Your stomach is an organ between your esophagus and small intestine. It is where digestion of protein begins. The stomach has three tasks. It stores swallowed food. It mixes the food with stomach acids. Then it sends the mixture on to the small intestine.

Most people have a problem with their stomach at one time or another. Indigestion and heartburn are common problems. You can relieve some stomach problems with over-the-counter medicines and lifestyle changes, such as avoiding fatty foods or eating more slowly. Other problems like peptic ulcers or GERD require medical attention.

You should see a doctor if you have any of the following:

• Blood when you have a bowel movement
• Severe abdominal pain
• Heartburn not relieved by antacids
• Unintended weight loss
• Ongoing vomiting or diarrhea

The stomach is an organ between the esophagus and the small intestine. It mixes food with stomach acid and helps digest protein. Stomach cancer mostly affects older people - two-thirds of people who have it are over age 65. Your risk of getting it is also higher if you:

• Have had a Helicobacter pylori infection
• Have had stomach inflammation
• Are a man
• Eat lots of salted, smoked, or pickled foods
• Smoke cigarettes
• Have a family history of stomach cancer

It is hard to diagnose stomach cancer in its early stages. Indigestion and stomach discomfort can be symptoms of early cancer, but other problems can cause the same symptoms. In advanced cases, there may be blood in your stool, vomiting, unexplained weight loss, jaundice, or trouble swallowing. Doctors diagnose stomach cancer with a physical exam, blood and imaging tests, an endoscopy, and a biopsy.

Because it is often found late, it can be hard to treat stomach cancer. Treatment options include surgery, chemotherapy, radiation or a combination.

KEY POINTS

• Gastric cancer is a disease in which malignant (cancer) cells form in the lining of the stomach.
• Age, diet, and stomach disease can affect the risk of developing gastric cancer.
• Symptoms of gastric cancer include indigestion and stomach discomfort or pain.
• Tests that examine the stomach and esophagus are used to diagnose gastric cancer.
• Certain factors affect prognosis (chance of recovery) and treatment options.

Gastric cancer is a disease in which malignant (cancer) cells form in the lining of the stomach.

The stomach is a J-shaped organ in the upper abdomen. It is part of the digestive system, which processes nutrients (vitamins, minerals, carbohydrates, fats, proteins, and water) in foods that are eaten and helps pass waste material out of the body. Food moves from the throat to the stomach through a hollow, muscular tube called the esophagus. After leaving the stomach, partly-digested food passes into the small intestine and then into the large intestine.

The wall of the stomach is made up of 5 layers of tissue. From the innermost layer to the outermost layer, the layers of the stomach wall are: mucosa, submucosa, muscle, subserosa (connective tissue), and serosa. Gastric cancer begins in the mucosa and spreads through the outer layers as it grows.

Stromal tumors of the stomach begin in supporting connective tissue and are treated differently from gastric cancer. 

Certain factors affect prognosis (chance of recovery) and treatment options.

The prognosis (chance of recovery) and treatment options depend on the following:

• The stage of the cancer (whether it is in the stomach only or has spread to lymph nodes or other places in the body).
• The patient’s general health.

A peptic ulcer is a sore in the lining of your stomach or your duodenum, the first part of your small intestine. A burning stomach pain is the most common symptom. The pain

• Starts between meals or during the night
• Briefly stops if you eat or take antacids
• Lasts for minutes to hours
• Comes and goes for several days or weeks

Peptic ulcers happen when the acids that help you digest food damage the walls of the stomach or duodenum. The most common cause is infection with a bacterium called Helicobacter pylori. Another cause is the long-term use of nonsteroidal anti-inflammatory medicines (NSAIDs) such as aspirin and ibuprofen. Stress and spicy foods do not cause ulcers, but can make them worse.

To see if you have an H. pylori infection, your doctor will test your blood, breath, or stool. Your doctor also may look inside your stomach and duodenum by doing an endoscopy or x-ray.

Peptic ulcers will get worse if not treated. Treatment may include medicines to reduce stomach acids or antibiotics to kill H. pylori. Antacids and milk can't heal peptic ulcers. Not smoking and avoiding alcohol can help. You may need surgery if your ulcers don't heal.

What is a peptic ulcer?

A peptic ulcer is a sore on the lining of your stomach or duodenum. Rarely, a peptic ulcer may develop just above your stomach in your esophagus. Doctors call this type of peptic ulcer an esophageal ulcer.

Causes of peptic ulcers include

• long-term use of nonsteroidal anti-inflammatory drugs (NSAIDs), such as aspirin and ibuprofen
• an infection with the bacteria Helicobacter pylori (H. pylori)
• rare cancerous and noncancerous tumors in the stomach, duodenum, or pancreas-known as Zollinger-Ellison syndrome (ZES)

Who is more likely to develop peptic ulcers caused by NSAIDs?

People of any age who take NSAIDs every day or multiple times per week are more likely to develop a peptic ulcer than people who do not take them regularly. NSAIDs are a class of pain killers, such as aspirin and ibuprofen. Long-term use of NSAIDs can cause peptic ulcer disease.

Your chance of having a peptic ulcer caused by NSAIDs, also called an NSAID-induced peptic ulcer, is increased if you

• are age 70 or older
• are female
• are taking more than two types of NSAIDs or have taken NSAIDs regularly for a long time
• have had a peptic ulcer before
• have two or more medical conditions or diseases
• are taking other medicines, such as corticosteroids​ and medicines to increase your bone mass
• drink alcohol or smoke

Who is more likely to develop peptic ulcers caused by H. pylori?

About 30 to 40 percent of people in the United States get an H. pylori infection. In most cases, the infection remains dormant, or quiet without signs or symptoms, for years. Most people get an H. pylori infection as a child.

Adults who have an H. pylori infection may get a peptic ulcer, also called an H. pylori-induced peptic ulcer. However, most people with an H. pylori infection never develop a peptic ulcer. Peptic ulcers caused by H. pylori are uncommon in children.

H. pylori are spiral-shaped bacteria that can damage the lining of your stomach and duodenum and cause peptic ulcer disease. Researchers are not certain how H. pylorispread. They think the bacteria may spread through

• unclean food
• unclean water
• unclean eating utensils
• contact with an infected person’s saliva and other bodily fluids, including kissing

Researchers have found H. pylori in the saliva of some infected people, which means anH. pylori infection could spread through direct contact with saliva or other bodily fluids.

Who develops peptic ulcers caused by tumors?

People who have Zollinger-Ellison syndrome (ZES) develop peptic ulcers caused by tumors. Anyone can have ZES, yet it is rare and only occurs in about one in every 1 million people. However, ZES is more common among men 30 to 50 years old. A child who has a parent with multiple endocrine neoplasia type 1 is also more likely to have Zollinger-Ellison syndrome.

What other problems can a peptic ulcer cause?

A peptic ulcer can cause other problems, including

• bleeding from a broken blood vessel in your stomach or small intestine
• perforation of your stomach or small intestine
• a blockage that can stop food from moving from your stomach into your duodenum
• peritonitis

You may need surgery to treat these problems.

The gram-negative bacterium Helicobacter pylori is able to tolerate the acidic environment of the human stomach and has been shown to be a major cause of peptic ulcers, which are ulcers of the stomach or duodenum. The bacterium is also associated with increased risk of stomach cancer (Figure). According to the CDC, approximately two-thirds of the population is infected with H. pylori, but less than 20% have a risk of developing ulcers or stomach cancer. H. pylori is found in approximately 80% of stomach ulcers and in over 90% of duodenal ulcers.

H. pylori colonizes epithelial cells in the stomach using pili for adhesion. These bacteria produce urease, which stimulates an immune response and creates ammonia that neutralizes stomach acids to provide a more hospitable microenvironment. The infection damages the cells of the stomach lining, including those that normally produce the protective mucus that serves as a barrier between the tissue and stomach acid. As a result, inflammation (gastritis) occurs and ulcers may slowly develop. Ulcer formation can also be caused by toxin activity. It has been reported that 50% of clinical isolates of H. pylori have detectable levels of exotoxin activity in vitro. This toxin, VacA, induces vacuole formation in host cells. VacA has no primary sequence homology with other bacterial toxins, and in a mouse model, there is a correlation between the presence of the toxin gene, the activity of the toxin, and gastric epithelial tissue damage.

