Organization of the Gastrointestinal System

The gastrointestinal tract is a tube that is specialized along its length for the sequential processing of food

The gastrointestinal (GI) tract consists of both the series of hollow organs stretching from the mouth to the anus and the several accessory glands and organs that add secretions to these hollow organs ( Fig. 41-1 ). Each of these hollow organs, which are separated from each other at key locations by sphincters, has evolved to serve a specialized function. The mouth and oropharynx are responsible for chopping food into small pieces, lubricating it, initiating carbohydrate and fat digestion, and propelling the food into the esophagus. The esophagus acts as a conduit to the stomach. The stomach (see Chapter 42 ) temporarily stores food and also initiates digestion by churning and by secreting proteases and acid. The small intestine (see Chapters 44 and 45 ) continues the work of digestion and is the primary site for the absorption of nutrients. The large intestine (see Chapters 44 and 45 ) reabsorbs fluids and electrolytes and also stores the fecal matter before expulsion from the body. The accessory glands and organs include the salivary glands, pancreas, and liver. The pancreas (see Chapter 43 ) secretes digestive enzymes into the duodenum, in addition to secreting to neutralize gastric acid. The liver secretes bile (see Chapter 46 ), which the gallbladder stores for future delivery to the duodenum during a meal. Bile contains bile acids, which play a key role in the digestion of fats.

Although the anatomy of the wall of the GI tract varies along its length, certain organizational themes are common to all segments. Figure 41-2 , a cross section through a generic piece of stomach or intestine, shows the characteristic layered structure of mucosa, submucosa, muscle, and serosa.

The mucosa consists of the epithelial layer, as well as an underlying layer of loose connective tissue known as the lamina propria, which contains capillaries, enteric neurons, and immune cells (e.g., mast cells), as well as a thin layer of smooth muscle known as the lamina muscularis mucosae (literally, the muscle layer of the mucosa). The surface area of the epithelial layer is amplified by several mechanisms. Most cells have microvilli on their apical surfaces. In addition, the layer of epithelial cells can be evaginated to form villi or invaginated to form crypts (or glands). Finally, on a larger scale, the mucosa is organized into large folds.

The submucosa consists of loose connective tissue and larger blood vessels. The submucosa may also contain glands that secrete material into the GI lumen.

The muscle layer, the muscularis externa, includes two layers of smooth muscle. The inner layer is circular, whereas the outer layer is longitudinal. Enteric neurons are present between these two muscle layers.

The serosa is an enveloping layer of connective tissue that is covered with squamous epithelial cells.

Assimilation of dietary food substances requires digestion as well as absorption

The sedentary human body requires ~30 kcal/kg body weight each day (see p. 1170 ). This nutrient requirement is normally acquired by the oral intake of multiple food substances that the GI tract then assimilates. Although antigenic amounts of protein enter the body via the skin and across the pulmonary epithelium, caloric uptake by routes other than the GI tract is not thought to occur. Both the small and large intestines absorb water and electrolytes, but only the small intestine absorbs lipids, carbohydrates, and amino acids. However, even without effective GI function, parenteral (i.e., intravenous) alimentation can provide sufficient calories to sustain adults and to support growth in premature infants. Total parenteral nutrition has been used successfully on a long-term basis in many clinical settings in which oral intake is impossible or undesirable.

Food substances are not necessarily—and often are—consumed in a chemical form that the small intestine can directly absorb. To facilitate absorption, the GI tract digests the food by both mechanical and chemical processes.

Mechanical disruption of ingested food begins in the mouth with chewing (mastication). Individuals without teeth usually require their solid food to be cut into smaller pieces before eating. The mechanical processes that alter food composition to facilitate absorption continue in the stomach (see p. 865 ), both to initiate protein and lipid enzymatic digestion and to allow passage of gastric contents through the pylorus into the duodenum. This change in the size and consistency of gastric contents is necessary because solids that are >2 mm in diameter do not pass through the pylorus.

The chemical form in which different nutrients are ingested and absorbed varies according to the specific nutrient in question. For example, although most lipids are consumed in the form of triacylglycerols, it is fatty acids and monoacylglycerols, not triacylglycerols, that are absorbed by the small intestine. Thus, a complex series of chemical reactions (i.e., lipid digestion) are required to convert dietary triacylglycerols to these smaller lipid forms (see pp. 927–928 ). Similarly, amino acids are present in food as proteins and large peptides, but only amino acids and small peptides—primarily dipeptides and tripeptides—are absorbed by the small intestine. Carbohydrates are present in the diet as starch, disaccharides, and monosaccharides (e.g., glucose). However, because the small intestine absorbs all carbohydrates as monosaccharides, most dietary carbohydrates require chemical digestion before their absorption.

