Intestinal wall

An increase in the total surface of the mucosa reflects the absorptive function of the small intestine. Four degrees of folding amplify the absorptive surface area of the mucosa (see Figure 16-2): (1) the plicae circulares (circular folds; also known as the valves of Kerkring), (2) the intestinal villi, (3) the intestinal glands, and (4) the microvilli on the apical surface of the lining epithelium of the intestinal cells (enterocytes).

A plica circularis is a permanent fold of the mucosa and submucosa encircling the intestinal lumen.

Plicae appear about 5 cm distal to the aborad outlet of the stomach, become distinct where the duodenum joins the jejunum, and diminish in size progressively to disappear halfway along the ileum.

The intestinal villi are finger-like projections of the mucosa covering the entire surface of the small intestine. Villi extend deep into the mucosa to form crypts ending at the muscularis mucosae. The length of the villi depends on the degree of distention of the intestinal wall and the contraction of smooth muscle fibers in the villus core.

Crypts of Lieberkühn, or intestinal glands, are simple tubular glands that increase the intestinal surface area. The crypts are formed by invaginations of the mucosa between adjacent intestinal villi.

The muscularis mucosae is the boundary between the mucosa and submucosa (see Figure 16-3). The muscularis consists of inner circular smooth muscle and outer longitudinal smooth muscle. The muscularis is responsible for segmentation and peristaltic movement of the contents of the small intestine (Figure 16-4). A thin layer of loose connective tissue is covered by the visceral peritoneum, a serosal layer lined by a simple squamous epithelium, or mesothelium. The parietal peritoneum covers the inner surface of the abdominal wall.

Figure 16-4 Intestinal motility: Muscular contraction patterns

Microcirculation of the small intestine

A difference from the microcirculation of the stomach (see Figure 15-8 in Chapter 15, Upper Digestive Segment) is that the intestinal submucosa is the main distribution site of blood and lymphatic flow (see Figure 16-3).

Branches of the submucosal plexus supply capillaries to the muscularis and intestinal mucosa. Arterioles derived from the submucosal plexus enter the mucosa of the small intestine and give rise to two capillary networks: (1) the villus capillary plexus supplies the intestinal villus and upper portion of the crypts of Lieberkühn; and (2) the pericryptal capillary plexus supplies the lower half of the crypts of Lieberkühn.

A single blind-ending central lymphatic vessel, the lacteal, is present in the core of a villus. The lacteal is the initiation of a lymphatic vessel that, just above the muscularis mucosae, forms a lymphatic plexus whose branches surround a lymphoid nodule in the mucosa-submucosa. Efferent lymphatic vessels of the lymphoid nodule anastomose with the lacteal and leave the digestive tube through the mesentery, together with the blood vessels.

Innervation and motility of the small intestine

Motility of the small intestine is controlled by the autonomic nervous system. The intrinsic autonomic nervous system of the small intestine, consisting of the submucosal plexus of Meissner and myenteric plexus of Auerbach, is similar to that of the stomach (see Figure 15-9 in Chapter 15, Upper Digestive Segment).

Neurons of the plexuses receive intrinsic input from the mucosa and muscle wall of the small intestine and extrinsic input from the central nervous system through the parasympathetic (vagus nerve) and sympathetic nerve trunks.

Contraction of the muscularis is coordinated to achieve two objectives (see Figure 16-4): (1) To mix and mobilize the contents within an intestinal segment. This is accomplished when muscular contraction activity is not coordinated and the intestine becomes transiently divided into segments. This process is known as segmentation. (2) To propel the intestinal contents when there is a proximal (orad) contraction coordinated with a distal (aborad; Latin ab, from; os, mouth; away from the mouth) relaxation. When coordinated contraction-relaxation occurs sequentially, the intestinal contents are propelled in an aborad direction. This process is known as peristalsis (Greek peri, around; stalsis, constriction).

Histologic differences between the duodenum, jejunum, and ileum

Each of the three major anatomic portions of the small intestine—the duodenum, jejunum, and ileum—has distinctive features that allow recognition under the light microscope (Figure 16-5).

Figure 16-5 Histologic differences: Duodenum, jejunum, and ileum

The duodenum extends from the pyloric region of the stomach to the junction with the jejunum and has the following characteristics: (1) It has Brunner’s glands in the submucosa. Brunner’s glands are tubuloacinar mucous glands producing an alkaline secretion (pH 8.8 to 9.3) that neutralizes the acidic chyme coming from the stomach. (2) The villi are broad and short (leaflike shape). (3) The duodenum is surrounded by an incomplete serosa and an extensive adventitia. (4) The duodenum collects bile and pancreatic secretions transported by the common bile duct and pancreatic duct, respectively. The sphincter of Oddi is present at the terminal ampullary portion of the two converging ducts. (5) The base of the crypts of Lieberkühn may contain Paneth cells.

The jejunum has the following characteristics: (1) It has long finger-like villi and a well-developed lacteal in the core of the villus. (2) The jejunum does not contain Brunner’s glands in the submucosa. (3) Peyer’s patches in the lamina propria may be present but they are not predominant in the jejunum. Peyer’s patches are a characteristic feature of the ileum. (4) Paneth cells are found at the base of the crypts of Lieberkühn.

The ileum has a prominent diagnostic feature: Peyer’s patches, lymphoid follicles (also called nodules) found in the mucosa and part of the submucosa. The lack of Brunner’s glands and the presence of shorter finger-like villi—when compared with the jejunum—are additional landmarks of the ileum. As in the jejunum, Paneth cells are found at the base of the crypts of Lieberkühn.

