Chapter 29 Patho Notes.pdf

Gastrointestinal (GI) disease takes many forms and affects people across the world in both industrialized and undeveloped countries. GI disorders are among the most common disorders encountered within the U.S. population; however, because many individuals self-medicate using over-the-counter medicat...

Gastrointestinal (GI) disease takes many forms and affects people across the world in both industrialized and undeveloped countries. GI disorders are among the most common disorders encountered within the U.S. population; however, because many individuals self-medicate using over-the-counter medications, many disorders go unreported and undiagnosed. The GI tract can be divided into upper and lower segments. The esophagus, stomach, and small intestine comprise the upper GI tract (see Fig. 29-1). These organs have the primary role of food and fluid digestion and absorption of essential nutrients, vitamins, and minerals. Any alteration in upper GI organ function can cause indigestion, malabsorption, malnutrition, or dehydration, all of which have profound effects on the whole body. Epidemiology One of the major disorders of the upper GI tract is gastroesophageal reflux disease (GERD). This disorder is diagnosed if a person has esophagitis more than a few times a week. GERD occurs in all ages, most commonly in infants and in persons older than age 40 years. Approximately 25% to 40% of Americans experience GERD at some point in their lives. A disorder that can be associated with esophagitis and GERD is peptic ulcer disease (PUD). In the United States, PUD affects approximately 4.5 million people annually. Approximately 10% of the U.S. population has evidence of a duodenal ulcer. If PUD goes untreated, there is the possibility of acute GI bleeding. This potentially life-threatening abdominal emergency is a common cause of hospitalization, affecting 100,000 individuals annually in the United States. The most common GI disorder across the world is gastroenteritis, although most cases are undiagnosed, unreported, and treated by affected individuals themselves. Most cases are caused by a virus that lasts 1 to 2 days. However, in many parts of the world, gastroenteritis is a potentially lethal condition. Basic Concepts of Esophageal, Stomach, and Small Intestine Function The upper GI tract consists of the esophagus, stomach, and small intestine. These organs are responsible for the major digestion and absorption of vital nutrients. Dysfunction of any of the upper GI organs can lead to malnutrition and dehydration. Esophagus The esophagus is a tubelike structure that lies behind the trachea in the thorax and extends from the pharynx to the stomach. A sphincter is located at each end of the esophagus: the upper esophageal sphincter (UES) and the lower esophageal sphincter (LES), also known as the cardiac sphincter. Both are contracted in their resting state and open in response to nerve stimulation. The UES directs food and liquids into the esophagus and prevents their aspiration into the airway. The epiglottis is a membrane that closes over the trachea during eating to prevent food from entering the respiratory system. In the esophagus, ingested food moves down by peristalsis. Peristalsis occurs by the contraction and relaxation of the muscle of the esophagus, innervations by the sensory neurons, and moisture from the mucosal membranes. The peristaltic waves continue to the LES, where the vagus nerve stimulates the opening of the sphincter and the bolus is pushed into the stomach cavity. Stomach The stomach is located in the upper part of the abdomen and consists of three portions: the fundus, the uppermost portion of the stomach; the body, the center and largest part of the stomach; and the pylorus, the lower portion of the stomach. Two sphincters help regulate the inflow and outflow of stomach contents—the LES, located between the lower esophagus and the stomach, and the pyloric sphincter, which separates the stomach from the duodenum. The digestive process in the stomach consists of three phases: 1. Cephalic phase 2. Gastric phase 3. Intestinal phase The cephalic phase occurs in response to a sensory stimulus, such as the sight, smell, or taste of food. It consists of activation of the vagal nerve, secretion of acetylcholine, and parasympathetic motor response. To follow this, cells prepare for the second phase of digestion, the gastric phase. As part of this preparation, histamine and gastrin are released from stomach cells. The gastric phase starts as food or fluids enter the stomach, stimulating the activity of mucus and gastric acid from stomach secretory cells. Types of stomach cells include gastric goblet cells, parietal cells, chief cells, and G cells. Gastric goblet cells secrete mucus, and parietal cells secrete hydrochloric acid (HCl) and intrinsic factor. HCl sterilizes and breaks down food, mainly proteins and carbohydrates. Intrinsic factor is necessary for the absorption of vitamin B12 in the small intestine. Within the parietal cells the proton pump regulates synthesis of acid. Acid is stimulated by acetylcholine, histamine, or gastrin. Acetylcholine, histamine, and gastrin bind to receptors on the parietal cells; this triggers the action of the proton pump, which elevates the stomach’s hydrogen (H+) ion concentration. Chief cells secrete pepsinogen, which in the acidic environment converts to pepsin, an enzyme utilized for protein digestion. The stomach’s cells are capable of secreting 1,500 mL of gastric secretions a day while maintaining an acidic pH of 1.5 to 2.0 because of HCl. To counteract the acid in the stomach, gastric mucosal cells secrete prostaglandin E2 (PGE2), a lipid-rich molecule, which exerts a strong protective effect. PGE2 stimulates gastric mucus production and pancreatic bicarbonate secretion, which reduce the effects of HCl. To digest proteins, G cells, located in the pylorus, secrete gastrin. G cells are endocrine-like cells that increase gastric motility, stimulate secretions from parietal and chief cells, and trigger the release of bile from the gallbladder and enzymes from the pancreas. The bile and pancreatic enzymes enter the digestive system via the common bile duct into the duodenum. The stomach’s peristaltic function enables the mixing of food and digestive enzymes. Food is broken down into small particles and enzymatically liquefied to form chyme. Chyme is then propelled toward the pyloric sphincter and into the duodenum for the final stages of digestion. This is the beginning of the third stage of digestion, the intestinal phase. Small Intestine The small intestine is the largest GI organ, measuring approximately 20 feet long, and its primary function is absorption and digestion. The duodenum marks the beginning of the small intestine, followed by the jejunum, ileum, and ileocecal valve. The mucosal lining of the small intestine is covered with thousands of tiny fingerlike projections known as villi; each villus contains goblet cells, whose functions are to release digestive enzymes, secrete mucus, and absorb nutrients. A unique characteristic of the small intestine is the presence of microvilli, located on the villi’s epithelial cells. This double set of villi is known as the brush border. The combination of the villi and microvilli double the surface area, significantly increasing the small intestine’s absorptive capacity (see Fig. 29-2). The final phase of the digestive process, the intestinal phase, includes neural and hormonal responses. The neural response, the enterogastric reflex, is responsible for the opening of the pyloric sphincter. This reflex is stimulated by intestinal distention and decreases gastric motility and acid production. In the duodenum, bile from the liver, enzymes from the pancreas, and chyme from the stomach come together to complete the digestive process. Both the duodenum and jejunum contain receptors that sense acidity, osmotic pressure, and such products of digestion as fats and peptides. Secretin, a hormone secreted by the intestine, inhibits gastric secretion. Gastric emptying into the duodenum is decreased if the duodenal pH is lower than 3.5. Acidic stomach contents enter the duodenum gradually at a rate that allows for neutralization by pancreatic bicarbonate. The primary function of the middle section of the intestine, the jejunum, is absorption. Nutrients such as amino acids; glucose; iron; calcium; and the fat-soluble vitamins A, D, E, and K are absorbed in the jejunum. The primary function of the ileum—the last and longest segment of the small intestine—is the reabsorption of vitamin B12 and the return of bile acids to the liver. The return of bile acids to the liver from the ileum is termed the enterohepatic circulation process. Bile acids are recycled by this process. The gastroileal reflex stimulates the opening of the ileocecal valve, which controls the release of digestive contents into the large intestine. Basic Pathophysiological Concepts of the Esophagus, Stomach, and Small Intestine The functions of the GI tract are to ingest, digest, absorb, and eliminate. Normal movement of gastric contents through the digestive tract is necessary for digestion and absorption of nutrients. An alteration in the ingestion process where contents cannot progress from one area of the GI tract to subsequent areas creates motility dysfunction. Contents that progress too quickly fail to be adequately broken down, which results in malabsorption; in contrast, contents that move too slowly often cause nausea and vomiting. Inflammation, as well as structural and cellular abnormalities, in any of the GI structures will also have a direct effect on motility and absorption. Assessment The history and physical examination of the patient provide information for initial evaluation of an upper GI disorder. In general, with regard to the GI tract, the patient should be questioned about swallowing, indigestion, eructation (belching), and abdominal pain. If swallowing pain is present, it needs to be fully explored regarding onset, location, and duration. Is the pain a burning, gnawing feeling, as occurs in esophagitis? Does the pain occur with or between meals? Is the pain relieved by food, as in peptic ulcer? Are there nocturnal symptoms, as in GERD? Is there any swallowing difficulty? Which is more difficult to swallow: solids or liquids? Is there a problem with regurgitation? Swallowing difficulty and regurgitation can be due to esophageal cancer, Zenker’s diverticulum, or Plummer–Vinson syndrome. The patient should also be asked about weight loss or anorexia. How much weight loss has occurred over what length of time? Unintentional weight loss of 10 lbs over 1 month should be investigated. If nausea or vomiting is a problem, the clinician should review the onset of nausea, triggering factors, the time frame in regard to eating, and whether vomiting occurs. Does the emesis (vomitus) contain blood, mucus, or bile? Does it have a coffee-ground appearance, as occurs in upper GI bleeding? Is blood visible in the vomitus? Does the patient take NSAIDs or aspirin? How much coffee does the patient drink? What other medications are taken? Does the patient take antacids, proton pump inhibitors (PPIs) such as lansoprazole (PrevacidR), or histamine-2 receptor blockers such as ranitidine (ZantacR) and how often? The patient’s medication list can often be responsible for GI symptoms or reveal information about symptoms. Questioning the patient about alcohol use and smoking is also important, as these often cause GI irritation. The clinician needs to ask about bowel movements. Has there been any diarrhea, as in malabsorptive diseases? Is there any bleeding or dark stools, as in GI bleeding? Black, tarry stools indicate GI blood loss. One of the major risk factors for upper GI problems is the use of NSAIDs, including aspirin. These medications are often associated with gastric irritation and erosion and can be the cause of PUD. Alcohol use and smoking are associated with esophagitis, peptic ulcer, and esophageal cancer. Alcohol abuse, the etiology of cirrhosis of the liver, can also cause problems for the upper digestive tract. Upper GI bleeding is often caused by esophageal varices, which occur in cirrhosis. Frequent heartburn can cause GERD, which is a precursor of Barrett’s esophagus, a precancerous change of the esophagus. Upper GI tract bleeding can also be due to a bleeding or perforated peptic ulcer. Patients who