Ulcerative colitis is an inflammatory bowel disease that affects the lining of the large intestine, also called the colon. The disease usually causes diarrhea, blood in the stool, and abdominal pain, 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, and activates a chronic immune reaction to the surface lining of the colon, or "colonic mucosa." What exactly the immune system is activated against is unknown, but it is the subject of much recent study. Researchers hypothesize that the immune response may be triggered by an allergen, bacteria or a virus, a genetic reaction, or a defective signal from the body's own cells-an autoimmune response. The strongest evidence is that the body may be acting against bacteria, because animals bred to develop ulcerative colitis do not develop colitis when raised in sterile environment. Additionally, the type of bacteria can ameliorate or exacerbate colitis in these animal studies. 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 bleeding and diarrhea. UC is a chronic condition by definition. Once it develops it rarely goes away although the symptoms may wax and wane, with intermittent periods of active inflammation followed by periods where no inflammation occurs, known as "remission." Relapses and remissions are often unpredictable, although medical therapy can help both induce and maintain remission. The only cure for ulcerative colitis is removing the entire colon surgically, an operation known as a total proctocolectomy (procto referring to the rectum, or end of the colon).
Ulcerative colitis develops more frequently among people in Western industrialized countries. The disease is much less common in Asia, Africa, and South America, though the incidence in these regions is increasing. Incidence rates are highest in Scandinavian countries, Great Britain, and North America: Some studies indicate UC affects more than 1 in every 1000 Americans. Both men and women are equally affected. It can occur at all ages, though most often it is diagnosed in early adulthood, between the ages of 15 and 35.
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 develops earlier in life and UC that involves the entire colon are at highest risk of cancer. As a result, cancer screening with colonoscopy is recommended in all patients after the disease has been present for eight to 10 years.
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 the entire colon and rectum, is necessary only in patients who do not respond well enough to or cannot tolerate medications or have developed colon cancer or precancerous changes in the colon (a condition known as dysplasia). However, surgery cures ulcerative colitis and most patients who now undergo surgery for ulcerative colitis no longer require an ostomy (an opening of the end of the intestine to the skin) for collection of waste, but rather have creation of a "pouch" from the end of the small intestine which is then connected to the anus to recapitulate normal bowel function.
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The colon, or large intestine, is a long, muscular tube about 2½ inches in diameter. It extends 5 or 6 feet from the cecum, a pouch that begins at the end of the small intestine, located in the lower right abdomen near the appendix. The colon runs up to just under the rib cage, below the liver and the stomach and then 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. In severe colitis, the lining of the colon may be essentially denuded. 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.
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 (known as "left-sided colitis"), extending some 15 inches from the rectum to the bend in the colon near the spleen.
Pancolitis is ulcerative colitis that extends for the entire length of the colon, including the cecum. Pancolitis is present in about 20% of patients. Pancolitis has the highest risk of developing sudden and severe inflammation (fulminant colitis) that requires urgent surgery. Although all forms of UC increase risk for colon cancer, this risk is greatest in pancolitis. Some patients' colitis begins as pancolitis from the outset, but often UC begins as proctitis or left-sided colitis and during the course of the disease inflammation extends to involve the entire colon in the form of pancolitis.
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:
Genetic factors play a role in who develops ulcerative colitis; indeed, the most firmly established risk factor is a family history of UC. Approximately 10 percent of patients with ulcerative colitis have a first-degree relative with the illness, with approximately an 8-fold increased risk of the disease compared to those without a UC family history. Jewish ancestry from middle and Eastern Europe (Ashkenazi Jews, the majority of Jews in the United States) heritage increases the risk of UC, but rates among Jews vary from country to country. The prevalence of UC is higher among people born in Europe or North America than for those born in Asia or Africa, suggesting that environmental factors also play a role. People with a family history of the other major chronic intestinal inflammatory bowel disease, Crohn's disease, have a three-fold greater risk of developing UC.
In epidemiological studies of twins, identical twins share a stronger risk of UC than do fraternal twins. However, there is only a modest increase in concordance of the disease among identical twins (approximately 6% concordance), providing further evidence that factors other than genetics, such as environment, also play a role. Additionally, UC may develop from different causes, some having a greater genetic predisposition than others. Presently about 15 unique regions of the human genome have been shown to contain DNA variations resulting in increased risk for UC. Several of these genes influence the body's immune function. These include variations in the human leukocyte antigen, known as HLA genes, which are required for the immune system to process antigens, and genes in proteins that regulate the chronicity of immune response, notably the interleukin 23 receptor. Interestingly, the majority of the genes and genomic regions identified are also associated with risk for Crohn's disease. It's likely that the UC predisposing genes work together, and, influenced by environmental factors, lead to increased risk of ulcerative colitis.
Among the possible environmental factors, no specific foods have been identified as a cause of ulcerative colitis. However, some 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 entirely 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. Some studies have shown benefit using nicotine for treatment of UC, while others have not. Larger studies are needed.
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 required to prevent toxic megacolon in patients with signs of fulminant colitis, where toxic megacolon is likely to develop. 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. 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 majority of people with this condition develop or have had ulcerative colitis. People with this complication have symptoms of fatigue, abdominal pain, fever, or jaundice. It can appear in men after 10 or 15 years of very mild, even subclinical (i.e. asymptomatic) pancolitis, and it is associated with a high risk for colon cancer. Primary sclerosing cholangitis can result in liver cirrhosis and necessitate liver transplant. Because primary sclerosing cholangitis does occur in patients without any evidence of UC (or Crohn's disease) and because relatively few patients with UC develop primary sclerosing cholangitis, it is likely these are two distinct diseases but with overlapping causes.
Last reviewed on 6/4/09
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