Signs and symptoms include nausea, lack of appetite, bloating, burping, and weight loss. Bleeding ulcers may produce dark stools. If no treatment is provided, the ulcers can become deeper, more tissues can be involved, and stomach perforation can occur. Because perforation allows digestive enzymes and acid to leak into the body, it is a very serious condition.

Helicobacter infection decreases mucus production and causes peptic ulcers. (credit top left photo: modification of work by "Santhosh Thomas"/YouTube; credit top right photo: modification of work by Moriya M, Uehara A, Okumura T, Miyamoto M, and Kohgo Y)

To diagnose H. pylori infection, multiple methods are available. In a breath test, the patient swallows radiolabeled urea. If H. pylori is present, the bacteria will produce urease to break down the urea. This reaction produces radiolabeled carbon dioxide that can be detected in the patient’s breath. Blood testing can also be used to detect antibodies to H. pylori. The bacteria themselves can be detected using either a stool test or a stomach wall biopsy.

Antibiotics can be used to treat the infection. However, unique to H. pylori, the recommendation from the US Food and Drug Administration is to use a triple therapy. The current protocols are 10 days of treatment with omeprazole, amoxicillin, and clarithromycin (OAC); 14 days of treatment with bismuth subsalicylate, metronidazole, and tetracycline (BMT); or 10 or 14 days of treatment with lansoprazole, amoxicillin, and clarithromycin (LAC). Omeprazole, bismuth subsalicylate, and lansoprazole are not antibiotics but are instead used to decrease acid levels because H. pylori prefers acidic environments.

Although treatment is often valuable, there are also risks to H. pylori eradication. Infection with H. pylori may actually protect against some cancers, such as esophageal adenocarcinoma and gastroesophageal reflux disease.

Nausea is when you feel sick to your stomach, as if you are going to throw up. Vomiting is when you throw up.

In the developing world, acute viral gastroenteritis is devastating and a leading cause of death for children. Worldwide, diarrhea is the second leading cause of mortality for children under age five, and 70% of childhood gastroenteritis is viral. As discussed, there are a number of bacteria responsible for diarrhea, but viruses can also cause diarrhea. E. coli and rotavirus are the most common causative agents in the developing world. In this section, we will discuss rotaviruses and other, less common viruses that can also cause gastrointestinal illnesses.

Gastroenteritis Caused by Rotaviruses

Rotaviruses are double-stranded RNA viruses in the family Reoviridae. They are responsible for common diarrheal illness, although prevention through vaccination is becoming more common. The virus is primarily spread by the fecal-oral route (Figure 24.24).

Figure 24.24 Rotaviruses in a fecal sample are visualized using electron microscopy. (credit: Dr. Graham Beards)

These viruses are widespread in children, especially in day-care centers. The CDC estimates that 95% of children in the United States have had at least one rotavirus infection by the time they reach age five. Due to the memory of the body’s immune system, adults who come into contact with rotavirus will not contract the infection or, if they do, are asymptomatic. The elderly, however, are vulnerable to rotavirus infection due to weakening of the immune system with age, so infections can spread through nursing homes and similar facilities. In these cases, the infection may be transmitted from a family member who may have subclinical or clinical disease. The virus can also be transmitted from contaminated surfaces, on which it can survive for some time.

Infected individuals exhibit fever, vomiting, and diarrhea. The virus can survive in the stomach following a meal, but is normally found in the small intestines, particularly the epithelial cells on the villi. Infection can cause food intolerance, especially with respect to lactose. The illness generally appears after an incubation period of about two days and lasts for approximately one week (three to eight days). Without supportive treatment, the illness can cause severe fluid loss, dehydration, and even death. Even with milder illness, repeated infections can potentially lead to malnutrition, especially in developing countries, where rotavirus infection is common due to poor sanitation and lack of access to clean drinking water. Patients (especially children) who are malnourished after an episode of diarrhea are more susceptible to future diarrheal illness, increasing their risk of death from rotavirus infection.

The most common clinical tool for diagnosis is enzyme immunoassay, which detects the virus from fecal samples. Latex agglutination assays are also used. Additionally, the virus can be detected using electron microscopy and RT-PCR.

Treatment is supportive with oral rehydration therapy. Preventive vaccination is also available. In the United States, rotavirus vaccines are part of the standard vaccine schedule and administration follows the guidelines of the World Health Organization (WHO). The WHO recommends that all infants worldwide receive the rotavirus vaccine, the first dose between six and 15 weeks of age and the second before 32 weeks.

Gastroenteritis Caused by Noroviruses

Noroviruses, commonly identified as Norwalk viruses, are caliciviruses. Several strains can cause gastroenteritis. There are millions of cases a year, predominately in infants, young children, and the elderly. These viruses are easily transmitted and highly contagious. They are known for causing widespread infections in groups of people in confined spaces, such as on cruise ships. The viruses can be transmitted through direct contact, through touching contaminated surfaces, and through contaminated food. Because the virus is not killed by disinfectants used at standard concentrations for killing bacteria, the risk of transmission remains high, even after cleaning.

The signs and symptoms of norovirus infection are similar to those for rotavirus, with watery diarrhea, mild cramps, and fever. Additionally, these viruses sometimes cause projectile vomiting. The illness is usually relatively mild, develops 12 to 48 hours after exposure, and clears within a couple of days without treatment. However, dehydration may occur.

Norovirus can be detected using PCR or enzyme immunoassay (EIA) testing. RT-qPCR is the preferred approach as EIA is insufficiently sensitive. If EIA is used for rapid testing, diagnosis should be confirmed using PCR. No medications are available, but the illness is usually self-limiting. Rehydration therapy and electrolyte replacement may be used. Good hygiene, hand washing, and careful food preparation reduce the risk of infection.

Gastroenteritis Caused by Astroviruses

Astroviruses are single-stranded RNA viruses (family Astroviridae) that can cause severe gastroenteritis, especially in infants and children. Signs and symptoms include diarrhea, nausea, vomiting, fever, abdominal pain, headache, and malaise. The viruses are transmitted through the fecal-oral route (contaminated food or water). For diagnosis, stool samples are analyzed. Testing may involve enzyme immunoassays and immune electron microscopy. Treatment involves supportive rehydration and electrolyte replacement if needed.

DISEASE PROFILE

Viral Infections of the Gastrointestinal Tract

A number of viruses can cause gastroenteritis, characterized by inflammation of the GI tract and other signs and symptoms with a range of severities. As with bacterial GI infections, some cases can be relatively mild and self-limiting, while others can become serious and require intensive treatment. Antimicrobial drugs are generally not used to treat viral gastroenteritis; generally, these illnesses can be treated effectively with rehydration therapy to replace fluids lost in bouts of diarrhea and vomiting. Because most viral causes of gastroenteritis are quite contagious, the best preventive measures involve avoiding and/or isolating infected individuals and limiting transmission through good hygiene and sanitation.

Figure 24.25

Hepatitis

Hepatitis is a general term meaning inflammation of the liver, which can have a variety of causes. In some cases, the cause is viral infection. There are five main hepatitis viruses that are clinically significant: hepatitisviruses A (HAV), B (HBV), C (HCV), D, (HDV) and E (HEV) (Figure 24.26). Note that other viruses, such as Epstein-Barr virus (EBV), yellow fever, and cytomegalovirus (CMV) can also cause hepatitis and are discussed in Viral Infections of the Circulatory and Lymphatic Systems.

Figure 24.26 Five main types of viruses cause hepatitis. HAV is a non-enveloped ssRNA(+) virus and is a member of the picornavirus family (Baltimore Group IV). HBV is a dsDNA enveloped virus, replicates using reverse transcriptase, and is a member of the hepadnavirus family (Baltimore Group VII). HCV is an enveloped ssRNA(+) virus and is a member of the flavivirus family (Baltimore Group IV). HDV is an enveloped ssRNA(–) that is circular (Baltimore Group V). This virus can only propagate in the presence of HBV. HEV is a non-enveloped ssRNA(+) virus and a member of the hepeviridae family (Baltimore Group IV).

