15. The Gastrointestinal System
Authors: Corwin, Elizabeth J.
Title: Handbook of Pathophysiology, 3rd Edition
Copyright 2008 Lippincott Williams & Wilkins
> Table of Contents > Unit V - Nutrition, Elimination, and reproductive function and dysfunction > Chapter 15 - The Gastrointestinal System
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Chapter 15
The Gastrointestinal System
The gastrointestinal (GI) tract extends from the mouth to the anus. The function of the GI tract is to allow for food ingestion, propulsion, and digestion, and for the absorption of nutrients necessary for our bodies to live and grow.
Physiologic Concepts
Anatomy
As shown in Figure 15-1, the GI tract begins with the oral cavity, and continues into the esophagus and stomach. Food is stored in the stomach until it is released into the small intestine. The small intestine is divided into three sections: the duodenum, the jejunum, and the ileum. Digestion and absorption of food occur primarily in the small intestine. From the small intestine, food is passed to the large intestine, which consists of the colon and rectum. Accessory organs include the liver, pancreas, gallbladder, and appendix.
The entire GI tract is composed of several tissue layers: the innermost mucosa (secreting) layer; a submucosa connective tissue layer; circular and longitudinal smooth muscle layers, called the muscularis externa; and an outermost serous membrane, called the peritoneum (or adventitial) layer (Fig. 15-2). These layers are connected to one another physically and through neural connections.
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Figure 15-1. Digestive system. (From Chaffee, E.E. & Lytle, I.M. [1980]. Basic physiology and anatomy [4th ed.]. Philadelphia: J.B. Lippincott. ) |
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Mucosa
The mucosa layer of the small intestine is the site of food absorption, as described later. The mucosa layer consists of a lining of epithelial cells, a thin connective tissue layer called the lamina propria, and an underlying layer called the muscularis mucosa. Food particles leave the gut and enter the internal environment of the body by moving across the epithelial cells.
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Figure 15-2. Transverse section of the digestive system. |
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Submucosa
The submucosa layer of the gut is a connective tissue matrix. It contains one of the two nerve networks of the gut, called the submucosal plexus, and a system of blood vessels and lymphatics. The submucosal plexus is primarily concerned with maintaining function within each very small section of the intestinal wall. For example, the submucosal plexus helps control local intestinal secretions, local absorption of food stuffs, and local contraction of the muscularis mucosa.
Muscularis Externa
The muscularis externa contains a thick circular muscle layer, and a thinner, longitudinal muscle layer. Contraction of the circular smooth muscle causes mixing of the food in the gut. Contraction of the longitudinal layer shortens the tube. Extending all the way along the intestine, in between the circular and longitudinal smooth muscle layers, is the second neural network of the gut, called the myenteric plexus. The myenteric plexus controls muscle contractions along the entire gut, in contrast to the localized effects of the submucosal plexus.
Neural Regulation of the Gut: The Enteric Nervous System
The two neural networks of the gut, the submucosal plexus and the myenteric plexus, make up the self-contained nervous system of the gut, referred to as the enteric nervous system. The nerves of this system fire on their own without external stimuli. Because the smooth muscle cells of the gut are connected to each other via gap junctions, firing of the nerves in one area spreads the entire length of the gut. The neurons in the two plexuses synapse on each other, as well as on the surrounding smooth muscle cells, the exocrine glands throughout the GI tract, and the epithelial
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cells. They can affect contraction of the smooth muscle, the production of mucus, and the release of digestive enzymes. The neurons of the enteric nervous system include both adrenergic and cholinergic nerves, as well as nerves that release a variety of other neurotransmitters, including nitric oxide, endorphin, and various intestinal peptides. Although the firing of the enteric nervous system can occur without external input, the plexuses also receive external stimuli that influence their rate of firing.
External Neural Input
Both the myenteric and the submucosal nerve plexuses are innervated by sympathetic and parasympathetic nerves. Sympathetic fibers originate in the spinal cord between the levels of T8 and L3 and innervate the plexuses throughout the gut. They inhibit firing of the plexus, slowing the basic rhythm. Sympathetic nerves release norepinephrine in the gut. Parasympathetic nerves travel in the vagus nerve to the esophagus, the stomach, the small intestine, and the upper half of the large intestine. Other parasympathetic fibers travel in sacral divisions and innervate the distal half of the large intestine. Parasympathetic nerves release acetylcholine and stimulate firing of both the plexuses, speeding peristalsis and increasing mixing. Innervation of this distal part of the large intestine is important for stimulating defecation.
Other External Input
In addition to external neural innervation, the cells of the enteric nervous system are affected by gut hormones as well as by a variety of irritants, including those present in some foods and in certain drugs. Toxins released by infectious agents and chemicals participating in the body's response to infection also increase the firing rate of the enteric nervous system.
The Musculature of the Gut
As described previously, the GI tract is composed of an outer longitudinal layer and an inner circular layer of muscle. A third muscle layer is thin, lying deep in the mucosal lining of the GI tract. The longitudinal and the circular muscle layers are responsible for mixing and moving the food throughout the entire GI tract.
The longitudinal and circular smooth muscles show an inherent rate of spontaneous muscle-cell depolarization at each segment of the GI tract. These inherent depolarizations cause action potentials, resulting in muscle contractions. The contractions in each segment may vary in strength in response to internal or external nervous input, hormonal stimuli, and stretch. Although they vary in strength, gut contractions vary little in frequency. Gut contractions are slow, calcium-dependent contractions that occur over a wide range of muscle length. The contractions of the muscles at each gut segment determine the motility of that segment (i.e., the propulsion of food and secretions from one area to the next).
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Gut Motility
Esophageal Motility
Movement of food in the esophagus occurs by the process known as peristalsis. When food enters the esophagus, the smooth muscle is stretched; this initiates a peristaltic wave that proceeds along the length of the esophagus, propelling the food with it. When the peristaltic wave reaches the end of the esophagus, the smooth muscle at the opening into the stomach relaxes and food moves into the stomach. The end of the esophagus, called the lower esophageal sphincter, is located in the abdominal cavity, below the level of the diaphragm. (Although called a sphincter, this area is not anatomically different than the rest of the esophagus and so is not a true sphincter.) When a peristaltic wave is not passing down the esophagus, the esophageal sphincter is relaxed and in the closed position, preventing reflux of stomach contents into the esophagus. Reflux is also prevented by the fact that the lower esophageal sphincter is in the abdominal rather than in the thoracic cavity; if this were not so, backflow of food from the high-pressure zone of the abdomen to the low-pressure thoracic area would easily occur. By having part of the esophagus in the abdominal cavity, the pressure difference is minimized.
Stomach Motility
When food enters the stomach, the stomach also responds with a peristaltic wave. As the wave of contraction reaches the lower end of the stomach, called the antrum, the wave picks up strength, which effectively mixes the food. This wave of contraction also causes the closure of the junction between the distal end of the stomach and the beginning of the duodenum, called the pyloric sphincter. This is a true sphincter and is normally relaxed when food is not entering the stomach.
Gastric peristaltic waves occur as a result of the depolarization of the smooth muscle cells of the stomach. Pacemaker cells in the smooth muscle of the stomach depolarize continually at an inherent rate; this is called the basic electrical rhythm of the stomach. Normally, the depolarizations associated with the basic electrical rhythm are too slight to cause the muscle of the stomach to reach threshold and therefore do not lead to contractions. With increased stretch of the stomach or with neural and hormonal stimulation, the smooth muscle does depolarize to threshold and the strength of gastric peristalsis increases.
As the peristaltic waves continue in the stomach, a small amount of material is forced through the pyloric sphincter into the duodenum. The more material in the stomach, the more rapid is the rate of emptying. Eventually, all of the stomach content empties into the small intestine.