Villi and crypts of Lieberkühn

The intestinal mucosa, including the crypts of Lieberkühn, are lined by a simple columnar epithelium containing four major cell types (Figure 16-6): (1) absorptive cells, or enterocytes, (2) goblet cells, (3) Paneth cells, and (4) enteroendocrine cells. Stem cells, Paneth cells, and enteroendocrine cells are found in the crypts of Lieberkühn (see Figure 16-6).

Figure 16-6 Epithelial cells of the villus and crypt of Lieberkühn

Absorptive intestinal cells, or enterocytes

The absorptive intestinal cell or enterocyte has an apical domain with a prominent brush border (also called a striated border), ending on a clear zone, called the terminal web, which contains transverse cytoskeletal filaments. The brush border of each absorptive cell contains about 3000 closely packed microvilli, which increase the surface luminal area 30-fold.

The length of a microvillus ranges from 0.5 to 1.0 μm. The core of a microvillus (Figure 16-7) contains a bundle of 20 to 40 parallel actin filaments cross-linked by fimbrin and villin. The actin bundle core is anchored to the plasma membrane by formin (protein of the cap), myosin I, and the calcium-binding protein calmodulin. Each actin bundle projects into the apical portion of the cell as a rootlet, which is cross-linked by an intestinal isoform of spectrin to an adjacent rootlet. The end portion of the rootlet attaches to cytokeratin-containing intermediate filaments. Spectrin and cytokeratins form the terminal web. The terminal web is responsible for maintaining the upright position and shape of the microvillus and anchoring the actin rootlets.

Figure 16-7 Intestinal epithelium

A surface coat or glycocalyx consisting of glycoproteins as integral components of the plasma membrane covers each microvillus.

The microvilli, forming a brush border, contain intramembranous enzymes, including lactase, maltase, and sucrase (Figure 16-8). These oligosaccharides reduce carbohydrates to hexoses, which can be transported into the enterocyte by carrier proteins. A genetic defect in lactase prevents the absorption of lactose-rich milk, leading to diarrhea (lactose intolerance). Therefore, the brush border not only increases the absorptive surface of enterocytes but is also the site where enzymes are involved in the terminal digestion of carbohydrates and proteins.

Figure 16-8 Digestion and absorption of proteins and carbohydrates

Final breakdown of oligopeptides, initiated by the action of gastric pepsin, is extended by pancreatic trypsin, chymotrypsin, elastase, and carboxypeptidases A and B. Enterokinase and aminopeptidase, localized in the microvilli, degrade oligopeptides into dipeptides, tripeptides, and amino acids before entering the enterocyte across symporter channels together with Na⁺. Cytoplasmic peptidases degrade dipeptides and tripeptides into amino acids, which then diffuse or are transported by a carrier-mediated process across the basolateral plasma membrane into the blood.

The absorption of lipids involves the enzymatic breakdown of dietary lipids into fatty acids and monoglycerides, which can diffuse across the plasma membrane of the microvilli and the apical plasma membrane of the enterocyte. Details of the process of fat absorption are depicted in Figure 16-9.

Figure 16-9 Digestion and absorption of lipids

Goblet cells

Goblet cells are columnar mucus-secreting cells scattered among enterocytes of the intestinal epithelium (see Figure 16-7).

Goblet cells have two domains: (1) a cup- or goblet-shaped apical domain containing large mucus granules that are discharged on the surface of the epithelium and (2) a narrow basal domain, which attaches to the basal lamina and contains the rough endoplasmic reticulum in which the protein portion of mucus is produced. The Golgi apparatus, which adds oligosaccharide groups to mucus, is prominent and situated above the basally located nucleus.

The secretory product of goblet cells contains glycoproteins (80% carbohydrate and 20% protein) released by exocytosis. On the surface of the epithelium, the mucus hydrates to form a protective gel coat to shield the epithelium from mechanical abrasion and bacterial invasion.

Enteroendocrine cells

In addition to its digestive function, the gastrointestinal tract is the largest diffuse endocrine gland in the body.

We have already studied the structural and functional features of enteroendocrine cells in the stomach (see Chapter 15, Upper Digestive Segment). As in the stomach, enteroendocrine cells secrete peptide hormones controlling several functions of the gastrointestinal system. The location and function of gastrin-, secretin-, and cholecystokinin-secreting cells are summarized in Figure 16-10.

Figure 16-10 Roles of gastrin, secretin, and cholecystokinin in digestion

Intestinal tight junction barrier

Intestinal tight junctions link adjacent enterocytes and provide a barrier function impermeable to most hydrophilic solutes in absence of specific transporters. Tight junctions establish a separation between the intestinal luminal content and the mucosal immune function that occurs within the lamina propria. Plasma cells, lymphocytes, eosinophils, mast cells and macrophages are present in the intestinal lamina propria.

Claudin and occludin are two transmembrane proteins of tight junctions that regulate solute permeability of the transcellular pathway. Flux of dietary proteins and bacterial lipopolysaccharides across leaky tight junctions can increase in the presence of tumor necrosis factor–α and interferon-γ, two proinflammatory cytokines that affect tight junction integrity. Many diseases associated with intestinal epithelial dysfunction, including inflammatory bowel disease and intestinal ischemia, are linked to increased levels of tumor necrosis factor.