Although the five hepatitis viruses differ, they can cause some similar signs and symptoms because they all have an affinity for hepatocytes (liver cells). HAV and HEV can be contracted through ingestion while HBV, HCV, and HDV are transmitted by parenteral contact. It is possible for individuals to become long term or chronic carriers of hepatitis viruses.

The virus enters the blood (viremia), spreading to the spleen, the kidneys, and the liver. During viral replication, the virus infects hepatocytes. The inflammation is caused by the hepatocytes replicating and releasing more hepatitis virus. Signs and symptoms include malaise, anorexia, loss of appetite, dark urine, pain in the upper right quadrant of the abdomen, vomiting, nausea, diarrhea, joint pain, and gray stool. Additionally, when the liver is diseased or injured, it is unable to break down hemoglobin effectively, and bilirubin can build up in the body, giving the skin and mucous membranes a yellowish color, a condition called jaundice (Figure 24.27). In severe cases, death from liver necrosis may occur.

Figure 24.27 (a) Hepatitis is inflammation of the liver resulting from a variety of root causes. It can cause jaundice. (b) Jaundice is characterized by yellowing of the skin, mucous membranes, and sclera of the eyes. (credit b left: modification of work by James Heilman, MD; credit b right: modification of work by “Sab3el3eish”/Wikimedia Commons)

Despite having many similarities, each of the hepatitis viruses has its own unique characteristics. HAV is generally transmitted through the fecal-oral route, close personal contact, or exposure to contaminated water or food. Hepatitis A can develop after an incubation period of 15 to 50 days (the mean is 30). It is normally mild or even asymptomatic and is usually self-limiting within weeks to months. A more severe form, fulminant hepatitis, rarely occurs but has a high fatality rate of 70–80%. Vaccination is available and is recommended especially for children (between ages one and two), those traveling to countries with higher risk, those with liver disease and certain other conditions, and drug users.

Although HBV is associated with similar signs and symptoms, transmission and outcomes differ. This virus has a mean incubation period of 120 days and is generally associated with exposure to infectious blood or body fluids such as semen or saliva. Exposure can occur through skin puncture, across the placenta, or through mucosal contact, but it is not spread through casual contact such as hugging, hand holding, sneezing, or coughing, or even through breastfeeding or kissing. Risk of infection is greatest for those who use intravenous drugs or who have sexual contact with an infected individual. Health-care workers are also at risk from needle sticks and other injuries when treating infected patients. The infection can become chronic and may progress to cirrhosis or liver failure. It is also associated with liver cancer. Chronic infections are associated with the highest mortality rates and are more common in infants. Approximately 90% of infected infants become chronic carriers, compared with only 6–10% of infected adults. Vaccination is available and is recommended for children as part of the standard vaccination schedule (one dose at birth and the second by 18 months of age) and for adults at greater risk (e.g., those with certain diseases, intravenous drug users, and those who have sex with multiple partners). Health-care agencies are required to offer the HBV vaccine to all workers who have occupational exposure to blood and/or other infectious materials.

HCV is often undiagnosed and therefore may be more widespread than is documented. It has a mean incubation period of 45 days and is transmitted through contact with infected blood. Although some cases are asymptomatic and/or resolve spontaneously, 75%–85% of infected individuals become chronic carriers. Nearly all cases result from parenteral transmission often associated with IV drug use or transfusions. The risk is greatest for individuals with past or current history of intravenous drug use or who have had sexual contact with infected individuals. It has also been spread through contaminated blood products and can even be transmitted through contaminated personal products such as toothbrushes and razors. New medications have recently been developed that show great effectiveness in treating HCV and that are tailored to the specific genotype causing the infection.

HDV is uncommon in the United States and only occurs in individuals who are already infected with HBV, which it requires for replication. Therefore, vaccination against HBV is also protective against HDV infection. HDV is transmitted through contact with infected blood.

HEV infections are also rare in the United States but many individuals have a positive antibody titer for HEV. The virus is most commonly spread by the fecal-oral route through food and/or water contamination, or person-to-person contact, depending on the genotype of the virus, which varies by location. There are four genotypes that differ somewhat in their mode of transmission, distribution, and other factors (for example, two are zoonotic and two are not, and only one causes chronic infection). Genotypes three and four are only transmitted through food, while genotypes one and two are also transmitted through water and fecal-oral routes. Genotype one is the only type transmitted person-to-person and is the most common cause of HEV outbreaks. Consumption of undercooked meat, especially deer or pork, and shellfish can lead to infection. Genotypes three and four are zoonoses, so they can be transmitted from infected animals that are consumed. Pregnant women are at particular risk. This disease is usually self-limiting within two weeks and does not appear to cause chronic infection.

General laboratory testing for hepatitis begins with blood testing to examine liver function (Figure 24.28). When the liver is not functioning normally, the blood will contain elevated levels of alkaline phosphatase, alanine aminotransferase (ALT), aspartate aminotransferase (AST), direct bilirubin, total bilirubin, serum albumin, serum total protein, and calculated globulin, albumin/globulin (A/G) ratio. Some of these are included in a complete metabolic panel (CMP), which may first suggest a possible liver problem and indicate the need for more comprehensive testing. A hepatitis virus serological test panel can be used to detect antibodies for hepatitis viruses A, B, C, and sometimes D. Additionally, other immunological and genomic tests are available.

Specific treatments other than supportive therapy, rest, and fluids are often not available for hepatitis virus infection, except for HCV, which is often self-limited. Immunoglobulins can be used prophylactically following possible exposure. Medications are also used, including interferon alpha 2b and antivirals (e.g., lamivudine, entecavir, adefovir, and telbivudine) for chronic infections. Hepatitis C can be treated with interferon (as monotherapy or combined with other treatments), protease inhibitors, and other antivirals (e.g., the polymerase inhibitor sofosbuvir). Combination treatments are commonly used. Antiviral and immunosuppressive medications may be used for chronic cases of HEV. In severe cases, liver transplants may be necessary. Additionally, vaccines are available to prevent infection with HAV and HBV. The HAV vaccine is also protective against HEV. The HBV vaccine is also protective against HDV. There is no vaccine against HCV.

Viral Hepatitis

Hepatitis involves inflammation of the liver that typically manifests with signs and symptoms such as jaundice, nausea, vomiting, joint pain, gray stool, and loss of appetite. However, the severity and duration of the disease can vary greatly depending on the causative agent. Some infections may be completely asymptomatic, whereas others may be life threatening. The five different viruses capable of causing hepatitis are compared in Figure 24.28. For the sake of comparison, this table presents only the unique aspects of each form of viral hepatitis, not the commonalities.

Figure 24.28

A wide range of gastrointestinal diseases are caused by bacterial contamination of food. Recall that foodborne disease can arise from either infection or intoxication. In both cases, bacterial toxins are typically responsible for producing disease signs and symptoms. The distinction lies in where the toxins are produced. In an infection, the microbial agent is ingested, colonizes the gut, and then produces toxins that damage host cells. In an intoxication, bacteria produce toxins in the food before it is ingested. In either case, the toxins cause damage to the cells lining the gastrointestinal tract, typically the colon. This leads to the common signs and symptoms of diarrhea or watery stool and abdominal cramps, or the more severe dysentery. Symptoms of foodborne diseases also often include nausea and vomiting, which are mechanisms the body uses to expel the toxic materials.

Most bacterial gastrointestinal illness is short-lived and self-limiting; however, loss of fluids due to severe diarrheal illness can lead to dehydration that can, in some cases, be fatal without proper treatment. Oral rehydration therapy with electrolyte solutions is an essential aspect of treatment for most patients with GI disease, especially in children and infants.

