I.               INTRODUCTION

The major functions of the gastrointestinal (GI) tract are digestion and movement of food, absorption of nutrients, and elimination of wastes. Scopes to allow direct visualization have helped greatly in the diagnosis and biopsy of lesions in the GI tract. Fiber optic endoscopy has been of particular value.

II.             THE ESOPHAGUS

The esophagus is located posterior to the trachea, and the two structures develop in close relation to one another. The esophagus is also located close to the aortic arch. The esophagus is a hollow, distensible, muscular tube that conducts food from the pharynx to the stomach. This movement is accomplished by peristalsis, the coordinated contraction of the smooth muscle that lines the entire intestinal tract. Stimulation of peristalsis involves both neural and hormonal mechanisms.

The lower part of the esophagus pierces the diaphragm. Where the esophagus joins the stomach, there is a physiological sphincter that prevents the backflow of food. This sphincter is composed of a thickening of the esophageal wall and also involves diaphragmatic muscles. Like peristalsis, the tone of the sphincter is under the control of nerve impulses and hormones. Certain substances, such as cigarettes and coffee, can cause relaxation of the sphincter, allowing reflux of gastric juices. The enzymes and acid in these gastric juices can damage the cells that line the esophagus.

A. Congenital esophageal diseases

• Tracheo-esophageal fistula: A fistula is an abnormal connection between two organs or two different parts of the same organ. In general, fistulas may be congenital or acquired after birth. A fistula between the trachea and esophagus may result from atresia (failure to develop properly) of the esophagus. When the trachea is abnormally connected to the lower esophagus, air passing into the trachea from normal breathing may find its way into the esophagus. This can lead to bloating due to massive amounts of air accumulating in the stomach. Also, swallowed food may get into the lungs, causing an aspiration pneumonia.

• The esophagus may also be constricted or end in a blind pouch, again due to abnormal development. The latter condition results in vomiting up of food. Both blind pouches and tracheo-esophageal fistula require surgical treatment.

B. Inflammatory esophageal disease (esophagitis)

Symptoms of esophageal disease include dysphagia (difficulty swallowing; a sense that food is "stuck") and pyrosis (burning retrosternal pain commonly called "heartburn"). Pyrosis is sometimes mistaken for pain of cardiac origin. Esophagitis is usually due to reflux; infections are a rarer cause.

• Reflux: refers to the abnormal movement of gastric juices from the stomach to the esophagus. These juices cause a chemical inflammation, since the esophagus does not have the same protective mechanisms against acids and enzymes as does the stomach. The acid from the stomach causes necrosis of the esophageal epithelium, which then evokes an inflammatory response. Under normal circumstances, reflux is prevented by the function of the lower esophageal sphincter described above. In reflux esophagitis, the tone of this sphincter is not optimal. Factors that contribute to reflux include chemicals, such as nicotine. Reflux is the most common cause of esophageal inflammation.

Hiatal hernia may also play a role, although there is controversy on this point. Hiatal hernia refers to a defect in the opening of the diaphragm that allows part of the stomach to protrude into the thoracic cavity. As a result, the diaphragmatic muscle fibers cannot serve their normal sphincter function.

With time, reflux may cause marked scarring (fibrosis), resulting in narrowing of the lumen of the esophagus. This, in turn, may result in dysphagia. Early cases of reflux can be treated medically (e.g., with changes in lifestyle and diet, antacids), but more advanced cases may require surgery.

• Infections: as mentioned, these are a relatively rare cause of esophagitis. Usually, these infections are seen in immunocompromised patients and involve opportunistic organisms, e.g., herpesviruses, cytomegalovirus, Candida.