Small Intestinal Motility
Once the food, now called chyme, enters the small intestine, it continues to be mixed as a result of smooth muscle contraction there. In the small intestine, the contractions result in mostly stationary mixing, with slow
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forward propulsion down the gut. The slow propulsion occurs as a result of segmentation. Segmentation refers to the process by which slightly more frequent contractions in the upper intestine, compared with the lower, eventually propel the chyme through the length of the small intestine. The thorough mixing during segmentation ensures that the chyme is acted upon by digestive enzymes and that it comes into repeated contact with the intestinal wall so that absorption is facilitated.
Large Intestine Motility
The large intestine consists of the cecum, followed by the ascending, transverse, and descending colon; the sigmoid colon; and the rectum. The appendix is a blind pouch, growing off of the cecum. The rectum ends at the anus, the exit point from the body. Contraction of the large intestine occurs at a slow rate compared with that of the small intestine. This means that food entering the large intestine takes approximately a day to travel the entire length of the structure. A few times a day, usually after a meal, a wave of contraction, called a mass movement, occurs. This is a powerful contraction that initiates the urge to defecate.
Hormones of the Gastrointestinal Tract
Many GI hormones, including gastrin, secretin, cholecystokinin (CCK), glucagon-like peptide-1 (GLP-1), and glucose-dependent insulinotropic polypeptide (GIP), play important roles in the digestive function of the GI tract. Other hormones released from the stomach or intestine, including ghrelin and peptide YY (PYY), are involved in controlling appetite. These hormones and their roles are discussed in the text that follows.
Gastrin is secreted from the stomach antrum in response to distention of the stomach after a meal and the presence of protein in the food. In addition, gastrin secretion is stimulated by the release of gastrin-releasing peptide from the nerves of the submucosal plexus as a result of parasympathetic stimulation. Gastrin acts to stimulate the secretion of histamine and gastric juices from the gut lining and hydrochloric acid (HCl) from the parietal cells of the stomach. Histamine also stimulates HCl secretion. HCl in turn activates pepsin, the most important digestive enzyme in the stomach. Pepsin and the gastric juices begin the digestion of protein in the stomach, removing the stimulation for further gastrin secretion. Thus, gastrin release is inhibited by excess acid, which is an excellent example of negative feedback. Gastrin also stimulates intestinal motility.
Secretin is secreted from the small intestine primarily in response to HCl present in the chyme entering the small intestine from the stomach. Secretin stimulates intestinal secretions of base as well as the pancreatic release of bicarbonate to neutralize the acid. Neutralization of acid is essential because the enzymes required for digestion in the small intestine cannot work in an acidic environment. Secretin also slows the further passage of food from the stomach into the small intestine, allowing adequate time for digestion of food already in the small intestine.
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Cholecystokinin (CCK) is secreted from the small intestine primarily in response to fat and other food particles entering the intestine in the chyme. CCK causes gallbladder contraction; it also causes the release of pancreatic and intestinal digestive enzymes and of bile. The digestive enzymes and bile serve to promote the digestion and absorption of the food particles.
GLP-1 and GIP are secreted from the upper small intestine in response to fatty acids, amino acids, and glucose in the chyme. These hormones function to slow further stomach emptying, thereby allowing the effective digestion of the food already present in the small intestine. They also increase the release of insulin from the pancreas; GLP-1 and GIP account for approximately 50 to 60% of the insulin released during a meal. Evidence suggests that a deficiency in GLP-1 and/or GIP may contribute to glucose intolerance and reduced insulin secretion characteristic of type 2 diabetes mellitus.
Ghrelin and PYY are both appetite-modulating hormones. First identified in 1999, ghrelin is secreted from the stomach and functions to regulate energy balance by stimulating food intake and decreasing fat metabolism. It appears to act with other signals to inform the central nervous system (CNS) regarding food intake and body fat mass. Ghrelin also stimulates growth hormone releasing hormone from the hypothalamus. It also appears to affect the hypothalamic-pituitary-gonadal axis.
PYY is co-secreted with GLP-1 from the small intestine in response to food entering from the stomach. PYY levels are proportional to meal energy content, and plasma levels peak postprandially after 1 hour. PYY acts as a satiety hormone in that it inhibits further food intake. It appears to function at the level of the CNS.
Digestion of Food
Digestion of food begins in the mouth with the release of saliva, continues in the stomach, and is mostly accomplished in the small intestine. The process of digestion involves enzymes that are secreted in response to specific foodstuffs and that act to break down carbohydrates into simple sugars, fats into free fatty acids and monoglycerides, and proteins into amino acids. It is only in these simple forms that these nutrients can be absorbed across the gut and used by the body.
Protein and Carbohydrate Digestion
Protein digestion begins in the stomach with the enzyme pepsin and is completed in the small intestine by the action of the pancreatic enzymes trypsin and chymotrypsin. Carbohydrate digestion begins in the mouth with the activity of the enzyme salivary amylase and is completed in the small intestine by the enzyme pancreatic amylase.
Fat Digestion
Fat digestion occurs in the small intestine, primarily as a result of the activity of the pancreatic enzyme lipase. Fats are digested by the action of lipase into
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free fatty acids and monoglycerides. Lipase, however, is a water-soluble enzyme; because fats are insoluble in water, their digestion by lipase would be extremely slow if it were not for emulsification, the process by which large fat complexes are broken up into smaller droplets. Emulsification increases the surface area of the fats available for digestion by pancreatic lipase. By increasing the surface area, lipase is a much more effective agent for digestion. Emulsification occurs by the mechanical mixing of the food in the intestine and by the action of bile in the small intestine. The emulsification and digestion of fat is illustrated in Figure 15-3.
Bile
Bile is a substance produced in the liver and contains bile salts, water, cholesterol, electrolytes, and bilirubin, which is a breakdown product of hemoglobin. Although bile is continually released from the liver, it is usually stored and concentrated in the gallbladder. Bile then is released from the gallbladder and travels to the small intestine via the common bile duct, in response to the hormone CCK. In individuals who do not have a gallbladder, bile is released directly from the liver into the common bile duct in response to CCK.
Although bile contains no digestive enzymes, it does contain bile salts, the substance that serves to emulsify fats. Bile salts are phospholipids that act as detergents to break down (emulsify) fats into small droplets. Once emulsified into droplets, lipase is then capable of digesting the fats into fatty acids and monoglycerides.
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Figure 15-3. Emulsification (step 1) and digestion (step 2) of fat (free fatty acid [FFA]; monoglyceride [MNG]). |
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Figure 15-4. Villus showing a central lacteal, capillary network, microvilli, and the epithelial cells across which nutrients are absorbed. |
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Absorption of Food
Although a small amount of lipid-soluble material may be absorbed across the stomach wall, most absorption of digested food occurs in the small intestine, across millions of finger-like projections called villi (singular: villus). Each villus consists of epithelial cells of the mucosal layer, a capillary network, and a central lymph vessel called a lacteal (Fig. 15-4). Nerve fibers of the intrinsic plexuses and smooth muscle cells also are present. The presence of villi on the mucosal surface of the intestine increases the surface area available for the absorption of food by at least 10-fold. Finally, each villus is topped by almost 1,000 microvilli, adding even more to the enormous surface area available for the absorption of food. Certain digestive enzymes (brush border enzymes) are produced by cells of the villus as well.
Absorption of food occurs when digested food particles enter a villus from the lumen of the gut and move either into the capillary or into the lacteal, thereby gaining access to the general circulation. The movement of food particles into the epithelial cells and across the capillary or the lacteal may occur by simple or facilitated diffusion or by active transport, depending on the substance.