Staphylococcal Food Poisoning

Staphylococcal food poisoning is one form of food intoxication. When Staphylococcus aureus grows in food, it may produce enterotoxins that, when ingested, can cause symptoms such as nausea, diarrhea, cramping, and vomiting within one to six hours. In some severe cases, it may cause headache, dehydration, and changes in blood pressure and heart rate. Signs and symptoms resolve within 24 to 48 hours. S. aureus is often associated with a variety of raw or undercooked and cooked foods including meat (e.g., canned meat, ham, and sausages) and dairy products (e.g., cheeses, milk, and butter). It is also commonly found on hands and can be transmitted to prepared foods through poor hygiene, including poor handwashing and the use of contaminated food preparation surfaces, such as cutting boards. The greatest risk is for food left at a temperature below 60 °C (140 °F), which allows the bacteria to grow. Cooked foods should generally be reheated to at least 60 °C (140 °F) for safety and most raw meats should be cooked to even higher internal temperatures (Figure 24.16).

Figure 24.16 This figure indicates safe internal temperatures associated with the refrigeration, cooking, and reheating of different foods. Temperatures above refrigeration and below the minimum cooking temperature may allow for microbial growth, increasing the likelihood of foodborne disease. (credit: modification of work by USDA)

There are at least 21 Staphylococcal enterotoxins and Staphylococcal enterotoxin-like toxins that can cause food intoxication. The enterotoxins are proteins that are resistant to low pH, allowing them to pass through the stomach. They are heat stable and are not destroyed by boiling at 100 °C. Even though the bacterium itself may be killed, the enterotoxins alone can cause vomiting and diarrhea, although the mechanisms are not fully understood. At least some of the symptoms may be caused by the enterotoxin functioning as a superantigen and provoking a strong immune response by activating T cell proliferation.

The rapid onset of signs and symptoms helps to diagnose this foodborne illness. Because the bacterium does not need to be present for the toxin to cause symptoms, diagnosis is confirmed by identifying the toxin in a food sample or in biological specimens (feces or vomitus) from the patient. Serological techniques, including ELISA, can also be used to identify the toxin in food samples.

The condition generally resolves relatively quickly, within 24 hours, without treatment. In some cases, supportive treatment in a hospital may be needed.

Shigellosis (Bacillary Dysentery)

When gastrointestinal illness is associated with the rod-shaped, gram-negative bacterium Shigella, it is called bacillary dysentery, or shigellosis. Infections can be caused by S. dysenteriae, S. flexneri, S. boydii, and/or S. sonnei that colonize the GI tract. Shigellosis can be spread from hand to mouth or through contaminated food and water. Most commonly, it is transmitted through the fecal-oral route.

Shigella bacteria invade intestinal epithelial cells. When taken into a phagosome, they can escape and then live within the cytoplasm of the cell or move to adjacent cells. As the organisms multiply, the epithelium and structures with M cells of the Peyer’s patches in the intestine may become ulcerated and cause loss of fluid. Stomach cramps, fever, and watery diarrhea that may also contain pus, mucus, and/or blood often develop. More severe cases may result in ulceration of the mucosa, dehydration, and rectal bleeding. Additionally, patients may later develop hemolytic uremic syndrome (HUS), a serious condition in which damaged blood cells build up in the kidneys and may cause kidney failure, or reactive arthritis, a condition in which arthritis develops in multiple joints following infection. Patients may also develop chronic post-infection irritable bowel syndrome (IBS).

S. dysenteriae type 1 is able to produce Shiga toxin, which targets the endothelial cells of small blood vessels in the small and large intestine by binding to a glycosphingolipid. Once inside the endothelial cells, the toxin targets the large ribosomal subunit, thus affecting protein synthesis of these cells. Hemorrhaging and lesions in the colon can result. The toxin can target the kidney’s glomerulus, the blood vessels where filtration of blood in the kidney begins, thus resulting in HUS.

Stool samples, which should be processed promptly, are analyzed using serological or molecular techniques. One common method is to perform immunoassays for S. dysenteriae. (Other methods that can be used to identify Shigella include API test strips, Enterotube systems, or PCR testing. The presence of white blood cells and blood in fecal samples occurs in about 70% of patients (Figure 24.17). Severe cases may require antibiotics such as ciprofloxacin and azithromycin, but these must be carefully prescribed because resistance is increasingly common.

Figure 24.17 Red and white blood cells can be seen in this micrograph of a stool sample from a patient with shigellosis.

Salmonellosis

Salmonella gastroenteritis, also called salmonellosis, is caused by the rod-shaped, gram-negative bacterium Salmonella. Two species, S. enterica and S. bongori, cause disease in humans, but S. enterica is the most common. The most common serotypes of S. enterica are Enteritidis and Typhi. We will discuss typhoid fever caused by serotypes Typhi and Paratyphi A separately. Here, we will focus on salmonellosis caused by other serotypes.

Salmonella is a part of the normal intestinal microbiota of many individuals. However, salmonellosis is caused by exogenous agents, and infection can occur depending on the serotype, size of the inoculum, and overall health of the host. Infection is caused by ingestion of contaminated food, handling of eggshells, or exposure to certain animals. Salmonella is part of poultry’s microbiota, so exposure to raw eggs and raw poultry can increase the risk of infection. Handwashing and cooking foods thoroughly greatly reduce the risk of transmission. Salmonella bacteria can survive freezing for extended periods but cannot survive high temperatures.

Once the bacteria are ingested, they multiply within the intestines and penetrate the epithelial mucosal cells via M cells where they continue to grow (Figure 24.18). They trigger inflammatory processes and the hypersecretion of fluids. Once inside the body, they can persist inside the phagosomes of macrophages. Salmonella can cross the epithelial cell membrane and enter the bloodstream and lymphatic system. Some strains of Salmonella also produce an enterotoxin that can cause an intoxication.

Infected individuals develop fever, nausea, abdominal cramps, vomiting, headache, and diarrhea. These signs and symptoms generally last a few days to a week. According to the Centers for Disease Control and Prevention (CDC), there are 1,000,000 cases annually, with 380 deaths each year. However, because the disease is usually self-limiting, many cases are not reported to doctors and the overall incidence may be underreported. Diagnosis involves culture followed by serotyping and DNA fingerprinting if needed. Positive results are reported to the CDC. When an unusual serotype is detected, samples are sent to the CDC for further analysis. Serotyping is important for determining treatment. Oral rehydration therapy is commonly used. Antibiotics are only recommended for serious cases. When antibiotics are needed, as in immunocompromised patients, fluoroquinolones, third-generation cephalosporins, and ampicillin are recommended. Antibiotic resistance is a serious concern.

Figure 24.18 Salmonella entering an intestinal epithelial cell by reorganizing the host cell’s cytoskeleton via the trigger mechanism. (credit: modification of work by National Institutes for Health)

Typhoid Fever

Certain serotypes of S. enterica, primarily serotype Typhi (S. typhi) but also Paratyphi, cause a more severe type of salmonellosis called typhoid fever. This serious illness, which has an untreated mortality rate of 10%, causes high fever, body aches, headache, nausea, lethargy, and a possible rash.

Some individuals carry S. typhi without presenting signs or symptoms (known as asymptomatic carriers) and continually shed them through their feces. These carriers often have the bacteria in the gallbladder or intestinal epithelium. Individuals consuming food or water contaminated with these feces can become infected.

S. typhi penetrate the intestinal mucosa, grow within the macrophages, and are transported through the body, most notably to the liver and gallbladder. Eventually, the macrophages lyse, releasing S. typhi into the bloodstream and lymphatic system. Mortality can result from ulceration and perforation of the intestine. A wide range of complications, such as pneumonia and jaundice, can occur with disseminated disease.

S. typhi have Salmonella pathogenicity islands (SPIs) that contain the genes for many of their virulence factors. Two examples of important typhoid toxins are the Vi antigen, which encodes for capsule production, and chimeric A2B5 toxin, which causes many of the signs and symptoms of the acute phase of typhoid fever.

Clinical examination and culture are used to make the diagnosis. The bacteria can be cultured from feces, urine, blood, or bone marrow. Serology, including ELISA, is used to identify the most pathogenic strains, but confirmation with DNA testing or culture is needed. A PCR test can also be used, but is not widely available.

The recommended antibiotic treatment involves fluoroquinolones, ceftriaxone, and azithromycin. Individuals must be extremely careful to avoid infecting others during treatment. Typhoid fever can be prevented through vaccination for individuals traveling to parts of the world where it is common.

