Salivation

The three pairs of salivary glands (the submandibular, sublingual, and parotid glands) (Figure 40-3) secrete about 1 L of saliva per day. Saliva consists mostly of water that contains varying amounts of mucus, sodium, bicarbonate, chloride, potassium, and salivary α-amylase (ptyalin), an enzyme that initiates carbohydrate digestion in the mouth and stomach.

The sympathetic and parasympathetic divisions of the autonomic nervous system control salivation. Because cholinergic parasympathetic fibers stimulate the salivary glands, atropine (an anticholinergic agent) inhibits salivation and makes the mouth dry. β-Adrenergic stimulation from sympathetic fibers also increases salivary secretion. The salivary glands are not regulated by hormones, although hormones are found in saliva.^1a

The composition of saliva depends on the rate of secretion. Aldosterone can decrease the rate of secretion by increasing an exchange of sodium for potassium. Sodium and water are conserved and potassium is excreted. The bicarbonate concentration of saliva sustains a pH of about 7.4, which neutralizes bacterial acids and prevents tooth decay. Saliva also contains immunoglobulin A (IgA), which helps prevent infection. Exogenous fluoride (e.g., fluoride in drinking water) is absorbed and then secreted in the saliva, providing additional protection against tooth decay.

Swallowing

The esophagus is a hollow muscular tube approximately 25 cm long that conducts substances from the oropharynx to the stomach (see Figure 40-1). The pharynx and upper third of the esophagus contain striated muscle that is directly innervated by skeletal motor neurons that control swallowing. The middle third contains a mix of striated and smooth muscle, and the lower third is smooth muscle that is innervated by preganglionic cholinergic fibers from the vagus nerve. Peristalsis is stimulated when afferent fibers distributed along the length of the esophagus sense changes in wall tension caused by stretching as food passes. The greater the tension, the greater the intensity of esophageal contraction. Occasionally, intense contractions cause pain similar to “heartburn” or angina.

Each end of the esophagus is opened and closed by a sphincter. The upper esophageal sphincter (cricopharyngeal muscle) prevents entry of air into the esophagus during respiration.² The lower esophageal sphincter (cardiac sphincter) prevents regurgitation from the stomach. The lower esophageal sphincter is located near the esophageal hiatus—the opening in the diaphragm where the esophagus ends at the stomach.³

Swallowing is a complex event mediated by the trigeminal nucleus, nucleus tractus solitarius, and reticular formation of the brainstem and also involves other brain regions, including the insula/claustrum and cerebellum.⁴

Swallowing occurs in two phases: the oropharyngeal (voluntary) phase and the esophageal (involuntary) phase. During the oral and pharyngeal phases of swallowing, food is segmented into a bolus by the tongue and forced posteriorly toward the pharynx as the tongue pushes upward against the hard palate. The superior constrictor muscle of the pharynx contracts, preventing movement of food into the nasopharynx. At the same time, respiration is inhibited and the epiglottis folds downward to prevent the bolus from entering the larynx and trachea. The movements of the tongue and pharyngeal constrictors propel the food into the esophagus in a series of coordinated events, taking less than 1 or 2 seconds.

During the esophageal phase of swallowing, the bolus is transported to the stomach by the coordinated sequential contraction and relaxation of outer longitudinal and inner circular layers of smooth muscle. The wave of relaxation reduces resistance and allows food to pass, after which the wave of contraction pushes food farther along. The terminal 1 to 2 cm portion of the musculature forms the lower esophageal sphincter, which relaxes just before the arrival of a peristaltic wave. The sphincter muscles return to their resting tone after the bolus of food passes into the stomach. The esophageal phase of swallowing takes 5 to 10 seconds, with the bolus moving 2 to 6 cm/second. Throughout swallowing, the sphincters and esophagus work in concert with the peristaltic wave that moves food from the mouth to the stomach.

Peristalsis that immediately follows the oropharyngeal phase of swallowing is called primary peristalsis. If a bolus of food becomes stuck in the esophageal lumen, the distention of the esophageal wall stimulates secondary peristalsis, a wave of contraction and relaxation that is independent of voluntary swallowing. This is in response to stretch receptors that are stimulated by increased wall tension, causing an increase in impulses from the swallowing center of the brain.

