Pathophysiology

Macroscopically, the majority of cases of UC arise in the rectum, with some patients
developing terminal ileitis (i.e., extending up to 30 cm) due to an incompetent
ileocaecal valve or backwash ileitis. The bowel wall is thin or of normal thickness,
but the presence of oedema, the accumulation of fat and hypertrophy of the muscle
layer may give the impression of a thickened bowel wall.
Microscopically, UC involves only the mucosa, with the formation of crypt abscesses
and a coexisting depletion of goblet cell Macing. In severe cases, the sub mucosa
can be involved, and in some cases, the deeper muscular layers of the colonic wall
can also be affected. Further microscopic changes include inflammation of the
crypts of Lieberkuhn and abscesses. Ulcerated areas are soon covered by
granulation tissue. The undermining of mucosa and the excesses of granulation
tissue form polypoidal mucosal excrescences, known as inflammatory polyps or
pseudopolyps. Early disease manifests as bleeding, petechial hemorrhages’ and
haemorrhagic inflammation with loss of the normal vascular pattern. Oedema is
present, and large areas become denuded of mucosa. Undermining of the mucosa
leads to the formation of crypt abscesses, which are the hallmark of the disease.
Acute severe colitis can result in a fulminant colitis or toxic megacolon, which is
characterised by a thin-walled, dilated colon that can eventually become perforated.
Pseudopolyp formation occurs in 15% to 20% of chronic cases. Chronic and severe
cases can exhibit areas of precancerous changes, such as carcinoma in situ or
dysplasia.
We studied the role of eosinophils as effector cells in the pathophysiology of
ulcerative colitis. In the active stage of this disease, the colonic mucosa exhibited
infiltration of numerous eosinophils positive to the EG2 antibody, which reacts
specifically with the secretory form of eosinophil cationic protein. Electron
microscopic studies demonstrated that the eosinophils had specific granules in
various stages of degranulation. Hence, it is strongly suggested that the eosinophils
infiltrating the inflamed mucosa are activated and may induce tissue damage
during the degranulation and release of this cationic protein. Changes in the levels
of serum eosinophil cationic protein in 14 patients who remained for in long-term
remission were studied. Four of these patients showed persistently high
concentrations of eosinophil cationic protein (equal to or greater than 30
micrograms/l) and persistently high percentage (mean, 30.2%) of hypodense
eosinophils (specific gravity < 1.082) in the peripheral blood. Such findings were
associated with mild active disease at colonoscopy. These features suggest that the
activation of eosinophils is one of the factors that contribute to the chronic
inflammation in ulcerative colitis.
Pathophysiology
Ulcerative colitis (UC) usually begins in the rectum. It may remain localized to the
rectum (ulcerative proctitis) or extend proximally, sometimes involving the entire
colon. Rarely, it involves most of the large bowel at once.
The inflammation caused by UC affects the mucosa and submucosa, and there is a
sharp border between normal and affected tissue. Only in severe disease is the
muscularis involved. In early cases, the mucous membrane is erythematous, finely
granular, and friable, with loss of the normal vascular pattern and often with
scattered hemorrhagic areas. Large mucosal ulcers with copious purulent exudate
characterize severe disease. Islands of relatively normal or hyperplastic
inflammatory mucosa (pseudopolyps) project above areas of ulcerated mucosa.
Fistulas and abscesses do not occur.
Toxic or fulminant colitis occurs when transmural extension of ulceration results
in localized ileus and peritonitis. Within hours to days, the colon loses muscular tone
and begins to dilate.
Risk factors
Ulcerative colitis affects about the same number of women and men. Risk factors
may include:
• Age. Ulcerative colitis can occur at any age, but ulcerative colitis often
affects people in their 30s. Some people may not develop the disease until
their 50s or 60s.
• Race or ethnicity. Although whites have the highest risk of the disease, it
can occur in any race. If you're of Jewish descent, your risk is even higher.
• Family history. You're at higher risk if you have a close relative, such as a
parent, sibling or child, with the disease.
• Isotretinoin (Accutane) use. Isotretinoin (Accutane) is a powerful
medication sometimes used to treat scarring cystic acne or acne that doesn't
respond to other treatments. Although cause and effect hasn't been proved,
studies have reported the development of inflammatory bowel disease with
isotretinoin use.
• Nonsteroidal anti-inflammatory medication. Although these medications
— ibuprofen (Advil, Motrin, others), naproxen (Aleve), diclofenac (Cataflam,
Voltaren), piroxicam (Feldene) and others — haven't been shown to cause
ulcerative colitis, they can cause similar signs and symptoms. Additionally,
these medications can make existing ulcerative colitis worse, and may make
your initial diagnosis more difficult.