Absorption of Amino Acids
Amino acids and small di- or tri-peptides, the result of protein digestion, are actively transported into the epithelial cells of the villus, mostly via sodium co-transport. Once in the villus, they move into the capillary by facilitated diffusion. In the bloodstream, they are delivered to body cells,
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especially the muscle cells, where they are used for protein synthesis. The amino acids and small peptides not used for protein synthesis travel to the liver, where they are converted to carbohydrates or fats and are either used for energy or stored throughout the body.
Absorption of Simple Sugars
Most of the simple sugars that result from carbohydrate digestion, including glucose and galactose, are transported from the lumen of the intestine into the epithelial cells through sodium-coupled active transport. Once in the epithelial cell, these sugars then move through the basolateral membrane into the space between cells via facilitated diffusion and, from there, into the blood. Other sugars, for example fructose, move both into and out of the epithelial cells only by facilitated diffusion. Once in the blood, sugars are delivered to all body cells and are used for energy production. Sugars not used immediately for energy production can be stored as fat or glycogen in all cells, especially liver cells.
Absorption of Free Fatty Acids and Monoglycerides
Even after being digested, the absorption of free fatty acids and monoglycerides would be extremely slow if it were not for the continued action of the bile salts. Bile salts further break the emulsified fat droplets into even smaller droplets called micelles (see Fig. 15-3). The micelles contain fatty acids and monoglycerides, bile salts and other phospholipids, cholesterol, and several fat-soluble vitamins all combined together. The micelles stay in equilibrium with a small amount of free fatty acids and monoglycerides; these free fatty acids and monoglycerides are the substances actually absorbed into the circulation. As each molecule of free fatty acid or monoglyceride is absorbed, the micelles release replacements, thereby continuing the cycle of absorption. Without the micelles, the fat molecules would once again clump together and be unavailable for absorption.
Because the free fatty acids and monoglycerides are lipid soluble, they move by passive diffusion into the intestinal epithelial cells. In the cells, they are changed back into triglycerides, a process requiring energy. Then, triglycerides join in the epithelial cell with cholesterol and phospholipids. This complex is encased in a protein coat, exits the epithelial cell, and moves by passive diffusion into the lacteal in the center of the villi. The complex of the triglyceride, cholesterol, and phospholipid is similar to a micelle and is called a chylomicron. Chylomicrons are carried in the lymph to the thoracic duct and then enter the general circulation.
Triglycerides can be used directly as an energy source for most cells of the body, or the glycerol portion can be changed into glucose in the liver and used as an energy source. Excess triglycerides are stored in adipose tissue.
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Secretion of Mucus
Mucus is secreted along the entire length of the gut. Mucus is a thick substance that coats the wall of the gut and serves to protect it from being digested by the enzymes to which it is exposed. It also serves to lubricate food, allowing for easier passage. Without the production of mucus, gut wall integrity would be severely compromised, especially in the stomach, where HCl is highly concentrated and is an essential component of protein digestion. In addition, without the lubricating effects of mucus, stools would be hard.
Recirculation of Bile
After the bile salts deliver fatty acids and monoglycerides to the villi, some travel back into the chyme to pick up more molecules and repeat the process. Most of the remaining bile salts are eventually reabsorbed at the end of the small intestine and are recycled back to the liver via the portal vein to be used again. This process is called enterohepatic circulation.
Elimination of Waste Products
Absorption, primarily of water and electrolytes, continues to occur in the large intestine. Most absorption occurs in the upper half of the colon. Of the approximately 1,000 mL of chyme that enters the large intestine each day, only 100 mL of fluid and virtually no electrolytes are excreted. Besides water, which makes up approximately 75% of feces, feces contain dead bacteria, some undigested fat and roughage, and a small amount of protein. Bilirubin byproducts give the feces its color.
The process of elimination, or defecation, occurs as a result of peristaltic contractions of the rectum. These contractions are produced in response to stimulation of the longitudinal and circular smooth muscles by the myenteric plexus. The myenteric plexus is stimulated by parasympathetic nerves traveling in sacral segments of the spinal cord. Mechanical stretching of the rectum with stool is also a strong stimulator of peristalsis. When a peristaltic wave is initiated, the internal anal sphincter, a smooth muscle, relaxes. If the external anal sphincter is also relaxed, defecation occurs. The external anal sphincter is a skeletal muscle and thus under voluntary control. In fact, relaxation of the internal sphincter causes reflex contraction of the external sphincter in all individuals except babies and some people who have spinal cord transection. Reflex contraction of the external sphincter effectively stops defecation. If the defecation reflex occurs at an acceptable time, the reflex contraction of the external sphincter can be consciously reversed to allow defecation.
Hunger and the Ingestion of Food
Hunger is controlled by an area of the brain in the lateral hypothalamus. Stimulation of this area causes a strong desire to seek out and to eat food.
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The lateral hypothalamus receives numerous inputs that can stimulate hunger. For instance, hunger can be stimulated by the occurrence in the stomach of hunger contractions. These contractions appear to increase in frequency and intensity the longer the stomach is empty. The exact mechanism by which they occur is unclear.
Hunger is also stimulated by a fall in blood nutrients, such as amino acids, fats, and glucose, and by a rise in the hormones that accompany nutrient deficit (e.g., glucagons and ghrelin). A decrease in the level of hormones present when food is plentiful may also stimulate hunger (e.g., decreased insulin and PYY). Input to the hypothalamic hunger center can include input from other areas of the brain as well. For instance, higher brain centers can stimulate hunger in response to certain situations or experiences. Likewise, input from the emotional center of the brain, the limbic system, may also stimulate hunger, as may different smells activating from the olfactory center.
Conversely, the ventromedial nucleus of the hypothalamus appears to be the site where satiety, the opposite of a hunger drive, occurs. This center is influenced by the fullness of the stomach and blood levels of nutrients and hormones, and also in the opposite direction, as is required for hunger stimulation. Emotions and habits may also influence the satiety center.
Tests of Gastrointestinal Functioning
Barium Contrast X-Ray Films: Upper and Lower Gastrointestinal Series
In these tests, a radiopaque solution is introduced into the upper or the lower GI tract, and then x-ray films are obtained to follow its progress. This technique is able to identify the positions and sizes of the GI structures and any obstructions that are present; however, its ability to identify ulcers, fissures, or early-stage cancers is poor.
Endoscopy
Endoscopy is the process whereby a thin, rigid or flexible scope is passed into the GI tract to visualize the esophagus (esophagoscopy), stomach (gastroscopy), upper small intestine (duodenoscopy), large intestine (colonoscopy), or sigmoid colon (sigmoidoscopy). With this instrument, the walls of the GI tract can be visualized, allowing identification of ulcerations, blockages, and other irregularities. Special tools at the end of the scope allow tissue to be sampled for biopsy and culture.
Whether patients should have colonoscopy or sigmoidoscopy for screening of colon cancer depends on personal risk factors, including age, family history of GI or other cancers, and personal history of polyps or cancer. With colonoscopy, the practitioner can fully visualize the entire large intestine. Patients are generally anesthetized for this procedure. Because many colon cancers develop in the sigmoid colon and because sigmoidoscopy is usually accomplished without general anesthesia, this procedure may be recommended for screening in low-risk populations.
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Ultrasound
Ultrasound is a procedure whereby sound waves are reflected from tissue to provide an image. It is a highly sensitive technique and can be used to visualize the structure of the abdominal organs to identify abnormalities, abscesses, stones, and other structures.
Computed Tomography
The process whereby a computer integrates images from several x-ray projections to provide a vivid cross-sectional image is called computed tomography (CT). CT is used to image all GI organs and to identify structural and other abnormalities.
