The stomach secretes several substances with various physiologic functions, including the following:

The stomach, although one structure, can be divided into three functional areas. Each area is associated with specific glands. These glands are composed of different cells, and these cells secrete different substances. Figure 50-1 shows the three functional areas of the stomach and the distribution of the associated types of stomach glands.

The gastric glands are highly specialized secretory glands composed of several different types of cells: parietal, chief, mucous, endocrine, and enterochromaffin. Each cell secretes a specific substance. The three most important cell types are parietal cells, chief cells, and mucous cells. These cells are depicted in Figure 50-1.

Parietal cells produce and secrete hydrochloric acid (HCl). They are the primary site of action for many of the drugs used to treat acid-related disorders. Chief cells secrete pepsinogen. Pepsinogen is a proenzyme (enzyme precursor) that becomes pepsin when activated by exposure to acid. Pepsin breaks down proteins and is therefore referred to as a proteolytic enzyme. Mucous cells are mucus-secreting cells that are also called surface epithelial cells. The secreted mucus serves as a protective coating against the digestive action of hydrochloric acid and digestive enzymes.

These three cell types play an important role in the digestive process. When the balance of these cells and their secretions is impaired, acid-related diseases can occur. The most harmful of these involve hypersecretion of acid and include peptic ulcer disease and esophageal cancer. However, the most common condition is mild to moderate hyperacidity. Many lay terms (e.g., indigestion, sour stomach, heartburn, acid stomach) have been used to describe this condition of overproduction of hydrochloric acid by the parietal cells. Hyperacidity is often associated with gastroesophageal reflux disease (GERD). This is the tendency of excessive and acidic stomach contents to back up, or reflux, into the lower (and even upper) esophagus. Over time, this condition can lead to more serious disorders such as erosive esophagitis and Barrett esophagus, a precancerous condition. Therefore, to prevent serious disorders from occurring and to promote patient comfort, GERD is aggressively treated with one or more of the medications described in this section.

Hydrochloric acid is secreted by the parietal cells in the lining of the stomach and maintains the environment of the stomach at a pH of 1 to 4. This acidity aids in the proper digestion of food and also serves as one of the body’s defenses against microbial infection via the gastrointestinal (GI) tract. Several substances stimulate hydrochloric acid secretion by the parietal cells, such as food, caffeine, chocolate, and alcohol. In moderation, any of these is usually not problematic. However, excessive consumption of large, fatty meals or alcohol, as well as emotional stress, may result in hyperproduction of hydrochloric acid and lead to hypersecretory disorders such as peptic ulcer disease.

The parietal cell is the primary target for many of the most effective drugs for the treatment of acid-related disorders. A closer look at how the parietal cell receives signals to produce and secrete hydrochloric acid will enhance the understanding of the mechanism of action of many of the drugs used to treat acid-related disorders.

The wall of the parietal cell contains three types of receptors: acetylcholine (ACh), histamine, and gastrin. When any one of these is occupied by its corresponding chemical stimulant (ACh, histamine, or gastrin, which can all be considered first messengers), the parietal cell will produce and secrete hydrochloric acid. Figure 50-2 shows the parietal cell with its three receptors. Once these receptors have become occupied, a second messenger is sent inside the cell. In the case of histamine receptors, occupation results in the production of adenylate cyclase. Adenylate cyclase converts adenosine triphosphate (ATP) to cyclic adenosine monophosphate (cAMP), which provides energy for the proton pump. The proton pump—or, more precisely, the hydrogen–potassium–adenosine triphosphatase (ATPase) pump—is a pump for the transport of hydrogen ions and is located in the parietal cells. The pump requires energy to work. If energy is present, the proton pump will be activated, and the pump will be able to transport hydrogen ions needed for the production of hydrochloric acid.

In the case of both ACh and gastrin receptors, the second messenger that drives the proton pump is not cAMP but is instead calcium ions. Anticholinergic drugs (see Chapter 21) such as atropine block ACh receptors, which also results in decreased hydrogen ion secretion from the parietal cells. However, these drugs are no longer used for this purpose and have been superseded by other drug classes discussed in this chapter. There is currently no drug to block the binding of the hormone gastrin to its corresponding receptor on the parietal cell surface.

Peptic ulcer disease is a general term for gastric or duodenal ulcers that involve digestion of the GI mucosa by the enzyme pepsin. Pepsin normally breaks down only food proteins and is the activated form of pepsinogen. Pepsinogen is produced by the chief cells of the stomach in response to hydrochloric acid released from the parietal cells. The sight, smell, and taste of food and its presence in the stomach are the primary stimulus for the release of hydrochloric acid from the parietal cells. Because the process of ulceration is driven by the proteolytic (protein breakdown) actions of pepsin together with the caustic effects of hydrochloric acid, peptic ulcer disease and related problems are also referred to by the more general term acid-peptic disorders.