are bulimic have frequent vomiting episodes that can cause esophageal tears, called Mallory–Weiss syndrome or Boerhaave syndrome. Both cause upper GI bleeding. Immunosuppressed individuals are susceptible to esophagitis caused by Candida infection, also called thrush. Candida-related esophagitis causes a white exudate over the oral cavity and tongue and painful swallowing. Other possible infectious agents include herpes virus, cytomegalovirus, and human papilloma virus (HPV). HPV is increasingly becoming a causative factor of oral and esophageal cancer. CLINICAL CONCEPT Chronic use of NSAIDS often causes peptic ulcer disease and GI bleeding. Diagnosis Often, esophageal or upper GI pain cannot be immediately distinguished from cardiac chest pain, so an acute coronary event needs to be ruled out before exploration of a GI disorder. If the patient has upper GI bleeding, hemodynamic stabilization of the patient is necessary; a nasogastric aspirate can be used to investigate the source of bleeding. If the stomach contains bile but no blood, upper GI bleeding is less likely. If the aspirate reveals clear gastric fluid, a duodenal site of bleeding may be possible. The most accurate method of diagnosing upper GI tract disorders is upper endoscopy. The endoscope can be used to diagnose, take a biopsy of tissue, and treat upper GI problems. Videocapsule endoscopy is an alternative if conventional endoscopy cannot be used. This vitamin-sized capsule contains a camera; when swallowed, it travels through the digestive tract, taking pictures of the internal GI tract. Upper GI barium x-rays, also called an upper GI series, may be done to highlight the anatomy of the upper GI tract. The patient is instructed to swallow barium, a radiopaque substance, which allows for visualization of the esophagus, stomach, and duodenum. Clinicians can also visualize the patient’s ability to swallow by using fluoroscopic x-ray procedures. Esophageal manometry studies are often performed to measure the strength of the esophageal sphincter muscles. Manometry is performed using a special nasogastric tube that is passed from the nostril to the stomach. Helicobacter pylori studies are done when peptic ulcer is suspected. Antibodies to H. pylori can be measured in the blood. Using an endoscope, a gastric mucosal biopsy can be sampled and tested for H. pylori. Fecal antigen testing identifies active H. pylori infection in the stool. Urea breath tests detect active H. pylori infection by analyzing the breath. If there is bleeding, type and crossmatch of the patient’s blood are necessary. Other laboratory tests that are commonly performed include complete blood count (CBC), electrolytes, blood urea nitrogen (BUN), serum creatinine, liver function tests, prothrombin time/partial thromboplastin time, and international normalized ratio (INR). A gastrin level is done to rule out Zollinger–Ellison syndrome (ZES), which causes peptic ulcers. Amylase and lipase levels are also checked to exclude a pancreatic disorder or perforation of an organ. Treatment Any disorder that includes bleeding, such as esophageal varices and perforated ulcer, requires primary hemodynamic stabilization. Patients with occasional indigestion should take antacids and make lifestyle modifications such as weight loss if obese, decreased alcohol and coffee intake, and smoking cessation, if appropriate. Esophagitis that occurs more often can be treated with PPIs such as lansoprazole (PrevacidR) for four to eight weeks. Some clinicians suggest PPIs or histamine-2 receptor antagonists such as ranitidine (ZantacR) for patients with ulcerlike symptoms. These agents decrease gastric acid production by inhibiting the proton pump mechanism and blocking histamine-2 receptors in gastric parietal cells. Patients with upper GI bleeding caused by esophageal varices often require esophagogastric balloon tamponade, which is the insertion of a catheter with an inflatable balloon on the tip. The esophagogastric tube can be used as a temporary measure to exert pressure on the esophageal veins to stave off bleeding. Endoscopy can be used in diagnosis and treatment. Endoscopic sclerotherapy, endoscopic band ligation, and other types of endoscopic ablation are used to treat esophageal varices and esophageal cancer. Another procedure, insertion of a transjugular intrahepatic portosystemic shunt (TIPS), can be used to permanently treat esophageal varices due to portal hypertension. Surgery is needed in patients with a perforated viscus, such as in perforated duodenal ulcer, perforated gastric ulcer, and Boerhaave syndrome (esophageal rupture). Surgery may involve a laparoscopic procedure to suture bleeding vessels in the esophagus, stomach, or duodenum; it might also involve cutting the vagus nerve to the stomach to cease acid stimulation. Disorders of the Esophagus, Stomach, and Small Intestine Disorders of each organ within the upper GI tract are different because of their distinct composition and function. The esophagus mainly undergoes inflammation. Although tumor growth is uncommon, stricture, spasm, or diverticula can occur. The stomach commonly undergoes inflammation or ulceration. Tumor growth is rare in the stomach. The small intestine disorders are mainly those of inflammation or obstruction, which can cause severe malabsorption, dehydration, and malnutrition. Disorders of the Esophagus The initial section of the GI tract, the esophagus, can undergo specific types of defects and alterations. The purpose of the esophagus is to propel food and fluid from the mouth to the stomach. A series of contractions and relaxations within the esophageal tract creates peristalsis, which facilitates the movement of food to the stomach. Alterations of esophageal motility, inflammation, or obstruction within the esophagus will result in the person’s inability to effectively swallow. Dysphagia Dysphagia, or swallowing difficulty, is a term that is widely used with disorders of the esophagus. A wide range of causes result in dysphagia, making incidence difficult to report. Dysphagia is associated with the lack of a gag reflex, as occurs in degenerative neurological diseases and stroke. Between 50% and 70% of individuals affected by stroke have a decreased gag reflex and dysphagia. In diseases such as myasthenia gravis or amyotrophic lateral sclerosis, dysphagia and loss of gag reflex occur late in the disease and can cause death. Etiology. Dysphagia most often occurs because of neuromuscular dysfunction; however, structural abnormalities of the esophagus are causes as well. Zenker’s diverticulum is a weakening in the wall of the esophagus that causes an outpouching or sac where food can accumulate. Food accumulates within the sac and fills to create an obstructive mass in the esophagus that interferes with swallowing. Esophageal strictures, rings, or tumors can also cause dysphagia. A Schatzki ring is a constrictive muscular band of esophageal tissue. This congenital abnormality is often found in the distal esophagus. Thin membranous webs of tissue can also form in the esophagus and cause dysphagia. In Plummer–Vinson syndrome, patients have trouble swallowing because of congenital or acquired webs of tissue in the upper esophagus. Another cause of dysphagia is an esophageal stricture, which is an abnormal thinning or narrowing of the esophagus. Strictures can occur as a result of chronic esophagitis, GERD, tumors, Barrett’s esophagus, inflammatory disorders such as scleroderma, or congenital abnormality. Achalasia is an esophageal motility problem that involves the smooth muscle of the esophagus. There is incomplete relaxation of the LES, as well as increased muscular tone. It is characterized by lack of peristalsis of the esophagus. Pathophysiology. Dysphagia frequently begins with difficulty swallowing solid foods and progresses to the inability to swallow liquids. An individual may complain of feeling as though the food gets stuck, and frequent attempts to swallow are necessary for movement of food. Structural abnormalities of the esophagus such as diverticula, stricture, webs, and rings cause mechanical problems of swallowing. Food becomes obstructed because of the anatomical abnormality. Damage or dysfunction of cranial nerves IX, X, or XII can also cause inability to swallow solids or liquids. These nerves can become dysfunctional in stroke, spinal cord injury, degenerative neurological diseases, and trauma. The esophagus lies posterior to the trachea, creating a high risk for aspiration. Any time there is altered motility of the esophagus, there is an increased risk of food or fluids entering the trachea rather than the esophagus, known as aspiration. The inhaled contents will follow the path of the trachea and eventually lodge within the sterile environment of the respiratory system, leading to an infection called aspiration pneumonia. Individuals with the greatest risk for aspiration pneumonia are those with a history of a stroke, trauma to the upper spinal cord, brain injury, or someone who is receiving enteral feedings. Aspiration pneumonia is demonstrated by the presence of pulmonary crackles, an elevated white blood cell (WBC) count, and fever. It most commonly occurs in the right lung. Clinical Presentation. The patient with dysphagia may exhibit evidence of cranial nerve dysfunction. A unilateral facial droop indicates that cranial nerve VII is dysfunctional. In a patient with an absent gag reflex, the tongue and uvula may be deviated to one side, which indicates dysfunction of cranial nerves IX, X, and XII. Regurgitation of food or fluids is associated with esophageal impairment; patients will have pooling of food or liquid in the back of the throat, and individuals may have drooling of food from one side of the mouth. Frequent coughing while eating is indicative of dysphagia and places the person at high risk for aspiration. Painful swallowing, or odynophagia, may occur as efforts to swallow are ineffective and necessitate repeated attempts to swallow. To assess the gag reflex, ask the patient to open the mouth and say “ah.” The uvula and soft palate should rise as the patient vocalizes. In addition, the uvula should be in the midline position. Diagnosis and Treatment. An upper GI series, also called a barium swallow test, is a specialized x-ray used to diagnose dysphagia. This fluoroscopic procedure demonstrates the patient’s ability to swallow. The presence of aspiration pneumonia can be confirmed with a conventional chest x-ray. An individual with dysphagia can be trained to swallow during rehabilitation. Often the patient requires pureed foods and thickened fluids. Individuals with a neurological impairment of the esophagus will require enteral nutrition, which is composed entirely of liquid and has a high caloric content. This form of nutrition is given through a tube that transports the food into the stomach or intestine (see Fig. 29-3). Esophagitis Esophagitis is an acute or chronic inflammation of the esophagus. This condition most commonly arises from an irritation to the mucosa of the esophageal lining by refluxed acid. It can also be caused by the fungal organism C. albicans in immunosuppressed individuals. Esophagitis is a disorder that can occur occasionally, or it can be a more serious condition that occurs frequently and is diagnosed as gastroesophageal reflux disease (GERD). Generally, 33% to 44% of the population endure esophageal reflux symptoms at some time during a month. However, up to 10% of people have daily symptoms, which indicates a diagnosis of GERD. Candida esophagitis, also called thrush, is the most common type of infectious esophagitis. Etiology Acute esophagitis occurs from an infection, chemical ingestion, medications, excessive vomiting, or occasional episodes of acid reflux. Obesity, pregnancy, smoking, alcohol, fatty foods, and coffee increase susceptibility to esophagitis. Some medications, such as calcium antagonists, anticholinergics, NSAIDs, and bisphosphonates, increase susceptibility to esophagitis. Chronic esophagitis is most often associated with the presence of poorly controlled GERD. Major predisposing factors for Candida esophagitis include antibiotic use, radiation therapy or chemotherapy, hematologic malignancies, and AIDS. Other conditions associated with an increased incidence of Candida esophagitis include esophageal stasis, alcoholism, malnutrition, and advanced age. Pathophysiology Esophagitis occurs as a result of an irritation