Specific Illnesses

The Gastrointestinal System

Upper gastrointestinal tract Lower gastrointestinal tract Liver Gallbladder Pancreas Appendix

Ulcerative colitis (UC) is a relapsing, remitting inflammatory disease of the colonic mucosa and submucosa. The prevalence of UC in the United States is 150200/100,000 of population. A genetic contribution to the disease is indicated by the increased incidence of UC (of 30 to 100 times that of the general poupulation) among firstdegree relative of patients with UC.

Ulcerative Colitis
Pathophysiology
Signs and symptoms
Abdominal cramping Nausea, vomiting, diarrhea Fever or weight loss Treatment Follow general treatment guidelines.
Causes unknown

The characteristic pathology is one of chronic inflammation characterized by large numbers of lymphocytes and histiocytes in the diseased mucosa and submucosa with an

acute inflammatory infiltrate composed of neutrophils

variably present.

UC: is a form of (IBD). It is a form of colitis, of that includes characteristic ulcers, or open sores, in the colon. The main symptom of active disease is usually diarrhea mixed with blood, of gradual onset.

UC is, however, a systemic disease that affects many parts

of the body outside the intestine. Because of the name, IBD is often confused with irritable bowel syndrome ("IBS"), a troublesome, but much less serious condition.

Cumulative Incidence for Colorectal Cancer Based on Extent of Disease at Time of Diagnosis
40 30 Cumulative CRC (%) 20 10 0 0 10 20 30 Years follow-up 40

pancolitis left-sided colitis

Ekbom, et al NEJM, 1990

UC is an intermittent disease, with periods of exacerbated symptoms, and periods that are relatively symptom-free.

Although the symptoms of UC can sometimes diminish on

their own, the disease usually requires treatment to go into remission.

Although UC has no known cause, there is a presumed genetic component to susceptibility. The disease may be triggered in a susceptible person by environmental factors. Although dietary modification may reduce the discomfort of a person with the disease, UC is not thought to be caused by dietary factors. Although UC is treated as though it were an autoimmune disease, there is no consensus that it is such.

UC is a systemic disease that affects many parts of the body.

Sometimes the extra-intestinal manifestations of the disease

are the initial signs, such as painful, arthritic knees in a

teenager. It is, however, unlikely that the disease will be

correctly

diagnosed

until

the

onset

of

the

intestinal

manifestations.

The clinical presentation of UC depends on the extent of the

disease process. Patients usually present with diarrhea mixed with blood and mucus, of gradual onset. They also may have signs of weight loss, and blood on rectal examination. The disease is usually accompanied with different degrees of abdominal pain, from mild discomfort to severely painful cramps.

Extent of involvement
UC is normally continuous from the rectum up the colon. The disease is classified by the extent of involvement, depending on how far up the colon the disease extends:
Distal colitis, potentially treatable with enemas: Proctitis: Involvement limited to the rectum.

Proctosigmoiditis:
Involvement of the rectosigmoid colon, the portion of the colon adjacent to the rectum. Left-sided colitis: Involvement of the descending colon, which runs along the patient's left side, up to the splenic flexure and the beginning of the transverse colon.

Extensive colitis, inflammation extending beyond the reach of enemas: Pancolitis: Involvement of the entire colon, extending from the rectum to the cecum, beyond which the small intestine begins.

Severity of disease
In addition to the extent of involvement, UC patients may also be characterized by the severity of their disease. Mild disease correlates with fewer than four stools daily, with or without blood, no systemic signs of toxicity, and a normal erythrocyte sedimentation rate (ESR). There may be mild abdominal pain or cramping. Patients may believe they are constipated when in fact they are experiencing tenesmus, which is a constant feeling of the need to empty the bowel accompanied by involuntary straining efforts, pain, and cramping with little or no fecal output. Rectal pain is uncommon.

Moderate disease correlates with more than four stools daily, but with minimal signs of toxicity. Patients may display anemia (not requiring transfusions), moderate abdominal

pain, and low grade fever, 38 to 39 C

Severe disease, correlates with more than six bloody stools a

day, and evidence of toxicity as demonstrated by fever,

tachycardia, anemia or an elevated ESR.

Fulminant disease correlates with more than ten bowel

movements daily, continuous bleeding, toxicity, abdominal tenderness and distension, blood transfusion requirement and colonic dilation. Patients in this category may have severe inflammation extending beyond just the mucosal

layer, causing impaired colonic motility and leading to toxic

megacolon. If the serous membrane is involved, colonic perforation may ensue. Unless treated, fulminant disease will soon lead to death.

Extraintestinal features
As UC is a systemic disease, patients may present with

symptoms and complications outside the colon. These

include the following: aphthous ulcers of the mouth .

Ophthalmic .
Iritis or uveit.

Episcleritis.