C. Varices in the distal esophagus

A varix (plural: varices) is a dilated, tortuous vein. Persons can develop varices in the submucosa of the distal esophagus due to abnormally high pressure in blood flowing from the portal vein (see the lecture on the liver). Rupture of these varices can result in massive hemorrhage, which may even prove fatal. Indeed, bleeding from such varices is a very common cause of death in patients with cirrhosis of the liver. Signs of bleeding in the GI tract include: 1) Hematemesis, which is vomiting of blood. The blood may be bright red, which indicates sudden and massive bleeding, or it may look like coffee grounds. A coffee-ground appearance may result if the bleeding is slow and chronic, allowing partial digestion of the blood. 2) Melena, which is the passage of black, tarry stools. This black, tarry appearance results from the presence of partially digested blood and is usually due to bleeding in the lower GI tract. Relatively large amounts of bleeding are needed to produce melena. Bleeding from hemorrhoids usually results in bright red blood appearing in the stool – the hemorrhoids are located so distally that there is no digestion of blood from them. There are tests to detect occult blood in the stool, i.e., blood that is not grossly visible. Treatment is often difficult.

D. Esophageal carcinoma

Carcinoma of the esophagus is uncommon in the US (~8000 cases/year). It usually occurs in males over the age of 50. The initial symptoms that it causes are often very nonspecific, making early diagnosis difficult. Symptoms may include dysphagia (due to obliteration of the lumen by the tumor), weight loss, hematemesis as the tumor erodes into vessels, and pain. Eighty percent of tumors occur in the mid- or lower esophagus. Almost all are squamous cell carcinomas that originate from the lining of the esophagus. Tumors may ulcerate into adjacent structures, such as the trachea (resulting in acquired tracheo-esophageal fistulas) or aorta (resulting in massive bleeding). Diagnosis is made by endoscopy, barium swallow radiographic studies, and biopsy. A marked geographic variation in the incidence of the disease points to environmental factors as a cause. Vitamin deficiencies and a high intake of nitrosamines in smoked or pickled foods may be involved. Tobacco use and alcohol abuse are also risk factors. Tumors in the early stages can be treated by surgical resection; radiation therapy and chemotherapy are not very effective. The two year survival rate is only about 5%.

III.           THE STOMACH

The esophagus joins the stomach at the cardia. The fundus is the upper part of the stomach, the corpus (body) is the central part, and the mucin-secreting antrum is the lower section. The pylorus is located where the antrum joins the duodenum, and it controls movement of substances from the stomach to the duodenum. There are four important types of cells in the stomach:

1. Chief cells: which make digestive enzymes, such as pepsinogen, which is converted into pepsin in the lumen of the stomach.
2. Parietal cells: which make hydrochloric acid and intrinsic factor, which is needed for the absorption of Vitamin B₁₂.
3. Mucus-producing cells: which serve a crucial protective role.
4. G cells: which secrete the hormone gastrin, which in turn stimulates parietal cells to make HCl.

Secretion of acid by the parietal cells is controlled by neural stimulation via acetylcholine, which can be triggered by the smell or taste of food or by distention of the stomach; gastrin, which is made by the G cells; and histamine, which is produced by mast cells.

The health of the gastric mucosa is maintained by an intact mucous layer, a normal flow of blood, normal production of acid and bicarbonate (the latter of which is produced in the distal stomach and duodenum), and normal secretion of gastrin. Destruction of the gastric mucosa is promoted by infection with Helicobacter pylori (formerly known as Campylobacter), increased production of acid, substances such as aspirin and other nonsteroidal anti-inflammatory drugs, smoking, and ischemia. H. pylori is a gram-negative bacterium that alters the normal mucous layer.

A. Gastritis

• Acute gastritis: refers to a relatively severe but short-lived inflammation, usually resulting from exposure to an irritant such as alcohol or aspirin. It can also be a consequence of physiological stress, such as stroke or severe burns. Symptoms may include pain, nausea, and hematemesis. Acute gastritis with hemorrhage can lead to shock and death. It can be worsened by cigarette smoking. It is related to acute (stress) ulcers (see below).