to the squamous epithelium, the protective lining of the esophagus. The body responds to the injury by initiating the inflammatory process. Edema will occur as a result of vasodilation. Pain is associated with the erosion, or destruction, of the epithelium. The area of injury is repeatedly irritated as the contractions of peristalsis and the progression of food or fluids moves through the esophagus. A risk for esophageal obstruction exists with severe esophageal inflammation because the edema and inflammation can block foods from being swallowed. In addition, chronic irritation to the esophagus can lead to ulcerations, scarring, or strictures. Thrush often begins as an infection in the mouth. Candida is yeast that is considered part of the normal flora of the oral cavity. When a person is immunosuppressed, overgrowth of Candida in the mouth is common. This condition is commonly found in neonates; individuals with AIDS; and those receiving chemotherapy, immunomodulators, or long-term antibiotic therapy. If thrush is not quickly identified or properly treated, the infection can progress into the esophagus, causing Candida esophagitis. H. pylori are aggressive bacteria that invade the lining of the stomach, leading to peptic ulcer disease (PUD). H. pylori resists acid and burrows under the stomach mucosa. In GERD, acid and H. pylori constantly reflux upward into the esophagus. The esophageal epithelial mucosa becomes severely irritated by acid, and H. pylori can cause ulceration in the lower esophageal cells. Other organisms that can cause esophagitis include herpes simplex, varicella zoster, cytomegalovirus, and HIV. A growing body of evidence is showing that HPV can also infect the esophagus. Chemical or corrosive esophagitis can occur with ingestion of household chemicals. Many chemicals consist of strong alkali or acid components that are corrosive to the esophagus’s lining. The caustic action of the ingested chemicals often leads to perforation and bleeding of the esophageal lumen. Vomiting should not be induced because of the risk for additional injury to the esophagus as the corrosive agents are expelled. Chronic use of NSAIDs or aspirin can cause drug-induced ulcerations of the esophagus. Additional medications that may be irritating to the esophageal lining include antibiotics, chemotherapy, bisphosphonates, and potassium. As these medications dissolve, they may become corrosive to the esophageal lining. Individuals should be encouraged to drink adequate amounts of water with these medications to ensure that the pills have not lodged against the wall of the esophagus. Persons taking bisphosphonates should sit upright or stand for 30 minutes after swallowing the drug in order to prevent esophagitis. The process of vomiting causes irritation to the epithelium of the esophagus as acidic gastric contents are forcefully expelled. The combination of the pressure of the expulsion and the acidity of gastric contents can lead to erosion of the esophagus and deterioration of the LES. Recurrent vomiting, as seen with eating disorders or pregnancy, can lead to esophagitis. Mallory–Weiss syndrome, which is a vertical tear in the lower esophagus, can occur with forceful, frequent bouts of vomiting. This may lead to esophageal bleeding and hematemesis. Boerhaave syndrome, a transmural rupture of the esophagus, can occur because of excessive, forceful vomiting or because of instrumentation of the esophagus. Severe hematemesis occurs with loss of an extensive amount of blood. Clinical Presentation In esophagitis, the most common complaint is a burning sensation in the throat or midsternal chest. Dysphagia, odynophagia, and heartburn are other symptoms associated with esophagitis. A complaint of a sore throat or tongue and white patches on the tongue, palate, or buccal mucosa are hallmark signs of thrush. Hematemesis, nausea, and vomiting can also occur. Diagnosis and Treatment The diagnosis and severity of esophagitis can be ascertained with endoscopy, which allows for visualization of ulcerations or perforations and provides the option to obtain a biopsy of the affected area. Barium studies can also be used in the diagnosis. Treatment of esophagitis is primarily focused on treating the inflammation and relieving symptoms. The clinician should advise lifestyle changes, such as smoking cessation, alcohol limitation, reduced caffeine intake, and avoidance of NSAIDs and aspirin. Pharmacological treatment includes histamine-2 receptor blockers such as ranitidine or PPIs such as omeprazole for 4 to 8 weeks. Sucralfate is a viscous adhesive substance that can augment the stomach’s protective lining. In Candida infection, antifungal agents such as fluconazole can be used. Surgery can be done when lifestyle and pharmacological management has been ineffective. Gastroesophageal Reflux Disease GERD is the most common and most costly GI disorder in the United States. Over 700,000 persons are hospitalized with GERD per year. However, many persons with GERD self-medicate with over-the-counter drugs, so there are many unreported cases. Approximately 20% of the U.S. population experiences GERD at least once per week. GERD is most common in infants and those older than age 40 years. Etiology The most common cause of GERD is a functional or mechanical problem that decreases muscular tone of the lower esophageal sphincter (LES). Relaxation of the LES allows for regurgitation of stomach contents into the esophagus. Different conditions, foods, and medications can cause decreased strength of the LES (see Box 29-1). Pathophysiology In GERD, the LES is weak and allows the contents of the stomach to reflux up into the esophagus. The stomach contents are acidic, so when refluxed upward, they irritate the esophageal squamous epithelium. Although the LES is dysfunctional in GERD, gastroparesis, the delayed emptying of gastric contents into the duodenum, is also a problem. Gastroparesis causes increased gastric distention that leads to increased pressure within the stomach against the LES. Any cause of increased gastric or intra-abdominal pressure can place tension on the LES. Obesity and pregnancy, for example, commonly cause GERD. A hiatal hernia also interferes with the closure of the LES, resulting in a reflux of gastric secretions into the esophagus. In GERD, the esophageal epithelial cells are not able to withstand the acidity of the refluxed stomach contents. The gastric acid can quickly erode the protective mucosal epithelial layer and lead to ulceration of the esophagus. Repeated injury to the epithelial layer commonly causes metaplasia, the change of esophageal epithelial cells into stomach like columnar epithelium. The metaplastic cellular change at the gastroesophageal junction, called Barrett’s esophagus, is a precancerous change of cells. Barrett’s esophagus requires periodic endoscopic examination to check for dysplastic cell changes. Clinical Presentation The most frequent symptoms associated with GERD are dysphagia, heartburn, epigastric pain, and regurgitation. Frequent heartburn may also be described as acid indigestion, or dyspepsia. Individuals often describe regurgitation as a bitter taste in their mouth. Respiratory complaints, such as chronic dry cough, asthma, and aspiration pneumonia, are also associated with the presence of GERD. Individuals frequently complain of increased pain following the ingestion of certain foods, such as those that have a high fat content and take longer to digest, thereby causing delayed gastric emptying and increased gastric distention. Postural positioning, such as lying flat or bending over, will also aggravate GERD. These positions will cause increased pressure from the stomach to the LES, forcing the LES to weaken and resulting in reflux of gastric contents. In severe cases of GERD, an individual may present with complaints of weight loss, frequent cough, aspiration pneumonia, GI bleeding, or anemia. Any of these symptoms carry an increased cause for concern because they represent a progression of the disease. The GI bleeding is related to chronic irritation of the mucosal tract and erosion into the cellular layer. Anemia may be related to blood loss or nutritional deficits. A frequent cough and repeated episodes of aspiration pneumonia are indicative of the progression of GERD further up the esophageal tract. GERD with aspiration can occur while the patient is asleep; the regurgitation of acidic contents into the lungs can often stimulate nocturnal asthma attacks. Diagnosis and Treatment The most effective diagnostic tools for GERD are endoscopy and manometry. Through an endoscope, the clinician can visualize the esophageal mucosa. Manometry can determine the pressure at the LES. Ambulatory 24-hour pH testing can be done to confirm acid reflux in patients with atypical presentations or when endoscopy fails to reveal reflux. Barium studies (also called upper GI series) can outline the esophageal tract and highlight any erosions or ulcers. If GERD has been present for 5 years or more, a biopsy should be done to screen for the presence of Barrett’s esophagus. Treatment for GERD is focused on lifestyle changes. These include eating small, frequent meals to prevent abdominal distention; not lying down for 2 to 3 hours following a meal; losing weight if obese; and smoking cessation. The clinician should also review the patient’s medications because the side effects of some are LES dysfunction. Pharmacological treatments of GERD focus on decreasing the acidity levels of gastric secretions and improving the function of the LES. PPIs, histamine-2 receptor antagonists, and antacids are commonly prescribed. Laparoscopic antireflux surgery (also called fundoplication) is the surgical procedure used when other treatments have failed. During fundoplication surgery, the fundus, which is the upper curve of the stomach, is wrapped around the esophagus and sutured into place. This surgery strengthens the LES to block acids from refluxing up into the esophagus. Another esophageal sphincter–strengthening device composed of magnets is called the LINXR Reflux Management System. This is a minimally invasive procedure that can also alleviate reflux in many patients. Endoscopic radiofrequency delivery, also called the Stretta technique, is another procedure that can reinforce strength of the LES. Radiofrequency waves applied to the LES stimulate growth of fibrotic tissue that can increase strength of the sphincter muscle. According to Ganz (2016), the Stretta technique has shown modest success. Lastly, a surgically implanted pacemaker, called the Endo-StimR device, can enhance the sphincter tone of the LES. This device is currently available in Europe and is under study in the United States. Upper Gastrointestinal Bleed The presence of bleeding in the esophagus, stomach, or duodenum is classified as an upper gastrointestinal bleed (UGIB). The bleeding can occur from a lesion, erosion, ulceration, varicosed vein, or tear to the GI lining. The incidence of UGIB is approximately 100 cases per 100,000 population per year. Bleeding from the upper GI tract is four times more common than bleeding from the lower GI tract, and mortality rates from UGIB are 6% to 10% overall. Etiology Several disorders, such as PUD, esophageal varices, Mallory–Weiss syndrome, Boerhaave syndrome, esophageal cancer, and hemorrhagic gastritis, can cause UGIB. The morbidity of GI bleeding is directly associated with the amount of blood loss. Pathophysiology UGIB can be classified as chronic or acute. An acute bleed is associated with a rupture, tear, or perforation in the esophageal or gastric lining, resulting in blood loss. The severity of clinical symptoms is associated with the amount of blood lost; for example, a large blood loss causes sudden hypotension and hypovolemia. An acute UGIB can quickly develop into hypovolemic shock. A chronic bleed is the result of a small tear or opening in the GI tract that causes a gradual, small amount of blood loss. A chronic bleed causes complaints of fatigue, low hemoglobin, and low iron levels. Slow UGIB often leads to iron-deficiency anemia. The stool contains blood in chronic blood loss, a condition referred to as melena. Clinical Presentation Classic symptoms of UGIB include hematemesis, melena, and occult blood. Hematemesis is vomitus with bright-red, bloody streaks or a dark, coffee-ground appearance. The presence of bright-red blood indicates a current bleed. Melena is