EYE ON ETHICS

Typhoid Mary

Mary Mallon was an Irish immigrant who worked as a cook in New York in the early 20^th century. Over seven years, from 1900 to 1907, Mallon worked for a number of different households, unknowingly spreading illness to the people who lived in each one. In 1906, one family hired George Soper, an expert in typhoid fever epidemics, to determine the cause of the illnesses in their household. Eventually, Soper tracked Mallon down and directly linked 22 cases of typhoid fever to her. He discovered that Mallon was a carrier for typhoid but was immune to it herself. Although active carriers had been recognized before, this was the first time that an asymptomatic carrier of infection had been identified.

Because she herself had never been ill, Mallon found it difficult to believe she could be the source of the illness. She fled from Soper and the authorities because she did not want to be quarantined or forced to give up her profession, which was relatively well paid for someone with her background. However, Mallon was eventually caught and kept in an isolation facility in the Bronx, where she remained until 1910, when the New York health department released her under the condition that she never again work with food. Unfortunately, Mallon did not comply, and she soon began working as a cook again. After new cases began to appear that resulted in the death of two individuals, the authorities tracked her down again and returned her to isolation, where she remained for 23 more years until her death in 1938. Epidemiologists were able to trace 51 cases of typhoid fever and three deaths directly to Mallon, who is unflatteringly remembered as “Typhoid Mary.”

The Typhoid Mary case has direct correlations in the health-care industry. Consider Kaci Hickox, an American nurse who treated Ebola patients in West Africa during the 2014 epidemic. After returning to the United States, Hickox was quarantined against her will for three days and later found not to have Ebola. Hickox vehemently opposed the quarantine. In an editorial published in the British newspaper The Guardian, Hickox argued that quarantining asymptomatic health-care workers who had not tested positive for a disease would not only prevent such individuals from practicing their profession, but discourage others from volunteering to work in disease-ridden areas where health-care workers are desperately needed.

What is the responsibility of an individual like Mary Mallon to change her behavior to protect others? What happens when an individual believes that she is not a risk, but others believe that she is? How would you react if you were in Mallon’s shoes and were placed in a quarantine you did not believe was necessary, at the expense of your own freedom and possibly your career? Would it matter if you were definitely infected or not?

E. coli Infections

The gram-negative rod Escherichia coli is a common member of the normal microbiota of the colon. Although the vast majority of E. coli strains are helpful commensal bacteria, some can be pathogenic and may cause dangerous diarrheal disease. The pathogenic strains have additional virulence factors such as type 1 fimbriae that promote colonization of the colon or may produce toxins. These virulence factors are acquired through horizontal gene transfer.

Extraintestinal disease can result if the bacteria spread from the gastrointestinal tract. Although these bacteria can be spread from person to person, they are often acquired through contaminated food or water. There are six recognized pathogenic groups of E. coli, but we will focus here on the four that are most commonly transmitted through food and water.

Enterotoxigenic E. coli (ETEC), also known as traveler’s diarrhea, causes diarrheal illness and is common in less developed countries. In Mexico, ETEC infection is called Montezuma’s Revenge. Following ingestion of contaminated food or water, infected individuals develop a watery diarrhea, abdominal cramps, malaise (a feeling of being unwell), and a low fever. ETEC produces a heat-stable enterotoxin similar to cholera toxin, and adhesins called colonization factors that help the bacteria to attach to the intestinal wall. Some strains of ETEC also produce heat-labile toxins. The disease is usually relatively mild and self-limiting. Diagnosis involves culturing and PCR. If needed, antibiotic treatment with fluoroquinolones, doxycycline, rifaximin, and trimethoprim-sulfamethoxazole (TMP/SMZ) may shorten infection duration. However, antibiotic resistance is a problem.

Enteroinvasive E. coli (EIEC) is very similar to shigellosis, including its pathogenesis of intracellular invasion into intestinal epithelial tissue. This bacterium carries a large plasmid that is involved in epithelial cell penetration. The illness is usually self-limiting, with symptoms including watery diarrhea, chills, cramps, malaise, fever, and dysentery. Culturing and PCR testing can be used for diagnosis. Antibiotic treatment is not recommended, so supportive therapy is used if needed.

Enteropathogenic E. coli (EPEC) can cause a potentially fatal diarrhea, especially in infants and those in less developed countries. Fever, vomiting, and diarrhea can lead to severe dehydration. These E. coli inject a protein (Tir) that attaches to the surface of the intestinal epithelial cells and triggers rearrangement of host cell actin from microvilli to pedestals. Tir also happens to be the receptor for Intimin, a surface protein produced by EPEC, thereby allowing E. coli to “sit” on the pedestal. The genes necessary for this pedestal formation are encoded on the locus for enterocyte effacement (LEE) pathogenicity island. As with ETEC, diagnosis involves culturing and PCR. Treatment is similar to that for ETEC.

The most dangerous strains are enterohemorrhagic E. coli (EHEC), which are the strains capable of causing epidemics. In particular, the strain O157:H7 has been responsible for several recent outbreaks. Recall that the O and H refer to surface antigens that contribute to pathogenicity and trigger a host immune response (“O” refers to the O-side chain of the lipopolysaccharide and the “H” refers to the flagella). Similar to EPEC, EHEC also forms pedestals. EHEC also produces a Shiga-like toxin. Because the genome of this bacterium has been sequenced, it is known that the Shiga toxin genes were most likely acquired through transduction (horizontal gene transfer). The Shiga toxin genes originated from Shigelladysenteriae. Prophage from a bacteriophage that previously infected Shigella integrated into the chromosome of E. coli. The Shiga-like toxin is often called verotoxin.

EHEC can cause disease ranging from relatively mild to life-threatening. Symptoms include bloody diarrhea with severe cramping, but no fever. Although it is often self-limiting, it can lead to hemorrhagic colitis and profuse bleeding. One possible complication is HUS. Diagnosis involves culture, often using MacConkey with sorbitol agar to differentiate between E. coli O157:H7, which does not ferment sorbitol, and other less virulent strains of E. coli that can ferment sorbitol.

Serological typing or PCR testing also can be used, as well as genetic testing for Shiga toxin. To distinguish EPEC from EHEC, because they both form pedestals on intestinal epithelial cells, it is necessary to test for genes encoding for both the Shiga-like toxin and for the LEE. Both EPEC and EHEC have LEE, but EPEC lacks the gene for Shiga toxin. Antibiotic therapy is not recommended and may worsen HUS because of the toxins released when the bacteria are killed, so supportive therapies must be used. Table 24.1 summarizes the characteristics of the four most common pathogenic groups.

Table24.1

Cholera and Other Vibrios

The gastrointestinal disease cholera is a serious infection often associated with poor sanitation, especially following natural disasters, because it is spread through contaminated water and food that has not been heated to temperatures high enough to kill the bacteria. It is caused by Vibrio cholerae serotype O1, a gram-negative, flagellated bacterium in the shape of a curved rod (vibrio). According to the CDC, cholera causes an estimated 3 to 5 million cases and 100,000 deaths each year.

Because V. cholerae is killed by stomach acid, relatively large doses are needed for a few microbial cells to survive to reach the intestines and cause infection. The motile cells travel through the mucous layer of the intestines, where they attach to epithelial cells and release cholera enterotoxin. The toxin is an A-B toxin with activity through adenylate cyclase. Within the intestinal cell, cyclic AMP (cAMP) levels increase, which activates a chloride channel and results in the release of ions into the intestinal lumen. This increase in osmotic pressure in the lumen leads to water also entering the lumen. As the water and electrolytes leave the body, it causes rapid dehydration and electrolyte imbalance. Diarrhea is so profuse that it is often called “rice water stool,” and patients are placed on cots with a hole in them to monitor the fluid loss (Figure 24.19).

Cholera is diagnosed by taking a stool sample and culturing for Vibrio. The bacteria are oxidase positive and show non-lactose fermentation on MacConkey agar. Gram-negative lactose fermenters will produce red colonies while non-fermenters will produce white/colorless colonies. Gram-positive bacteria will not grow on MacConkey. Lactose fermentation is commonly used for pathogen identification because the normal microbiota generally ferments lactose while pathogens do not. V. cholerae may also be cultured on thiosulfate citrate bile salts sucrose (TCBS) agar, a selective and differential media for Vibrio spp., which produce a distinct yellow colony.