Magnetic Resonance Imaging
Magnetic resonance imaging (MRI) is the process whereby shifts in the magnetic axis of atoms in response to externally applied electromagnetic fields are transformed by computer to produce a cross-sectional image of the structures of the GI tract. MRI is used extensively to identify structural abnormalities, alterations in blood flow, and vessel patency.
Pathophysiologic Concepts
Anorexia
Defined as a loss of appetite or desire for food, anorexia often occurs as a symptom with other GI alterations, including nausea, vomiting, and diarrhea. It can also be present with conditions not associated with the GI tract, such as cancer.
Anorexia nervosa is a condition in which one chooses not to eat because of a morbid fear of being fat. The term anorexia nervosa is actually a misnomer because individuals who have this disorder still have a desire to eat and are still hungry; so by definition they are not truly anorectic.
ediatric Consideration
Most people who develop anorexia nervosa are adolescent or postadolescent females, frequently perfectionists for whom being thin is a sign of success or athletes who may believe that their performance depends on a level of thinness only possible by the strict avoidance of food. Although less common, young men may also develop anorexia nervosa. In young men, the condition may be associated with depression or concerns about sexual orientation. Some male athletes who participate in sports with strict weight categories, such as wrestling, may also develop anorexia nervosa. Anyone who has anorexia nervosa needs intense and prolonged therapy to overcome the condition.
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Nausea
Nausea is a subjective, unpleasant sensation that often precedes vomiting. Nausea is caused by distention or irritation anywhere in the GI tract, but it can also be stimulated by higher brain centers. Interpretation of nausea occurs in the medulla, which is either adjacent to or part of the vomiting center.
Vomiting
Vomiting is a complex reflex mediated through the vomiting center in the medulla oblongata of the brain. Afferent impulses travel to the vomiting center as both vagal and sympathetic afferents. Afferent impulses originate in the stomach or duodenum in response to excessive distention or irritation, or sometimes they originate in response to chemical stimulation by emetics (agents that cause vomiting), such as syrup of ipecac. Hypoxia and pain can also stimulate vomiting by means of activation of the vomiting center. Vomiting can also occur through direct stimulation of an area of the brain adjacent to the vomiting center in the brain. Certain drugs initiate vomiting by activating this center, called the chemoreceptor trigger zone, which lies in the floor of the fourth ventricle. Vomiting as a result of rapid motion change is believed to work through stimulation of this trigger zone. Activation of the chemoreceptor trigger zone can cause vomiting either directly or indirectly by its subsequent activation of the vomiting center. Input from higher brain centers in the cortex and increased intracranial pressure (ICP) can also stimulate vomiting, probably by directly stimulating the vomiting center. Projectile vomiting occurs when the vomiting center is directly stimulated, frequently by increased ICP.
When the vomiting reflex is initiated in the vomiting center, it is carried out by activation of several cranial nerves to the face and throat, and spinal motor neurons to the diaphragm and abdominal muscles. Excitation of these pathways results in the coordinated response of vomiting. Certain symptoms generally precede vomiting, including nausea, tachycardia, and sweating.
Diarrhea
Diarrhea is an increase in fluidity and frequency of stools. It may be large or small volume and may or may not contain blood. Large-volume diarrhea can occur as a result of the presence of a non-absorbable solute in the stool, called osmotic diarrhea, or as a result of irritation of the intestinal tract. The most common cause of large-volume diarrhea due to irritation is a viral or bacterial infection of the large intestine or the distal small intestine.
Irritation of the intestines by a pathogen affects the mucosal layer, leading to increased secretory products, including mucus. Microbial irritation also affects the muscular layer, leading to increased motility. Increased motility causes large amounts of water and electrolytes to be lost in the
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stool because the time available for their reabsorption in the colon is reduced. An individual who has severe diarrhea can die from hypovolemic shock and electrolyte irregularities. Cholera toxin released from the cholera bacteria is an example of a substance that strongly stimulates motility and directly causes secretion of water and electrolytes into the large intestine, contributing to the devastating loss of these important plasma constituents. Other infectious agents can also cause diarrhea, either severe or mild. Infection with Escherichia coli O157, found in undercooked ground beef, causes a severe bloody diarrhea. Large-volume diarrhea can also be caused by psychological factors, such as fear or some types of stress, mediated through parasympathetic stimulation of the gut.
Small-volume diarrhea is characterized by frequent loss of small amounts of stool. Causes of this type of diarrhea include ulcerative colitis and Crohn's disease. Both of these illnesses have physical and psychogenic components and are discussed later in this chapter.
ediatric Consideration
Infants and children are especially susceptible to the severe effects of diarrhea and should be monitored closely for early signs of dehydration. In developing countries, diarrhea from infectious disease, especially cholera, is the number one cause of infant and early childhood death. Any child who has moderate or severe diarrhea should receive fluid replacement with osmotically balanced products.
Constipation
Constipation is defined as difficult or infrequent defecation. Because frequency of stool varies among individuals, the second half of this definition is subjective and should be interpreted as a relative decrease in the number of stools for that particular individual. In general, however, bowel movements fewer than once every 3 days are considered to indicate constipation.
Defecation can become difficult if the stool is hard and compact. This can occur when an individual is dehydrated or if a bowel movement is delayed, which allows more water to be absorbed out of the stool as it sits in the large intestine. Bulk or high-fiber diets keep stools moist by osmotically drawing water into the stool and by stimulating peristalsis of the colon by distention. Therefore, people who eat low-bulk diets or highly refined foods are at a greater risk for constipation. Exercise promotes defecation by physical stimulation of the GI tract. Therefore, individuals who lead sedentary lives are at higher risk of suffering from constipation.
Fear of pain during defecation can be a psychological stimulus to withhold a bowel movement and can cause constipation. Other psychological
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inputs might also cause delay of defecation. Sympathetic stimulation of the GI tract decreases motility and can slow defecation. Sympathetic activity is increased in individuals who have long-term stress. Certain drugs such as antacids and opiates also may cause constipation.
Spinal cord trauma, multiple sclerosis, intestinal neoplasm, and hypothyroidism can result in constipation. A disease characterized by a dysfunctional myenteric plexus in the large intestine, called Hirschsprung's disease (congenital megacolon), also causes constipation. This disease should be apparent soon after birth.
Peritonitis
Inflammation of the peritoneum, a membrane that lines the abdominal cavity, is called peritonitis. Peritonitis usually occurs as a result of the passage of bacteria through the GI tract or abdominal organs into the peritoneal space as a result of perforation of the gut or rupture of an organ. GI surgery or a penetrating wound to the gut also may result in spillage into the peritoneal cavity. The severe infection that occurs with movement of gut contents into the peritoneal cavity emphasizes the fact that the GI tract is really external to the body, rather than part of the internal environment.
Peritonitis is characterized by pain, especially over the inflamed area. Pain may change in location, being centrally located at first, and then becoming more site-specific as the inflammation worsens. Pain may be rebound in nature; that is, the person may complain of more pain when pressure on the abdomen is removed quickly. Rebound pain is related to the sudden wave of movement that occurs through the peritoneal fluid when pressure is released.
Individuals who have peritonitis frequently demonstrate increased heart rate as a result of hypovolemia occurring from the movement of fluid into the peritoneum. They also may experience nausea and vomiting, and demonstrate a rigid abdomen indicative of widespread inflammation. In addition, general signs of inflammation such as fever, an increase in white blood cell count, and increased sedimentation rate are usually present. Sepsis leading to multi-organ failure may occur without appropriate treatment. Treatment usually includes surgery, antibiotics, and fluid and electrolyte replacement.