occult blood in the stool that causes a black, tarry appearance. Occult blood is the presence of blood in the stool that is not visible. Individuals experiencing a slow, chronic GI bleed may have vague symptoms of fatigue and lethargy. Pain may or may not be present. A sudden or massive UGIB may present with rapid onset of anxiety, dizziness, weakness, shortness of breath, or change in mental status. Tachycardia and tachypnea will occur because of decreased cardiac output. The skin will be pale and clammy as a result of the body’s effort to shut down peripheral blood flow. In hematemesis, blood that has a coffee-ground appearance indicates the blood has mixed with the stomach’s acid. If bright-red blood is apparent, bleeding is currently occurring from a blood vessel. Diagnosis and Treatment A slow GI bleed may reveal low hemoglobin and low iron levels, which confirm the presence of anemia. A stool guaiac test, also known as a fecal occult blood test (FOBT), can determine the presence of blood in a stool sample. BUN levels will be elevated secondary to decreased fluid volume and the absorption of blood proteins into the small intestine. Diagnostic tests include endoscopy, CBC, and stool samples for occult blood. A video capsule endoscopy can visualize the entire GI tract, including the walls of the small intestine. However, it does not offer the option to obtain biopsy or perform any surgical repair, as compared with traditional endoscopic procedures. A positive FOBT occurs when there is blood in the stool (melena). For increased accuracy, three tests should be done on 3 different days. Treatment for an acute GI bleed includes rapid fluid replacement, insertion of a nasogastric tube to prevent abdominal distention from accumulation of blood, and administration of blood transfusions. Numerous therapeutic endoscopic strategies can be used for hemostasis of an UGIB. These include injection of sclerosing agents or fibrin glue, electrocoagulation, laser and argon coagulation, band ligation, and application of hemoclips. Insertion of a TIPS is recommended for some patients with esophageal varices. Transcatheter angiographic embolization is recommended for patients with bleeding peptic ulcers who are poor surgical candidates. Laparoscopy and surgical repair at the site of the bleeding are often done for acute episodes with large amounts of blood loss. A chronic UGIB is treated primarily with PPIs such as omeprazole (PrilosecR) for 4 to 8 weeks. Sucralfate is a viscous adhesive medication that can be used to augment the gastric lining if ulceration is present. Esophageal Varices Esophageal varices are engorged varicose veins that develop in the lower third of the esophagus because of portal vein hypertension in the liver. Cirrhosis of the liver is the major cause of esophageal varices. Etiology Portal vein hypertension, which occurs in liver disease, is the cause for the development of esophageal varices. Alcoholic and viral cirrhosis of the liver are the major diseases associated with esophageal varices. In long-term alcohol abuse, individuals often suffer hematemesis from esophageal varices. Pathophysiology The portal vein of the liver drains all the venous blood from the GI system before the blood enters the inferior vena cava. Liver disease, most often cirrhosis, causes congestion and high pressure within the portal vein (portal hypertension). The pressurized portal vein develops backup pressure into the veins of the GI system. In an attempt to decrease pressure within the portal vein, collateral veins develop, particularly around the lower esophagus. The esophageal veins, in turn, take on the pressure of the portal vein and gradually take on more pressure as conditions in the liver worsen. The pressurized, engorged esophageal veins eventually become enlarged and protrude into the esophageal lumen. The venous pressure weakens the esophageal venous walls, creating the risk for rupture. When rupture occurs, bleeding into the esophagus, hematemesis, and hemorrhage occur. Clinical Presentation The patient with esophageal varices usually presents with symptoms of cirrhosis of the liver. The patient will have jaundice, nausea, vomiting, weight loss, dark urine, and abdominal distention because of liver dysfunction. The primary clinical symptoms of esophageal varices include hematemesis and melena if there is a slow leak of blood from the veins. However, the esophageal veins often rupture and cause major hemorrhage. In the event of hemorrhage, the patient will present with bright red blood in the vomitus, hypotension, tachycardia, abdominal pain, and confusion. The clinical presentation is an acute UGIB with massive blood loss. Ten percent of episodes of UGIB are caused by bleeding from esophageal varices. Esophageal varices have fragile membranes, so rupture with hemorrhage is common. In patients with long-term cirrhosis, there is a 60% to 70% chance of esophageal variceal bleeding. Diagnosis and Treatment Ultrasound can be used to diagnose portal hypertension in cases of esophageal varices. In addition, computerized tomography (CT) and magnetic resonance imaging (MRI) can be used if ultrasound findings are inconclusive. Diagnosis of esophageal varices is confirmed with endoscopy. Treatment is focused on the prevention of a rupture. Beta-adrenergic blockers and isosorbide mononitrate will help decrease blood pressure, thereby decreasing portal hypertension. Ruptured esophageal veins require immediate surgical treatment and often carry a poor prognosis. Esophageal balloon tamponade can be used as a temporary measure to stop bleeding. This involves insertion of a specialized tube with an inflatable tip that is placed against the area of an acute bleed. Vasopressin, somatostatin, and octreotide are strong vasoconstrictors that can be administered intravenously to control the bleeding. Sclerotherapy, vein ligation, or banding of the esophageal veins, are common treatments. Other procedures include the surgical portal decompression shunt or TIPS. UGIB caused by esophageal varices requires emergency medical treatment. Esophageal Cancer Esophageal cancer is a disease with a poor prognosis and high mortality rate. In 2016, approximately 17,000 patients were diagnosed with esophageal cancer and 16,000 died of the disease. Squamous cell carcinoma and adenocarcinoma are the major causes of esophageal cancer, together accounting for 95% of cases. The incidence of squamous cell carcinoma is approximately 3 to 6 cases per 100,000 persons and is most common in China, other Asian countries, and Africa. Males and females are affected equally, with most persons between ages 60 and 70 years of age. Higher numbers of African Americans are affected than Caucasians. However, adenocarcinoma of the esophagus affects more persons in the United States and Europe, with an incidence of 12 to 16 per 100,000 persons. Males are affected eight times more than females; African Americans are affected five times more than Caucasians. Etiology Currently, adenocarcinoma accounts for more than 70% of all new cases of esophageal cancer in the United States. The cancer most often arises in the distal esophagus and gastroesophageal junction. Tobacco use, GERD, and Barrett’s esophagus, a complication of GERD, are the primary risk factors for adenocarcinoma of the esophagus. In squamous cell carcinoma, cancer cells invade the lining of the esophagus. Chronic alcohol consumption and tobacco use are risk factors for squamous cell carcinoma. Drinking whiskey is associated with a higher incidence of cancer than other alcoholic beverages. Recent studies are also showing that HPV infection increases incidence of esophageal cancer. HPV is a common sexually transmitted infection that is a leading cause of oropharyngeal, cervical, and anal cancer. A genome study has identified susceptible gene loci on chromosomes 5q11, 6p21, 10q23, 12q24, and 21q22. Persons with mutations of the tumor suppressor gene TP53 and Barrett’s esophagus develop adenocarcinoma. The findings suggest that there is involvement of both genes and environment in the development of esophageal cancer. The risk of esophageal adenocarcinoma among patients with Barrett’s esophagus has been estimated to be 30 to 60 times that of the general population. Pathophysiology Chronic irritation of the epithelial cells that line the esophagus causes chronic cellular injury. Commonly, the irritation is caused by acid from GERD. In GERD, a metaplastic change often occurs at the lower esophagus, called Barrett’s esophagus. From metaplasia, over time, the cells become dysplastic and gradually turn into adenocarcinoma. The proliferation of cancerous cells is apparent with alterations in the size, shape, function, and density of cells. The reproduction of multiple abnormal cells leads to the development of tumor growth and the potential for metastasis of cancerous cells to other parts of the body. Clinical Presentation The clinical symptoms of esophageal cancer appear late in the course of the disease. Dysphagia is the most common complaint that occurs when the disease is in advanced stages. The inability to swallow is initially noted with solids and eventually progresses to liquids and saliva. Weight loss and change of eating patterns frequently occur in response to dysphagia. The inability to swallow effectively increases the risk of aspiration pneumonia. Additional complaints include chest pain or a burning sensation behind the sternum. The area and size of the cancer can cause pressure on nerves, leading to such symptoms as hiccups, hoarse voice, pain at the back of the throat, chronic cough, and odynophagia (painful swallowing). Difficulty breathing can arise if the pressure on nerves limits the rise and fall of the diaphragm. Diagnosis and Treatment Diagnosis is confirmed with endoscopy and tissue biopsy. Chromoendoscopy (application of stains to mucosal tissue to improve visualization of growths) and narrow-band imaging (use of blue and green light to improve visualization of blood vessels and other features of tumor growths) are often used during endoscopy to improve identification of suspicious lesions. An endoscopic ultrasound is commonly done to visualize the depth of the tumor. Chest and abdominal CT scan with and without contrast is usually done. Bronchoscopy may be performed to identify areas of metastasis. Tumors are staged according to the tumor size, lymph node involvement, and existence of metastasis. Positron emission tomography (PET) scans are used to detect distant metastasis sites. Treatment involves surgical resection, chemotherapy, and chemoradiotherapy. An esophagectomy can be done via endoscope or open abdominal surgery. Esophageal stents and brachytherapy (local radiotherapy) are often used. Palliative therapy for nonresectable tumors includes surgical jejunostomy, gastrostomy, or esophageal bypass. The use of chemotherapy before and after surgical treatment for individuals with adenocarcinoma has shown an increase in survival rates. Over 75% of adenocarcinomas of the esophagus are incurable and at an advanced stage upon diagnosis. Overall, the 5-year survival rate is 5%. Disorders of the Stomach Gastric dysfunction can be caused by structural problems, inflammatory disorders, or neoplasms of the stomach. Structural problems include hiatal hernia and pyloric stenosis. Inflammatory disorders of the stomach include gastritis and PUD. Stomach cancer is rare in the United States, but its incidence is rising for unclear reasons. Hiatal Hernia A hernia is a protrusion of an organ into surrounding tissue as the result of an anatomical defect in the barrier that normally contains it. A hiatal hernia occurs when part of the stomach pushes up through the opening in the diaphragm and protrudes into the thoracic cavity (see Fig. 29-6). Hiatal hernia is a very common disorder; however, many are undiagnosed, asymptomatic, and discovered incidentally. They become more common with advanced age, and incidence increases significantly after age 60 years. Seventy percent of cases occur in persons over age 70. Etiology There are two types of hiatal hernias: a sliding hiatal hernia, also referred to as a direct hernia, and a paraesophageal hernia, or rolling hiatal hernia. The sliding type of hernia is the most common, accounting for 90% to 95% of cases. Any cause of increased intra-abdominal pressure can cause hiatal hernia; for example, obesity and pregnancy are major risk factors for the