Ulcerative Colitis Channel

Overview

Ulcerative colitis is an inflammatory bowel disease that affects the lining of the large intestine, called the colon . The disease usually causes diarrhea, abdominal pain, and blood in the stool and can also lead to nausea, lack of appetite, weight loss, and anemia.

In ulcerative colitis, or UC, inflammation results when the body's immune system perceives an injury or foreign invader in the colon. The exact nature of this invader, or antigen, is unknown, but it is the subject of much recent study. Researchers hypothesize that the immune response may be triggered by an allergen, a bacteria or virus, a genetic reaction, or a defective signal from the body's own cells-an autoimmune response. In any case, inflammation is the body's natural attempt to heal by sending immune cells to the site of the insult. Inflammation results in pain, heat, redness, and swelling; chronic inflammation, over months or years, impairs the proper function of tissues and organs.

In UC, the mucosa, or mucus membrane, lining the colon breaks down and sores or ulcers develop, resulting in pain, bleeding, and diarrhea. Ulcerative colitis can be acute-severe for a short period of time-or chronic, lasting over many years. Relapses and remissions occur and may be unpredictable.

Ulcerative colitis develops more frequently among people in industrialized countries. The disease is uncommon in Asia, Africa, and South America, though data from less developed nations is lacking. Incidence rates are highest in Scandinavian countries, Great Britain, and North America: Some studies indicate UC affects as many as 1 in every 2,000 Americans , both men and women, though slightly more women develop the disease than men. It is often diagnosed in early adulthood, between the ages of 15 and 30; though some people develop UC in their 50s, 60s, or later.

The risk of developing colon cancer is increased in people diagnosed with ulcerative colitis. After living with UC for 30 years, about 22 percent of people develop colon cancer. Patients with UC that involves the entire colon, or those who have had UC on the left, or distal, side of their colon for more than 10 to 15 years are at highest risk of cancer. As a result, cancer screening with colonoscopy is recommended after a patient has had the disease for eight to 10 years, no matter what his or her age.

In the past decade, major advances have been made in treating ulcerative colitis. A variety of medications now exist, and which one proves most effective with the least side effects depends upon the patient and the extent of the disease. About 70 percent of people with ulcerative colitis experience remission with proper medical therapy. Surgery to remove all or part of the colon is necessary only in patients who do not respond to medications and have serious complications.

Anatomy

The colon, or large intestine, is a long, muscular tube about 2A? inches in diameter. It extends 5 or 6 feet from the cecum , a pouch that opens to the small intestine, located in the lower right abdomen near the appendix. The colon runs up to just under the rib cage, around and down into the S-shaped region in the lower left abdomen referred to as the sigmoid colon , and then to the end of the gastrointestinal tract, the rectum and anal canal , through which waste passes. The colon is the site of salt and water absorption, and glands in the colon secrete slippery mucus to lubricate the intestines, and aid decomposition of undigested food, cell debris, dead bacteria, and other wastes that must leave the body. Maintaining proper potassium balance is also a task of the colon. The tissue lining the colon absorbs and secretes potassium as needed to maintain proper bodily functions, including heart rate.

Inflammation from ulcerative colitis damages the mucosa , and sores form in the lining of the colon. Under a microscope, the tissue may appear only red and irritated, or florid ulceration may be present. Bleeding and pain are common.

The typical lesion doctors see in ulcerative colitis is called a "crypt abscess." The lining of a healthy colon is like a honeycomb. In ulcerative colitis, the spaces in the honeycomb, or crypts, which maintain the delicate structure of the lining, fill up with polymorphonuclear cells . These are white blood cells summoned by the body to fight against infection, injury or foreign invasion, and are the first cells on the scene at the site of inflammation. Over time, chronic inflammation destroys the crypts, and the normal architecture of the mucosa is lost, replaced by ulcers and scarring, which can shorten or narrow the colon. In severe disease, obstruction of the colon can occur.

While diarrhea, pain, and blood in the feces are common with UC, the extent of disease varies greatly from person to person. In about one third of patients, the disease affects only the rectum, about the first 6 inches inward from the anus. This condition is also called ulcerative proctitis . Proctitis may result in swelling, redness, pain in the anal canal and rectum, and the urge to pass feces, even if only blood, mucus, and pus are present.

The disease may also involve only the left or distal side of the colon , extending some 15 inches from the rectum to the bend in the colon near the spleen. In patients with distal ulcerative colitis, tissue under a microscope indicates chronic inflammation and the destruction of the cell architecture of the colon lining. Those with distal UC for 10 to 15 years are at higher risk of developing colon cancer.

Pancolitis is ulcerative colitis that extends for the entire length of the colon. Diarrhea and blood in the feces are common and may be accompanied by abdominal pain and cramps, fever, and weight loss. In severe UC, the lining of the colon may develop nodules, discrete ulcer craters, abnormal cells, or carcinoma. Patients who have suffered pancolitis for eight to 10 years are at increased risk of colon cancer.