Patients with ulcerative colitis can occasionally have aphthous ulcers involving the tongue, lips, palate and pharynx

Ulcerative Colitis

Pathophysiology

Causes unknown

Signs and symptoms

Abdominal cramping Nausea, vomiting, diarrhea Fever or weight loss Treatment Follow general treatment guidelines.

Crohns Disease (1 of 2)

Pathophysiology
Causes unknown Can affect the entire GI tract Pathologic inflammation:

Damages mucosa Hypertrophy and fibrosis of underlying muscle Fissures and fistulas

Comparisons of various factors in Crohn's disease and ulcerative colitis

Crohn's Disease
Involves terminal ileum Commonly

Ulcerative Colitis
Seldom

Involves colon? Involves rectum? Peri-anal involvement

Bile duct involvement? Distribution of Disease

Usually Seldom Commonl

Not associated Patchy areas of inflammation

Always Usually Seldom

Higher rate of Primary sclerosing cholangitis Continuous area of inflammation

Endoscopy
Depth of inflammation

Linear and serpiginous (snake-like) ulcers

May be transmural, deep into tissues

Continuous ulcer
Shallow, mucosal

Endoscopic
The best test for diagnosis of UC remains endoscopy. Full colonoscopy to the cecum and entry into the terminal ileum is attempted only if diagnosis of UC is unclear. Otherwise, a flexible sigmoidoscopy is sufficient to support the diagnosis. The physician may elect to limit the extent of the exam if severe colitis is encountered to minimize the risk of perforation of the colon. Endoscopic findings in UC include the following:

Loss of the vascular appearance of the colon, Erythema (or redness of the mucosa) and friability of the mucosa Superficial ulceration, which may be confluent, and Pseudopolyps.

UC is usually continuous from the rectum, with the

rectum almost universally being involved. There is rarely

peri-anal disease, but cases have been reported. The

degree of involvement endoscopically ranges from proctitis or inflammation of the rectum, to left sided colitis, to pancolitis, which is inflammation involving the ascending colon

Endoscopic image of ulcerative colitis affecting the left side of the colon. The image shows confluent superficial ulceration and loss of mucosal architecture. Crohn's disease may be similar in appearance, a fact that can make diagnosing UC a challenge.

Course and complications

Progression or remission
Patients with UC usually have an intermittent course, with periods of disease inactivity alternating with "flares" of disease. Patients with proctitis or left-sided colitis usually

have a more benign course: only 15% progress proximally

with their disease, and up to 20% can have sustained remission in the absence of any therapy. Patients with

more extensive disease are less likely to sustain remission,

but the rate of remission is independent of the severity of disease

UC and colorectal cancer

There is a significantly increased risk of colorectal cancer

in patients with UC after 10 years if involvement is beyond

the splenicflexure. Those with only proctitis or

rectosigmoiditis usually have no increased risk.

It is recommended that patients have screening

colonoscopies with random biopsies to look for dysplasia after eight years of disease

PSC and Colon Cancer Risk

50 45 40 35 30 25 20 15 10 5 0 10 years 20 years 30 years
Cumulative Incidence (%) .

No PSC PSC

Primary sclerosing cholangitis (PSC)

UC has a significant association with (PSC), a progressive

inflammatory disorder of small and large bile ducts. As

many as 5% of patients with UC may progress to develop

(PSC).

Mortality
The effect of UC on mortality is unclear, but it is thought that the disease primarily affects quality of life, and not lifespan.

Treatment
Standard treatment for UC depends on extent of involvement and disease severity.

The goal is to induce remission initially with medications, followed by the administration of maintenance medications to prevent a relapse of the disease. The concept of induction of remission and maintenance of remission is very important.

Drugs used
Aminosalicylates are the mainstay of UC pharmacotherapy for induction and

maintenance of remission for patietns with mild to

moderate disease. Sulfasalazine has been a major agent in the therapy of

mild to moderate UC for over 50 years. In 1977 Mastan

S.Kalsi et al determined that 5-aminosalicyclic acid (5-ASA and mesalazine) was the therapeutically active compound in sulfasalazine. Since then many 5-ASA compounds have been developed with the aim of maintaining efficacy but reducing the common side effects associated with the sulfapyridine moiety in sulfasalazine.

Mesalazine,

also

known

as

5-aminosalicylic

acid,

mesalamine, or 5-ASA. (Asacol, Pentasa, Mezavant, Lialda, and Salofalk). Sulfasalazine, also known as Azulfidine. Balsalazide - Disodium , also known as Colazal.

Olsalazine, also known as Dipentum.

Corticosteroids
It is often required for the one-third of patients who fail to respond to 5-ASAs, But it is not useful for maintenance of remission and carry significnat undesirable side effects, as osteoporosis, glucose intolerance, and increased risk of infection.

Moderate

Severe Extensive Colitis

NO Remission High dose 5-ASA

Steroids

NO Remission

CsA AZA / 6-MP

Remission Remission

Remission

Failure

High dose maintenance

5-ASA

AZA/6-MP maintenance

Colectomy