• Chronic gastritis: is often mediated by H. pylori. The bacterium does not directly injure the cells lining the stomach; rather, it disrupts the normal mucous layer, allowing acid and enzymes to injure the underlying cells. This condition can result in atrophy of the lining cells. Rarely, this disease has an immunological cause. For example, autoimmune destruction of the parietal cells may lead to pernicious anemia, since Vitamin B₁₂ cannot be absorbed in the absence of intrinsic factor (see the lecture on blood). Diagnosis is by a breath test or biopsy.

B. Gastric ulcers

An ulcer is defined as a discrete area of necrosis in the epithelial or mucosal lining of an organ. Gastric ulcers are classified as acute or chronic.

• Acute (stress) ulcers: arise as an extension of acute gastritis or from severe physiological stress to the body, such as major trauma or surgery, a severe head injury, or hypotensive shock. Stress ulcers are often small but multiple, and they may cause massive bleeding. These ulcers tend to resolve quickly once the source of the stress is removed.

• Chronic (peptic) ulcers: are deep, chronic ulcers that are often solitary and bigger than stress ulcers. They are quite common, affecting 10% of the population, and occur more frequently than do stress ulcers. They can occur at any age, but are most frequently seen in males over the age of 40. They arise from excessive erosion of the mucosa by peptic juices. About 80% of chronic ulcers affect the duodenum (the first segment of the small intestine) and are due to increased secretion of acid. The remaining 20% that affect the stomach itself (usually the antrum) result from defects in the resistance of the mucosa to acid. That is, there is an imbalance between normal protective mechanisms and the inherent destructive tendencies of the gastric juices. The acid production is often normal or even decreased. H. pylori certainly plays a role, as 90% of cases of peptic ulcer are associated with infection by this organism. Smoking, alcohol, and NSAIDs are also risk factors.

As mentioned, these ulcers are usually large, deep, and solitary. The may erode into an artery in the stomach or duodenal wall, leading to hemorrhage, or they may even bore completely through the wall, resulting in massive peritonitis. The most common complication is an upper GI bleed, which accounts for 25% of deaths from ulcers. Perforation is a rarer event, but since it is so serious, it is the most common cause of death in these patients. Scarring and fibrosis may lead to obstruction, in which case surgical intervention is required. Perforation can cause air to accumulate beneath the diaphragm, which can be seen by x-ray. Chronic gastric ulcers may erode into adjacent structures. For example, erosion into the pancreas causes local destruction, leading to pancreatitis.

A highly characteristic symptom of chronic ulcers is epigastric pain that occurs one to three hours after a meal (since food tends initially to “sop up” the acid). The pain is often relieved by taking antacids or eating more food. Fortunately, these ulcers are usually not fatal, but they can be chronic and recurring. Treatment is directed toward decreasing production of acid, e.g., by using acid pump inhibitors or drugs that block H2 receptors for histamine. Antibiotic therapy to eliminate H. pylori is also important.

C. Gastric cancer

This incidence of this disease shows great geographic variation. It is low and decreasing in the US, but high in Japan, Chile, northern Europe, and China. It is thought that environmental factors, particularly diet, are important, since countries with high dietary levels of nitrosamines have the highest incidences. It is also associated with infection by H. pylori. It can occur in younger people, but it is most common in those over 50. Early symptoms are vague and nonspecific, including indigestion, anorexia, nausea, pain, weight loss, vomiting, and feeling full with little eating. As a consequence, early diagnosis is unusual. In Japan, where the incidence is high, aggressive screening by endoscopy has resulted in earlier detection and a generally better prognosis.

These tumors may resemble ulcers. They may also be fungating (filling up the stomach) or more diffuse in their growth. The diffuse tumors may give the stomach a stiff, "leather-bottle" quality.  Gastric cancer tends to spread to the regional lymph nodes, the peritoneal cavity, the liver, and the ovaries. The tumors usually develop from glandular cells lining the stomach; therefore, they are classified as adenocarcinomas. If the tumor can be resected, treatment is surgical. Chemotherapy is not very effective. In the US, the 5 year survival rate is only 10%.

