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Chapter 1 : Functional Morphology of the Intestinal Mucosae: From Crypts to Tips

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Abstract:

This chapter focuses on structure and function of the intestinal mucosa and its relevance to absorption, secretion, and microbial pathogenesis. In the small intestine, the crypt is populated by stem cells, goblet cells, undifferentiated secretory cells, enteroendocrine cells, Paneth cells, and occasional rarer cell types, such as tuft cells. The carbohydrate binding sites present on mucins may serve as decoys that compete with epithelial binding sites for attachment of pathogenic bacteria. Enteroendocrine cells are found throughout the intestinal mucosa, interspersed among other epithelial cell types, and arise from the same stem cells as enterocytes, goblet cells, and Paneth cells. In severe cases, features of chronic colitis, including branched crypts, may occasionally be present and are evidence of cyclical mucosal injury and regeneration. When it was first discovered that some epithelia had permeabilities far greater than those explained by the serial conductances of the apical and basolateral membranes, epithelia were classified as leaky (e.g., proximal tubule, gallbladder, small intestine, and colon) or tight (e.g., skin, urinary bladder). To evaluate the potential of myosin oligopeptide as a therapeutic agent, it was applied to cultured cell monolayers after infection with enteropathogenic but before transepithelial electrical resistance fell. Further study of this oligopeptide may lead to the development of a novel class of therapeutic agents that restore intestinal barrier function following noncytolytic epithelial injury.

Citation: Turner J. 2003. Functional Morphology of the Intestinal Mucosae: From Crypts to Tips, p 1-22. In Hecht G (ed), Microbial Pathogenesis and the Intestinal Epithelial Cell. ASM Press, Washington, DC. doi: 10.1128/9781555817848.ch1

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Image of FIGURE 1
FIGURE 1

Human duodenum. The mucosa (M) and submucosa (SM) are drawn into a prominent ridge, or plica circularis, at the right side of the photomicrograph. The mucosa, composed of epithelium, lamina propria, and muscularis mucosa, is organized into crypts and villi. The submucosa contains numerous Brunner's glands (B), found only in the duodenum. A prominent lymphoid aggregate (L) can also be seen. The epithelium overlying this area lacks villi and assumes a dome-shaped configuration. M cells are found at this site. The inner circular layer of the muscularis propria (MP) can be seen at the bottom of the field. Together with the outer longitudinal layer, these layers of smooth muscle effect peristalsis.

Citation: Turner J. 2003. Functional Morphology of the Intestinal Mucosae: From Crypts to Tips, p 1-22. In Hecht G (ed), Microbial Pathogenesis and the Intestinal Epithelial Cell. ASM Press, Washington, DC. doi: 10.1128/9781555817848.ch1
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Image of FIGURE 2
FIGURE 2

Human duodenal villus tip. The lamina propria of the villus core contains a prominent vascular supply (black arrows). Absorptive enterocytes cover the villus tip. At the apical (luminal) edge, the microvillus brush border (see Fig. 4 ) can be appreciated as a faint fuzzy area. Just beneath the brush border, the terminal bar (white arrow) can be seen as an area of increased density. This structure is composed of the terminal web and apical junctional complex. The epithelial cells rest on a thin layer of collagen, the basement membrane (black arrowhead).

Citation: Turner J. 2003. Functional Morphology of the Intestinal Mucosae: From Crypts to Tips, p 1-22. In Hecht G (ed), Microbial Pathogenesis and the Intestinal Epithelial Cell. ASM Press, Washington, DC. doi: 10.1128/9781555817848.ch1
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Image of FIGURE 3
FIGURE 3

Human duodenum. The small intestinal mucosa is organized into villi (V) and crypts (C). Epithelial cell proliferation occurs within the crypt. The crypt is also functionally specialized for water and ion secretion. As enterocytes migrate to the villus, they mature and become specialized for ion and nutrient absorption.

Citation: Turner J. 2003. Functional Morphology of the Intestinal Mucosae: From Crypts to Tips, p 1-22. In Hecht G (ed), Microbial Pathogenesis and the Intestinal Epithelial Cell. ASM Press, Washington, DC. doi: 10.1128/9781555817848.ch1
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Image of FIGURE 4
FIGURE 4

Human duodenal villus. Digestive enzyme expression increases during enterocyte migration to the villus. This micrograph shows brush border alkaline phosphatase expression (white band indicated by arrow). Expression increases progressively from crypt (C) to villus (V).

Citation: Turner J. 2003. Functional Morphology of the Intestinal Mucosae: From Crypts to Tips, p 1-22. In Hecht G (ed), Microbial Pathogenesis and the Intestinal Epithelial Cell. ASM Press, Washington, DC. doi: 10.1128/9781555817848.ch1
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Image of FIGURE 5
FIGURE 5

Human small intestinal epithelium. This intermediate-magnification electron micrograph of the apical region of absorptive enterocytes emphasizes the dense, well-developed microvillus brush border and overlying mucous gel. Microfilament rootlets can be seen protruding into the apical cytoplasm (arrow), where they become embedded within the terminal web (bracket).