Causes

The cause of ulcerative colitis remains unknown. The immune system in the mucosa of the large intestine is exposed to a variety of antigens from food products and billions of bacteria live there. In theory, any of these may trigger the release of proteins that sets off an immune reaction, bringing inflammatory cells to the colon lining. Recently, scientists searching for the cause of UC have developed three major hypotheses :

• That unidentified pathogens, most likely harmful bacteria or viruses in the colon, trigger the body's immune response, which is natural. But the immune cells are not effective in destroying the pathogens. Therefore, chronic inflammation results, harming the lining of the colon.
• That a common dietary antigen or a nonpathogenic microbe is present in the colon of people with UC. Their immune systems overreact , mounting an abnormally intense response to these common substances. It's possible that people who develop UC are genetically predisposed to the immune overreaction, whereas others have no immune response to these same dietary antigens or microbes. One example of this hypothesis in action occurs when some people ingest the protein in cows' milk. Cows' milk is known to cause undesirable symptoms in many people with ulcerative colitis-their immune systems send cells to fight the milk protein. On the other hand, people with healthy colons often have no negative reaction to cows' milk.
• That UC is triggered by proteins present on the surface of the patient's own intestinal cells. The theory holds that the body mounts an appropriate immune response to an antigen it discovers in the colon. But because of similarities between the proteins on the surface of the antigen and those on cells in the colon, the immune system wrongly attacks the lining of the patient's colon. This is called an autoimmune response . It results in inflammation, which destroys the cells lining the colon.

Over the next few years, further research may answer which of these theories holds the most promise for future treatment.

Risk Factors

Genetic factors play a role in who develops ulcerative colitis; indeed, the most firmly established risk factor is a family history of it. Approximately 10 percent of patients with ulcerative colitis have a first-degree relative with the illness. Jewish heritage greatly increases the risk of UC, but rates among Jews vary from country to country. The prevalence of UC is higher among Jews born in Europe or the United States than for those born in Asia or Africa, suggesting that environmental factors also play a role.

In epidemiological studies of twins, identical twins share a stronger risk of UC than do fraternal twins. However, there is not a perfect concordance of the disease among identical twins, providing further evidence that factors other than genetics, such as environment, also play a role. It's likely that a group of genes working together, and influenced by environmental factors, lead to ulcerative colitis, although these genes have not been identified.

Among the possible environmental factors, no specific foods have been identified as a cause of ulcerative colitis. However, many people with UC are intolerant of cows' milk and find that dairy products may aggravate symptoms.

Cigarette smoking actually reduces the risk , though what component of tobacco has a beneficial effect on the colon lining is not clear. Smokers have only about 40 percent of the risk of developing ulcerative colitis of nonsmokers. Among one group of 30 intermittent smokers with UC, resuming smoking a pack of cigarettes per day over a six-week period led to an improvement in symptoms in 50 percent of these patients. Stopping smoking seems to increase the risk of developing UC. Former smokers are about 1.7 times more likely to develop the disease than are those who have never smoked. Some researchers have theorized that nicotine could be the element in tobacco that reduces the risk of UC. Controlled trials of a nicotine patch as therapy for UC suggest nicotine may play a role in preventing the disease. On the other hand, a high proportion of nonsmokers experienced unacceptable side effects from nicotine patches. A trial of nicotine gum among patients with UC was unsuccessful.

Complications

Life-threatening complications can result from ulcerative colitis. These include toxic megacolon, colonic perforation, strictures, and a liver disorder called primary sclerosing cholangitis.

Toxic megacolon: The most feared complication from severe ulcerative colitis is toxic megacolon. This condition occurs as a result of extension of the inflammation beyond the submucosa of the colon into the smooth muscle layer in the wall of the colon. This causes the colon to lose its ability to contract, ultimately resulting in a dilated colon, fever, weakness, racing heart, an abnormally elevated white cell count, abdominal tenderness, and other signs of toxicity. X-rays of the abdomen are done to diagnose the condition. Colonic perforation, or a hole in the wall of the colon, is a common complication with toxic megacolon, leading to peritonitis, and possibly death.

Medical therapy to reduce the likelihood of perforation of the colon wall and to return the colon to normal motor activity is the first step in treating toxic megacolon. Because patients should take nothing by mouth, a nasogastric tube is placed in the stomach for suction and decompression of the gastrointestinal tract. The use of a rolling technique during which the patient lies on his abdomen for 10 to 15 minutes every two hours while awake, allows gas to pass and the dilated colon to decompress. Intravenous fluids are given. Broad-spectrum antibiotics are begun in anticipation of possible peritonitis from a perforation. Intravenous steroids to reduce inflammation are usually administered. The patient's condition is closely monitored for signs of deterioration.

If the patient does not show signs of improvement during the first 24 to 48 hours of drug therapy, the risk of perforation increases markedly and surgical intervention is undertaken. Removal of the colon takes place in about 25 percent of patients who suffer toxic megacolon, and some 50 percent of patients with pancolitis (colitis affecting the entire colon). If surgery is performed before there is colonic perforation, the mortality rate is only about 2 percent. But in cases where there has been bowel perforation, the rate increases to 44 percent.

Perforation: Perforations can also occur in severe ulcerative colitis even if toxic megacolon does not develop. Most perforations occur in the left colon, commonly in the sigmoid colon. Perforations tend to occur more often during first episodes of colitis. Perforations must be treated surgically.

Strictures: Though uncommon in ulcerative colitis, strictures, or narrowings of the colon, are evident in about 12 percent of surgically removed colons. Strictures tend to occur late in the disease, usually 10 to 20 years after onset. The most common symptom is fecal incontinence. Strictures have been associated with colon cancer, and biopsy of the stricture is warranted.

Primary sclerosing cholangitis: This is a chronic liver disease in which the flow of bile in the liver is interrupted by fibrous tissue in the bile ducts. The abnormal tissue forms as a result of chronic inflammation. The condition is frequently associated with ulcerative colitis. People with this complication have symptoms of fatigue, abdominal pain, fever, or jaundice. It usually appears in men after 10 or 15 years of very mild, even subclinical pancolitis. The disease can become so severe it may necessitate liver transplant in some patients.