condition. Pathophysiology The esophageal hiatus is the opening in the diaphragm that allows the esophagus and vagus nerve to connect with the stomach. This opening weakens and widens with age, and the stomach is able to protrude upward through the aperture into the thorax. The fundus of the stomach pushes upward into the thoracic cavity, which prevents the LES from properly closing, thereby allowing reflux of gastric contents into the esophagus; this creates esophagitis or GERD. A sliding hiatal hernia can easily protrude above the diaphragm when the person is lying supine. When the person stands, the hernia slides back into the abdominal cavity. A paraesophageal hernia is the protrusion of only the fundus part of the stomach into the thorax while the gastroesophageal junction stays below the diaphragm. This type of hernia is less common and has a higher risk for complications because the fundus of the stomach pushes into the thorax cavity and remains above the diaphragm. This leads to the potential for gastritis, ulcer formation, or strangulation of the herniated portion of the stomach. Clinical Presentation Clinical symptoms of sliding hiatal hernia usually occur as a result of esophagitis or GERD, which include dysphagia, substernal burning, belching, and epigastric discomfort. A paraesophageal hernia rarely has symptoms associated with reflux because the gastroesophageal junction remains below the diaphragm. The pain is associated with strangulation of the hernia and presents as acute chest pain or dysphagia. Diagnosis and Treatment The diagnosis of a hiatal hernia is easily confirmed with endoscopy or an upper GI barium x-ray. Treatment aims to prevent reflux and accumulation of acid contents in the esophagus. Lifestyle changes that assist in treatment include weight loss, small meals, coffee limitation, and smoking cessation. Individuals should also refrain from lying down after eating. Sleeping with the head of the bed elevated or the use of two pillows will help decrease gastric reflux. Pharmacological agents such as histamine-2 blockers (e.g., ranitidine) or PPIs (e.g., omeprazole) relieve symptoms of hiatal hernia associated with GERD. Surgical repair called laparoscopic fundoplication can decrease episodes of reflux and may be needed if symptoms do not respond to other treatments. Pyloric Stenosis Pyloric stenosis is a constriction of the pyloric sphincter, the muscular valve that connects the stomach to the duodenum. The narrowing of this region impairs the movement of gastric contents into the small intestine. In infants, this is a congenital abnormality. The incidence of infantile pyloric stenosis is 2 to 4 per 1,000 live births. It occurs most commonly in Caucasian newborns and has a 4 to 1 incidence in males compared with females. This is an uncommon condition in the adult but may develop secondary to an ulceration or fibrosis of tissue surrounding the pyloric sphincter. The role of the pyloric sphincter is to control the release of gastric contents from the stomach into the duodenum. The stenosis, or inadequate opening, of the pyloric sphincter delays the emptying of the gastric contents, causing gastroparesis (distended stomach). Pyloric stenosis can develop into pyloric obstruction, which occurs when the stenosis becomes severe and the passage through the sphincter is blocked. The accumulation of food and fluids in the stomach leads to abdominal pain and distention. Nausea and vomiting are common symptoms. Weight loss, dehydration, and electrolyte imbalances also can occur. The abdomen will be firm upon palpation, particularly over the pylorus, and visible peristalsis may be noted. Projectile vomiting of undigested food eaten a few hours earlier is associated with a pyloric obstruction. Diagnosis is confirmed with x-ray, upper GI series, and ultrasound. Surgical repair is necessary, with a resulting good prognosis. Acute Gastritis Acute gastritis, also known as erosive gastritis, is an inflammation in the lining of the stomach. It can be caused by a number of medications and factors such as infection, allergy, acute stress, bile reflux, alcohol abuse, radiation, and direct trauma. Chronic use of aspirin, NSAIDs, or corticosteroids commonly causes gastritis. These medications suppress the inflammatory response and irritate the stomach lining by blocking gastric mucus production. They are known to frequently cause GI bleeding or PUD. The wall of the stomach consists of three layers: an inner mucosal lining, a middle muscle layer, and an outer serous coat. Inflammation associated with acute gastritis is limited to the mucosa layer. An irritant to the mucosa, such as an NSAID, triggers an inflammatory response. With inflammation, WBCs rush to the area and increase the blood supply, causing edema. The swelling creates increased pressure within the tissue layers, causing pain. NSAIDs are prostaglandin inhibitors; prostaglandins cause the pain in inflammation, but also stimulate the production of gastric mucus. Although NSAIDs relieve the inflammation, they deplete the gastric mucus. By eradicating prostaglandins, NSAIDs impair the stomach’s protective mechanism. Without mucus, the gastric lining is exposed to acidic contents that increase the pain. Clinical symptoms include complaints of heartburn, nausea, and epigastric pain. Diagnosis is based on history, physical examination, and endoscopy; treatment is focused on the cause of injury. Acute gastritis will typically heal within a few days when causative agents are removed. Antacids, histamine-2 receptor antagonists, or PPIs are prescribed for gastritis. Chronic use of NSAIDs will diminish the formation of gastric mucus, which can lead to gastritis and PUD. Chronic Gastritis Chronic gastritis, also known as nonerosive gastritis, is associated with an underlying disease or severe infection. It is different than acute gastritis because it causes atrophy of the glandular stomach lining, a condition called atrophic gastritis. The presence of the H. pylori bacterium, which usually affects the fundus of the stomach, is the most common cause. H. pylori bacterium attacks the mucosal layer of the stomach wall. If the mucosal wall is eroded, it is unable to repair or regenerate cells. The death of chief cells and parietal cells diminishes the production of pepsin, HCl, and intrinsic factor. With low HCl levels, gastrin is repeatedly secreted in efforts to increase acid production. HCl is constantly stimulated and destroys mucosal cells. Erosion of the mucosa occurs, which enhances the environment for replication of H. pylori. A vicious cycle of bacterial replication and cellular tissue death occurs. The total destruction of parietal cells eventually leads to achlorhydria, which is a marked reduction in acid secretion. Atrophy of the gastric wall and loss of HCl results. Additionally, there is an insufficient level of intrinsic factor, which decreases the body’s ability to absorb vitamin B12, causing pernicious anemia. Chronic gastritis is a precursor for the development of stomach cancer. Symptoms associated with chronic gastritis include burning or gnawing epigastric pain, nausea, weight loss, anorexia, and hematemesis. Diagnosis is confirmed with endoscopy and a biopsy of the affected tissue. Antibiotics will be prescribed to eradicate the H. pylori. Antacids, PPIs, or histamine-2 antagonists may be indicated to decrease the acid level in the stomach. Replacement of vitamin B12 will be required. Peptic Ulcer Disease PUD is an inflammatory erosion in the stomach (gastric ulcer) or duodenal lining (duodenal ulcer). Duodenal ulceration is four times more common than gastric ulceration. Duodenal ulcers commonly occur in the region termed the duodenal bulb, the upper portion of the duodenum near the pyloric sphincter, because of its proximity to the highly acidic gastric contents of the stomach. Approximately 4.5 million persons are affected annually in the United States, and approximately 10% of the U.S. population has evidence of a duodenal ulcer at some time in their lives. The hospitalization rate for PUD is approximately 30 patients per 100,000 cases. The incidence of PUD is equal in males and females. Etiology The most frequent causes of PUD are the bacterium H. pylori and the use of NSAIDs or aspirin. Low-dose aspirin for the prevention of cardiovascular disease has become an important cause of symptomatic ulcer, as well as the complications of bleeding and perforation of peptic ulcer. Co-therapy of NSAIDs with steroids, anticoagulants, other NSAIDs, low dose aspirin, selective serotonin reuptake inhibitors (SSRIs), and bisphophonates dramatically increase the risk of ulcer complications. Though most adults are colonized with the H. pylori bacteria, it is unclear exactly how the bacterium is contracted or transmitted. However, not all persons colonized by H. pylori develop ulcer disease. Genetic susceptibility is believed to play a role in PUD development. A genetic polymorphism of the hepatic cytochrome P450 system delays the metabolism of several NSAIDs, which prolongs duration of the drugs and enhances their ulcerogenic effect. Individuals who have a first-degree relative diagnosed with a duodenal ulcer are three times more likely to develop one. Additional risk factors include stress, alcoholic cirrhosis, excessive caffeine, smoking, pancreatitis, hyperthyroidism, and chronic obstructive pulmonary disease. Stressful conditions such as severe burns, sepsis, central nervous system (CNS) trauma, and severe hypotension can also cause peptic ulcers. NSAIDs and aspirin cause PUD because they counteract prostaglandin E secretion, the major stimulant of gastric mucus production, and diminish the stomach’s protective layer. However, the most significant risk factor is the presence of H. pylori. Persons have a high risk of ulcer when NSAIDs and/or aspirin are used frequently and H. pylori is present. Pathophysiology The underlying pathophysiology of PUD is hypersecretion of HCl, ineffective GI mucus production, and poor cellular repair. These abnormalities lead to the erosion of the mucous membrane in the stomach or duodenum. In PUD, the protective mechanisms of the intestinal mucosal barrier are damaged by H. pylori, which are helically shaped, gram-negative bacteria that secrete the enzyme urease. Urease breaks down urea, which is a normal component of stomach mucus, into carbon dioxide and ammonia (NH3). The ammonia is converted to ammonium (NH4) by accepting a proton (H+) from HCl; the acid is then neutralized. This neutralization of acid protects the integrity of the H. pylori colony. The ammonia produced by the breakdown of urea is toxic to the epithelial cells of the stomach and duodenum. Intestinal cell damage also occurs because of other products of H. pylori, such as proteases, cytotoxins, and phospholipases. The erosion in the mucosal lining of the stomach or duodenum permits the diffusion of HCl into the stomach wall and blood vessels. This stimulates an inflammatory response with the release of prostaglandins and histamine. Prostaglandins trigger the stomach cells to release additional mucus and bicarbonate in an attempt to neutralize the acid. However, the parietal cells keep releasing histamine and HCl, substances that are required for normal digestion. The HCl irritates and destroys the stomach lining as it continues to trigger inflammation. Histamine causes vasodilation and stimulates the release of pepsin, a proteolytic enzyme, and gastrin, a hormone that stimulates acid, which together damage the unprotected stomach lining. Cellular repair can occur, but repeated episodes of elevated gastric acidity will cause scarring and fibrosis of the GI lining. Fibrosis prevents the reproduction of healthy cells, thereby decreasing the mucus and bicarbonate production to protect the gastric lining. Ulcers can vary in size from millimeters to centimeters; depending on the depth of penetration into the cellular layer, the worn area may be classified as an erosion or as an ulcer (see Fig. 29-7). If the superficial layer of the gastric mucosa is affected and does not extend into the muscularis layer, it is considered an erosion. An ulcer extends beyond the mucosa and into the muscularis layer. Clinical Presentation The main symptom of gastric and duodenal ulcers is epigastric abdominal pain. Episodes of pain occur between meals, about 2 to 3 hours after eating. The pain is described as an intense, burning, and gnawing sensation that