In 1983, a gram-negative spiral bacterium, Campylobacter pylori, was isolated from several patients with gastritis. Over the next few years this bacterium was studied further, and it became implicated in the pathophysiology of peptic ulcer disease. The official name of the bacterium was changed to Helicobacter pylori because it was felt to have more characteristics of the Helicobacter genus. The prevalence of H. pylori as measured by serum antibody tests is approximately 40% to 60% for patients older than 60 years of age but only 10% for those younger than 30 years of age. The bacterium is found in the GI tracts of roughly 90% of patients with duodenal ulcers and 70% of those with gastric ulcers. This bacterium is also found in many patients who do not have peptic ulcer disease, and its presence is not associated with acute, perforating ulcers. These latter observations suggest that more than one factor is involved in ulceration. The American College of Gastroenterologists published treatment guidelines in 2007 for H. pylori infections. First-line therapy includes a 10- to 14-day course of a proton pump inhibitor (discussed later in the chapter) and the antibiotics clarithromycin and either amoxicillin or metronidazole (see Chapters 38 and 39) or a combination of a proton pump inhibitor, bismuth subsalicylate (see Chapter 51), and the antibiotics tetracycline and metronidazole (see Chapters 38 and 39). Many different combinations are used, but all incorporate the aforementioned key drugs.

Stress-related mucosal damage is an important issue for critically ill patients. Stress ulcer prophylaxis (or therapy to prevent severe GI damage) is undertaken in almost every critically ill patient in an intensive care unit (ICU) and for many patients on general medical surgical units. GI lesions are a common finding in ICU patients, especially within the first 24 hours after admission. The etiology and pathophysiology of stress-related mucosal damage is multifactorial and is not fully understood. Factors include decreased blood flow, mucosal ischemia, hypoperfusion, and reperfusion injury. Procedures performed commonly in critically ill patients, such as passing nasogastric (NG) tubes, placing patients on ventilators, and others, predispose patients to bleeding of the GI tract. Coagulopathy, a history of peptic ulcer or GI bleed, sepsis, use of steroids, ICU stay of longer than 1 week, and occult bleeding are considered to indicate high risk of GI lesions. Guidelines suggest that all such patients receive either a histamine receptor–blocking drug or a proton pump inhibitor, both of which are discussed in detail in this chapter.

Antacids work primarily by neutralizing gastric acidity. They do not prevent the overproduction of acid but instead help to neutralize acid secretions. It is also believed that antacids promote gastric mucosal defensive mechanisms, especially at lower dosages. They do this by stimulating the secretion of mucus, prostaglandins, and bicarbonate from the cells inside the gastric glands. Mucus serves as a protective barrier against the destructive actions of hydrochloric acid. Bicarbonate helps buffer the acidity of hydrochloric acid. Prostaglandins prevent histamine from binding to its corresponding parietal cell receptors, which inhibits the production of adenylate cyclase. Without adenylate cyclase, no cAMP can be formed and no second messenger is available to activate the proton pump (see Figure 50-2).

The primary drug effect of antacids is the reduction of the symptoms associated with various acid-related disorders, such as pain and reflux (“heartburn”). A dose of antacid that raises the gastric pH from 1.3 to 1.6 (only 0.3 point) reduces gastric acidity by 50%, whereas acidity is reduced by 90% if the pH is raised an entire point (e.g., 1.3 to 2.3). Antacid-associated pain reduction is thought to be a result of base-mediated inhibition of the protein-digesting ability of pepsin, increase in the resistance of the stomach lining to irritation, and increase in the tone of the cardiac sphincter, which reduces reflux from the stomach.

The adverse effects of the antacids are limited. The magnesium preparations, especially milk of magnesia, can cause diarrhea. Both the aluminum- and calcium-containing formulations can result in constipation. Calcium products can also cause kidney stones. Excessive use of any antacid can theoretically result in systemic alkalosis. This is more common with sodium bicarbonate. Another adverse effect that is more common with the calcium-containing products is rebound hyperacidity, or acid rebound, in which the patient experiences hyperacidity when antacid use is discontinued. Long-term self-medication with antacids may mask symptoms of serious underlying disease such as bleeding ulcer or malignancy. Patients with ongoing symptoms need to undergo regular medical evaluations, because additional medications or other interventions may be needed. Box 50-1 lists several specific nursing concerns for patients taking antacids.

Antacids are capable of causing several interactions when administered with other drugs (see Table 50-1). There are four basic mechanisms by which antacids cause interactions:

TABLE 50-1

ANTACIDS: DRUG INTERACTIONS

INTERACTING DRUG	MECHANIsM	RESULT
Benzodiazepines Sulfonylureas Sympathomimetics valproic acid		pH effects	Increased activity of interacting drugs
allopurinol tetracycline Thyroid hormones captopril Corticosteroids digoxin Histamine antagonists phenytoin isoniazid ketoconazole methotrexate nitrofurantoin Phenothiazines Salicylates Quinolone antibiotics		Decreased GI absorption	Reduced effects of interacting drugs

For dosage information on selected antacid drugs, see the table on p. 820.