Digestion requires enzymes secreted in the mouth, stomach, pancreas, and small intestine

Digestion involves the conversion of dietary food nutrients to a form that the small intestine can absorb. For carbohydrates and lipids, these digestive processes are initiated in the mouth by salivary and lingual enzymes: amylase for carbohydrates and lipase for lipids. Protein digestion is initiated in the stomach by gastric proteases (i.e., pepsins), whereas additional lipid digestion in the stomach occurs primarily as a result of the lingual lipase that is swallowed, although some gastric lipase is also secreted. Carbohydrate digestion does not involve any secreted gastric enzymes.

Digestion is completed in the small intestine by the action of both pancreatic enzymes and enzymes at the brush border of the small intestine. Pancreatic enzymes, which include lipase, chymotrypsin, and amylase, are critical for the digestion of lipids, protein, and carbohydrates, respectively. The enzymes on the luminal surface of the small intestine (e.g., brush-border disaccharidases and dipeptidases) complete the digestion of carbohydrates and proteins. Digestion by these brush-border enzymes is referred to as membrane digestion.

The material presented to the small intestine includes both dietary intake and secretory products. The food material entering the small intestine differs considerably from the ingested material because of the mechanical and chemical changes just discussed. The load to the small intestine is also significantly greater than that of the ingested material. Dietary fluid intake is 1.5 to 2.5 L/day, whereas the fluid load presented to the small intestine is 8 to 9 L/day. The increased volume results from substantial quantities of salivary, gastric, biliary, pancreatic, and small-intestinal secretions. These secretions contain large amounts of protein, primarily in the form of the digestive enzymes discussed above.

Ingestion of food initiates multiple endocrine, neural, and paracrine responses

Digestion of food involves multiple secretory, enzymatic, and motor processes that are closely coordinated with one another. The necessary control is achieved by neural and hormonal processes that are initiated by dietary food substances; the result is a coordinated series of motor and secretory responses. For example, chemoreceptors, osmoreceptors, and mechanoreceptors in the mucosa in large part generate the afferent stimuli that induce gastric and pancreatic secretions. These receptors sense the luminal contents and initiate a neurohumoral response.

Endocrine, neural, and paracrine mechanisms all contribute to digestion. All three include sensor and transmitter processes. An endocrine mechanism (see p. 47 ) involves the release of a transmitter (e.g., peptide) into the blood.

For example, protein in the stomach stimulates the release of gastrin from antral G cells. Gastrin then enters the blood and stimulates H ⁺ release from parietal cells in the body of the stomach. A neural mechanism involves the activation of nerves and neurotransmitters that influence either secretory or motor activity. Neural transmission of these responses may involve the enteric nervous system ( ENS; see pp. 339–340 ) or the central nervous system (CNS). An example of neural control is activation of the vagus nerve in response to the smell of food. The resultant release of the neurotransmitter acetylcholine (ACh) also releases H ⁺ from parietal cells in the stomach.

The third mechanism of neurohumoral control is paracrine (see p. 47 ). In this mechanism, a transmitter is released from a sensor cell, and it affects adjacent cells without either entering the blood or activating neurons. For example, paracrine mechanisms help regulate gastric acid secretion by parietal cells: the histamine released from so-called enterochromaffin-like (ECL) cells in the body of the stomach stimulates H ⁺ release from neighboring parietal cells.

In addition to the primary response that leads to the release of one or more digestive enzymes, other signals terminate these secretory responses. Enteric neurons are important throughout the initiation and termination of the responses.

Although the endocrine, neural, and paracrine responses are most often studied separately, with considerable effort made to isolate individual events, these responses do not occur as isolated events. Rather, each type is part of an integrated response to a meal that results in the digestion and absorption of food. This entire series of events that results from the ingestion of food can best be described as an integrated response that includes both afferent and efferent limbs.

In addition to its function in nutrition, the GI tract plays important roles in excretion, fluid and electrolyte balance, and immunity

Although its primary roles are digesting and absorbing nutrients, the GI tract also excretes waste material. Fecal material includes nondigested/nonabsorbed dietary food products, colonic bacteria and their metabolic products, and several excretory products. These excretory products include (1) heavy metals such as iron and copper, whose major route of excretion is in bile; and (2) several organic anions and cations, including drugs, that are excreted in bile but are reabsorbed either poorly or not at all by either the small or large intestine.

As noted above, the small intestine is presented with 8 to 9 L/day of fluid, an amount that includes ~1 L/day that the intestine itself secretes. Almost all this water is reabsorbed in the small and large intestine; therefore, stool has relatively small amounts of water (~0.1 L/day). Diarrhea (an increase in stool liquidity and weight, >200 g/day) results from either increased fluid secretion by the small or large intestine, or decreased fluid reabsorption by the intestines. An important clinical example of diarrhea is cholera, especially in developing countries. Cholera can be fatal because of the water and electrolyte imbalance that it creates. Thus, the GI tract plays a crucial role in maintaining overall fluid and electrolyte balance (see Chapter 44 ).

