Porth's Essentials of Pathophysiology, 4e

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Gastrointestinal and Hepatobiliary Function

U N I T 8

Irritable bowel disease is characterized by persistent or recurrent symptoms of abdominal pain, altered bowel function, and varying complaints of flatulence, bloat- ing, nausea and anorexia, constipation or diarrhea, and anxiety or depression. A hallmark of IBS is abdominal pain that is relieved by defecation and associated with a change in consistency or frequency of stools. Abdominal pain usually is intermittent, cramping, and in the lower abdomen. It does not usually occur at night or inter- fere with sleep. The condition is believed to result from dysregulation of intestinal motor and sensory func- tions modulated by the CNS. Persons with IBS tend to experience increased motility and abnormal intestinal contractions in response to psychological and physi- ologic stresses. Although changes in intestinal activity are normal responses to stress, these responses appear to be exaggerated in persons with IBS. Women tend to be affected more often than men. Menarche often is associated with onset of the disorder. Women frequently notice an exacerbation of symptoms during the premen- strual period, suggesting a hormonal component. The diagnosis of IBS is usually based on signs and symptoms of abdominal pain or discomfort, bloating, and constipation or diarrhea, or alternating bouts of con- stipation and diarrhea. A commonly used set of diagnos- tic criteria requires continuous or recurrent symptoms of at least 12 weeks’ duration (which may be nonconsecu- tive) of abdominal discomfort or pain in the preceding 12 months, with two of three accompanying features: relief with defecation, onset associated with a change in bowel frequency, and associated with a change in form (appear- ance) of stool. Other symptoms that support the diagno- sis of IBS include abnormal stool frequency (more than three times per day or less than three times per week), abnormal stool form (lumpy/hard or loose/watery), abnormal stool passage (straining, urgency, or feeling of incomplete evacuation), passage of mucus, and bloating or feeling of abdominal distention. A history of lactose intolerance should be considered because intolerance to lactose and other sugars may be a precipitating factor in some persons. The acute onset of symptoms raises the likelihood of organic disease, as do weight loss, anemia, fever, occult blood in the stool, nighttime symptoms, or signs and symptoms of malabsorption. These signs and symptoms require additional investigation. The treatment of IBS focuses on methods of stress man- agement, particularly those related to symptom produc- tion. Reassurance is important. Usually, no special diet is indicated, although adequate fiber intake usually is recom- mended. Avoidance of offending dietary substances such as fatty and gas-producing foods, alcohol, and caffeine-con- taining beverages may be beneficial. Various pharmaco- logic agents, including antispasmodic and anticholinergic drugs, have been used with varying success in treatment of the disorder. Alosetron is a serotonin antagonist that has been approved by the U.S. Food and Drug Administration (FDA) for treatment of women with severe IBS. The drug appears to act by reducing intestinal secretion, decreasing visceral afferent nerve activity (thereby reducing abdomi- nal pain), and reducing intestinal motility. Because the drug has serious side effects, including severe constipation

and ischemic colitis, its use is restricted to women with severe IBS with diarrhea who have not responded to con- ventional treatment and have been educated about the relative risks and benefits of the agent. Inflammatory Bowel Disease The term inflammatory bowel disease (IBD) is used to designate two related inflammatory intestinal dis- orders: Crohn disease and ulcerative colitis. 6,7,27–29 Although the two diseases differ sufficiently to be distinguishable, they have many features in common. Both diseases produce inflammation of the bowel, both lack confirming evidence of a proven causative agent, both have a pattern of familial occurrence, and both can be accompanied by systemic manifestations. Crohn disease most commonly affects the distal small intes- tine and proximal colon but can affect any area of the gastrointestinal tract from the esophagus to the anus, whereas ulcerative colitis is confined to the colon and rectum (Fig. 29-5). In Crohn disease the inflammation is often transmural, whereas in ulcerative colitis it is typically confined to the mucosa. The clinical manifestations of both Crohn disease and ulcerative colitis are ultimately the result of activation of inflammatory cells with elaboration of inflammatory mediators that cause nonspecific tissue damage. Both dis- eases are characterized by remissions and exacerbations of diarrhea, fecal urgency, and weight loss. Acute com- plications, such as intestinal obstruction, may develop during periods of fulminant disease. The distinguishing characteristics of Crohn disease and ulcerative colitis are summarized in Table 29-1. A number of systemic manifestations have been iden- tified in persons with Crohn disease and ulcerative coli- tis. These include axial arthritis affecting the spine and sacroiliac joints and oligoarticular arthritis affecting the large joints of the arms and legs; inflammatory condi- tions of the eye, usually uveitis; skin lesions, especially erythema nodosum; inflammation of the mucous mem- brane of the mouth (stomatitis); blood disorders (ane- mia, hypercoagulability); and inflammation of the bile

Crohn disease

Ulcerative colitis

A

B

FIGURE 29-5. Distribution patterns of disease with (A) skip lesions in Crohn disease and (B) continuous involvement of the colon, beginning with the rectum, in ulcerative colitis.