Secretory Functions of the Alimentary Tract

Parasympathetic Stimulation Increases Alimentary Tract Glandular Secretion Rate

Stimulation of the parasympathetic nerves to the alimentary tract almost invariably increases the rates of alimentary glandular secretion. This increased secretion rate is especially true of the glands in the upper portion of the tract (innervated by the glossopharyngeal and vagus parasympathetic nerves) such as the salivary glands, esophageal glands, gastric glands, pancreas, and Brunner's glands in the duodenum. It is also true of some glands in the distal portion of the large intestine, which are innervated by pelvic parasympathetic nerves. Secretion in the remainder of the small intestine and in the first two-thirds of the large intestine occurs mainly in response to local neural and hormonal stimuli in each segment of the gut.

Sympathetic Stimulation Has a Dual Effect on Alimentary Tract Glandular Secretion Rate

Stimulation of the sympathetic nerves going to the gastrointestinal tract causes a slight to moderate increase in secretion by some of the local glands. However, sympathetic stimulation also constricts the blood vessels that supply the glands. Therefore, sympathetic stimulation can have a dual effect: (1) sympathetic stimulation alone usually slightly increases secretion, and (2) if parasympathetic or hormonal stimulation is already causing copious secretion by the glands, superimposed sympathetic stimulation usually reduces secretion, sometimes significantly, mainly because of vasoconstrictive reduction of the blood supply.

Regulation of Glandular Secretion by Hormones

In the stomach and intestine, several different gastrointestinal hormones help regulate the volume and composition of the secretions. These hormones are liberated from the gastrointestinal mucosa in response to the presence of food in the lumen of the gut. The hormones are then absorbed into the blood and carried to the glands, where they stimulate secretion. This type of stimulation is particularly valuable to increase the output of gastric juice and pancreatic juice when food enters the stomach or duodenum.

Chemically, the gastrointestinal hormones are polypeptides or polypeptide derivatives and will be discussed in more detail later.

Secretion of Organic Substances

Although all the basic mechanisms by which glandular cells function are not known, experimental evidence points to the following principles of secretion, as shown in Figure 65-1 .

• 1.

  The nutrient material needed for formation of the secretion must first diffuse or be actively transported by the blood in the capillaries into the base of the glandular cell.

• 2.

  Many mitochondria located inside the glandular cell near its base use oxidative energy to form adenosine triphosphate (ATP).

• 3.

  Energy from the ATP, along with appropriate substrates provided by the nutrients, is then used to synthesize the organic secretory substances; this synthesis occurs almost entirely in the endoplasmic reticulum and Golgi complex of the glandular cell. Ribosomes adherent to the reticulum are specifically responsible for formation of proteins that are secreted.

• 4.

  The secretory materials are transported through the tubules of the endoplasmic reticulum, passing in about 20 minutes all the way to the vesicles of the Golgi complex.

• 5.

  In the Golgi complex, the materials are modified, added to, concentrated, and discharged into the cytoplasm in the form of secretory vesicles, which are stored in the apical ends of the secretory cells.

• 6.

  These vesicles remain stored until nervous or hormonal control signals cause the cells to extrude the vesicular contents through the cells' surface. This action probably occurs in the following way. The hormone binds to its receptor and, through one of several possible cell signaling mechanisms, increases the cell membrane permeability to calcium ions. Calcium enters the cell and causes many of the vesicles to fuse with the apical cell membrane. The apical cell membrane then breaks open, thus emptying the vesicles to the exterior; this process is called exocytosis.

Water and Electrolyte Secretion

A second necessity for glandular secretion is secretion of sufficient water and electrolytes to go along with the organic substances. Secretion by the salivary glands, discussed in more detail later, provides an example of how nervous stimulation causes water and salts to pass through the glandular cells in great profusion, washing the organic substances through the secretory border of the cells at the same time. Hormones acting on the cell membrane of some glandular cells also cause secretory effects similar to those caused by nervous stimulation.

