The Large Intestine 1

The Large Intestine

The large intestine is
the terminal part of
the alimentary canal.
The primary function
of this organ is to
finish absorption of
nutrients and water,
synthesize certain
vitamins, form feces,
and eliminate feces
from the body.
 Structure
The large intestine runs from the appendix to the anus. It
frames the small intestine on three sides. Despite its being
about one-half as long as the small intestine, it is called large
because it is more than twice the diameter of the small
intestine, about 3 inches.
 Subdivisions
The large intestine is
subdivided into four
main regions: the
cecum, the colon, the
rectum, and the
anus. The ileocecal
valve, located at the
opening between the
ileum and the large
intestine, controls the
flow of chyme from
the small intestine to
the large intestine.
 Cecum
The first part of the large intestine is the cecum,
a sac-like structure that is suspended inferior to
the ileocecal valve. It is about 6 cm long, receives
the contents of the ileum, and continues the
absorption of water and salts. The appendix (or
vermiform appendix) is a winding tube that
attaches to the cecum. Although the 7.6-cm (3-in)
long appendix contains lymphoid tissue,
suggesting an immunologic function, this organ is
generally considered vestigial.
 However, at least one recent report postulates a
survival advantage conferred by the appendix: In
diarrheal illness, the appendix may serve as a
bacterial reservoir to repopulate the enteric bacteria
for those surviving the initial phases of the illness.
Moreover, its twisted anatomy provides a haven for
the accumulation and multiplication of enteric
bacteria. The mesoappendix, the mesentery of the
appendix, tethers it to the mesentery of the ileum.
 Colon
The cecum blends seamlessly with the colon.
Upon entering the colon, the food residue first
travels up the ascending colon on the right side
of the abdomen. At the inferior surface of the
liver, the colon bends to form the right colic
flexure (hepatic flexure) and becomes
the transverse colon. The region defined as
hindgut begins with the last third of the
transverse colon and continues on.
 Food residue passing through the transverse colon travels
across to the left side of the abdomen, where the colon angles
sharply immediately inferior to the spleen, at the left colic
flexure (splenic flexure). From there, food residue passes
through the descending colon, which runs down the left side
of the posterior abdominal wall. After entering the pelvis
inferiorly, it becomes the s-shaped sigmoid colon, which
extends medially to the midline. The ascending and
descending colon, and the rectum (discussed next) are located
in the retroperitoneum. The transverse and sigmoid colon are
tethered to the posterior abdominal wall by the mesocolon.
 Histology

The wall of the large intestine has far more

intestinal glands, which contain a vast
population of enterocytes and goblet cells.
These goblet cells secrete mucus that eases
the movement of feces and protects the
intestine from the effects of the acids and
gases produced by enteric bacteria. The
enterocytes absorb water and salts as well as
vitamins produced by intestinal bacteria.
 Anatomy
Three features are unique to the large intestine: teniae coli,
haustra, and epiploic appendages. The teniae coli are three bands
of smooth muscle that make up the longitudinal muscle layer of
the muscularis of the large intestine, except at its terminal end.
Tonic contractions of the teniae coli bunch up the colon into a
succession of pouches called haustra(singular = hostrum), which
are responsible for the wrinkled appearance of the colon.
Attached to the teniae coli are small, fat-filled sacs of visceral
peritoneum called epiploic appendages. The purpose of these is
unknown. Although the rectum and anal canal have neither teniae
coli nor haustra, they do have well-developed layers of muscularis
that create the strong contractions needed for defecation.
 INFLAMMATORY BOWEL DISEASE
The term ‘inflammatory bowel disease’ is reserved for
conditions characterised by the presence of idiopathic
intestinal inflammation, i.e. ulcerative colitis (UC) and
Crohn’s disease (CD). Conditions such as infective or
ischemic colitis or enteritis are thus excluded.
 ULCERATIVE COLITIS
Ulcerative colitis is a disease
of the rectum and colon
with extraintestinal
manifestations. The
incidence is 10 per 100 000
in the UK with. It is most
commonly diagnosed
between the ages of 20 and
40. The cause of UC is
unknown. There is clearly a
genetic contribution as 10–
20 per cent of patients with
UC have a first-degree
relative with inflammatory
bowel disease.
 Symptoms
The main symptoms will be rectal bleeding, tenesmus and
mucous discharge. The disease remains confined to the rectum
in 90 per cent of cases but proctitis may spread proximally
over time. Colitis is almost always associated with bloody
diarrhoea and urgency that can be incapacitating. Pain is
unusual. Extensive colitis is also associated with systemic
illness, characterised by malaise, loss of appetite and fever.
Diarrhoea may be profuse and bloody, resulting in anaemia,
hypoproteinaemia and electrolyte disturbance. Approximately
30 per cent of patients have inflammation extending to the
sigmoid colon and spread proximal to the splenic flexure
occurs in 20 per cent.
 Investigations