Conditions of Disease or Injury
Gastroesophageal Reflux Disease
The condition of gastroesophageal reflux disease (GERD) is caused by the reflux of stomach contents into the esophagus. GERD is commonly called heartburn because of the pain that occurs when the acid, normally present only in the stomach, enters and burns or irritates the esophagus.
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GERD is a significant problem in Western societies but relatively uncommon in Asian countries. Risk factors for GERD include male gender, increased body mass index (BMI), smoking, and regular alcohol intake. Epidemiological studies have shown a negative relationship between Helicobacter pylori (H. pylori) infection and GERD, perhaps related to a reduced ability of the stomach to produce acid over time in patients with H. pylori or perhaps related to the proton-pump inhibitors used in the treatment of H. pylori as described later in this chapter.
Causes of GERD
GERD usually occurs after a meal and results from conditions that either weaken the tone of the esophageal sphincter or increase the pressure in the stomach compared with the esophagus. By either of these mechanisms, acidic stomach contents move into the esophagus.
The contents of the stomach are usually prevented from entering the esophagus by the esophageal sphincter (recall that this is not actually a sphincter, but an area of increased muscle tone; see page C11 for illustrations). This sphincter normally opens only when a peristaltic wave delivering a bolus of food moves down the esophagus. When this happens, the smooth muscle of the sphincter relaxes, and food enters the stomach. It is important that the esophageal sphincter always remains closed except at this time, because many organs are crowded together in the abdominal cavity, causing abdominal pressure to be greater than thoracic pressure. Therefore, the tendency is for contents of the stomach to be pushed up into the esophagus. If one has a weakened or incompetent sphincter, it will not remain closed to stomach contents. Reflux will occur from the high-pressure zone (the stomach) to the low-pressure zone (the esophagus). A weakened sphincter can be a congenital defect or a result of damage to the esophagus. Repeated episodes of GERD may themselves worsen the condition by causing inflammation and scarring in the lower esophageal area.
In some circumstances, even if the sphincter has normal tone, reflux will occur if there is an unusually high pressure gradient at the sphincter. For example, if stomach contents are excessive, abdominal pressure may increase significantly. This may result from an extra large meal, pregnancy, or obesity. High abdominal pressures tend to push the esophageal sphincter into the thoracic cavity; this exaggerates the pressure gradient between the esophagus and the abdominal cavity. Lying down, especially after a large meal, also contributes to reflux.
A hiatal hernia may also cause reflux. A hiatal hernia is a protrusion of a part of the stomach through the opening in the diaphragm. If this occurs, high pressure in that part of the stomach results in stomach contents being pushed into the esophagus. Reflux of stomach contents irritates the esophagus because of the high acid content in the stomach. Although the esophagus also has mucus-producing cells, they are not as active or as prevalent as they are in the stomach.
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Clinical Manifestations
Burning pain in the epigastric area, called dyspepsia, may occur, and may radiate to shoulders, back, or neck.
Belching and a sour taste may accompany the pain.
Pain usually occurs within 30 to 60 minutes after a meal or during sleep, when the individual is lying down.
Diagnostic Tools
A good history identifies many individuals at risk of GERD.
A pH probe passed into the lower esophageal area may reveal an abnormally low pH (below 4.0) in individuals who have GERD. False positives and false negatives exist.
Barium swallows are ineffective in identifying GERD.
Complications
Barrett's esophagitis is an irritation of the lining of the esophagus characterized by cell changes that can result from chronic reflux. It is a pre-malignant condition that may lead to esophageal carcinoma.
Chronic irritation of the esophagus can cause chronic inflammation, spasm of the muscles, and scarring of the esophagus, all of which may lead to stricture development, thereby interfering with or blocking food passage.
Vomiting and dysphagia (difficulty swallowing) with eating may occur.
Treatment
Abdominal pressure can be reduced by eating more frequent small meals rather than large meals. If obesity is a problem, nutritional and exercise counseling are advised.
Sitting up during and after eating, and sleeping with the head elevated, will reduce abdominal pressure on the esophageal sphincter.
Drinking extra fluids will help wash refluxed material out of the esophagus.
Histamine type-2 (H2) receptor antagonists and proton pump inhibitors are used to reduce acid secretion by the stomach, in combination with the behavioral changes described above.
Proton pump inhibitor therapy is the treatment of choice in acute cases of GERD and as maintenance therapy for patients with documented esophageal erosion.
Anti-reflux surgery may be considered if symptoms are resistant to treatment or are caused by hiatal hernia.
Antacids may be used to neutralize the acidic content of the stomach.
Peptic Ulcer
The term peptic ulcer refers to an erosion of the mucosal layer anywhere in the GI tract; however, it usually refers to erosions in the stomach or duodenum. Gastric ulcer refers only to an ulcer in the stomach.
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Causes of Peptic Ulcer
There are two main causes of ulcers: (1) too little mucus production or (2) too much acid being produced in the stomach or delivered to the intestine. A variety of conditions may cause either or both of these disturbances.
Decreased Mucus Production as a Cause of Ulcer
Ulcers most commonly develop when the mucosal cells of the gut do not produce adequate mucus to protect against acid digestion. Causes of decreased mucus production can include anything that decreases blood flow to the gut, causing hypoxia of the mucosal layer and injury to or death of mucus-producing cells. This type of ulcer is called an ischemic ulcer. Decreased blood flow occurs with all types of shock. A particular type of ischemic ulcer that develops after a severe burn is called a Curling ulcer.
Decreased mucus production in the duodenum also can occur as a result of inhibition of mucus-producing glands, called Brunner's glands, located there. Their activity is inhibited by sympathetic stimulation. Sympathetic stimulation is increased by chronic stress, thus making a connection between chronic stress and ulcer development.
The main cause of decreased mucus production is related to infection with the bacterium H. pylori. H. pylori colonizes the mucus-secreting cells of the stomach and duodenum, reducing their ability to produce mucus. Approximately 90% of patients who have duodenal ulcer and 70% of patients who have gastric ulcer show H. pylori infection. H. pylori infection is endemic in some countries. Infection appears to occur by means of ingestion of the microorganism.
The use of various drugs, especially non-steroidal anti-inflammatory drugs (NSAIDs), is also associated with an increased risk of ulcer development. Aspirin, especially, causes irritation of the mucosal wall, as do the other NSAIDs and glucocorticosteroids. These drugs contribute to ulcer development by inhibiting protective prostaglandins both systemically and in the gut wall. Approximately 10% of patients taking NSAIDs develop an active ulcer while a much higher percentage develops less serious erosions. Gastric or intestinal bleeding can occur from NSAIDs, with little early warning. The elderly are especially susceptible to GI injury from NSAIDs. Other drugs or foods associated with ulcer development include caffeine, alcohol, and nicotine. These drugs seem to injure the protective mucosal layer also.
Excess Acid as a Cause of Ulcer
Acid production in the stomach is necessary for activation of stomach digestive enzymes. Hydrochloric acid (HCl) is produced by the parietal cells in response to certain foods, drugs, hormones (including gastrin), histamine, and parasympathetic stimulation. Foods and drugs such as caffeine and alcohol stimulate the parietal cells to produce acid. Some individuals might be over-reactive in their parietal response to these
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substances or other foods, or they may simply have a greater number of parietal cells than normal and therefore release excess acid. Aspirin is an acid, which may directly irritate or erode the lining of the stomach.
Because gastrin stimulates the production of acid, anything that increases the secretion of gastrin can lead to excess acid production. The main example of this condition is called Zollinger-Ellison syndrome, a disease characterized by tumors of the gastrin-secreting endocrine cells. Other causes of excess acid include excessive vagal stimulation to the parietal cells that is seen after severe brain injury or trauma. Ulcers that develop under these circumstances are called Cushing ulcers. Excess vagal stimulation during psychological stress may also cause excess HCl production.
