Lower gastrointestinal tract

Published on 19/03/2015 by admin

Filed under Pathology

Last modified 19/03/2015

Print this page

rate 1 star rate 2 star rate 3 star rate 4 star rate 5 star
Your rating: none, Average: 0 (0 votes)

This article have been viewed 906 times

164

17.2 Ischaemia and infarction167
17.3 Immunological disorders167
17.4 Neoplasia168
17.5 Miscellaneous conditions171

Self-assessment: questions173
Self-assessment: answers175

17.1. Inflammation and infection

Learning objectives
You should:

• be aware of the types of pathogens that can cause enterocolitis
• be able to describe the differences between ulcerative colitis and Crohn’s disease
• understand the pathogenesis and complications of acute appendicitis and diverticular disease.

Infectious enterocolitis

Infectious diseases of the bowel most commonly present with diarrhoea, which is an increase in stool mass, stool frequency or stool fluidity. Diarrhoea can result from a number of mechanisms (see Table 28). The pathogen responsible – which may be bacterial, viral, parasitic, protozoal or fungal – varies with patient age, nutrition, immune status and environment, and is identifiable in only approximately half of all cases.
Table 28 Mechanisms and causes of diarrhoea
Type of diarrhoea Mechanism Major causes
Secretory diarrhoea Stimulation of gut secretion Viral infection
Bacterial infection
Neoplasms producing secretagogues
Osmotic diarrhoea Excessive osmotic forces exerted by increased concentration of luminal solutes Laxative therapy
Malabsorption (many causes)
Lactase deficiency
Exudative diarrhoea Stools containing blood and inflammatory debris secondary to tissue damage Crohn’s disease
Ulcerative colitis
Bacterial infections
Protozoal infections
Abnormal gut motility Various causes of altered gut transit time and motility Irritable bowel syndrome
Diabetic neuropathy
Post-bowel surgery

Viruses

Rotavirus affects primarily children aged 6months to 2years, and is responsible for an estimated 140 million cases of infective enterocolitis and 1 million deaths per year. Viral infection damages mature surface epithelial cells in the small intestine mucosa, which are replaced by immature secretory cells. This results in a loss of absorptive ability and increased gut secretions, producing a mixed osmotic and secretory diarrhoea (see Table 28). In older children and young adults, the majority of non-bacterial gastroenteritis is due to Norwalk-like viruses. Viral infection typically provokes cellular immunity involving cytotoxic T lymphocytes. Biopsies of intestinal mucosa are rarely undertaken in suspected viral infection, as symptoms of vomiting and diarrhoea are often self-limiting and of short duration. However, in an immunocompetent individual, the microscopic appearance of established viral infection would characteristically include epithelial cell damage and lymphocytic infiltration of the mucosa indicative of host immune response.

Bacteria

Bacteria cause disease in the gut by a number of mechanisms:

• effects of preformed bacterial toxins present in contaminated food
• toxin production by organisms within the gut
• enteroinvasive infection, in which organisms proliferate, invade and destroy the intestinal mucosal epithelium.
Enterotoxins Enterotoxins are polypeptides which cause diarrhoea. Some, such as cholera toxin, cause massive secretion of fluid in the absence of tissue damage (secretory and osmotic diarrhoea). Cholera toxin exerts its effects by persistently activating the cytoplasmic enzyme adenylate cyclase, causing profound secretion of chloride, sodium and water.
Secretory toxins Secretory toxins produced by Escherichia coli are the major cause of traveller’s diarrhoea.
Cytotoxins Cytotoxins produced, for example, by Shigella and cytotoxic strains of E. coli, cause tissue damage with epithelial cell necrosis and an acute inflammatory reaction. Cytotoxins usually induce ‘dysentery’ – low volume, painful, bloody diarrhoea.
Although bacterial infection is frequently confined to the gut, systemic disease may occasionally occur. Organisms may enter the bloodstream (causing a bacteraemia), multiply (septicaemia) and spread to other organs (dissemination). Inflammatory mediators activated by bacterial toxins or by products of damaged host cells may result in fever, lowered blood pressure and ultimately septic shock (see Ch. 5), which is often fatal. Typhoid fever is the name given to the generalised illness caused by infection by Salmonella typhimurium, which can include chronic inflammation of the biliary tree, joints, bones and meninges in addition to intestinal involvement.

Pseudomembranous colitis

Pseudomembranous colitis is an acute infectious disease of the colorectum, which is a common cause of diarrhoea in hospitalised patients receiving broad spectrum antibiotic therapy. The organism responsible (Clostridium difficile) is a normal toxin-producing commensal of the gut. Antibiotic therapy appears to alter the balance of the gut flora, allowing C. difficile to flourish. The toxin damages the colonic mucosa, causing an acute inflammatory reaction with the formation of a typical ‘pseudomembrane’. The pseudomembrane is visible endoscopically as an irregular dark yellow coating over the bowel surface; microscopically it contains mucus and acute inflammatory debris including fibrin and degenerate neutrophils. The toxin of C. difficile can be identified in the stool of symptomatic patients.

