Ulcerative Colitis

PATHOGENESIS & PATHOLOGY

Pathogenesis
UC is a chronic disease of unknown cause
characterized by ulceration of the colon and
rectum, with rectal bleeding, mucosal crypt
abscesses, inflammatory pseudopolyps,
abdominal pain, and diarrhea; frequently
causes anemia, hypoproteinemia, and
electrolyte imbalance; sometimes
complicated by peritonitis, toxic megacolon,
or carcinoma of the colon.
 Genetic susceptibility
There are 12 regions of the genome which
may be linked to ulcerative colitis.
This includes chromosomes 16, 12, 6, 14, 5, 19, 1,
16, and 3 in the order of their discovery. However,
none of these loci has been consistently shown to be
at fault, suggesting that the disorder arises from the
combination of multiple genes.
There are even HLA associations which may be at
work. In fact, this linkage on chromosome 6 may be
the most convincing and consistent of the genetic
candidates.
 Role of intestinal flora
Microbes could exacerbate immune reactions by
providing by providing antigens and inducing
costimulators and cytokines, of all of which
contribute to T-cell activation
Defects in the barrier function of the intestinal
epithelium could allow luminal flora to gain access
to the mucosal lymphoid tissue, and trigger
immune response
 Abnormal T-cell responses

It is believed that the exagerated local immune

response in IBD is a consequence of too much T-cell
activation and/or too little control by regulatory T
lymphocytes

In both CD and UC, the prime culprits appear to be

T-cells, particularly CD4+ T-cells, and the lesions
are likely caused by T-cells and their products.
However, it is not clear that this autoantibodies play
a pathogenic role
 Pathology
(Macroscopic picture)
UC is a mucosal disease- usually involve the
rectum and extends proximally to involve all
part or part of the colon
About 4050% of patients have disease

limited to the rectum and rectosigmoid

3040% have disease extending beyond the

sigmoid but not involving the whole colon

20% have a total colitis
 Pathology
(Macroscopic picture)
When the whole colon is involved, the
inflammation extends 12 cm into the
terminal ileum in 1020% of patients. This is
called backwash ileitis and is of little clinical
significance
With mild inflammation, the mucosa is,
Erythematous
Has a fine granular surface that looks like
sandpaper.
In more severe disease, the mucosa is
hemorrhagic, edematous, and ulcerated
 Pathology
(Macroscopic picture)
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.
 Pan-ulcerative colitis. Mucosa has a lumpy,
bumpy appearance because of areas of inflamed
but intact mucosa separated by ulcerated areas
 Microscopic pictures
The process is limited to the mucosa and
superficial submucosa, with deeper layers
unaffected except in fulminant disease.
In UC, two major histologic features suggest

chronicity and help distinguish it from

infectious or acute self-limited colitis.
First, the crypt architecture of the colon is distorted;
crypts may be bifid and reduced in number, often with
a gap between the crypt bases and the muscularis
mucosae.
Second, some patients have basal plasma cells and
multiple basal lymphoid aggregates
 Microscopic pictures
Mucosal vascular congestion, with edema
and focal hemorrhage, and an inflammatory
cell infiltrate of neutrophils, lymphocytes,
plasma cells, and macrophages may be
present.
The neutrophils invade the epithelium,

usually in the crypts, giving rise to cryptitis

and, ultimately, to crypt abscesses
 Medium power view of colonic mucosa in ulcerative
colitis showing diffuse mixed inflammation, basal
lymphoplasmacytosis, crypt atrophy and irregularity
and superficial erosion. These features are typical of
chronic active ulcerative colitis