Endoscopy and biopsy has a key role in diagnosis

and management:
• to establish the extent of inflammation;
• to distinguish between UC and Crohn’s colitis
• to monitor the response to treatment;
• to assess long-standing cases for malignant change.

Radiology:
A plain abdominal film may indicate the severity of disease in
the acute setting and is particularly valuable in demonstrating
the development of toxic megacolon
 Extraintestinal manifestations

Arthritis occurs in around 15% of patients and is typically a large joint

polyarthropathy, affecting knees, ankles, elbows and wrists. Sacroiliitis
and ankylosing spondylitis are 20 times more common in patients with
UC than the general population and are associated with the HLA-B27
genotype. Sclerosing cholangitis is associated with UC and can
progress to cirrhosis and hepatocellular failure. Patients with UC and
sclerosing cholangitis are also at a significantly greater risk of
development of large bowel cancer. Cholangiocarcinoma is an
extremely rare association and its frequency is not influenced by
colectomy. The skin lesions erythema nodosum and pyoderma
gangrenosum are associated with UC and both normally resolve with
good colitis control. The eyes can also be affected by uveitis and
episcleritis.
 Acute colitis

Approximately 5% of patients present with severe acute (fulminant) colitis.

Intensive medical treatment leads to remission in 70% but the remainder require
urgent surgery. Toxic dilatation should be suspected in patients who develop
severe abdominal pain and confirmed by the presence on a plain abdominal
radiograph of a colon with a diameter of more than 6 cm. A reduction in stool
frequency is not always a sign of improvement in patients with severe UC, and a
falling stool frequency, abdominal distension and abdominal pain (resulting from
progression of the inflammatory process through the colonic wall) are strongly
suggestive of disintegrative colitis and impending perforation. Plain abdominal
radiographs should be obtained daily in patients with severe colitis, and a
progressive increase in colon diameter despite medical therapy is an indication
for urgent surgery. Colonic perforation is a grave complication with a mortality
rate of 40%. Steroids may mask the physical signs. Severe haemorrhage is
uncommon (1–2%) but may occasionally require urgent surgical intervention.
 Cancer risk in colitis

The risk of cancer in ulcerative colitis increases with duration of

disease. At 10 years from diagnosis it is approximately 1%, increasing
to 10–15% at 20 years and 20% at 30 years. Patients with pancolitis
(defined as the presence of inflammation proximal to the splenic
flexure) of more than ten years duration should be entered into
screening programmes in order to detect clinically silent dysplasia,
which is predictive of increased cancer risk. The value of screening
programmes remains somewhat controversial, however, with most
UC patients who develop cancer (approximately 3.5% of all patients)
presenting with their tumours in-between attendances for screening
colonoscopy. Carcinoma is more likely to occur if the whole colon is
involved or if the disease started early in life.
 Treatment

MEDICAL TREATMENT
Medical therapy is based on anti-inflammatory agents. The 5-aminosalicylic
acid (5-ASA) derivatives can be given topically (per rectum) or systemically.
They act as inhibitors of the cyclo-oxygenase enzyme system and are
formulated to protect the aspirin-related drug from degradation before
reaching the colon. They can be used long term as maintenance therapy.
Corticosteroids are the mainstay of treatment for ‘flareups’, either topically
or systemically, and have a widespread anti-inflammatory action. The
immunosuppressive drugs azathioprine and cyclosporin can be used to
maintain remission and as ‘steroid-sparing’ agents. The monoclonal
antibodies infliximab and adalimumab both act against antitumour necrosis
factor alpha, which has a central role in inflammatory cascades. Most
recently, vedolizumab, which blocks integrins, has been used as ‘rescue
therapy’ for severe colitis, to try and avoid emergency colectomy.
 INDICATIONS FOR SURGERY