When it is closed, the lower esophageal sphincter serves as a barrier between the stomach and esophagus. Cholinergic vagal stimulation and the digestive hormone gastrin increase sphincter tone. Nonadrenergic, noncholinergic vagal impulses relax the lower esophageal sphincter, as do the hormones progesterone, secretin, and glucagon. Relaxation during swallowing is mediated by the vagus nerve.⁵

Gastric Motility

In its resting state the stomach is small and contains about 50 ml of fluid. There is little wall tension, and the muscle layers in the fundus contract very little. Swallowing causes the fundus to relax (receptive relaxation) to receive a bolus of food from the esophagus. Relaxation is coordinated by efferent, nonadrenergic, noncholinergic vagal fibers and is facilitated by gastrin and cholecystokinin, two polypeptide hormones secreted by the gastrointestinal mucosa. (The actions of digestive hormones are summarized in Table 40-1.) Food is stored in vertical or oblique layers as it arrives in the fundus, whereas fluids flow relatively quickly down to the antrum.

Gastric (stomach) motility increases with the initiation of peristaltic waves, which sweep over the body of the stomach toward the antrum. The rate of peristaltic contractions is approximately three per minute and is influenced by neural and hormonal activity. Gastrin and motilin (small intestine hormones) and the vagus nerve increase contraction by making the threshold potential of muscle fibers less negative. (The neural and biochemical mechanisms of muscle contraction are described in Chapter 43.) Sympathetic activity and secretin (another small intestine hormone) are inhibitory and make the threshold potential more negative. The rate of peristalsis is mediated by pacemaker cells that initiate a wave of depolarization (basic electrical rhythm), which moves from the upper part of the stomach to the pylorus.

Gastric mixing and subsequent emptying of gastric contents (chyme) from the stomach take several hours (3 to 6 hours depending on the composition and volume of food intake). Mixing occurs as food is propelled toward the antrum. As food approaches the pylorus, the velocity of the peristaltic wave increases, forcing the contents back toward the body of the stomach. This retropulsion effectively mixes food with digestive juices, and the oscillating motion breaks down large food particles. With each peristaltic wave a small portion of the chyme passes through the pylorus and into the duodenum. The pyloric sphincter is about 1.5 cm long and is always open about 2 mm. It opens wider during antral contraction. Normally there is no regurgitation from the duodenum into the antrum.

The rate of gastric emptying (movement of gastric contents into the duodenum) depends on the volume, osmotic pressure, and chemical composition of the gastric contents. Larger volumes of food increase gastric pressure, peristalsis, and rate of emptying. Solids, fats, and nonisotonic solutions delay gastric emptying.⁶ (Osmotic pressure and tonicity are described in Chapters 1 and 3.) Products of fat digestion, which are formed in the duodenum by the action of bile from the liver and enzymes from the pancreas, stimulate the secretion of cholecystokinin.⁷ This hormone inhibits food intake, reduces gastric motility, and decreases gastric emptying so that fats are not emptied into the duodenum at a rate that exceeds the rate of bile and enzyme secretion. Osmoreceptors in the wall of the duodenum are sensitive to the osmotic pressure of duodenal contents. The arrival of hypertonic or hypotonic gastric contents activates the osmoreceptors, which delays gastric emptying to facilitate formation of an isosmotic duodenal environment. The rate at which acid enters the duodenum also influences gastric emptying. Secretions from the pancreas, liver, and duodenal mucosa neutralize gastric hydrochloric acid in the duodenum. The rate of emptying is adjusted to the duodenum’s ability to neutralize the incoming acidity. Peristaltic activity in the stomach is also affected by blood glucose levels. Low blood glucose levels stimulate the vagus nerve and gastric smooth muscles, increasing the rate of contraction.⁸

Gastric Secretion

Stimulated by eating, the stomach produces large volumes of gastric secretions. Specialized cells located throughout the gastric mucosa produce mucus, acid, enzymes, hormones, intrinsic factor, and gastroferrin. Intrinsic factor is necessary for the intestinal absorption of vitamin B₁₂ and gastroferrin facilitates small intestinal absorption of iron. The hormones are secreted into the blood and travel to target tissues in the bloodstream. The other gastric secretions are released directly into the stomach lumen under neural and hormonal regulation.⁹ Mucus covering the entire mucosa, intercellular tight junctions, bicarbonate secretion, and submucosal acid sensors form a protective barrier against acid and proteolytic enzymes, which otherwise would damage the gastric lining.¹⁰

In the fundus and body of the stomach the gastric glands of the mucosa are the primary secretory units (Figure 40-5). Several of these glands (three to seven) empty into a common duct known as the gastric pit. The parietal cells (oxyntic cells) within the glands secrete hydrochloric acid, intrinsic factor, and gastroferrin. The chief cells within the glands secrete pepsinogen, an enzyme precursor that is readily converted to pepsin (a proteolytic enzyme) in the gastric fluid. The pyloric gland mucosa in the antrum synthesizes and releases the hormone gastrin from G cells. Enterochromaffin-like cells secrete histamine, and D cells secrete somatostatin.