Saliva Contains a Serous Secretion and a Mucus Secretion

The principal glands of salivation are the parotid, submandibular, and sublingual glands; in addition, there are many tiny buccal glands. Daily secretion of saliva normally ranges between 800 and 1500 ml, as shown by the average value of 1000 ml in Table 65-1 .

Saliva contains two major types of protein secretion: (1) a serous secretion that contains ptyalin (an α-amylase ), which is an enzyme for digesting starches, and (2) mucus secretion that contains mucin for lubricating and for surface protective purposes.

The parotid glands secrete almost entirely the serous type of secretion, whereas the submandibular and sublingual glands secrete both serous secretion and mucus. The buccal glands secrete only mucus. Saliva has a pH between 6.0 and 7.0, which is a favorable range for the digestive action of ptyalin.

Secretion of Ions in Saliva

Saliva contains especially large quantities of K ⁺ and HCO ₃ ⁻ . Conversely, the concentrations of both Na ⁺ and Cl ⁻ are several times less in saliva than in plasma. One can understand these special concentrations of ions in the saliva from the following description of the mechanism for secretion of saliva.

Figure 65-2 shows secretion by the submandibular gland, a typical compound gland that contains acini and salivary ducts. Salivary secretion is a two-stage operation. The first stage involves the acini, and the second stage involves the salivary ducts. The acini secrete a primary secretion that contains ptyalin and/or mucin in a solution of ions with concentrations not greatly different from those of typical extracellular fluid. As the primary secretion flows through the ducts, two major active transport processes take place that markedly modify the ionic composition of the fluid in the saliva.

First, Na ⁺ is actively reabsorbed from all the salivary ducts and K ⁺ is actively secreted in exchange for Na ⁺ . Therefore, Na ⁺ concentration of the saliva becomes greatly reduced, whereas K ⁺ concentration becomes increased. However, there is excess Na ⁺ reabsorption compared with K ⁺ secretion, which creates electrical negativity of about −70 millivolts in the salivary ducts; this negativity in turn causes Cl ⁻ to be reabsorbed passively. Therefore, Cl ⁻ concentration in the salivary fluid falls to a very low level, matching the ductal decrease in Na ⁺ concentration.

Second, HCO ₃ ⁻ is secreted by the ductal epithelium into the lumen of the duct. This secretion is at least partly caused by passive exchange of bicarbonate for Cl ⁻ , but it may also result partly from an active secretory process.

The net result of these transport processes is that under resting conditions, the concentrations of Na ⁺ and Cl ⁻ in saliva are only about 15 mEq/L each, about one-seventh to one-tenth their concentrations in plasma. Conversely, K ⁺ concentration is about 30 mEq/L, seven times as great as in plasma, and HCO ₃ ⁻ concentration is 50 to 70 mEq/L, about two to three times that of plasma.

During maximal salivation, the salivary ionic concentrations change considerably because the formation rate of primary secretion by the acini can increase as much as 20-fold. This acinar secretion then flows through the ducts so rapidly that the ductal reconditioning of the secretion is considerably reduced. Therefore, when copious quantities of saliva are being secreted, the sodium chloride concentration is about one-half or two-thirds that of plasma, and potassium concentration rises to only four times that of plasma.

Function of Saliva for Oral Hygiene

Under basal awake conditions, about 0.5 ml of saliva, almost entirely of the mucous type, is secreted each minute; however, during sleep, little secretion occurs. This secretion plays an exceedingly important role for maintaining healthy oral tissues. The mouth is loaded with pathogenic bacteria that can easily destroy tissues and cause dental caries. Saliva helps prevent the deteriorative processes in several ways:

• 1.

  The flow of saliva helps wash away pathogenic bacteria, as well as food particles that provide their metabolic support.

• 2.

  Saliva contains several factors that destroy bacteria. One of these is thiocyanate ions and another is several proteolytic enzymes— most important, lysozyme— that (a) attack the bacteria, (b) aid thiocyanate ions in entering the bacteria where these ions in turn become bactericidal, and (c) digest food particles, thus helping further to remove the bacterial metabolic support.

• 3.