can be relieved slightly by food and can be strong enough to awaken a person from sleep. Approximately 70 percent of peptic ulcers are asymptomatic. Bleeding peptic ulcer presents with nausea, hematemesis (bright-red or coffee-ground emesis), and melena (black, tarry stools). Between 43% and 87% of patients with bleeding peptic ulcers present without prior symptoms. If the ulceration progresses to perforation of the stomach or intestinal wall, symptoms include sudden, excruciating abdominal pain that radiates to the back, abdominal rigidity, pale skin, hematemesis, and cold sweat. Complications of peptic ulcer include bleeding and perforation. Older adults and individuals on NSAIDs or aspirin are more likely to endure ulcer complications. Diagnosis. Identifying the characteristics, region, and timing of the abdominal pain is important in determining the diagnosis. The pain of PUD is distinct because it occurs when the stomach is empty. Patients with suspected cases of PUD are tested for the presence of H. pylori; a blood sample is analyzed for the presence of antibodies to H. pylori. This is the most common method of preliminary diagnosis in PUD. Upper endoscopy is the most accurate diagnostic procedure for confirming PUD. It is done to visualize the location and severity of the ulceration, obtain a biopsy specimen, check for the presence of H. pylori, and rule out cancer. Although cancer is uncommon, it is found more often with gastric ulceration than with duodenal ulcer. A rapid urease test is the endoscopic diagnostic test of choice for detection of H. pylori. The biopsy specimen is tested for the presence of the bacterial product urease, which confirms H. pylori infection. Alternatively, a fecal H. pylori antigen test can be performed on a stool sample to identify active H. pylori infection. An upper GI series (also called barium radiography) is used less frequently, but can visualize the ulceration on x-ray. Another diagnostic test that is available but seldom used is the urea breath test. Patients swallow urea with radiolabeled carbon 14. After 10 to 30 minutes, the detection of radioactive carbon dioxide in the patient’s exhaled breath indicates that the urea was split, indicating the presence of H. pylori bacteria. Treatment Once the underlying cause is identified, the focus of treatment is to reduce acid levels and protect the gastric mucosal lining. Triple or quadruple drug therapy for 10 to 14 days is a common treatment regimen. Healing the ulcer requires interrupting acid secretion and eradicating H. pylori bacteria. An antibiotic, a histamine-2 receptor antagonist, and a PPI are commonly prescribed. The choice of antibiotic is influenced by the patient’s genotype and strain of H. pylori. Polymorphisms in the patient’s CYP2C19 gene and antibiotic susceptibility of the H. pylori influence the choice of antibiotic. Histamine-2 receptor antagonists inhibit the release of histamine, which in turn decreases the production of gastric acid. PPIs block the generation of gastric acid. Bismuth is sometimes added to the medication regimen to coat the gastric mucosa. Lifestyle changes are necessary to decrease the risk of relapse during the healing process. Individuals should try to avoid caffeine, alcohol, and tobacco because they stimulate acid production. Foods that are spicy, high in fat, or are acidic in nature should also be avoided. NSAIDs and aspirin should be avoided, as they block prostaglandins that stimulate gastric mucus production. For patients who must continue aspirin or NSAIDs, co-therapy with a PPI or misoprostol is recommended. Alternatively, changing to a cyclooxygenase (COX)-2 selective inhibitor is an option. Complications Complications of peptic ulcer include bleeding, penetration, and perforation through the gastric or intestinal wall and gastric outlet obstruction. IV high-dose PPI therapy is necessary in bleeding ulcer. Somatostatin and octreotide reduce intestinal blood flow, inhibit gastric acid secretion, and may protect the gastric mucosa. Prokinetic agents such as metoclopromide or erythromycin may be given to push blood forward and enhance endoscopy efficacy. Therapeutic endoscopic treatment is used to promote hemostasis if there is active bleeding or high risk of bleeding from the ulcer. Treatments include epinephrine injection therapy, thermal coagulation therapy, hemostatic clips, fibrin sealant, or hemostatic nanopowder spray. For persistent or recurrent peptic ulcer bleeding, angiography with transarterial embolization (TAE) is another treatment modality. In refractory cases of bleeding peptic ulcer, vagotomy, surgical resection with gastric drainage, and suturing of the bleeding tissue may be necessary. Vagotomy decreases the stomach’s ability to produce acid. Certain types of surgical procedures may also be performed. A gastroduodenostomy, also known as Billroth I, is the removal of the distal portion of the stomach; the remainder of the stomach is then directly connected to the duodenum. The benefit of surgery is the removal of the parietal cells, which are responsible for release of HCL. A gastrojejunostomy, also known as Billroth II, is the removal of the lower stomach, with the remaining portion of the stomach connected to the jejunum. This surgery eliminates the gastrin-producing properties of the lower stomach and the duodenum. Perforated duodenal ulcers can generally be treated by closure with a piece of omentum, which is called a Graham patch. For perforated ulcers close to the pylorus, vagotomy with pyloroplasty (widening of the pyloric sphincter) is performed. There is a 90% chance that an ulcer with H. pylori can be cured if patients take the full dose of recommended antibiotics. However, patients need to continue taking the medication even when symptoms may have subsided. Zollinger–Ellison Syndrome ZES is a rare disorder that accounts for fewer than 1% of duodenal or gastric ulcers. It is most commonly caused by a gastrin-secreting tumor (gastrinoma) of the pancreas. The tumor may alternatively be located in the duodenum, lymph nodes, or another site. In ZES, there is constant secretion of gastrin from a tumor. Gastrin stimulates the proliferation of parietal cells, which yield excessive HCl. The high level of HCl eventually leads to ulceration of the GI mucosa. ZES may occur sporadically or as part of an autosomal-dominant familial syndrome called multiple endocrine neoplasia type 1 (MEN type 1). The pathophysiology of cellular destruction is similar to that of PUD, with erosion of the mucosa and constant HCl secretion. Clinical symptoms are similar to those of a peptic ulcer, although more severe. Common complaints include abdominal pain, diarrhea, nausea, vomiting, weight loss, fatigue, and GI bleeding. Complications include hemorrhage secondary to ulcer perforation and obstruction related to inflammation. Hypergastrinemia can be detected in serum blood tests and through a fasting serum gastrin level. CT scan or MRI scan can visualize the tumor. PPIs also can be used because these medications inhibit the activity of the parietal cells and decrease their ability to manufacture acid. Surgical removal of the pancreatic tumor or a gastrectomy, which is the removal of all or a portion of the stomach, is frequently required. Bariatric Surgery Obesity is a public health problem that has reached epidemic proportions in the United States. Up to two-thirds of the U.S. population is overweight, and half of the people in this group can be classified as obese. Obesity is defined as a body mass index (BMI) greater than 30 (for more information about obesity, see Chapter 5). Obesity is associated with increased risk of many disorders, including cardiovascular disease, diabetes, cancer, sleep apnea, and arthritis. For those who are morbidly obese, with a BMI of greater than 40, diet and exercise are recommended as primary treatment. However, when conservative treatment has proven unsuccessful, bariatric surgery can significantly reduce morbidity and mortality associated with obesity. Indications for bariatric surgery include a BMI of greater than or equal to 40, a BMI of 35 to 39.9 with an obesity-related comorbidity (e.g., diabetes, hypertension, GERD, osteoarthritis), or a BMI of 30 to 34.9 with difficult-to-control type 2 diabetes mellitus or dysmetabolic syndrome X. Bariatric surgery induces weight loss through two basic mechanisms: malabsorption and restriction. Procedures have restrictive and/or malabsorptive components. There is also growing recognition that bariatric surgical procedures contribute to neurohormonal effects on metabolism and hunger control. Types of Bariatric Procedures Sleeve Gastrectomy. This is the surgical procedure most commonly performed for obesity in the United States. The greater curvature of the stomach is largely removed, leaving a smaller, tubular stomach (see Fig. 29-8). Sleeve gastrectomy is mainly a restrictive procedure, but gastric motility changes and ghrelin-producing cells are largely removed. This cellular change causes less hunger, less insulin resistance, and enhanced glycemic control. At 2 years postsurgery, patients can expect 60% weight loss. Roux-en-Y Gastric Bypass (RYGB) This is another procedure that reduces stomach size and attaches it to a section of jejunum. The duodenum and part of the jejunum are left as blind tracts. RYGB creates a stomach with a capacity of approximately 20 mL, which gives the patient a feeling of fullness after eating a small meal. There is intentional malabsorption because it detours around the distal stomach, the entire duodenum, and part of the jejunum (see Fig. 29-9). In addition, RYGB induces physiological and hormonal responses; ghrelin levels are reduced and leptin levels are enhanced, which results in decreased hunger and increased satiety, respectively. Gastric Banding Gastric banding involves placing an inflatable band around the upper portion of the stomach to restrict the amount of food the individual can consume (see Fig. 29-10). The inflatable gastric band is connected to a tube that is brought out through the skin to a port. Using the port, the band can be gradually tightened during a slow period of treatment, which is about 1 to 2 years for weight loss. Patients are advised about dietary changes to accommodate the smaller stomach. Biliopancreatic Diversion Biliopancreatic diversion with duodenal switch involves a 75% gastrectomy, resulting in a tubular stomach. The distal end of the ileum is attached to the duodenum (see Fig. 29-11). Weight loss occurs from both restriction and malabsorption: restriction of feedings because of the small stomach, and malabsorption because the procedure detours around the jejunum. There is an optional appendectomy and cholecystectomy. Compared with other bariatric surgery, this procedure causes less malabsorption of fats and proteins. Results of Bariatric Surgery Results of studies of gastric bypass procedures demonstrate that patients lose an average of 69% of their excess weight by 12 months and 83% at 24 months postsurgery. Studies show weight loss after gastric banding has been 50% to 60% of excess body weight over approximately 2 years. Patients followed after sleeve gastrectomy have been found to lose 33% to 83% of their excess weight after a period of 6 months to 3 years. In contrast, biliopancreatic diversion has resulted in 75% to 85% of excess body weight loss by 18 months. The Swedish Obese Subjects (SOS) study compared 2,000 morbidly obese subjects who underwent bariatric surgery with a control group of 2,000 morbidly obese patients who had conventional weight loss methods used in the primary health-care system. Compared to the control group, obese adults who underwent surgery experienced a reduced number of cardiovascular deaths and a lower incidence of heart attack and stroke. Other similar comparative studies have shown an 11-year remission of diabetes in patients who underwent surgery versus 2-year remission in patients who received conventional treatment. A recent Cochrane review from 2014 that included 22 trials with 1,798 participants concluded that surgical treatment of obesity yielded greater improvement in weight loss and weight-associated comorbidities than nonsurgical interventions did, regardless of the type of procedure. The RYGB and sleeve gastrectomy had comparable outcomes, and both had better outcomes than adjustable gastric banding. Dumping Syndrome Dumping syndrome is caused by rapid gastric