The composition of gastric fluid depends on volume and flow rate (Figure 40-6). Potassium level remains relatively constant, but its concentration is greater in gastric secretions than in plasma. The rate of secretion varies with the time of day; lower in the morning and higher in the afternoon and evening. Loss of gastric secretions through vomiting, drainage, or suction may decrease body stores of sodium, potassium, hydrogen, and chloride.

Acid

The major functions of gastric hydrochloric acid are to dissolve food fibers, act as a bactericide against swallowed organisms, and convert pepsinogen to pepsin. The production of acid by the parietal cells requires the transport of hydrogen and chloride from the parietal cells to the stomach lumen. Acid is formed in the parietal cells, primarily through the hydrolysis of water (Figure 40-7). At a high rate of gastric secretion, bicarbonate moves into the plasma, producing an “alkaline tide” in the venous blood, which also may result in a more alkaline urine.¹¹

Acid secretion by parietal cells is stimulated by acetylcholine (ACh) (a neurotransmitter), gastrin (a hormone), and histamine (a biochemical mediator). The vagus nerve releases ACh and stimulates the secretion of histamine and gastrin-releasing peptide (GRP), which stimulates release of gastrin.¹² Histamine secretion is also stimulated by gastrin. Histamine is stored in enterochromaffin cells (mast cells; see Chapter 7) in the gastric mucosa. Histamine receptors in the gastric mucosa are H2 receptors (unlike those in the bronchial mucosa, which are H1 receptors). Gastric lipase is produced by glands in the fundus of the stomach and is most effective in an acidic environment. Caffeine stimulates acid secretion, as does calcium. Prostaglandins, enterogastrones (such as gastric inhibitory peptide), somatostatin, and secretin inhibit acid secretion.¹³

Phases of Gastric Secretion

The secretion of gastric juice is influenced by numerous stimuli that together facilitate the process of digestion. The phases of gastric secretion are the cephalic phase, gastric phase, and intestinal phase (Figure 40-8).

Cephalic Phase

The anticipatory and sensory experiences of smelling, seeing, tasting, chewing, and swallowing food contribute to the cephalic phase of secretion.¹⁵ The cephalic phase of gastric secretion is mediated by the vagus nerve through the myenteric plexus. Acetylcholine stimulates the parietal and chief cells to secrete acid and pepsinogen, respectively. The G cells in the antrum release gastrin, which circulates through the bloodstream to the gastric glands and stimulates acid and pepsinogen secretion.

Insulin secretion by the endocrine pancreas, stimulated by hyperglycemia, also is a strong stimulus for gastric secretion and is mediated by the vagus nerve through sensors located in the hypothalamus. Maintenance of steady serum glucose levels suppresses the gastric response to insulin.

Gastric Phase

The gastric phase of secretion begins with the arrival of food in the stomach. Two major stimuli have a secretory effect: (1) distention of the stomach, and (2) the presence of digested protein. The vagus and enteric nerve plexuses are stimulated by distention and contribute to gastric secretion through a local reflex. Both neural reflexes are mediated by ACh and can be blocked by atropine. As digestion proceeds, products of protein break down, stimulating the release of more gastrin from G cells.

Intestinal Phase

The movement of chyme from the stomach into the duodenum initiates the intestinal phase of secretion. This phase represents a deceleration of the gastric secretory response; however, the presence of digested protein and amino acids in the duodenum continues to stimulate some gastric secretion.

Concurrently, in response to low duodenal pH and the presence of lipids, inhibitory vagal and enteric reflexes decrease gastric motility when chyme enters the duodenum. The release of secretin and cholecystokinin stimulate pancreatic secretions and inhibit gastric secretions.