Acute appendicitis

Acute inflammation of the appendix is the most common acute abdominal condition requiring surgery. It can occur at any age, although it is relatively rare in the very young and very old. Most cases are thought to arise secondary to obstruction of the appendiceal lumen by faeces. The exact sequence of events is unknown, but may involve a combination of bacterial proliferation and increased intraluminal pressure causing vascular obstruction and ischaemia. The affected appendix shows the hallmarks of acute inflammation – intense neutrophil polymorph infiltration and oedema, with tissue necrosis and peritonitis in advanced cases. The serosal surface of the organ becomes covered with an acute inflammatory exudate composed of fibrin and neutrophils. If surgery is delayed there is a risk of appendiceal rupture, with localised abscess formation or generalised peritonitis with septicaemia. Chronic inflammation is very unusual in the appendix. Small scarred appendices, presumably representing the fibrotic end stage of repeated acute inflammation, are sometimes seen in older adults.

Peritonitis

Generalised acute inflammation of the peritoneum can arise secondary to bacterial invasion or chemical irritation. Bacterial peritonitis may complicate many inflammatory processes, including acute appendicitis, cholecystitis, perforated peptic ulcer, diverticulitis, bowel ischaemia and salpingitis. Infective peritonitis may also follow abdominal trauma or medical intervention (e.g. peritoneal dialysis). Chemical inflammation of the peritoneum may occur when bile, pancreatic enzymes, foreign material or blood (endometriosis, trauma, surgery) are released into the peritoneal cavity. Healing of peritonitis can result in the formation of fibrous adhesions between bowel loops. These adhesions can subsequently cause abdominal pain and bowel obstruction.

Crohn’s disease and ulcerative colitis

Crohn’s disease and ulcerative colitis are often grouped together under the term chronic idiopathic inflammatory bowel disease. As this term suggests, Crohn’s disease and ulcerative colitis are of unknown aetiology, and it has been suggested that they may represent different parts of the spectrum of a single disease process. However, there are important clinical and pathological differences between these two conditions.

Crohn’s disease

Crohn’s disease is characterised by discontinuous, sharply demarcated areas (‘skip lesions’) of transmural chronic inflammation. Microscopically, aggregates of lymphocytes are seen in all layers of affected bowel wall. Non-necrotising granulomas, composed of epithelioid macrophages with multinucleated giant cells, are seen in approximately 60% of cases. Fissuring ulcers are another characteristic histological feature of Crohn’s disease; these linear ulcers can also be seen with the naked eye, and often impart a ‘cobblestone’ appearance to the bowel mucosa when viewed endoscopically or in a surgical resection specimen. The intestinal wall becomes thickened by oedema in acute stages and flare-ups of Crohn’s disease, and by fibrosis in chronic disease, leading to stricture formation. Extension of fissuring ulceration through to the serosal surface of the bowel can result in perforation, abscess formation, adhesions, fistulas and sinus tracts. A fistula is an abnormal communication between two epithelial surfaces (e.g. a colovesical fistula joins colonic mucosa to bladder mucosa). The fistulous tract itself is lined by epithelium or by granulation tissue. A sinus is a blind-ending tract, which connects with the skin or another epithelial surface at one end.
Crohn’s disease manifests clinically with intermittent diarrhoea, fever and abdominal pain. Symptoms of the initial attack may mimic acute appendicitis. The terminal ileum is the commonest single site of disease and involvement of this region by Crohn’s disease can cause symptoms relating to malabsorption. Crohn’s disease typically waxes and wanes with recurrent attacks over many years, but there are intervening symptom-free periods of remission. Later presentations include bowel obstruction secondary to fibrous stricturing and symptoms related to fistula formation. There is a slight increased risk of colorectal cancer. The features of Crohn’s disease are summarised in Figure 43A.