Increased Delivery of Acid as a Cause of Duodenal Ulcer
Too rapid movement of stomach contents into the duodenum can overwhelm the protective mucus layer there. This occurs with irritation of the stomach by certain foods or microorganisms, as well as by excess gastrin secretion or abnormal distention.
Rapid movement of stomach contents into the intestine also occurs in the condition called dumping syndrome. Dumping syndrome happens when the ability of the stomach to hold and slowly release chyme into the duodenum is compromised. One cause of dumping syndrome is surgical removal of a large part of the stomach. Dumping syndrome not only results in rapid delivery of acid to the intestine, but it can cause cardiovascular hypotension. Hypotension occurs because the delivery of multiple food particles to the intestine all at once results in a large amount of water moving from the circulation into the gut by osmosis.
Clinical Manifestations
Burning abdominal pain (dyspepsia) often occurs at night. The pain is usually located in the midline epigastric area, and is often rhythmic in nature.
Pain that occurs when the stomach is empty (for example, at night) often signifies a duodenal ulcer. This is most common.
Pain that occurs immediately after or during eating suggests a gastric ulcer. Occasionally, the pain may be referred to the back or shoulder as well.
The occurrence of pain often comes and goes; it sometimes occurs daily for several weeks and then disappears altogether until the next exacerbation.
Weight loss is common with gastric ulcers. Weight gain may occur with duodenal ulcers because eating relieves the discomfort.
Diagnostic Tools
Ulcers are diagnosed primarily by history and endoscopy. With endoscopy, not only can the gut lining be viewed for ulcers, but tissue samples can also be taken for biopsy and the presence or absence of H. pylori can be determined.
H. pylori infection may also be diagnosed by blood tests for antibody and by breath tests that measure metabolic waste production by the microbe.
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Complications
An ulcer may in some instances go through all mucosal layers, causing perforation of the gut. Because gut contents are not sterile, this can lead to infection of the abdominal cavity. The pain of perforation is severe and radiating. It is unrelieved by eating or antacids.
Obstruction of the lumen of the GI tract may occur as a result of repeated episodes of injury, inflammation, and scarring. Obstruction is most often at the pylorus, the narrow passageway between the stomach and the small intestine. Obstruction causes feelings of stomach and epigastric distention, heaviness, nausea, and vomiting.
Hemorrhage may occur when the ulcer has eroded an artery or vein in the gut. This can result in hematemesis (vomiting of blood) or in melena (passage of upper GI blood in the stool). If bleeding is extensive and sudden, symptoms of shock may occur. If bleeding is slow and insidious, microcytic hypochromic anemia may develop.
Treatment
Identify and instruct patients to avoid foods that cause excess HCl secretion; doing so improves symptoms for some individuals.
Educate patients that avoidance of alcohol and caffeine improves symptoms and increases healing of a pre-existing ulcer.
Discontinue or reduce NSAID ingestion; this often relieves symptoms in mild cases.
Strongly urge individuals who smoke to quit because tobacco both irritates the gut and delays healing.
Prescribe antihistamines or proton pump inhibitors to neutralize stomach acid and to relieve symptoms of an ulcer.
Individuals documented to have an ulcer caused by H. pylori the majority of patients by far are treated with the addition of an antibiotic to the standard antacid therapy previously used. Typically, patients are placed on one or two effective antibiotics, including an antifungal, or on a proton pump inhibitor and antibiotics. Adding antibiotics to the acid-lowering strategies used previously can truly cure many patients of their ulcers rather than just temporarily improving their symptoms.
Stress management, relaxation techniques, or sedatives can be used to relieve psychological influences.
Malabsorption
Failure of the small intestine to absorb certain foodstuffs is called malabsorption. Inability to absorb can be (1) of one type of amino acid, fat,
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sugar, or vitamin; (2) of all amino acids, fats, sugars; or (3) of all fat-soluble vitamins. Malabsorption of everything absorbed in one segment of the small intestine can also occur, with other small-intestine segments being spared.
Causes of malabsorption include pancreatic digestive enzyme deficiency; microorganism infection; damage to the mucosal layer of the gut; or, for fats and fat-soluble vitamins, impairment of bile production or lymph function. Genetic deficiencies in specific enzymes may also occur. Lactose malabsorption can result from the inability to break down lactose into absorbable monosaccharides. Lactose malabsorption can result from a congenital deficiency in the enzyme lactase or a decrease in lactase after an intestinal disease. Crohn's disease and bowel resection are common causes of malabsorption, as is sprue, a disease characterized by injury to the villi that apparently is caused by a hypersensitivity to gluten, a product of wheat, barley, rye, and oats.
Clinical Manifestations
Clinical manifestations of malabsorption depend on what is not being absorbed and whether other areas of the bowel can compensate. Specific symptoms are related to the dietary deficiency that occurs. Generalized symptoms usually include those related to the GI tract or to the loss of fat-soluble vitamins:
Fat malabsorption results in steatorrhea (fat in the stool). Diarrhea, flatulence, bloating, and cramps often occur. Stools are bulky but of light weight, float, and are malodorous.
Bile salt deficiency results in malabsorption of fat-soluble vitamins, causing the following:
Vitamin A deficiency night blindness.
Vitamin D deficiency bone demineralization and increased risk of fractures.
Vitamin K deficiency poor coagulation with prolonged prothrombin time, easy bruising, and petechia (hemorrhagic spots on the skin).
Vitamin E deficiency perhaps resulting in poor immune function.
Lactose malabsorption results in osmotic diarrhea and flatulence (gas).
Diagnostic Tools
The presence of over 7 g of fat per day in the stool of an adult consuming a typical American diet is considered malabsorption. Weight loss or failure to gain weight in infancy or young childhood may indicate malabsorption.
Complications
Failure to thrive may occur in severe cases, leading to malnutrition, infection, and even death.
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Treatment
Identification of the cause of malabsorption.
Provision of needed nutrients through other food sources or supplements.
Appendicitis
Inflammation of the appendix, known as appendicitis, may occur (1) for no obvious reason, (2) after obstruction of the appendix with stool, or (3) from either the organ or its blood supply being twisted. The inflammation results in a swollen, tender appendix, which can lead to gangrene of the organ as blood supply is compromised. The appendix may also burst; this typically happens between 36 and 48 hours after the onset of symptoms.
Clinical Manifestations
Abrupt or gradual onset of diffuse pain in the epigastric or periumbilical area is common.
Over the next few hours, the pain becomes more localized and may be described as a pinpoint tenderness in the lower right quadrant.
Rebound tenderness (pain that occurs when pressure is removed from the tender area) is a classic symptom of peritonitis and is common with appendicitis. Guarding of the abdomen occurs.
Fever.
Nausea and vomiting.
Diagnostic Tools
The diagnosis of appendicitis continues to be difficult for clinicians. In at least 20% of cases of appendicitis, the diagnosis is missed; in another 15 to 40% of cases, the appendix is normal in patients sent to surgery for suspected appendicitis. Diagnostic criteria for identifying appendicitis include:
Elevated white cell count greater than 10,000/mL.
Fever greater than 37.50 C (99.5 F).
The presence of pain in the right lower quadrant.
CT scanning is an excellent tool for the diagnosis of appendicitis, especially appendiceal CT used in the emergency department by radiologists trained in its use. Ultrasound may also be effective.
Complications
Peritonitis can occur if the swollen appendix bursts. Peritonitis significantly increases the risk of postoperative complications.
Treatment
Surgical removal of the appendix.
If the appendix bursts before surgery, antibiotics are necessary to reduce the risk of peritonitis and sepsis.
ediatric Consideration
The peak age of incidence of appendicitis in children is between ages 10 and 12. In children, especially infants and toddlers, appendicitis is often misdiagnosed, with a perforation incidence greater than 90% in children less than 3 years of age.