Intestinal Digestion and Absorption

The process of intestinal digestion is initiated in the stomach by the actions of gastric hydrochloric acid and pepsin, which break down food fibers and proteins. The chyme that passes into the duodenum is a liquid that contains small particles of undigested food. Digestion is continued in the proximal portion of the small intestine by the action of pancreatic enzymes, intestinal brush-border enzymes, and bile salts (Box 40-1). Here carbohydrates are broken down to monosaccharides and disaccharides; proteins are degraded further to amino acids and peptides; and fats are emulsified and reduced to fatty acids and monoglycerides (Figure 40-10). These nutrients, along with water, vitamins, and electrolytes, are absorbed across the intestinal mucosa and into the blood by active transport, diffusion, or facilitated diffusion. Products of carbohydrate and protein breakdown move into villus capillaries and then to the liver through the hepatic portal vein. Digested fats move into the lacteals and eventually reach the liver through the systemic circulation. Intestinal motility exposes nutrients to a large mucosal surface area by mixing chyme and moving it through the lumen. Different segments of the gastrointestinal tract absorb different nutrients. Digestion and absorption of all major nutrients occur in the small intestine. Sites of absorption are shown in Figure 40-11.

Water and Electrolyte Transport by the Small Intestine

The epithelial cell membranes of the small intestine are formed of lipids and therefore are hydrophobic, or tend to repel water. (The properties of cell membranes are described in Chapter 1.) Therefore, water and electrolytes are transported in both directions (toward the capillary blood or toward the intestinal lumen) through the tight junctions and intercellular spaces rather than across cell membranes. Water diffuses passively across hydrostatic pressure and osmotic gradients established by the active transport of sodium and other substances. Approximately 85% to 90% of the water that enters the gastrointestinal tract each day is absorbed in the small intestine. The remaining water and electrolytes are absorbed at a constant rate in the large intestine.¹⁸ Sodium passes through the tight junctions and is actively transported across cell membranes. Sodium and glucose share a common active transport carrier (sodium-glucose ligand transporter1 [SGLT1]) so that sodium absorption is enhanced by glucose transport^18a (Figure 40-12). Potassium moves passively across the tight junctions with changes in the electrochemical gradient. Chloride is actively secreted throughout the large and small intestines.

Fats

Approximately 90 to 100 g of fat is consumed daily by the average American. Fat is an important source of calories and is a primary structural component of cell membranes and organelles. Sources of dietary fat are reviewed in Box 40-2. Although triglycerides are the major dietary lipids, cholesterol, phospholipids, and fat-soluble vitamins also have nutritional importance. The digestion and absorption of fat occur in four phases: (1) emulsification and lipolysis, (2) micelle formation, (3) fat absorption, and (4) resynthesis of triglycerides and phospholipids.

The mechanical action of the stomach and small intestine disperses the triglyceride droplets into small particles. Emulsification is the process by which emulsifying agents (fatty acids, monoglycerides, lecithin, cholesterol, protein, bile salts) in the small intestinal lumen cover the small fat particles and prevent them from re-forming into fat droplets. Emulsified fat is then ready for lipolysis (lipid hydrolysis) by pancreatic lipase, phospholipase, and hydrolase. Lipase breaks down triglycerides to diglycerides, monoglycerides, free fatty acids, and glycerol (see Figure 40-10). The action of lipase requires the presence of colipase, a pancreatic enzyme that allows lipase to penetrate the triglyceride molecule. Phospholipase cleaves fatty acids from phospholipids, and cholesterol esterase breaks cholesterol esters into fatty acids and glycerol.

The products of lipid hydrolysis must be made water soluble if they are to be absorbed efficiently from the intestinal lumen. This is accomplished by the formation of water-soluble molecules known as micelles (Figure 40-13). Micelles are formed of bile salts (see p. 1411), the products of fat hydrolysis, fat-soluble vitamins, and cholesterol. The fats form the core of the micelle, and the polar bile salts form an outer shell, with the hydrophobic (“water-hating”) side facing the interior and the hydrophilic (“water-loving”) side facing the aqueous (water-like) content of the intestinal lumen. Because the unstirred layer of the brush border is aqueous, the micelles readily diffuse through it. The micelles maintain the fat molecules in the dissolved or solubilized form, which allows them to move more rapidly from the micelle toward the absorbing surface of the intestinal epithelium. The fat products of the micelle then readily diffuse through the epithelial cell membrane, while the bile salts remain in the lumen and proceed to the ileum, where they are absorbed into the circulation and returned to the liver via the enterohepatic circulation (Figure 40-14 and Figure 40-20, p. 1411). Almost all of the bile salts are recycled in this way.