The GI tract also contributes to immune function. The mucosal immune system, or gut-associated lymphoid tissue (GALT), consists of both organized aggregates of lymphoid tissue (e.g., Peyer's patches; see Fig. 41-2 B ) and diffuse populations of immune cells. These immune cells include lymphocytes that reside between the epithelial cells lining the gut, as well as lymphocytes and mast cells in the lamina propria. GALT has two primary functions: (1) to protect against potential microbial pathogens, including bacteria, protozoans, and viruses; and (2) to permit immunological tolerance to both the potentially immunogenic dietary substances and the bacteria that normally reside primarily in the lumen of the large intestine.

The mucosal immune system is important because the GI tract has the largest area of the body in potential direct contact with infectious, toxic, and immunogenic material. Approximately 80% of the immunoglobulin-producing cells are found in the small intestine. Although GALT has some interaction with the systemic immune system, GALT is operationally distinct. Finally, evidence indicates communication between the GALT and mucosal immune systems at other mucosal surfaces, such as the pulmonary epithelia.

Certain nonimmunological defense processes are also important in protecting against potential luminal pathogens and in limiting the uptake of macromolecules from the GI tract. The nonimmunological mechanisms that are critical in maintaining the ecology of intestinal flora include gastric acid secretion, intestinal mucin, peristalsis, and the epithelial-cell permeability barrier. Thus, whereas relatively low levels of aerobic bacteria are present in the lumen of the small intestine of physiologically normal subjects, individuals with impaired small-intestinal peristalsis often have substantially higher levels of both aerobic and anaerobic bacteria in their small intestine. A consequence may be diarrhea or steatorrhea (i.e., increased fecal fat excretion). The clinical manifestation of impaired intestinal peristalsis is referred to as either blind loop syndrome or stagnant bowel syndrome.

The ENS is a “minibrain” with sensory neurons, interneurons, and motor neurons

The ENS (see pp. 339–340 ) is the primary neural mechanism that controls GI function and is one of the three divisions of the autonomic nervous system (ANS), along with the sympathetic and parasympathetic divisions. One indication of the importance of the ENS is the number of neurons consigned to it. The ENS consists of ~100 million neurons, roughly the number in the spinal cord or in the rest of the entire ANS. The ENS is located solely within GI tissue, but it can be modified by input from the brain. Neurons of the ENS are primarily, but not exclusively, clustered in one of two collections of neurons ( Fig. 41-3 A ): the submucosal plexus and the myenteric plexus. The submucosal (or Meissner's ) plexus is found in the submucosa only in the small and large intestine. The myenteric (or Auerbach's ) plexus is located between the circular and longitudinal muscle layers throughout the GI tract from the proximal end of the esophagus to the rectum.

The ENS is a complete reflex circuit and can operate totally within the GI tract, without the participation of either the spinal cord or the cephalic brain. As with other neurons, the activity of the ENS is the result of the generation of action potentials by single neurons and the release of chemical neurotransmitters that affect either other neurons or effector cells (i.e., epithelial or muscle cells). The ENS consists of sensory circuits, interneuronal connections, and secretomotor neurons (see Fig. 41-3 B ). Sensory (or afferent ) neurons monitor changes in luminal activity, including distention (i.e., smooth-muscle tension), chemistry (e.g., pH, osmolality, levels of specific nutrients), and mechanical stimulation. These sensory neurons activate interneurons, which relay signals that activate efferent secretomotor neurons that in turn stimulate or inhibit a wide range of effector cells: smooth-muscle cells, epithelial cells that secrete or absorb fluid and electrolytes, submucosal blood vessels, and enteric endocrine cells.

The largely independent function of the ENS has given rise to the concept of a GI “minibrain.” Because the efferent responses to several different stimuli are often quite similar, a generalized concept has developed that the ENS possesses multiple preprogrammed responses. For example, both mechanical distention of the jejunum and the presence of a bacterial enterotoxin in the jejunum can elicit identical responses: stimulation of profuse fluid and electrolyte secretion, together with propagated, propulsive, coordinated smooth-muscle contractions. Such preprogrammed efferent responses are probably initiated by sensory input to the enteric interneuronal connections. However, efferent responses controlled by the ENS may also be modified by input from autonomic ganglia, which are in turn under the influence of the spinal cord and brain (see p. 336 ). N41-1 In addition, the ENS receives input directly from the brain via parasympathetic nerves (i.e., the vagus nerve).

N41-1

Hierarchical Reflex Loops in the ANS