The greatest likelihood of a patient with UC requiring surgery is during the first
year after diagnosis. The overall risk of colectomy is 20%. Indications for surgery in
UC are:
●● severe or fulminating disease failing to respond to medical therapy;
●● chronic disease with anaemia, frequent stools, urgency and tenesmus;
●● steroid-dependent disease – here, the disease is not severe but remission
cannot be maintained without substantial doses of steroids;
●● inability of the patient to tolerate medical therapy required to control the
disease (steroid psychosis or other side effects, azathioprine-induced pancreatitis),
such that remission cannot be maintained;
●● neoplastic change: patients who have severe dysplasia or carcinoma on review
colonoscopy;
●● extraintestinal manifestations;
●● rarely, severe haemorrhage or stenosis causing obstruction.
 CROHN’S DISEASE (REGIONAL
ENTERITIS)
publication by Burrill Crohn and colleagues in 1932.
CD is characterised by a chronic full thicknes
inflammatory process that can affect any part of the
gastrointestinal tract from the lips to the anal margin. It
is most common in North America and Northern Europe
with an incidence of 5 per 100 000. It is slightly more
common in women than in men, and is most commonly
diagnosed in young patients between the ages of 25 and
40 years. There does, however, seem to be a second
peak of incidence around the age of 70 years.
 Clinical features
Presentation depends upon the pattern of
disease. Very infrequently, CD presents acutely
with acute ileal inflammation and symptoms
and signs resembling those of acute
appendicitis, or even free perforation of the
small intestine, resulting in a local or diffuse
peritonitis. CD may present with fulminant
colitis but this is considerably less common
than in UC.
 Colonic involvement is found in 30% of patients with CD,
frequently in association with perianal disease and it may
coexist with small bowel pathology. Colonic CD presents with
symptoms of colitis and proctitis as described for UC, although
toxic megacolon is much less common. Colonic strictures may
form just as are seen in small bowel CD. Endoscopic dilatation
may be performed in expert hands as an alternative to surgical
resection. Distinguishing between CD and UC is often difficult
and requires clinical and pathological patterns to be combined.
The presence of skip lesions, rectal sparing, non-caseating
granulomas or perianal disease will point to CD.
Colonoscopic examination may be normal or show patchy
inflammation. There will be areas of normal colon or
rectum in between areas of inflamed mucosa that are
irregular and ulcerated, with a mucopurulent exudate. The
earliest appearances are aphthous ulcers surrounded by a
rim of erythematous mucosa. These become larger and
deeper with increasing severity of disease. There may be
stricturing, and it is important to exclude malignancy in
these sites. An irregular Crohn’s stricture with polypoid
mucosa may be almost indistinguishable from malignancy.
 Treatment

There is great overlap in the treatment of Crohn’s colitis and

UC. Disease activity can be controlled with 5-ASA compounds and
flare-ups treated with steroids. Rectal agents can be particularly
effective if the disease activity is localised to the rectum.
Immunomodulatory agents are frequently used, particularly if
there is evidence of CD activity in large and small bowel.
Although CD is usually regarded as a contraindication to pouch
surgery, the other options (panproctocolectomy or total colectomy
with ileorectal anastomosis) are frequently appropriate and there
may be considerable rectal sparing in CD, justifying the latter.
Where the diagnosis of CD is firmly established, segmental rather
than total colectomy may be appropriate.
 INFECTIONS OF THE LARGE
INTESTINE

Campylobacter
Infection with Campylobacter jejuni (a gram-negative
rod with a distinctive spiral shape) is the commonest
form of gastroenteritis in the UK, typically acquired
from eating infected poultry. It causes diarrhea and
abdominal pain. Severe cases may resemble UC. The
organism may take several days to isolate on stool
culture. Treatment is supportive as it usually resolves
without antibiotics, but severe colitis and even
perforation may occur. It is a notifiable disease.
 Intestinal amoebiasis