IV.           THE INTESTINE

Infections are the most common maladies of the intestine, and the most common manifestation of these is diarrhea. Tumors rarely occur in the small intestine. The term gastroenteritis refers to infections of the stomach and/or small intestine.

The major function of the small intestine is absorption of digested food. A very large surface area for such absorption is provided by mucosal folds, villi, and microvilli on individual cells. Any disease affecting the cells that line the intestine will interfere with absorption and result in diarrhea.

A. Inflammatory bowel disease

There are two major conditions that fall in this category: Crohn’s disease (also called regional enteritis) and ulcerative colitis. Both of these diseases are idiopathic (without a known unifying cause). No infection that is consistently present has been identified. Both diseases may have autoimmune, genetic, and/or emotional components. Both diseases also have a number of other features in common, including:

• Both are chronic, relapsing diseases.
• Both affect women more frequently than men and are seen most often in people in their 20’s.
• Both cause intermittent diarrhea.
• The severity of both diseases is quite variable, ranging from a single mild episode to chronic, severe disease. The response to therapy is also variable.

However, each disease also has its own unique features. The following are typical of Crohn’s disease:

• It can affect the GI tract anywhere from the mouth to the anus, but, most typically, the small intestine and/or colon are involved.
• It causes transmural inflammation, affecting all layers of the intestinal wall.
• It is characterized by patchy, discontinuous inflammation ("skip areas").
• Granulomas (collections of macrophages) are typically seen; these may spread to lymph nodes.
• Fistulas tend to form, either between loops of bowel or with the skin, bladder, or vagina.
• Elongated, linear ulcerations give the intestinal wall a "cobblestone" appearance.
• May cause fibrosis, resulting in narrowing of the intestinal lumen.

Ulcerative colitis is typified by the following:

• It almost invariably involves the rectum; from there it may involve variable lengths of the distal colon.
• Inflammation is usually confined to the mucosal layer.
• Inflammation is usually continuous, with no skip areas.
• Long-standing, severe ulcerative colitis increases the risk of developing colon cancer. About 10% of patients with severe UC get colon cancer; in contrast, there is only a very slight increased risk with Crohn’s disease. Colon cancer developing in the setting of ulcerative colitis is hard to diagnose, as inflammation may obscure the signs and symptoms produced by the tumor.

Ulcerative colitis is easier to treat surgically than Crohn’s disease, because the disease is confined to a certain area. Moreover, surgery in the setting of Crohn’s disease may increase the risk of developing fistulas. Severe cases of UC may require total removal of the colon. The rate of recurrence after surgery is near zero for UC but close to 50% for Crohn's disease. Medical treatment of inflammatory bowel disease includes steroids and antibiotics. Although both forms of IBD respond to steroids, UC does so more consistently.

V.             THE APPENDIX

The appendix is located off the cecum in the proximal part of the colon. It has no known function, but it is rich in lymphoid tissue. Appendicitis is common, particularly in people under the age of 20. Appendicitis usually develops due to an obstruction at the base of the appendix, such as food, fecolith (hardened stool), or hyperplasia of lymphoid tissue. Obstruction can lead to ischemia and bacterial overgrowth. Symptoms include pain in the right lower quadrant (initially, the pain may be periumbilical), fever, abdominal tenderness, nausea, and an elevated WBC count. Appendicitis needs to be treated surgically before rupture of the organ occurs. Rupture can result in acute peritonitis due to spillage of intestinal contents. Before modern surgery, acute appendicitis was almost invariably fatal! Many people have mild cases that may resolve on their own, but they must be followed carefully.

VI.           THE COLON

The distal small intestine feeds into the colon in the area of the cecum. In order, the parts of the colon are the ascending colon, the transverse colon, the descending colon, the sigmoid colon, and the rectum. The proximal, ascending area (cecum) is wider than the distal, descending (sigmoid) colon. The function of the colon is absorption of water and electrolytes and production of the waste product known as stool.