emptying. This is a common complication following any surgical procedure that removes part or all of the stomach, such as bariatric surgery. Poorly digested material enters the intestine before its breakdown in the stomach. The material tends to be hypertonic, causing a shift of fluid out of the intestinal cells into the intestinal lumen. The fluid shift reduces blood volume, creates hypotension, and stimulates the sympathetic nervous system to increase heart rate. The abdomen becomes distended because of the ingested contents and the fluid shift into the jejunum. Peristalsis and intestinal motility increase in response to the abdominal distention. The pancreas releases excess insulin in response to gastric fullness and increased peristalsis, creating a risk for hypoglycemia. Clinical Presentation Dumping syndrome has two phases: early and late. The early phase occurs within 30 minutes of eating. Abdominal cramping, nausea, hyperactive bowel sounds, diarrhea, tachycardia, diaphoresis, and palpitations are common symptoms and are associated with the fluid shift that occurs from the bloodstream into the small intestine and the decrease in blood volume. The late phase occurs 2 to 3 hours after eating and includes epigastric fullness, syncope, palpitations, and symptoms associated with hypoglycemia. The epigastric discomfort of dumping syndrome is the result of excess fluid volume in the stomach pushing upward upon the diaphragm. The risk for hypoglycemia is related to the pancreatic release of excessive amounts of insulin stimulated by gastric fullness. Diagnosis and Treatment Endoscopy and upper GI series will show a partial stomach. Treatment focuses on dietary management. Frequent, small feedings are recommended to decrease the volume ingested at one time. The patient should be prescribed a low-carbohydrate, high-protein, high-fat diet. Simple carbohydrates should be eliminated, as they increase intestinal osmolarity. Drinking fluids in between meals rather than with food consumption is an alternative to reduce rapid filling of the intestine. Medications that delay gastric emptying may be prescribed. Patients should supplement their diet with multivitamins, iron, and calcium, usually on a twice-daily basis. Ursodiol may be given to minimize the risk of developing gallstones during the period of acute weight loss. Patients must modify their eating habits by avoiding chewy meats and other foods that inhibit normal emptying of their stomach pouch. Nutritional and metabolic blood tests must be performed on a periodic basis. Disorders of the Small Intestine The small intestine is the main part of the intestinal tract that absorbs nutrients. A long length and distinctive villous mucosal epithelium provide a large amount of surface area. Different kinds of disorders affect the small intestine. A loop of intestine can herniate through a weak muscle in the abdominal wall. Inflammation of the intestine can occur because of ingestion of pathogens. Autoimmune and allergic reactions can cause inflammation of the mucosal lining of the small intestine, leading to malabsorption. Hernia A hernia is a protrusion of a section of the small intestine through a weakened abdominal wall muscle. As much as 10% of the population develops some type of hernia during their lifetime. More than a half-million hernia operations are performed in the United States each year. Males have a higher rate than females. Etiology There are several different types of hernia: umbilical, inguinal, obturator, femoral, or incisional. The most common is an inguinal hernia, which occurs when a loop of the small intestine protrudes down into the inguinal canal in the groin. Its occurrence is significantly higher in males because of the anatomical location of the scrotal sac. Between the scrotum and abdominal cavity there is a gap in the membranes that allows displacement of the intestines. It is most likely to occur before the first year of life or in the later stages of puberty. Inguinal hernias can also develop with advanced age as abdominal muscles weaken. Risk factors include positive family history for inguinal hernia, obesity, ascites, pregnancy, heavy lifting, chronic cough, or chronic constipation. Pathophysiology The pathophysiological processes are similar for all types of hernias. They differ based on the location of the protrusion of the loop of bowel. An inguinal hernia is directly related to the anatomical location of the scrotum and weak abdominal muscle wall. The pressure within the intestines pushes against the lower abdominal wall, eventually forcing the weakened area to separate, permitting protrusion of the intestine into the inguinal canal. It is possible that a severe herniation could extend into the entire scrotal sac. Hernias can be reducible, incarcerated, or strangulated. A reducible hernia is one in which the loop of bowel can be pushed back into normal position with manual pressure. Incarceration occurs when the loop of intestine becomes trapped in between muscle fibers. Strangulation of a hernia occurs when blood supply to the incarcerated loop of intestine is obstructed and at risk for ischemia. Clinical Presentation Clinical symptoms and severity will be dependent upon the location and degree of the protrusion of intestine. The patient may be asymptomatic or have pain near the hernia site. Coughing or straining can cause the herniation to protrude and induce pain. If the hernia is pressing toward the bladder, urinary frequency or incomplete bladder emptying can occur. Pain occurs if strangulation of the hernia occurs with intestinal ischemia. Diagnosis and Treatment Diagnosis is based on the patient’s history and the physical examination. The patient can usually demonstrate the bulging of the hernia in the abdomen. During the examination, the clinician will instruct the patient to cough or strain; this will raise intra-abdominal pressure, which will make the hernia protrude, thus confirming diagnosis. Some hernias can be manually reduced with gentle pressure while the patient is placed in the supine position, whereas others require surgical repair. A surgical hernia repair, called a herniorrhaphy, involves reinforcement of the weakened muscle with synthetic surgical material. Gastroenteritis Gastroenteritis occurs from an irritation to the lining of the stomach, small intestine, or large intestine by a pathogen or toxin. The disease can occur from a virus, bacteria, parasite, or chemical toxin. Gastroenteritis is transmitted from person to person or can be a waterborne or foodborne illness. The incidence of gastroenteritis is difficult to estimate because most cases are not reported. In the United States, as many as 100 million cases occur per year, accounting for several million health-care visits and thousands of hospitalizations. Children account for more than 1.5 million outpatient visits. According to the Centers for Disease Control and Prevention, probably more than 21 million cases a year and nearly 50% of foodborne outbreaks in adults are caused by norovirus, the most common etiologic agent of gastroenteritis. Etiology Norovirus is highly contagious and transmitted through the fecal-oral route or through close contact. In children, rotavirus is a common etiologic agent that is also transmitted via the fecal-oral route. Some bacterial organisms, such as Enterotoxigenic Escherichia coli, Salmonella, Shigella, and Campylobacter, can cause severe illness with bloody diarrhea. Recent antibiotic use or hospitalization can predispose the patient to Clostridium difficile infection. Parasites such as Ameba and Giardia can cause dysentery, which is a severe diarrheal condition with dehydration. Box 29-2 lists organisms that cause gastroenteritis. Individuals who are in close contact with others, such as those in nursing homes, day-care centers, cruise ships, and dormitories, are at increased risk for viral or bacterial gastroenteritis. Pathophysiology Infectious microorganisms are usually responsible for acute gastroenteritis and are often contracted via the oral route. These microorganisms cause diarrhea by adherence to the mucosa, invasion into the mucosal layer, or toxin production. The end result of most microbial infections is increased fluid to shift into the lumen of the intestine, to a point where the excessive fluid cannot be adequately reabsorbed. This fluid shift results in watery, small intestinal contents that pass into the large intestine and are then excreted as diarrhea. The fluid shift also can cause dehydration and loss of electrolytes and nutrients. Gastroenteritis diarrheal illness can occur by different mechanisms: Osmotic diarrhea occurs because of an increase in the osmotic load presented to the intestinal lumen because of diminished absorption. Inflammatory diarrhea occurs when the mucosal lining of the intestine is inflamed, edematous, and unable to reabsorb fluid or nutrients. Secretory diarrhea occurs when an organism stimulates the intestine to secrete fluid and mucus. Motility diarrhea is caused by intestinal neuromuscular disorders. Pathogens or toxins either act directly on the intestinal epithelium, causing inflammation and malabsorption, or stimulate secretory mechanisms that produce watery diarrhea. The epithelium of the microvilli, which provides the surface area of the small intestine, is often the target of the infectious agent. The virus or bacteria attaches to the epithelium and impairs the small intestine’s ability to absorb carbohydrates, fats, fluids, or electrolytes. Sometimes the infectious agent secretes a toxin that irritates the intestinal membrane. The infectious agent or its toxin stimulates inflammation of the GI tract and destruction of the epithelial lining. The villi are often damaged, which decreases the absorptive ability of the intestinal brush border. With lack of absorption, intestinal contents become hypertonic compared with the surrounding intestinal cells. An osmotic exchange of fluids and salts occurs at the intestine, resulting in water entry into the intestine. An osmotic diarrhea also occurs, producing watery stool and loss of electrolytes. A secretory diarrhea can result if microorganisms stimulate the intestine to produce mucus and fluids. In any of the mechanisms, excess water and essential electrolytes are lost from the GI tract. Dehydration and electrolyte imbalance are the result of any type of gastroenteritis. Clinical Presentation The primary clinical presentation is nausea, vomiting, abdominal cramping, and diarrhea. If the gastroenteritis is associated with a virus, symptoms can usually persist between 12 and 72 hours. A bacterial form of gastroenteritis will produce symptoms until the causative agent is eradicated. Hyperactivity of the intestine produces intestinal cramping as well as high-pitched bowel sounds, known as borborygmi. Hyponatremia and hypokalemia can occur as a result of fluid loss, as well as acid–base imbalances of metabolic acidosis or alkalosis. Individuals must be closely monitored for dehydration. Clinical signs or “red flags” that may indicate a need for hospitalization in patients with acute gastroenteritis include: Severe volume depletion/dehydration Abnormal electrolytes or renal function Bloody stool/rectal bleeding Weight loss Severe abdominal pain Prolonged symptoms (more than 1 week) Hospitalization or antibiotic use in the past 3 to 6 months Age 65 or older Comorbidities (e.g., diabetes mellitus, immunocompromised) Pregnancy Diagnosis and Treatment. Diagnosis is aimed at identifying the causative factor. Stool cultures can be tested for WBCs, parasites, ova, or bacteria. Treatment is aimed at relieving symptoms and preventing transmission. Medical management is focused on resting the bowel and providing fluid replacement. Fluid replacement should be accomplished with broths and sports drinks or oral rehydration products that contain electrolytes. For patients with severe hypovolemia or inability to tolerate oral rehydration, IV normal saline or Ringer’s lactate is required. Medications to suppress the vomiting and the diarrhea may be indicated. Antibiotics are routinely ordered if gastroenteritis is identified as bacterial. After fluids and broths are tolerated, the patient can move to a bland diet that can include cereals, potatoes, boiled vegetables, noodles, rice, toast, and crackers. The BRAT diet (bananas, rice, applesauce, and toast) is often recommended. Milk products should be avoided until symptoms