Cholera may be self-limiting and treatment involves rehydration and electrolyte replenishment. Although antibiotics are not typically needed, they can be used for severe or disseminated disease. Tetracyclines are recommended, but doxycycline, erythromycin, orfloxacin, ciprofloxacin, and TMP/SMZ may be used. Recent evidence suggests that azithromycin is also a good first-line antibiotic. Good sanitation—including appropriate sewage treatment, clean supplies for cooking, and purified drinking water—is important to prevent infection (Figure 24.19)

Figure 24.19 (a) Outbreaks of cholera often occur in areas with poor sanitation or after natural disasters that compromise sanitation infrastructure. (b) At a cholera treatment center in Haiti, patients are receiving intravenous fluids to combat the dehydrating effects of this disease. They often lie on a cot with a hole in it and a bucket underneath to allow for monitoring of fluid loss. (c) This scanning electron micrograph shows Vibrio cholera. (credit a, b: modification of work by Centers for Disease Control and Prevention; credit c: modification of work by Janice Carr, Centers for Disease Control and Prevention)

V. cholera is not the only Vibrio species that can cause disease. V. parahemolyticus is associated with consumption of contaminated seafood and causes gastrointestinal illness with signs and symptoms such as watery diarrhea, nausea, fever, chills, and abdominal cramps. The bacteria produce a heat-stable hemolysin, leading to dysentery and possible disseminated disease. It also sometimes causes wound infections. V. parahemolyticus is diagnosed using cultures from blood, stool, or a wound. As with V. cholera, selective medium (especially TCBS agar) works well. Tetracycline and ciprofloxacin can be used to treat severe cases, but antibiotics generally are not needed.

Vibrio vulnificus is found in warm seawater and, unlike V. cholerae, is not associated with poor sanitary conditions. The bacteria can be found in raw seafood, and ingestion causes gastrointestinal illness. It can also be acquired by individuals with open skin wounds who are exposed to water with high concentrations of the pathogen. In some cases, the infection spreads to the bloodstream and causes septicemia. Skin infection can lead to edema, ecchymosis (discoloration of skin due to bleeding), and abscesses. Patients with underlying disease have a high fatality rate of about 50%. It is of particular concern for individuals with chronic liver disease or who are otherwise immunodeficient because a healthy immune system can often prevent infection from developing. V. vulnificus is diagnosed by culturing for the pathogen from stool samples, blood samples, or skin abscesses. Adult patients are treated with doxycycline combined with a third generation cephalosporin or with fluoroquinolones, and children are treated with TMP/SMZ.

Two other vibrios, Aeromonas hydrophila and Plesiomonas shigelloides, are also associated with marine environments and raw seafood; they can also cause gastroenteritis. Like V. vulnificus, A. hydrophila is more often associated with infections in wounds, generally those acquired in water. In some cases, it can also cause septicemia. Other species of Aeromonas can cause illness. P. shigelloides is sometimes associated with more serious systemic infections if ingested in contaminated food or water. Culture can be used to diagnose A. hydrophila and P. shigelloides infections, for which antibiotic therapy is generally not needed. When necessary, tetracycline and ciprofloxacin, among other antibiotics, may be used for treatment of A. hydrophila, and fluoroquinolones and trimethoprim are the effective treatments for P. shigelloides.

Campylobacter jejuni Gastroenteritis

Campylobacter is a genus of gram-negative, spiral or curved bacteria. They may have one or two flagella. Campylobacter jejuni gastroenteritis, a form of campylobacteriosis, is a widespread illness that is caused by Campylobacter jejuni. The primary route of transmission is through poultry that becomes contaminated during slaughter. Handling of the raw chicken in turn contaminates cooking surfaces, utensils, and other foods. Unpasteurized milk or contaminated water are also potential vehicles of transmission. In most cases, the illness is self-limiting and includes fever, diarrhea, cramps, vomiting, and sometimes dysentery. More serious signs and symptoms, such as bacteremia, meningitis, pancreatitis, cholecystitis, and hepatitis, sometimes occur. It has also been associated with autoimmune conditions such as Guillain-Barré syndrome, a neurological disease that occurs after some infections and results in temporary paralysis. HUS following infection can also occur. The virulence in many strains is the result of hemolysin production and the presence of Campylobacter cytolethal distending toxin (CDT), a powerful deoxyribonuclease (DNase) that irreversibly damages host cell DNA.

Diagnosis involves culture under special conditions, such as elevated temperature, low oxygen tension, and often medium supplemented with antimicrobial agents. These bacteria should be cultured on selective medium (such as Campy CV, charcoal selective medium, or cefaperazone charcoal deoxycholate agar) and incubated under microaerophilic conditions for at least 72 hours at 42 °C. Antibiotic treatment is not usually needed, but erythromycin or ciprofloxacin may be used.

Peptic Ulcers

The gram-negative bacterium Helicobacter pylori is able to tolerate the acidic environment of the human stomach and has been shown to be a major cause of peptic ulcers, which are ulcers of the stomach or duodenum. The bacterium is also associated with increased risk of stomach cancer (Figure 24.20). According to the CDC, approximately two-thirds of the population is infected with H. pylori, but less than 20% have a risk of developing ulcers or stomach cancer. H. pylori is found in approximately 80% of stomach ulcers and in over 90% of duodenal ulcers.

H. pylori colonizes epithelial cells in the stomach using pili for adhesion. These bacteria produce urease, which stimulates an immune response and creates ammonia that neutralizes stomach acids to provide a more hospitable microenvironment. The infection damages the cells of the stomach lining, including those that normally produce the protective mucus that serves as a barrier between the tissue and stomach acid. As a result, inflammation (gastritis) occurs and ulcers may slowly develop. Ulcer formation can also be caused by toxin activity. It has been reported that 50% of clinical isolates of H. pylori have detectable levels of exotoxin activity in vitro. This toxin, VacA, induces vacuole formation in host cells. VacA has no primary sequence homology with other bacterial toxins, and in a mouse model, there is a correlation between the presence of the toxin gene, the activity of the toxin, and gastric epithelial tissue damage.

Signs and symptoms include nausea, lack of appetite, bloating, burping, and weight loss. Bleeding ulcers may produce dark stools. If no treatment is provided, the ulcers can become deeper, more tissues can be involved, and stomach perforation can occur. Because perforation allows digestive enzymes and acid to leak into the body, it is a very serious condition.

Figure 24.20 Helicobacter infection decreases mucus production and causes peptic ulcers. (credit top left photo: modification of work by "Santhosh Thomas"/YouTube; credit top right photo: modification of work by Moriya M, Uehara A, Okumura T, Miyamoto M, and Kohgo Y)

To diagnose H. pylori infection, multiple methods are available. In a breath test, the patient swallows radiolabeled urea. If H. pylori is present, the bacteria will produce urease to break down the urea. This reaction produces radiolabeled carbon dioxide that can be detected in the patient’s breath. Blood testing can also be used to detect antibodies to H. pylori. The bacteria themselves can be detected using either a stool test or a stomach wall biopsy.

Antibiotics can be used to treat the infection. However, unique to H. pylori, the recommendation from the US Food and Drug Administration is to use a triple therapy. The current protocols are 10 days of treatment with omeprazole, amoxicillin, and clarithromycin (OAC); 14 days of treatment with bismuth subsalicylate, metronidazole, and tetracycline (BMT); or 10 or 14 days of treatment with lansoprazole, amoxicillin, and clarithromycin (LAC). Omeprazole, bismuth subsalicylate, and lansoprazole are not antibiotics but are instead used to decrease acid levels because H. pylori prefers acidic environments.

Although treatment is often valuable, there are also risks to H. pylori eradication. Infection with H. pylori may actually protect against some cancers, such as esophageal adenocarcinoma and gastroesophageal reflux disease.

