Ulcerative colitis - Chrons disease

Ulcerative colitis

Inflammatory bowel disease is thought to result

from inappropriate and ongoing activation of the mucosal

immune system driven by the presence of normal

luminal flora.

the absolute risk of inflammatory bowel disease

is approximately 7 percent among first-degree

family members. Collectively, these findings lend compelling support

to the inference that susceptibility is inherited

and that the genetic contribution to the development

of disease is more important in Crohn’s disease than

in ulcerative colitis.

This gene encodes

a cytoplasmic protein designated NOD2 (also referred

to as CARD 15 [caspase activation and recruitment

domain]), which is expressed in macrophages and may

serve as a so-called pattern-recognition receptor for

bacterial lipopolysaccharide, perhaps regulating nuclear

factork B activation and macrophage apoptosis.

“only” 45 percent of pairs

of identical twins are concordant for Crohn’s disease. early appendectomy, which is associated with a reduced incidence of ulcerative colitis. Smoking may

modify the phenotype; it protects against ulcerative

colitis but increases the risk of Crohn’s disease.

Rta immune: In contrast, the mucosa in patients with ulcerative colitis

may be dominated by CD4+ lymphocytes with an

atypical type 2 helper-T-cell (Th2) phenotype, characterized by the production of transforming growth factorb(TGFb) and interleukin-5 but not interleukin-4

The activation of central immune-cell populations

is eventually accompanied by the production of a wide

variety of nonspecific mediators of inflammation (Fig.

2). These include many other cytokines, chemokines,

and growth factors as well as metabolites of arachidonic

acid (e.g., prostaglandins and leukotrienes) and

reactive oxygen metabolites such as nitric oxide. T_H2 cells and related natural killer T cells that secrete IL-13 induce superficial mucosal inflammation resembling UC, and T_H17 cells may be responsible for neutrophilic recruitment. in an IBD patient, the normal flora is likely perceived as if it were a pathogen. Anaerobic organisms, particularly Bacteroides and Clostridia species, and some aerobic species such as Escherichia may be responsible for the induction of inflammation.

UC is a mucosal disease that usually involves the rectum and extends proximally to involve all or part of the colon. About 40–50% of patients have disease limited to the rectum and rectosigmoid, 30–40% have disease extending beyond the sigmoid but not involving the whole colon, and 20% have a total colitis. Proximal spread occurs in continuity without areas of uninvolved mucosa. When the whole colon is involved, the inflammation extends 1–2 cm into the terminal ileum in 10–20% of patients. This is called backwash ileitis and is of little clinical significance. Although variations in macroscopic activity may suggest skip areas, biopsies from normal-appearing mucosa are usually abnormal. Thus, it is important to obtain multiple biopsies from apparently uninvolved mucosa, whether proximal or distal, during endoscopy.

With mild inflammation, the mucosa is erythematous and has a fine granular surface that looks like sandpaper. In more severe disease, the mucosa is hemorrhagic, edematous, and ulcerated (Fig. 289-1). In long-standing disease, inflammatory polyps (pseudopolyps) may be present as a result of epithelial regeneration. The mucosa may appear normal in remission, but in patients with many years of disease it appears atrophic and featureless and the entire colon becomes narrowed and shortened. Patients with fulminant disease can develop a toxic colitis or megacolon where the bowel wall thins and the mucosa is severely ulcerated; this may lead to perforation.

Clinical

The major symptoms of UC are diarrhea, rectal bleeding, tenesmus, passage of mucus, and crampy abdominal pain. The severity of symptoms correlates with the extent of disease. Although UC can present acutely, symptoms usually have been present for weeks to months. Occasionally, diarrhea and bleeding are so intermittent and mild that the patient does not seek medical attention. Patients with proctitis usually pass fresh blood or blood-stained mucus, either mixed with stool or streaked onto the surface of a normal or hard stool. They also have tenesmus, or urgency with a feeling of incomplete evacuation, but rarely have abdominal pain. With proctitis or proctosigmoiditis, proximal transit slows, which may account for the constipation commonly seen in patients with distal disease. When the disease extends beyond the rectum, blood is usually mixed with stool or grossly bloody diarrhea may be noted. Colonic motility is altered by inflammation with rapid transit through the inflamed intestine. When the disease is severe, patients pass a liquid stool containing blood, pus, and fecal matter. Diarrhea is often nocturnal and/or postprandial. Although severe pain is not a prominent symptom, some patients with active disease may experience vague lower abdominal discomfort or mild central abdominal cramping. Severe cramping and abdominal pain can occur with severe attacks of the disease. Other symptoms in moderate to severe disease include anorexia, nausea, vomiting, fever, and weight loss.

Ulcerative Colitis

Patients with long-standing UC are at increased risk for developing colonic epithelial dysplasia and carcinoma (Fig. 289-9).

The risk of neoplasia in chronic UC increases with duration and extent of disease. The risk of cancer rises 0.5–1% per year after 8–10 years of disease in patients with pancolitis. The only prospective surveillance study reported a lower rate of cancer; 2.5% at 20 years of disease, 7.6% at 30 years of disease, and 10.8% at 40 years. The rates of colon cancer are higher than in the general population, and colonoscopic surveillance is the standard of care