Citation: Turner J. 2003. Functional Morphology of the Intestinal Mucosae: From Crypts to Tips, p 1-22. In Hecht G (ed), Microbial Pathogenesis and the Intestinal Epithelial Cell. ASM Press, Washington, DC. doi: 10.1128/9781555817848.ch1
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Image of FIGURE 6
FIGURE 6

Goblet cell. This low-magnification electron micrograph shows abundant mucin granules (G) within the apical cytoplasm of the goblet cell. These granules are ready for discharge into the lumen (L). The nucleus (N) is located basally.

Citation: Turner J. 2003. Functional Morphology of the Intestinal Mucosae: From Crypts to Tips, p 1-22. In Hecht G (ed), Microbial Pathogenesis and the Intestinal Epithelial Cell. ASM Press, Washington, DC. doi: 10.1128/9781555817848.ch1
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Image of FIGURE 7
FIGURE 7

Human small intestinal crypt. The most basal portions of the small intestinal crypt are populated by Paneth cells (P). These cells contain an abundance of large apically located granules. In contrast, enteroendocrine cell (E) granules are small and basally oriented. The stem cell zone (S) is located several cell diameters above the crypt base. Goblet cells (G) are also abundant in the crypt.

Citation: Turner J. 2003. Functional Morphology of the Intestinal Mucosae: From Crypts to Tips, p 1-22. In Hecht G (ed), Microbial Pathogenesis and the Intestinal Epithelial Cell. ASM Press, Washington, DC. doi: 10.1128/9781555817848.ch1
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Image of FIGURE 8
FIGURE 8

Crypt abscess in human colon. The crypt epithelium (E) is damaged and, at the lower right, penetrated (arrow) by a migrating mass of neutrophils (PMN) that fill the crypt lumen.

Citation: Turner J. 2003. Functional Morphology of the Intestinal Mucosae: From Crypts to Tips, p 1-22. In Hecht G (ed), Microbial Pathogenesis and the Intestinal Epithelial Cell. ASM Press, Washington, DC. doi: 10.1128/9781555817848.ch1
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Image of FIGURE 9
FIGURE 9

C. difficile-associated pseudomembranous colitis. The colonic crypt (arrow) is lined by flattened, severely damaged epithelium. The crypt lumen contains purulent debris primarily composed of neutrophils and mucus. This seems to explode from the crypt, forming a volcano-shaped eruption that, at the surface, becomes confluent with exudate from other damaged crypts. Dense sheets of purulent debris, pseudomembranes (PM), cover the mucosal surface.

Citation: Turner J. 2003. Functional Morphology of the Intestinal Mucosae: From Crypts to Tips, p 1-22. In Hecht G (ed), Microbial Pathogenesis and the Intestinal Epithelial Cell. ASM Press, Washington, DC. doi: 10.1128/9781555817848.ch1
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Image of FIGURE 10
FIGURE 10

(A) Immunofluorescence microscopy of human small intestinal mucosa demonstrates tight junctions to be dot-like areas at the apical portion of each cell-cell junction site (arrows), as shown by immunostaining for occludin. (B) Electron microscopy of the apical junctional complex of a small intestinal enterocyte shows an area of tight membrane apposition, the tight junction (solid arrow) at the most apical region of the lateral membrane. The adherens junction (dashed arrow) is located subapical to the tight junction.

Citation: Turner J. 2003. Functional Morphology of the Intestinal Mucosae: From Crypts to Tips, p 1-22. In Hecht G (ed), Microbial Pathogenesis and the Intestinal Epithelial Cell. ASM Press, Washington, DC. doi: 10.1128/9781555817848.ch1
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Image of FIGURE 11
FIGURE 11

Human jejunal mucosae were double-labeled with antiphosphorylated myosin regulatory light chain antisera (A) and antitotal myosin regulatory light chain antisera (B). Focal enrichment of phosphorylated myosin regulatory light chain is obvious at cell-cell junctions (arrows), although total myosin regulatory light chain content is not increased in these areas (B).

Citation: Turner J. 2003. Functional Morphology of the Intestinal Mucosae: From Crypts to Tips, p 1-22. In Hecht G (ed), Microbial Pathogenesis and the Intestinal Epithelial Cell. ASM Press, Washington, DC. doi: 10.1128/9781555817848.ch1
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Image of FIGURE 12
FIGURE 12

In monolayer culture, the Caco-2 human intestinal epithelial cell line has many of the morphological characteristics common to villus enterocytes, including a well-developed microvillus brush border, terminal web (arrow), and mature apical junction complexes (bracket).

Citation: Turner J. 2003. Functional Morphology of the Intestinal Mucosae: From Crypts to Tips, p 1-22. In Hecht G (ed), Microbial Pathogenesis and the Intestinal Epithelial Cell. ASM Press, Washington, DC. doi: 10.1128/9781555817848.ch1
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