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Inflammatory Bowel Disease
Inflammatory bowel disease includes Crohn's disease and ulcerative colitis. Both of these conditions appear to be autoimmune diseases of unknown cause, with widespread activation of pro-inflammatory cytokines contributing to the scarring and inflammation of the tissue. They both have strong genetic influences and are exacerbated by stress.
Crohn's Disease
Crohn's disease is a chronic inflammatory disease of the bowel characterized by inflammation of all layers of the GI tract. It especially affects the submucosal layer and the small and large intestines.
The inflammation of Crohn's occurs as sharply outlined granulomatous lesions that appear in skip pattern scattered throughout the affected area of the gut. Interspersed between areas of inflammation is normal gut tissue. With chronic inflammation, fibrosis and scarring occur and make the bowel stiff and inflexible. If the fibrosis occurs in the small intestine, it can significantly interfere with the absorption of nutrients. If the disease is primarily localized in the colon, water and electrolyte balances can be disturbed. Abnormal connections or fistulas sometimes develop between different parts of the digestive tract and between the GI tract and the vagina, bladder, or rectum. These fistulas can contribute to malabsorption and cause infection.
Clinical Manifestations
Intermittent, usually non-bloody diarrhea.
Colicky pain.
Weight loss.
Malabsorption.
Fluid and electrolyte imbalances may result.
Malaise.
Low-grade fevers.
Diagnostic Tools
Colonoscopy reveals irregular, scarred bowel.
Complications
Toxic megacolon, dilation of the colon resulting from interference with its neural or vascular integrity, may occur. This condition can be life threatening.
Obstruction of the intestine caused by scarring may occur. Fistulas between the colon and other abdominal organs may occur.
Systemic manifestations of Crohn's disease include arthritis, skin lesions, and various blood disorders, including autoimmune anemia and hypercoagulability. Persons may demonstrate signs of depression.
Children afflicted with Crohn's disease may experience growth retardation, resulting from malabsorption as well as from the anti-inflammatory drugs used to treat the disease.
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Treatment
Anti-inflammatory drugs are used to interrupt the constant cycle of inflammation.
Nutritional supplementation and diet education.
Surgery involving gut resection may be required.
Psychological support.
Total parenteral nutrition, which involves food solutions being delivered intravenously, may be needed during exacerbations to allow the gut to heal.
Given the role of pro-inflammatory cytokines in contributing to the course of Crohn's disease, use of antibodies against one pro-inflammatory cytokine in particular, tumor necrosis factor alpha (TNF- ) is an effective treatment for many.
Ulcerative Colitis
Ulcerative colitis is an inflammatory disease of the rectum and colon that primarily affects the mucosal layer of the large intestine. It is spread continuously throughout the affected area. There is no skip pattern. Ulcerative lesions in the crypts located in the base of the mucosal layer, called Lieberkuhn's crypts, become inflamed, causing hemorrhage and abscess formation. Thickening of the wall of the bowel can occur.
Ulcerative colitis typically goes through stages of exacerbations and remissions. The disease can be mild, moderate, or fulminating. Bloody diarrhea mixed with mucus is characteristic of each stage, but it is intensified with increasing severity of the disease.
Clinical Manifestations
Mild cases demonstrate small-volume, chronic, bloody diarrhea.
With worsening cases, more and more of the colon is affected, resulting in increasing diarrhea, with loss of electrolytes.
Fever.
Weight loss.
Abdominal pain increasing with severity of disease.
Diagnostic Tools
Sigmoidoscopy reveals hemorrhagic mucosa with ulceration.
Blood analysis demonstrates anemia and low serum potassium.
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Complications
Toxic megacolon may develop.
Perforation of the gut wall with peritonitis may occur.
There is an increased risk of colon cancer with ulcerative colitis.
Systemic manifestations of ulcerative colitis include arthritis, skin lesions, and various blood disorders, including autoimmune anemia and hypercoagulability.
Children afflicted with ulcerative colitis may experience growth retardation, resulting from the malabsorption and diarrhea, as well as from the anti-inflammatory drugs used to treat the disease.
Treatment
Anti-inflammatory drugs.
Nutritional supplementation.
Bulk-free diet to decrease stool frequency.
Psychological support.
Surgical resection of the bowel may be necessary.
Diverticular Disease
Diverticular disease is characterized by one or multiple herniations of the mucosal layer of the colon through the muscular layers. Herniations of the mucosal layer are believed to occur when an individual frequently exerts high pressures inside the lumen of the colon while straining to pass a low-bulk stool. This disease is more common among people who eat low-fiber, low-bulk meals.
Clinical Manifestations
Some individuals may be asymptomatic. However, clinical manifestations usually include the following:
A change in bowel habits.
Excess gas.
Diagnostic Tools
A good history and physical examination assist diagnosis.
An enema containing the contrast medium barium followed by x-ray may identify diverticula. Barium enemas should be avoided if risk of perforation is high.
Complications
Diverticulitis, an inflammation or infection of the diverticula, may occur. The diverticula may become infected if bacteria-rich pieces of
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stool become trapped in the diverticula. Systemic signs of an infection, including fever and elevated white cell count, occur.Perforation of the gut from severe diverticulitis may occur. With perforation, pain (usually in the lower left quadrant), nausea, and vomiting occur. Fever and elevated white cell count are present.
Treatment
Dietary modification to increase stool bulk.
Exercise to increase the rate of stool passage.
Diverticulitis is usually treated with antibiotics and the withholding of solid food until healing occurs.
Perforation requires surgery and antibiotic therapy.
Hirschsprung's Disease
Hirschsprung's disease, also called congenital megacolon, results from the congenital absence of autonomic ganglia innervating the myenteric plexus in the anorectal junction and some or most of the rectum and colon. In most cases, the absence of ganglia is restricted to the sigmoid (distal) colon, although in approximately 20% of cases, the disorder extends proximally as well. Involvement of the entire bowel is rare and fatal. Autonomic ganglia to the myenteric plexus normally stimulate motility and ensure the passage of stool. With Hirschsprung's, stool accumulates in the bowel. The prevalence of Hirschsprung's is about 1:5,000 live births, with most cases (approximately 85%) occurring sporadically or without a clear autosomal dominant pattern. Nevertheless, there are at least nine genes involved in affecting susceptibility to the disorder. Nearly 1 in 3 afflicted children will have an additional congenital malformation. In adults, Hirschsprung's disease may develop following damage to the myenteric plexus.
Clinical Manifestations
Failure to pass the first stool within 48 hours of birth carries a high suspicion of Hirschsprung's.
A distended abdomen and/or vomiting may occur in an infant.
Chronic constipation in an older child or adult may signify the disorder.
Diagnostic Tools
Rectal biopsy that demonstrates an absence of ganglion cells confirms diagnosis.
Complications
Electrolyte disturbances and perforation of the bowel if distention is unrelieved.
Fecal impaction.
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Treatment
Surgical resection of the affected area.
Esophageal Cancer
Esophageal cancer is relatively uncommon in the United States; in other countries, this is not true. Worldwide, the highest rate of esophageal squamous cell carcinoma is in North Central China. Esophageal cancer is primarily related to alcohol and tobacco use. In some countries, such as China, these standard risks are combined with exposure to polycyclic aromatic hydrocarbons and malnutrition. Injury to the esophagus from accidental exposure to caustic materials or from the repeated ingestion of extremely hot liquids (such as tea) also has been implicated. And finally, chronic GERD may stimulate development of Barrett's esophagus and esophageal cancer. Prognosis for esophageal cancer has traditionally been poor, but it is improving with better diagnostic techniques that allow for earlier recognition and treatment.