Entamoeba histolytica has a worldwide distribution and is

transmitted mainly in contaminated drinking water. It can cause
colonic ulcers, which are described as ‘bottlenecked’ because they
have considerably undermined edges. The ulcers typically also have a
yellow necrotic floor, from which blood and pus exude. In the majority
of cases they are confined to the distal sigmoid colon and the rectum.
Clinically amoebiasis can mimic UC, most commonly causing bloody
diarrhoea, but more severe colonic complications can occur, including
severe haemorrhage, stricture formation or perforation. A pericolitis is
not uncommon and results in adhesions and may cause intestinal
obstruction. Amoebiasis may cause liver abscesses or an amoebic
mass (‘amoeboma’) of the caecum or sigmoid which is difficult to
distinguish from a carcinoma.
Endoscopic biopsies or fresh hot stools are examined
to look for the presence of amoebae. It is important
to emphasise, however, that the presence of the
parasite does not indicate that it is pathogenic. It is
especially important to exclude amoebic infection in
patients suspected of having UC. Treatment is by
metronidazole in the acute setting, three times daily
for 7–10 days. Diloxanide furoate is effective against
chronic infections associated with the passage of cysts
in stools.
 Salmonellosis, typhoid and
paratyphoid

Salmonella are a family of gram-negative rods that can cause a

range of enteric infections. Salmonella gastroenteritis is typically
caused by S. enteritidis from poultry, and is most often a self-limiting
illness comprising headache, fever and watery diarrhea. When
severe, antibiotics and indeed hospitalization and intravenous fluids
may be needed. The diagnosis is based on stool culture.
Shigella and enteropathogenic strains of E. coli may cause similar
diarrheal illnesses.
Typhoid fever is caused by S. typhi and presents with fever and
abdominal pain after a 10–20-day incubation period. Over the next
week, the patient can develop distension, diarrhoea, splenomegaly
and characteristic ‘rose spots’ on the abdomen caused by a vasculitis.
A number of surgical complications
can result:
●● paralytic ileus;
●● intestinal hemorrhage;
●● perforation;
●● cholecystitis.
In addition, invasion of the systemic circulation, which is a
characteristic feature of salmonellosis, may cause severe gram-
negative sepsis and septic shock may develop. Some patients may
develop metastatic sepsis, including septic arthritis and
osteomyelitis, meningitis, encephalitis and pancreatitis.
 Tuberculosis of the intestine
Tuberculosis, like Crohn’s disease, can affect
any part of the gastrointestinal tract from the
mouth to the anus. The sites affected most
often are the ileum, proximal colon and
peritoneum. There are two principal
presentations: Ulcerative tuberculosis;
Hyperplastic tuberculosis
 Ulcerative tuberculosis
Ulcerative tuberculosis is secondary to
pulmonary tuberculosis and arises as a result of
swallowing tubercle bacilli. Multiple ulcers,
lying transversely, develop in the terminal ileum
and the overlying serosa is thickened, reddened
and covered in tubercles. Patients typically
present with diarrhoea and weight loss,
although subacute obstruction and even local
perforation and fistula formation can occur.
 Hyperplastic tuberculosis
This is caused by the ingestion of
Mycobacterium tuberculosis by patients with a
high resistance to the organism. The infection
usually occurs in the ileocaecal region, although
solitary and multiple lesions in the lower ileum
are also sometimes seen. The infection establishes
itself in lymphoid follicles, and the resulting
chronic inflammation causes thickening of the
intestinal wall and narrowing of the lumen.
 Clostridium difficile

Clostridium difficile is a toxin producing Gram-positive bacillus

that is an increasing worry in many hospitals. Although normally
present in around 2 per cent of the population, it seems to
proliferate after antibiotic treatment (especially cephalosporins)
and can cause antibiotic-associated diarrhoea and
pseudomembranous colitis.
Clinically, C. difficile infection presents with diarrhoea, abdominal
pain and fever. It may progress to pseudomembranous colitis, so
called because on visualisation of the bowel, plaques of
inflammatory exudate between oedematous mucosa are seen.
Treatment is by metronidazole or vancomycin alongside
supportive care. If the colitis does not settle, an emergency.