper left quadrants of the abdominal cavity, protected by the ribcage. The liver is enclosed in a capsule of fibrous connective tissue (Glisson’s capsule); a serous covering (visceral peritoneum) surrounds the capsule, except where the liver adheres directly to the diaphragm or the other organs. The liver is anatomically divided by deep grooves into two large lobes (the right and left lobes) and two smaller lobes (the quadrate and caudate lobes; Fig. 18.1). This anatomic division has only topographic importance because it relates lobes of the liver to other abdominal organs. Division into functional or surgical segments that correspond to the blood supply and bile drainage is more clinically important.


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Histology_Ross. In the embryo, the liver develops as an endodermal evagination from the wall of the foregut (specifically the site that will become the duodenum) to form the hepatic diverticulum. The diverticulum proliferates, giving rise to the hepatocytes, which become arranged in cellular (liver) cords, FIGURE 18.1 • Anatomic structure of the liver. This diagram shows the gross view of the diaphragmatic and visceral surfaces of the liver, with labeled anatomic landmarks found on both surfaces. The enlarged cross-sectional area of the liver (bottom) shows the general microscopic organization of the liver into lobules. Note the presence of hepatic portal triads at the periphery of each lobule, with the terminal hepatic venule (central vein) in the center of the lobule.


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Histology_Ross. thus forming the parenchyma of the liver. The original stalk of the hepatic diverticulum becomes the common bile duct. An outgrowth from the common bile duct forms the cystic diverticulum that gives rise to the gallbladder and cystic duct. Many circulating plasma proteins are produced and secreted by the liver. The liver plays an important role in the uptake, storage, and distribution of both nutrients and vitamins from the bloodstream. It also maintains the blood glucose level and regulates circulating levels of very low-density lipoproteins (VLDLs). In addition, the liver degrades or conjugates numerous toxic substances and drugs, but it can be overwhelmed by such substances and damaged. The liver is also an exocrine organ; it produces a bile secretion that contains bile salts, phospholipids, and cholesterol. Finally, the liver performs important endocrine-like functions. The liver produces most of the body’s circulating plasma proteins.


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Histology_Ross. The circulating plasma proteins produced by the liver include  albumins, which are involved in regulating plasma volume and tissue fluid balance by maintaining the plasma colloid osmotic pressure.  lipoproteins, in particular, VLDLs. The liver synthesizes most VLDLs, which participate in the transport of triglycerides from the liver to other organs. The liver also produces small amounts of other plasma lipoproteins, such as low-density lipoproteins (LDLs) and high-density lipoproteins (HDLs). LDLs transport cholesterol esters from the liver to other tissues. HDLs remove cholesterol from the peripheral tissues and transport it to the liver (see Folder 18.1).  glycoproteins, which include proteins involved in iron transport such as haptoglobin, transferrin, and hemopexin.  prothrombin and fbrinogen, important components of the blood-clotting cascade. nonimmune -globulins and -globulins, which also help maintain plasma colloid osmotic pressure and serve as carrier proteins for


Histology_Ross

Histology_Ross. and fbrinogen, important components of the blood-clotting cascade. nonimmune -globulins and -globulins, which also help maintain plasma colloid osmotic pressure and serve as carrier proteins for various substances (see Chapter 10, page 270).