Page 581 - Textbook of Pathology, 6th Edition

therapy, normal morphology is completely restored in In healed cases, stricture formation, malabsorption and 565
superficial lesions, while deeper lesions may heal by fibrosis short bowel syndrome are the usual complications.
leading to stricture formation.
INFLAMMATORY BOWEL DISEASE
Ischaemic Colitis (CROHN’S DISEASE AND ULCERATIVE COLITIS)
Although this condition affects primarily colon in the region DEFINITION. The term ‘inflammatory bowel disease (IBD)’
of splenic flexure, it is described here due to its apparent is commonly used to include 2 idiopathic bowel diseases
pathogenetic relationship with ischaemic injury. Ischaemic having many similarities but the conditions usually have
colitis is characterised by chronic segmental colonic distinctive morphological appearance. These 2 conditions are
ischaemia followed by chronic inflammation and healing by Crohn’s disease (regional enteritis) and ulcerative colitis:
fibrosis and scarring causing obstruction (ischaemic
stricture). 1. Crohn’s disease or Regional enteritis is an idiopathic
chronic ulcerative IBD, characterised by transmural, non-
Grossly, most frequently affected site is the splenic flexure; caseating granulomatous inflammation, affecting most
other site is rectum. Ischaemic colitis passes through 3 commonly the segment of terminal ileum and/or colon,
stages: infarct, transient ischaemia and ischaemic stricture. though any part of the gastrointestinal tract may be involved.
However, the surgical submitted specimens generally are 2. Ulcerative colitis is an idiopathic form of acute and
of the ischaemic stricture. External surface of the affected chronic ulcero-inflammatory colitis affecting chiefly the
area is fusiform or saccular. On cut section, there are mucosa and submucosa of the rectum and descending colon,
patchy, segmental and longitudinal mucosal ulcers. Thus, though sometimes it may involve the entire length of the
the gross appearance can be confused with either of the large bowel.
two types of inflammatory bowel disease. Both these disorders primarily affect the bowel but may
Microscopically, the ulcerated areas of the mucosa show have systemic involvement in the form of polyarthritis,
granulation tissue. The submucosa is characteristically uveitis, ankylosing spondylitis, skin lesions and hepatic
thickened due to inflammation and fibrosis. The involvement. Both diseases can occur at any age but are more
muscularis may also show inflammatory changes and frequent in 2nd and 3rd decades of life. Females are affected CHAPTER 20
patchy replacement by fibrosis. The blood vessels may slightly more often.
show atheromatous emboli, organising thrombi and ETIOPATHOGENESIS. The exact etiology of IBD remains
endarteritis obliterans.
unknown. However, multiple factors are implicated which
can be considered under the following 3 groups:
NECROTISING ENTEROCOLITIS
1. Genetic factors. Genetic factors are implicated in the
Necrotising enterocolitis is an acute inflammation of the etiopathogenesis of IBD is supported by the following
terminal ileum and ascending colon, occurring primarily in evidences:
premature and low-birth-weight infants within the first week i) There is about 3 to 20 times higher incidence of occurrence
of life and less commonly in full-term infants. of IBD in first-degree relatives. This is due to genetic defect
ETIOLOGY. The condition has been considered as a variant causing diminished epithelial barrier function. The Gastrointestinal Tract
of the spectrum of ischaemic bowel disease. Important factors ii) Overall, there is approximately 50% chance of develop-
in the etiology of this disorder, thus, are as follows: ment of IBD (Crohn’s disease about 60% concordance,
1. Ischaemia ulcerative colitis about 6% concordance) in monozygotic
2. Hypoxia/anoxia of the bowel due to bypassing of blood twins.
from the affected area iii) Although no specific and consistent gene association with
3. Bacterial infection and endotoxins IBD has been seen, genome wide search has revealed that
4. Establishment of feeding disease-predisposing loci are present in chromosomes 16q,
5. Infants fed on commercial formulae than breast-fed, 12p, 6p, 14q and 5q. In particular, CARD15 (caspase-
implying the role of immunoprotective factors. associated recruitment domain containing protein 15) on
chromosome 16q is expressed by several cells in the intestinal
MORPHOLOGIC FEATURES. Grossly, the affected mocosa which in mutated form results in loss of its function
segment of the bowel is dilated, necrotic, haemorrhagic and renders an individual about 50-times higher risk to
and friable. Bowel wall may contain bubbles of air develop Crohn’s disease.
(pneumatosis intestinalis). iv) HLA studies show that ulcerative colitis is more common
Microscopically, the changes are variable depending upon in HLA-DRB1-alleles while Crohn’s disease is more common
the stage. Initial changes are confined to mucosa and show in HLA-DR7 and DQ4 alleles.
oedema, haemorrhage and coagulative necrosis. A 2. Immunologic factors. Defective immunologic regulation
pseudomembrane composed of necrotic epithelium, fibrin in IBD has been shown to play significant role in the
and inflammatory cells may develop. As the ischaemic pathogenesis of IBD:
process extends to the subjacent layers, muscle layer is i) Defective regulation of immune suppression. In a normal
also involved and may lead to perforation and peritonitis. individual, there is lack of immune responsiveness to dietary