resolve. Probiotics may augment the immune response through interaction with the gut-associated microorganisms. Some research has demonstrated a modest reduction in the duration of infectious diarrhea with the use of probiotics. Individuals with acute gastroenteritis should maintain diligent hand hygiene to help prevent spread of infection to their family and contacts. Chlorine-based products can be used for disinfection of surfaces. Children and elderly individuals are at high risk of dehydration in gastroenteritis. Often hospitalization is needed to administer IV fluids to replace losses. Celiac Disease Celiac disease, also known as sprue and gluten-sensitive enteropathy, is a condition that occurs from a hypersensitivity reaction to gluten, a by-product of wheat, barley, and rye. The cause is unknown, but it is considered an autoimmune disease. It occurs in 1% of the American population; however, many individuals with the disorder go undiagnosed, as another 3 million people in the United States are estimated to be affected. Onset of celiac disease can appear in young children as foods are being introduced into the diet. In adults, celiac disease can occur between the ages of 20 and 50 years. Etiology In celiac disease, a gluten-derived peptide called gliadin damages the intestinal mucosa in persons with genetic predisposition to this disease. The exact etiology is unknown, but T cells predominate in an autoimmune inflammatory reaction against intestinal villi. There is a higher prevalence in those with a first-degree relative, such as a parent or sibling, with celiac disease, type 1 diabetes, or Down syndrome. More than 90% of affected persons have the cell surface marker HLA-DQ2.5. Pathophysiology The pathophysiology of celiac disease is related to an autoimmune, inflammatory process that destroys the intestinal villi. This destruction leads to a decreased surface area, causing atrophy of the intestinal wall. The atrophy creates a flattened appearance of the intestinal villi, greatly reducing the absorptive and transport properties of the small intestine. The decreased surface area impairs the absorption of all nutrients, vitamins, minerals, electrolytes, and bile salts. The inability to digest carbohydrates leads to a buildup of gases within the intestinal system, causing abdominal bloating and diarrhea. The inability to absorb proteins impairs the body’s ability to build and maintain muscle tone, causing muscle wasting. When fats are not absorbed, vitamins A, D, E, and K are not absorbed, causing fat to be excreted in the stool. Steatorrhea is the loss of fat in the stool; with steatorrhea, stool is light colored and soft. Deficiency of vitamin A will cause visual disturbances, particularly difficulty with vision in diminished light, a condition called night blindness. Vitamin D is necessary for the absorption of calcium. With vitamin D deficiency, calcium absorption is diminished and hypocalcemia occurs. Hypocalcemia causes symptoms such as muscle spasms and tetany; it also stimulates parathyroid hormone (PTH). PTH causes breakdown of bone with resulting osteomalacia and susceptibility to fractures. Vitamin E, which protects cellular membranes, is also not absorbed. Red blood cells and platelet membranes become excessively fragile, leading to hemolysis, anemia, and thrombocytopenia. Deficiency of vitamin K causes defective clotting mechanisms, leading to spontaneous bleeding and bruising. In addition, iron is not absorbed, causing iron-deficiency anemia. Clinical Presentation Numerous clinical symptoms are associated with celiac disease, mainly caused by malabsorption of essential nutrients, vitamins, and minerals. Weight loss occurs early in the disease, and if diarrheal illness occurs, dehydration is also common. Initial symptoms are fatigue, abdominal pain, bloating, and steatorrhea. As the disease progresses, symptoms associated with vitamin deficiencies will present, including anemia, high incident of fractures or bone pain, abnormal growth, bruising, poor skin turgor, and dehydration. Diagnosis and Treatment A serology celiac panel can determine if an immune reaction to gluten is present. Affected individuals show a positive antibody titer of IgA antitissue transglutaminase (IgA TTG). If the results of this test are positive, a biopsy of the duodenum or jejunum is necessary. Treatment of celiac disease is aimed at making dietary changes. A consultation with a nutritionist is recommended to identify and eliminate gluten products in the diet. The patient frequently needs vitamin replacement. If the immune response is extreme, corticosteroids may be prescribed. Short-Bowel Syndrome The average length of the small intestine is 600 cm. Short-bowel syndrome is a result of any disease, traumatic injury, vascular accident, or other pathology that leaves less than 200 cm of small intestine, which is approximately one-third of the size of the normal small intestine. Studies show that, in the United States, approximately 10,000 to 20,000 patients receive total parenteral nutrition for short-bowel syndrome per year. Etiology Intestinal abnormalities that may require a partial removal of the small intestine include Crohn’s disease, trauma to the bowel, strictures, tumors, radiation enteritis, mesenteric ischemia, strangulated hernia, and volvulus. Short-bowel syndrome can also occur because of congenital defects. Pathophysiology Short-bowel syndrome is directly associated with the amount of bowel that is remaining, the segment of the intestine that was removed, the health of the remaining intestine, and the functioning ability of the ileocecal valve. The ileum is the largest segment of the small intestine; it is responsible for absorption of fluids, electrolytes, fats, carbohydrates, proteins, vitamin B12, and the return of bile to the liver. Removing any part of the ileum reduces the GI absorptive surface and can lead to nutritional deficiencies. In short-bowel syndrome, the remaining intestine gradually adapts to the changes. The remaining intestinal villi increase in number and enlarge to accommodate the need for increased absorption. It is necessary for individuals with small-bowel syndrome to receive enteral nutrition during the postoperative period until the intestine adapts sufficiently to adjust to oral feedings. Clinical Presentation. Short-bowel syndrome is divided into three phases: 1. Acute phase 2. Adaptation phase 3. Maintenance phase The acute phase presents with symptoms of dehydration; electrolyte imbalance; weight loss; loss of folic acid; and loss of fat-soluble vitamins A, D, E, and K and vitamin B12. These signs and symptoms are related to the small intestine’s inability to absorb nutrients because of lost surface area and length. Fluid loss can be 6 to 8 liters per day. Malnutrition can rapidly develop, leading to muscle wasting, fatigue, skin irritation, and anemia. The acute phase lasts up to 3 months, followed by the adaptation phase, which may last 12 to 18 months. During this phase, the body begins to adjust by lengthening the microvilli, which creates an increased surface area for reabsorption. During the maintenance phase, the patient accommodates diet to the changed intestine, focusing on what amount of oral intake can be consumed without causing nausea, vomiting, or diarrhea. Diagnosis and Treatment The most definitive diagnostic test for short-bowel syndrome is a barium-contrast x-ray series. This allows for visualization and measurement of the small intestine. Abdominal CT scan with contrast and ultrasound may also be done. If the length of the bowel is less than 200 cm, short-bowel syndrome is confirmed. Treatment goals are to slowly increase fluid and nutrient intake. The need for enteral or total parenteral nutritional replacement to meet caloric and nutritional demands may be required. Oral intake should be encouraged with a trial-and-error approach of slowly adding new foods into the diet. Medications such as somatropin, which is a synthetic form of growth hormone, can stimulate intestinal cell proliferation. Teduglutide, an analog of glucagon-like peptide, can be used to enhance the absorptive ability of the remaining intestinal mucosa. PPIs and histamine-2 blockers can reduce the effect of acid on the intestine. Diphenoxylate/atropine (LomotilR), codeine, and loperamide hydrochloride (ImodiumR) are used to reduce diarrhea. Octreotide, a somatostatin analog, is used in cases of severe diarrhea. Small Bowel Obstruction A small bowel obstruction (SBO) can be acute or chronic and partial or complete. An acute obstruction has a sudden onset that can occur with adhesions or a herniation of the bowel, whereas a chronic obstruction is often seen with inflammatory disease or tumors. A partial obstruction decreases the flow of intestinal contents through the bowel, whereas a complete obstruction prevents passage of all contents and fluid through the bowel and is considered a surgical emergency. Etiology The major cause of SBO is postsurgical adhesions (60%), followed by malignancy, Crohn’s disease, and hernias. Postoperatively, surgeries that most often cause adhesions are appendectomy, colorectal surgery, and gynecological and upper GI procedures. Pathophysiology Adhesions are bands of connective tissue that form between tissues and organs, often as a result of injury during surgery. In the abdomen, adhesions commonly bond sections of intestine together. The adhesions cause obstruction and interfere with the intestine’s normal function. Intestinal contents cannot move forward through the bowel. At the point of obstruction, there is increased peristalsis and mucus accumulation that worsen the blockage. Clinical Presentation The presentation of intestinal symptoms is directly related to the severity of the obstruction. The larger the obstruction, the more dramatic the symptoms. Abdominal distention, pain, nausea, vomiting, and hyperactive bowel sounds occur. Abdominal distention occurs proximal to the site of obstruction from the accumulation of chyme and intestinal gases. Pain is sharp, cramping, and intermittent, occurring with the contractions of hyperactive peristalsis. Pain that is continuous and steadily increases in severity is associated with a strangulation of the intestine. This indicates ischemia or necrosis of the intestinal lumen and requires emergency surgery. Nausea and vomiting can cause fluid and electrolyte depletion, which could potentially lead to dehydration, hypotension, or hypovolemic shock. Diarrhea is present with a partial obstruction because liquid intestinal contents can leak around an obstruction in the lumen. Diagnosis and Treatment Abdominal x-ray provides visualization of the area of obstruction and severity of the blockage. X-ray will show excessive gas in the area of intestine proximal to the obstruction. CT and ultrasound can also be used to identify the obstruction. A nasogastric tube is inserted to decompress the bowel and remove the accumulation of fluid within the bowel. IV fluids are given to assure adequate fluid and electrolyte balance. The majority of partial SBOs can resolve with medical treatment. Pain management, antiemetic medications, and antibiotics are frequently necessary. Complete obstructions usually require surgical intervention. Peritonitis The peritoneal membrane is the serous membrane that surrounds the abdominal cavity and covers the organs. The peritoneal cavity is a sterile environment and can become contaminated with intestinal or organ rupture. Peritonitis is the inflammation of the peritoneal membrane caused by bacterial infection or leakage of intestinal contents into the peritoneal cavity. The overall incidence of peritonitis is unclear because it often occurs as a complication of another condition or surgical complication and is diagnosed as part of that disorder. Etiology Peritonitis most often occurs when organ rupture introduces bacteria, bile, acids, or enzymes into the sterile peritoneal environment. Less often, peritonitis is caused by hematogenous spread of infection from bacteremia. Most often, intestinal perforation allows E. coli, anaerobic bacteria, and other microorganisms to spill into the peritoneal cavity and cause abdominal sepsis. A perforated gallbladder or a lacerated liver can cause bile to enter the peritoneal cavity; gastric acid from a perforated ulcer can also leak into the peritoneal cavity. Peritonitis can also result from traumatic injury. Women can endure peritonitis