Porth's Essentials of Pathophysiology, 4e

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Gastrointestinal and Hepatobiliary Function

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have infection rates second only to the common cold. Most infections are spread by the oral–fecal route, often through contaminated water or food. Viral Infections Most viral infections affect the superficial epithelium of the small intestine, destroying these cells and disrupt- ing their absorptive function. Repopulation of the small intestinal villi with immature enterocytes and preserva- tion of crypt secretory cells leads to net secretion of water and electrolytes compounded by incomplete absorption of nutrients and osmotic diarrhea. Symptomatic disease is caused by several distinct viruses, including the rota- virus, which most commonly affects children 6 to 24 months of age; the norovirus (previously known as the Norwalk virus), which is responsible for the majority of cases of nonbacterial food-borne epidemic gastroen- teritis in all age groups: and enteric adenoviruses, which primarily affect children. 6 Rotavirus. Worldwide, rotavirus is estimated to cause more than 111 million cases of diarrhea in children younger than 5 years of age. In the United States, the disease causes 3 million cases of diarrhea, 80,000 hospi- talizations, and 20 to 40 deaths per year. 31 The disease tends to be most severe in children 3 to 24 months of age. Infants younger than 3 months of age are relatively protected by transplacental antibodies and possibly by breast-feeding. The virus is spread by a fecal–oral route and outbreaks are common in children in day care cen- ters. The virus is shed before and for days after clinical illness. Very few infectious virions are needed to cause disease in a susceptible host. Rotavirus infection typically begins after an incuba- tion period of less than 24 hours, with mild to moder- ate fever and vomiting, followed by onset of frequent watery stools. The fever and vomiting usually disappear on about the second day, but the diarrhea may continue for 5 to 7 days. Dehydration may develop rapidly, par- ticularly in infants. Treatment is largely supportive. Currently, there are two licensed vaccines that protect infants from rotavirus infection: a live, oral, pentavalent vaccine (RotaTeq) containing five reassortment rota- viruses isolated from human and bovine hosts, and a monvalent vaccine (Rotarix) that is effective against all of the serotypes that cause infection in children. 31 Bacterial Infections Infectious enterocolitis can be caused by a number of bacteria. There are several pathogenic mechanisms for development of bacterial enterocolitis: ingestion of pre- formed toxins that are present in contaminated food, infection by toxigenic organisms that proliferate in the gut lumen and produce an enterotoxin, and infection by enteroinvasive organisms that proliferate in the lumen and invade and destroy mucosal epithelial cells. The pathogenic effects of bacterial infections depend on the ability of the organism to adhere to the mucosal epi- thelial cells, elaborate enterotoxins, and then invade the mucosal epithelial cells.

In general, bacterial infections produce more severe effects than viral infections. The complications of bacte- rial enterocolitis result frommassive fluid loss or destruc- tion of intestinal mucosa and include dehydration, sepsis, and perforation. Among the organisms that cause bacte- rial enterocolitis are Staphylococcus aureus (toxins asso- ciated with “food poisoning”), Shiga toxin-producing Escherichia coli, Shigella species, nontyphoid salmo- nella, and campylobacter. 32 Two particularly serious forms of bacterial enterocolitis are caused by C. difficile and E. coli O157:H7. Clostridium difficile Colitis. C. difficile (so named because it is difficult to culture) is a gram-positive, spore- forming bacillus that is part of the normal flora in some healthy people. The spores are resistant to the acid envi- ronment of the stomach and convert to vegetative forms in the colon. 33 In general, C. difficile is noninvasive and development of C. difficile colitis requires disruption of normal intestinal flora, acquisition and germination of the spores, overgrowth of the bacillus, and toxin pro- duction. The toxins bind to and damage the intestinal mucosa, causing hemorrhage, inflammation, and necro- sis. The toxins also interfere with protein synthesis, attract inflammatory cells, increase capillary permeabil- ity, and stimulate intestinal peristalsis. Treatment with broad-spectrum antibiotics predisposes to disruption of the normal protective bacterial flora of the colon. After antibiotic therapy has made the bowel susceptible to infection, colonization by C. difficile occurs by the oral– fecal route. 34 C. difficile infection usually is acquired in the hospital, where the organism is commonly encoun- tered. Nearly all antibiotics have been implicated in the disease. A new and hypervirulent fluoroquinolone-resistant strain of Clostridium difficile (NAP1/B1/027) has been implicated in C. difficile outbreaks since the early 2000s. 34,35 This epidemic form has caused more severe and refractory disease leading to complications that include intensive care unit admission, colectomies, and death. Before 2002, C. difficile– associated colitis was rare, but its prevalence has increased significantly. 35 The risk of C. difficile -associated diarrhea is increased not only by factors, such as antibiotic exposure, but also by gastrointestinal surgery/manipulation, prolonged stay at a health care facility, serious underlying disease, immune-compromising conditions, and aging. Persons on proton pump inhibitors are at elevated risk, as are peripartum women and heart transplant recipients. However, C. difficile infection has emerged in popula- tions not previously considered at risk. 34,35 These include young and previously healthy persons who have not received antimicrobial therapy or been exposed to the hospital environment. In these cases the only risk fac- tor was close contact with someone who had C. difficile infection. 35 C. difficile colitis commonly manifests with diarrhea that is mild to moderate and sometimes is accompanied by lower abdominal cramping. Typically, symptoms begin within 1 to 2 weeks after antibiotic treatment has been initiated, although it can vary from 1 day to