Clostridium perfringens Gastroenteritis

Clostridium perfringens gastroenteritis is a generally mild foodborne disease that is associated with undercooked meats and other foods. C. perfringens is a gram-positive, rod-shaped, endospore-forming anaerobic bacterium that is tolerant of high and low temperatures. At high temperatures, the bacteria can form endospores that will germinate rapidly in foods or within the intestine. Food poisoning by type A strains is common. This strain always produces an enterotoxin, sometimes also present in other strains, that causes the clinical symptoms of cramps and diarrhea. A more severe form of the illness, called pig-bel or enteritis necroticans, causes hemorrhaging, pain, vomiting, and bloating. Gangrene of the intestines may result. This form has a high mortality rate but is rare in the United States.

Diagnosis involves detecting the C. perfringens toxin in stool samples using either molecular biology techniques (PCR detection of the toxin gene) or immunology techniques (ELISA). The bacteria itself may also be detected in foods or in fecal samples. Treatment includes rehydration therapy, electrolyte replacement, and intravenous fluids. Antibiotics are not recommended because they can damage the balance of the microbiota in the gut, and there are concerns about antibiotic resistance. The illness can be prevented through proper handling and cooking of foods, including prompt refrigeration at sufficiently low temperatures and cooking food to a sufficiently high temperature.

Clostridium difficile

Clostridium difficile is a gram-positive rod that can be a commensal bacterium as part of the normal microbiota of healthy individuals. When the normal microbiota is disrupted by long-term antibiotic use, it can allow the overgrowth of this bacterium, resulting in antibiotic-associated diarrhea caused by C. difficile. Antibiotic-associated diarrhea can also be considered a nosocomial disease. Patients at the greatest risk of C. difficile infection are those who are immunocompromised, have been in health-care settings for extended periods, are older, have recently taken antibiotics, have had gastrointestinal procedures done, or use proton pump inhibitors, which reduce stomach acidity and allow proliferation of C. difficile. Because this species can form endospores, it can survive for extended periods of time in the environment under harsh conditions and is a considerable concern in health-care settings.

This bacterium produces two toxins, Clostridium difficile toxin A (TcdA) and Clostridium difficile toxin B (TcdB). These toxins inactivate small GTP-binding proteins, resulting in actin condensation and cell rounding, followed by cell death. Infections begin with focal necrosis, then ulceration with exudate, and can progress to pseudomembranous colitis, which involves inflammation of the colon and the development of a pseudomembrane of fibrin containing dead epithelial cells and leukocytes (Figure 24.21). Watery diarrhea, dehydration, fever, loss of appetite, and abdominal pain can result. Perforation of the colon can occur, leading to septicemia, shock, and death. C. difficile is also associated with necrotizing enterocolitis in premature babies and neutropenic enterocolitis associated with cancer therapies.

Figure 24.21 Clostridium difficile is able to colonize the mucous membrane of the colon when the normal microbiota is disrupted. The toxins TcdA and TcdB trigger an immune response, with neutrophils and monocytes migrating from the bloodstream to the site of infection. Over time, inflammation and dead cells contribute to the development of a pseudomembrane. (credit micrograph: modification of work by Janice Carr, Centers for Disease Control and Prevention)

Diagnosis is made by considering the patient history (such as exposure to antibiotics), clinical presentation, imaging, endoscopy, lab tests, and other available data. Detecting the toxin in stool samples is used to confirm diagnosis. Although culture is preferred, it is rarely practical in clinical practice because the bacterium is an obligate anaerobe. Nucleic acid amplification tests, including PCR, are considered preferable to ELISA testing for molecular analysis.

The first step of conventional treatment is to stop antibiotic use, and then to provide supportive therapy with electrolyte replacement and fluids. Metronidazole is the preferred treatment if the C. difficile diagnosis has been confirmed. Vancomycin can also be used, but it should be reserved for patients for whom metronidazole was ineffective or who meet other criteria (e.g., under 10 years of age, pregnant, or allergic to metronidazole).

A newer approach to treatment, known as a fecal transplant, focuses on restoring the microbiota of the gut in order to combat the infection. In this procedure, a healthy individual donates a stool sample, which is mixed with saline and transplanted to the recipient via colonoscopy, endoscopy, sigmoidoscopy, or enema. It has been reported that this procedure has greater than 90% success in resolving C. difficile infections.

Foodborne Illness Due to Bacillus cereus

Bacillus cereus, commonly found in soil, is a gram-positive endospore-forming bacterium that can sometimes cause foodborne illness. B. cereus endospores can survive cooking and produce enterotoxins in food after it has been heated; illnesses often occur after eating rice and other prepared foods left at room temperature for too long. The signs and symptoms appear within a few hours of ingestion and include nausea, pain, and abdominal cramps. B. cereus produces two toxins: one causing diarrhea, and the other causing vomiting. More severe signs and symptoms can sometimes develop.

Diagnosis can be accomplished by isolating bacteria from stool samples or vomitus and uneaten infected food. Treatment involves rehydration and supportive therapy. Antibiotics are not typically needed, as the illness is usually relatively mild and is due to toxin activity.

Foodborne Illness Due to Yersinia

The genus Yersinia is best known for Yersinia pestis, a gram-negative rod that causes the plague. However, Y. enterocolitica and Y. pseudotuberculosis can cause gastroenteritis. The infection is generally transmitted through the fecal-oral route, with ingestion of food or water that has been contaminated by feces. Intoxication can also result because of the activity of its endotoxin and exotoxins (enterotoxin and cytotoxin necrotizing factor). The illness is normally relatively mild and self-limiting. However, severe diarrhea and dysentery can develop in infants. In adults, the infection can spread and cause complications such as reactive arthritis, thyroid disorders, endocarditis, glomerulonephritis, eye inflammation, and/or erythema nodosum. Bacteremia may develop in rare cases.

Diagnosis is generally made by detecting the bacteria in stool samples. Samples may also be obtained from other tissues or body fluids. Treatment is usually supportive, including rehydration, without antibiotics. If bacteremia or other systemic disease is present, then antibiotics such as fluoroquinolones, aminoglycosides, doxycycline, and trimethoprim-sulfamethoxazole may be used. Recovery can take up to two weeks.

DISEASE PROFILE

Bacterial Infections of the Gastrointestinal Tract

Bacterial infections of the gastrointestinal tract generally occur when bacteria or bacterial toxins are ingested in contaminated food or water. Toxins and other virulence factors can produce gastrointestinal inflammation and general symptoms such as diarrhea and vomiting. Bacterial GI infections can vary widely in terms of severity and treatment. Some can be treated with antibiotics, but in other cases antibiotics may be ineffective in combating toxins or even counterproductive if they compromise the GI microbiota. Figure 24.22 and Figure 24.23 the key features of common bacterial GI infections.

Figure 24.22

Figure 24.23

Nearly everyone has had indigestion at one time. It's a feeling of discomfort or a burning feeling in your upper abdomen. You may have heartburn or belch and feel bloated. You may also feel nauseated, or even throw up.

You might get indigestion from eating too much or too fast, eating high-fat foods, or eating when you're stressed. Smoking, drinking too much alcohol, using some medicines, being tired, and having ongoing stress can also cause indigestion or make it worse. Sometimes the cause is a problem with the digestive tract, like an ulcer or GERD.

Avoiding foods and situations that seem to cause it may help. Because indigestion can be a sign of a more serious problem, see your health care provider if it lasts for more than two weeks or if you have severe pain or other symptoms. Your health care provider may use x-rays, lab tests, and an upper endoscopy to diagnose the cause. You may need medicines to treat the symptoms.

What is indigestion?

Indigestion, also called dyspepsia or upset stomach, is a general term that describes a group of gastrointestinal symptoms that occur together. These symptoms most often include

• pain, a burning feeling, or discomfort in your upper abdomen
• feeling full too soon while eating a meal
• feeling uncomfortably full after eating a meal

Indigestion may be

• occasional—happening once in a while
• chronic—happening regularly for a few weeks or months
• functional—having chronic symptoms without a specific cause

Indigestion is not a disease. However, indigestion may be a sign of certain digestive tract diseases or conditions. Indigestion is not always related to eating.