Ulcerative colitis

Ulcerative colitis is also a chronic relapsing inflammatory condition. It is slightly more common than Crohn’s disease (incidence of ulcerative colitis is 4–6 per 100 000) but shares peak onset in early adulthood, equal frequency in males and females and predilection for white people. Unlike Crohn’s disease, ulcerative colitis is characterised by continuous disease extending proximally from the rectum, involving a variable distance of colon up to and occasionally including the terminal ileum. Isolated small intestinal disease does not occur in ulcerative colitis. Inflammation is restricted to the colonic mucosa, with occasional involvement of the submucosa. During acute attacks of colitis, there may be extensive mucosal ulceration, from which multiple islands of surviving epithelium stand proud as ‘pseudopolyps’. Microscopically the lamina propria of residual mucosa shows diffuse chronic inflammation with lymphocytes and plasma cells, and acute inflammation of mucosal glandular crypts. Granulomas are characteristically absent. With progressive disease the mucosa becomes atrophic, with disruption of glandular architecture and gland loss. There is a risk of epithelial dysplasia and subsequent carcinoma developing in longstanding ulcerative colitis. This risk is greatest in patients having involvement of the entire large intestine (pancolitis). The features of ulcerative colitis are summarised in Figure 43B.
Ulcerative colitis commonly manifests as recurrent attacks of bloody, mucoid diarrhoea and abdominal pain. Occasionally patients present with severe bleeding and fluid imbalance. Severe acute ulcerative colitis is one of the causes of toxic megacolon (see Box 23). As inflammation is restricted to the mucosa and submucosa, fistulae and strictures do not occur in ulcerative colitis.
Box 23

Definition: Marked dilatation of colon
Causes:

• toxic megacolon – a complication of severe acute inflammation, most commonly seen in ulcerative colitis
• obstruction – neoplasia, inflammatory stricture
• infection – destruction of enteric nerve plexuses in Chagas’ disease
• congenital – Hirschsprung’s disease
Clinical course: High risk of gangrene and perforation in toxic megacolon

Diverticular disease

A diverticulum is essentially a blind pouch, which is lined by epithelium and communicates with the bowel lumen. The wall of a true (congenital) diverticulum contains all layers of the bowel wall (mucosa, submucosa and muscularis propria). Diverticula occur in the small intestine as the solitary Meckel’s diverticulum (a remnant of the embryonic vitelline duct) or as multiple jejunal lesions. However, the distal large intestine is the most common site. Approximately half of all adults over 60 have developed (acquired) multiple, small, flask-like or spherical outpouchings in the sigmoid colon. The diverticula extend from the luminal surface into the deep muscularis mucosa and pericolic fat, and are a frequent incidental finding on barium enema examination in elderly patients. Obstruction of a diverticulum by faeces can cause inflammation (diverticulitis), pericolic abscess formation and local or generalised peritonitis. Chronic inflammation and fibrosis may complicate acute diverticulitis, leading to fistula formation and colonic stricture.
Diverticula formation occurs at points of weakness in the colonic wall where vessels and nerves penetrate the muscle coat. Low-fibre diet is thought to contribute to pathogenesis; low stool bulk results in exaggerated peristalsis and increased intraluminal pressure in the affected colon. Symptomatic diverticular disease may present with cramping or continuous lower abdominal pain, constipation or alternating bowel habit, and chronic blood loss.

17.2. Ischaemia and infarction

Learning objective
You should:

• understand the pathogenesis and clinical consequences of intestinal ischaemia.
Intestinal ischaemia can be acute or chronic, and result from both arterial and venous disease. Elderly adults are most frequently affected. Atherosclerosis is often the underlying pathology. Mesenteric arteries supplying the gut may be blocked by thrombosis superimposed on atherosclerosis, or by embolisation of fragments of atheromatous plaque originating from the aorta. Non-occlusive bowel ischaemia can follow hypoperfusion due to, for example, cardiac failure, shock or dehydration. The ‘watershed areas’ of the colon – splenic flexure and rectum – which lie between the major arterial blood supplies are especially vulnerable. Mesenteric venous thrombosis can complicate sepsis, neoplasia, liver cirrhosis and abdominal surgery. Therapeutic radiotherapy used in the treatment of malignant disease can cause vascular damage with progressive narrowing and occlusion of arteries. Radiation enterocolitis most commonly occurs in the small intestine of patients receiving treatment for carcinoma of the cervix.
Ischaemic injury may be restricted to the mucosa and submucosa of the gut or may involve all layers of the bowel wall. In full-thickness acute bowel infarction, the serosal surface of the gut appears plum coloured due to congestion and reflow of blood into the damaged tissue. The intestinal lumen usually contains blood or blood-stained mucus. Histological changes of infarction (ischaemic necrosis) and oedema are present. Acute small bowel infarction has a high mortality, due to the short time interval between onset of symptoms and development of bowel perforation or septicaemia. The poor prognosis is partly due to coexistent cardiac and vascular disease in the at-risk elderly population. Less severe vascular occlusion which develops gradually can present as chronic ischaemic colitis, with patchy mucosal ulceration. Chronic ischaemia involving the submucosa may heal by fibrosis, causing colonic stricture.

17.3. Immunological disorders

Learning objective
You should:

• understand the pathology of coeliac disease and the reason for excluding gluten from the diet.

Coeliac disease

Buy Membership for Pathology Category to continue reading. Learn more here