Clinical Manifestations
Dysphagia (difficulty swallowing) is the most common symptom.
Anorexia and weight loss follow.
Pain from bone metastases often is the first symptom that stimulates a person to seek care.
Diagnostic Tools
Endoscopy followed by tissue biopsy is used to diagnose esophageal cancer.
X-ray or other diagnostic tests may be used to identify the secondary tumors.
Treatment
Surgical resection, radiation, and chemotherapy.
Stomach Cancer
Stomach cancer has decreased in the United States; however, it is still the seventh leading cause of death in this country. There appears to be a genetic predisposition to stomach cancer and an increased risk associated with consumption of preserved and smoked meats. Stomach cancer also has been linked to H. pylori infection. It has been suggested that the decreasing rates of stomach cancer in the United States over the last several decades may be due to the frequent use of antibiotics and hence the eradication of H. pylori. Decreased use of nitrate preservatives with better refrigeration has also contributed.
Clinical Manifestations
Stomach cancer is frequently asymptomatic until advanced. When symptoms are present they include the following:
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Vague abdominal discomfort.
Indigestion.
Weight loss.
Anorexia.
Fatigue.
A palpable abdominal mass may be present.
Diagnostic Tools
A careful history and the use of endoscopy followed by tissue biopsy enable diagnosis.
Treatment
Partial or complete surgical resection of the stomach.
Chemotherapy and/or radiation therapy may be used.
Colorectal Cancer
Colorectal or intestinal cancer is common in the United States. Most colorectal cancers are carcinomas and usually begin in the secretory glands of the mucosal layer. Most colorectal cancers begin in pre-existing polyps.
Risk factors for colorectal cancer include a high-fat and low-fiber diet, as well as high consumption of red meat and processed meats. Withholding stools may also allow toxins present in the stool to initiate or promote cancer. There is a genetic risk factor for colorectal cancer, and specific genes associated with colon cancer have been identified. The presence or history of polyps in the colon and rectum indicates an increased risk of cancer development. In regard to prevention, high intake of fruits and vegetables may protect against the development of colorectal cancer by increasing dietary bulk and by providing antioxidants that may protect cells from damage by carcinogens. Long-term (>10 years) use of aspirin and other NSAIDs significantly reduces the risk of colorectal cancer in a dose-dependent manner. However, risks associated with aspirin and NSAIDs, including GI bleeding, also increase with usage and dose. Finally, although still under investigation, there is evidence to suggest that colon cancer risk is lower in individuals taking statins for treatment of hyperlipidemia, although the mechanism by which this occurs is unclear.
Clinical Manifestations
Changes in bowel habits resulting in diarrhea or constipation may occur.
Occult or frank blood in the stool is a strong warning sign.
Fatigue.
Diagnostic Tools
Anemia may show up in a complete blood count (CBC), prompting further evaluation.
A palpable mass may be felt by digital examination.
Tests for occult blood in the stool may indicate cancer.
Early identification of polyps with digital examination, sigmoidoscopy, or colonoscopy (examination of the entire rectum and colon with a fiber-optic lens), and surgical removal of any visualized polyps may prevent cancer from developing.
Genetic markers for colon cancer may predict who is at greatest risk of developing the disease, thus allowing appropriate preventive measures to be initiated.
Blood tests for specific antigens associated with colorectal cancer, especially carcinoembryonic antigen (CEA), can be useful in the early identification of a recurring colorectal cancer. CEA levels are poor screening tools for cancer for the general population because measurable levels of CEA are only present with advanced disease. In addition, false-positive results (prediction of cancer when it is not present) frequently occur.
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Treatment
Preventive measures are important and include dietary education on increasing roughage, fruits, vegetables, and grains to increase bulk, decrease fat, and provide protective antioxidants.
Staging of the disease based on dissemination of tumor cells to regional lymph nodes is important in determining the prognosis and treatment of the disease. Identification of even micrometastases can influence outcome.
If colorectal cancer is present, surgery is required with or without follow-up chemotherapy.
eriatric Consideration
Colorectal cancer usually occurs in the elderly. Recommendations for digital examination and tests for occult blood in the stool usually begin after the age of 40, and visualization of the rectum and colon is recommended after the age of 50. Individuals who have a first-degree relative with colon cancer are advised to undergo colonoscopy before the age of 50.
Selected Bibliography
Behrend, L., Mohr, A., Dick, T., & Zwacka, R.M. (2005). Manganese superoxide dismutase induces p53-dependent senescence in colorectal cancer cells. Molecular and Cellular Biology 25, 7758 7769.
Brooks, A.S., Oostra, B.A., & Hofstra, R.M.W. (2005). Studying the genetics of Hirschsprung's disease: Unraveling an oligogenic disorder. Clinical Genetics 67, 6 14.
Chan, A.T., Giovannucci, E.L., Meyerhardt, J.A., Schernhammer, E.S., Curhan, G.C., & Fuchs, C.S. (2005), Long-term use of aspirin and nonsteroidal anti-inflammatory drugs and risk of colorectal cancer. Journal of the American Medical Association 294, 914 923.
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Chao, A., Thun, M.J., Connell, C.J., McCullough, M.L., Jacobs, E.J., Flanders, W.D., et al. (2005). Meat consumption and risk of colorectal cancer. Journal of the American Medical Association 293, 172 182.
Guyton, A.C., & Hall, J. (2006). Textbook of medical physiology (11th ed.). Philadelphia: W.B. Saunders.
Kahi, C.J., & Rex, D.K. (2005). Screening and surveillance of colorectal cancer. Gastrointestinal Endoscopy Clinics of North America 15, 533 547.
Moayyedi, P., & Axon, A.T.R. (2005). Review article: Gastro-oesophageal reflux disease The extent of the problem. Alimentary Pharmacology Therapeutics 22, 11 19.
Old, J.L., Dusing, R.W., Yap, W., & Dirks, J. (2005). Imaging for suspected appendicitis. American Family Physician 71, 71 78.
Otto, B., Spranger, J., Benoit, S.C., Clegg, D.J., & Tsch p, M.H. (2005). The many faces of ghrelin: New perspectives for nutrition research? British Journal of Nutrition 93, 765 771.
Porth, C.M. (2005). Pathophysiology: Concepts of altered health states (7th ed.). Philadelphia: Lippincott Williams & Wilkins.
Poynter, J.N., Gruber, S.B., Higgins, P.D.R., Almog, R., Bonner, J.D., Rennert, H.S., et al. (2005). Statins and the risk of colorectal cancer. New England Journal of Medicine 352, 2184 2192.
Ratnasinghe, L.D., Abnet, C., Qiao, Y.-L., Modali, R., Stolzenberg-Solomon, R., Dong, Z.-W., et al. (2005). Polymorphisms of XRCC1 and risk of esophageal and gastric cardia cancer. Cancer Letters 216, 157 164.
Sandborn, W.J. (2005). New concepts in anti-tumor necrosis factor therapy for inflammatory bowel disease. Review of Gastroenterological Disorders 5, 10 18.
Schou, J.H., Pilgaard, K., Vilsb ll, T., Jensen, C.B., Deacon, C.F., & Holst, J.J. (2005). Normal secretion and action of the gut incretin hormones glucagon-like peptide-1 and glucose-dependent insulinotropic polypeptide in young men with low birth weight. Journal of Clinical Endocrinology and Metabolism 90, 4912 4919.
Suerbaum, S., and Michetti, P. (2002). Helicobacter pylori infection. New England Journal of Medicine 347, 1175 1186.
Resources
Crohn's and Colitis Foundation, 386 Park Avenue, New York, NY 10016. Phone: (800) 343-3637.
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