A. Diverticulosis and diverticulitis

Diverticulosis is an abnormal outpouching of the lining and wall of the colon. It is seen in a fairly high percentage (30-50%) of people over the age of 50. It occurs more commonly in the distal colon. Since the lumen of the distal colon is narrower, higher pressures are found there than more proximally. The lining cells tend to pouch out in areas of inherent weakness in the intestinal wall, e.g., where blood vessels pass through the wall.

Diverticulosis is most common in Western countries, where the diet tends to be low in fiber. It has been theorized that low-fiber diets result in a slower passage of stool, and more pressure is required to pass these less bulky stools. However, the relationship between fiber in the diet and diverticulosis remains controversial. Often, there are no symptoms, but the diverticuli may become inflamed due to obstruction by food or fecal matter. Inflammation of the diverticuli is called diverticulitis. Symptoms similar to those of appendicitis may then develop (e.g., acute abdominal pain, elevated WBC count, fever, etc.) The diverticuli may rupture, leading to peritonitis. Chronic inflammation may lead to scarring and obstruction. Fistulas may form, or bleeding from erosion into blood vessels can occur. In some patients, brisk bleeding may be life-threatening. Inflamed diverticuli may need to be removed surgically if treatment with antibiotics fails.

B. Colonic polyps

Polyps in the colon are very common, affecting as much as 50% of the older population. These polyps may cause changes in bowel function. Even more important, certain types of polyps may lead to cancer. Three common types of polyps and their malignant potential are:

• Hyperplastic: little or no malignant potential
• Adenomatous: occasionally become malignant. Some adenomatous polyps are attached to the intestinal wall by a stalk and are called pedunculated. Others sit right on the mucosal lining and are referred to as sessile.
• Villous: ~35% of these are associated with cancer

Nearly all cases of cancer of the colon arise from polyps. Therefore, there is a real need for and benefit of screening for polyps and promptly removing them. Smaller polyps can be visualized, biopsied, and removed by endoscopy. Obviously, it is easier to remove a pedunculated polyp by this method than a sessile polyp.

C. Colon cancer

Colon cancer is the second most common cancer in the US, with some 150,000 cases and 60,000 deaths each year. It usually affects people in their 60’s and 70’s (but not always; Darryl Strawberry is a case in point). It is more common in the US and northwestern Europe than in Asia and Africa. It has been thought that colon cancer is associated with a diet that is high in animal fats and low in fiber. Fat can be converted to carcinogens. As for diverticulosis, the theory is that with a low-fiber diet, the less bulky stool will have a slower transit time, and the carcinogens will be more concentrated. Consequently, the cells lining the intestine will be in contact with higher amounts of carcinogens for a longer time. However, a recent, large-scale epidemiological study showed no correlation between incidence of colon cancer and the amount of fiber in the diet.

Symptoms of colon cancer include nonspecific GI complaints, changes in bowel habits, constipation, and blood in the stool (which may be occult and detectable only by clinical tests). Diagnosis is by barium enema (where the tumors may have an "apple-core" appearance) or endoscopy with biopsy. Most cancers of the colon occur in the distal colon; 50 to 60% occur in the rectum. Cancers in the distal colon tend to cause obstruction relatively early due to the narrower lumen there. Proximally located cancers may get quite large without causing obstruction. Colon cancers can lead to chronic bleeding and, consequently, iron-deficiency anemia. They tend to metastasize to regional lymph nodes or to the liver through the portal system.

The spread (i.e., stage) of colon cancers is classified by the Dukes’ system. Dukes’ A tumors show the least invasion and are located mostly in the mucosa and submucosa. Dukes’ B tumors show local invasion deep into the wall of the colon, and Dukes’ C cancers show extension and spread to local nodes. If caught early, the prognosis is excellent. Treatment is mainly surgical. Chemotherapy is not effective; sometimes, radiation therapy is used. The overall rate of survival after five years is 40%. Regular surveillance by tests for blood in the stool or, even better, by colonoscopy is the best defense against this disease.

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