  Saliva often contains significant amounts of antibodies that can destroy oral bacteria, including some that cause dental caries. In the absence of salivation, oral tissues often become ulcerated and otherwise infected, and caries of the teeth can become rampant.

Basic Mechanism of Hydrochloric Acid Secretion

When stimulated, the parietal cells secrete an acid solution that contains about 160 mmol/L of hydrochloric acid, which is nearly isotonic with the body fluids. The pH of this acid is about 0.8, demonstrating its extreme acidity. At this pH, the H ⁺ concentration is about 3 million times that of the arterial blood. To concentrate the H ⁺ this tremendous amount requires more than 1500 calories of energy/L of gastric juice. At the same time that H ⁺ is secreted, HCO ₃ ⁻ diffuses into the blood so that gastric venous blood has a higher pH than arterial blood when the stomach is secreting acid.

Figure 65-5 shows schematically the functional structure of a parietal cell (also called an oxyntic cell ), demonstrating that it contains large branching intracellular canaliculi. The hydrochloric acid is formed at the villus-like projections inside these canaliculi and is then conducted through the canaliculi to the secretory end of the cell.

The main driving force for hydrochloric acid secretion by the parietal cells is a hydrogen-potassium pump ( H ⁺ -K ⁺ adenosine triphosphatase [ATPase]). The chemical mechanism of hydrochloric acid formation is shown in Figure 65-6 and consists of the following steps:

• 1.

  Water inside the parietal cell becomes dissociated into H ⁺ and hydroxide (OH ⁻ ) in the cell cytoplasm. The H ⁺ is then actively secreted into the canaliculus in exchange for K ⁺ , an active exchange process that is catalyzed by H ⁺ -K ⁺ ATPase. Potassium ions transported into the cell by the Na ⁺ -K ⁺ ATPase pump on the basolateral (extracellular) side of the membrane tend to leak into the lumen but are recycled back into the cell by the H ⁺ -K ⁺ ATPase. The basolateral Na ⁺ -K ⁺ ATPase creates low intracellular Na ⁺ , which contributes to Na ⁺ reabsorption from the lumen of the canaliculus. Thus, most of the K ⁺ and Na ⁺ in the canaliculus is reabsorbed into the cell cytoplasm, and H ⁺ takes their place in the canaliculus.

• 2.

  The pumping of H ⁺ out of the cell by the H ⁺ -K ⁺ ATPase permits OH ⁻ to accumulate and form HCO ₃ ⁻ from CO ₂ , either formed during metabolism in the cell or while entering the cell from the blood. This reaction is catalyzed by carbonic anhydrase. The HCO ₃ ⁻ is then transported across the basolateral membrane into the extracellular fluid in exchange for Cl ⁻ ions, which enter the cell and are secreted through chloride channels into the canaliculus, giving a strong solution of hydrochloric acid in the canaliculus. The hydrochloric acid is then secreted outward through the open end of the canaliculus into the lumen of the gland.

• 3.

  Water passes into the canaliculus by osmosis because of extra ions secreted into the canaliculus. Thus, the final secretion from the canaliculus contains water, hydrochloric acid at a concentration of about 150 to 160 mEq/L, potassium chloride at a concentration of 15 mEq/L, and a small amount of sodium chloride.

To produce a concentration of H ⁺ as great as that found in gastric juice requires minimal backleak into the mucosa of the secreted acid. A major part of the stomach's ability to prevent backleak of acid can be attributed to the gastric barrier due to the formation of alkaline mucus and to tight junctions between epithelia cells, as described later. If this barrier is damaged by toxic substances, such as occurs with excessive use of aspirin or alcohol, the secreted acid does leak down an electrochemical gradient into the mucosa, causing stomach mucosal damage.

The Basic Factors That Stimulate Gastric Secretion Are Acetylcholine, Gastrin, and Histamine

Acetylcholine released by parasympathetic stimulation excites secretion of pepsinogen by peptic cells, hydrochloric acid by parietal cells, and mucus by mucous cells. In comparison, both gastrin and histamine strongly stimulate acid secretion by parietal cells but have little effect on the other cells.