Sometimes digestive tract diseases such as peptic ulcer disease, gastritis, and stomach cancer cause chronic indigestion. However, most often doctors do not know what causes chronic indigestion. Chronic indigestion without a health problem or digestive tract disease that could explain symptoms is called functional dyspepsia.

How common is indigestion?

Indigestion is a common condition, affecting about 1 in 4 people in the United States each year.

Of those people with indigestion who see a doctor, almost 3 in 4 are diagnosed with functional dyspepsia.

Who is more likely to get indigestion?

You are more likely to get indigestion if you

• drink
  • too many alcoholic beverages
  • too much coffee or too many drinks containing caffeine
• eat
  • too fast or too much during a meal
  • spicy, fatty, or greasy foods
  • foods that contain a lot of acid, such as tomatoes, tomato products, and oranges
• feel stressed
• have certain health problems or digestive tract diseases
• smoke
• take certain medicines

What are the complications of indigestion?

In most cases, indigestion does not have complications, although it may affect your quality of life.

Have you ever had the "stomach flu?" What you probably had was gastroenteritis - not a type of flu at all. Gastroenteritis is an inflammation of the lining of the intestines caused by a virus, bacteria or parasites. Viral gastroenteritis is the second most common illness in the U.S. The cause is often a norovirus infection. It spreads through contaminated food or water, and contact with an infected person. The best prevention is frequent hand washing.

Symptoms of gastroenteritis include diarrhea, abdominal pain, vomiting, headache, fever and chills. Most people recover with no treatment.

The most common problem with gastroenteritis is dehydration. This happens if you do not drink enough fluids to replace what you lose through vomiting and diarrhea. Dehydration is most common in babies, young children, the elderly and people with weak immune systems.

Viral gastroenteritis is an infection of your intestines that typically causes watery diarrhea, pain or cramping in your abdomen, nausea or vomiting, and sometimes fever.

Viral gastroenteritis is caused by viruses. Viruses invade normal cells in your body. Many viruses cause infections that can be spread from person to person.

People commonly call viral gastroenteritis “stomach flu,” but the term is not medically correct. Viral gastroenteritis is an infection of the intestines, not the stomach, and it is not caused by influenza (flu) viruses. The flu vaccine does not protect against viral gastroenteritis.

Viral gastroenteritis is acute, meaning it happens suddenly and lasts a short time. Most cases of viral gastroenteritis last less than a week, and most people get better on their own without medical treatment. In some cases, viral gastroenteritis may cause severe symptoms or may lead to dehydration.

Viral gastroenteritis is very common. Norovirus is the most common cause of viral gastroenteritis. In the United States, norovirus causes 19 to 21 million cases of viral gastroenteritis each year. Other viruses that cause gastroenteritis are less common.

Your abdomen extends from below your chest to your groin. Some people call it the stomach, but your abdomen contains many other important organs. Pain in the abdomen can come from any one of them. The pain may start somewhere else, such as your chest. Severe pain doesn't always mean a serious problem. Nor does mild pain mean a problem is not serious.

Call your health care provider if mild pain lasts a week or more or if you have pain with other symptoms. Get medical help immediately if

• You have abdominal pain that is sudden and sharp
• You also have pain in your chest, neck or shoulder
• You're vomiting blood or have blood in your stool
• Your abdomen is stiff, hard and tender to touch
• You can't move your bowels, especially if you're also vomiting

Gastritis and gastropathy are conditions that affect the stomach lining, also known as the mucosa. In gastritis, the stomach lining is inflamed. In gastropathy, the stomach lining is damaged, but little or no inflammation is present. The majority of people with gastritis or gastropathy don’t have any symptoms. In some cases, gastritis and gastropathy cause symptoms of indigestion or of bleeding in the stomach. Helicobacter pylori infection is the most common cause of gastritis.

Your doctor may order an upper GI endoscopy with biopsies or other tests to diagnose gastritis or gastropathy, find the cause, and check for complications. Other tests may include blood, stool, and breath tests and an upper GI series. Your doctor will recommend treatments based on the type of gastritis or gastropathy you have and its cause. Treating gastritis and gastropathy can improve symptoms, if present, and lower your chance of complications.

Researchers have not found that eating, diet, and nutrition play an important role in causing the majority of cases of gastritis or gastropathy. H. pylori gastritis can cause problems absorbing iron from food, and autoimmune gastritis can cause problems absorbing iron and vitamin B12 from food.

Your stomach lining has an important job. It makes acid and enzymes that help break down food so you can extract the nutrients you need. The lining also protects itself from acid damage by secreting mucus. But sometimes the lining gets inflamed and starts making less acid, enzymes and mucus. This type of inflammation is called gastritis, and it can cause long-term problems.

Some people think they have gastritis when they have pain or an uncomfortable feeling in their upper stomach. But many other conditions can cause these symptoms. Gastritis can sometimes lead to pain, nausea and vomiting. But it often has no symptoms at all. If left untreated, though, some types of gastritis can lead to ulcers (sores in the stomach lining) or even stomach cancer.

People used to think gastritis and ulcers were caused by stress and spicy foods. But research studies show that bacteria called Helicobacter pylori are often to blame. Usually, these bacteria cause no symptoms. In the United States, 20% to 50% of the population may be infected with H. pylori.

H. pylori breaks down the inner protective coating in some people’s stomachs and causes inflammation. “I tell people H. pylori is like having termites in your stomach,” says Dr. David Graham, an expert in digestive diseases at Baylor College of Medicine in Texas. “You usually don’t know you have termites until someone tells you, and you ignore it at your own risk.” H. pylori can spread by passing from person to person or through contaminated food or water. Infections can be treated with bacteria-killing drugs called antibiotics.

One type of gastritis, called erosive gastritis, wears away the stomach lining. The most common cause of erosive gastritis is long-term use of medications called non-steroidal anti-inflammatory drugs. These include aspirin and ibuprofen. “When you stop taking the drugs, the condition usually goes away,” says Graham. Doctors might also recommend reducing the dose or switching to another class of pain medication.

Less common causes of gastritis include certain digestive disorders (such as Crohn’s disease) and autoimmune disorders, in which the body’s protective immune cells mistakenly attack healthy cells in the stomach lining.

Gastritis can be diagnosed with an endoscope, a thin tube with a tiny camera on the end, which is inserted through the patient’s mouth or nose and into the stomach. The doctor will look at the stomach lining and may also remove some tissue samples for testing. Treatment will depend on the type of gastritis you have.

Although stress and spicy foods don’t cause gastritis and ulcers, they can make symptoms worse. Milk might provide brief relief, but it also increases stomach acid, which can worsen symptoms. Your doctor may recommend taking antacids or other drugs to reduce acid in the stomach.

Talk with a health care provider if you’re concerned about ongoing pain or discomfort in your stomach. These symptoms can have many causes. Your doctor can help determine the best course of action for you.

Watch for Ulcers

Gastritis can lead to ulcers over time. Symptoms of ulcers include pain between the belly button and breastbone that:

• starts between meals or during the night
• briefly stops if you eat or take antacids
• lasts for minutes to hours
• comes and goes for several days or weeks

Contact your doctor right away if you have:

• sudden sharp stomach pain that doesn’t go away
• black or bloody stools
• vomit that is bloody or looks like coffee grounds

H. pylori gastritis is the most common type of gastritis, and nearly everyone who is infected with H. pylori develops chronic gastritis. About half of the world’s population is infected with H. pylori bacteria, and this infection is more common in developing countries than in developed countries. About 35 percent of the U.S. population is infected with H. pylori.

Reactive gastropathy, caused by contact with irritating substances, is also relatively common, affecting about 15 percent of people in the United States.

Other forms of gastritis and gastropathy are less common.

Gastroparesis, also called delayed gastric emptying, is a disorder that slows or stops the movement of food from your stomach to your small intestine. Normally, after you swallow food, the muscles in the wall of your stomach grind the food into smaller pieces and push them into your small intestine to continue digestion. When you have gastroparesis, your stomach muscles work poorly or not at all, and your stomach takes too long to empty its contents. Gastroparesis can delay digestion, which can lead to various symptoms and complications.