INFLAMMATORY BOWEL DISEASE

Prof.Dr.Cengiz Bölükbaş

The main source of this lecture is Harrison’s principles of internal medicine edited by Kasper D.L. et al, which is our course book (as
you already know ).
 Anatomy of the colon
• The colon is a tubular organ that extends from the ileocecal valve to
the proximal rectum. It is approximately 90–150 cm in length. Its
principal functions are absorption of water and electrolytes as well as
storage of intraluminal contents to permit controlled elimination of
the feces.
• The ascending colon, descending colon, rectum, and posterior surface
of the hepatic and splenic flexures are fixed retroperitoneal
structures. The cecum, transverse colon, and sigmoid colon are
intraperitoneal and are prone to volvulus because of their location
and relative lack of fixation.
• The longitudinal muscle is an incomplete layer and is seen as three
bands of muscle, called taeniae coli.
• Haustra coli are sacculations between the taeniae and are separated
by crescent-shaped folds called plicae semilunares.
 Anorectal anatomy

The rectal wall consists of mucosal, submucosal,

inner circular, and outer longitudinal muscular
layers. There is no serosal layer in the rectum.
The rectum is approximately 12–15 cm in length
and extends from the sigmoid colon to the anal
canal, following the curve of the sacrum. The
proximal rectum begins at the sacral promontory
(third sacral vertebra), at which point the taeniae
fan out to form a complete layer of longitudinal
muscle.

The anal canal is approximately 4 cm long

and appears as a collapsed anteroposterior
slit in the normal patient
Arterial blood supply of colon
and rectum
 Histology
• The colonic wall consists of mucosa,
submucosa, inner circular muscle,
outer longitudinal muscle, and
serosa.
• The colonic mucosa is similar in
organization to the small intestine
mucosa except that it lacks villi. The
mucosa is lined by a simple
columnar epithelium that forms
straight tubular crypts that are
about 0.5 mm in length.
The lamina propria extends from the
simple columnar epithelium to the
muscularis mucosae and contains many
cells involved in immunological functions
of the gut. Numerous
immunoglobulin-secreting plasma cells,
macrophages, and lymphocytes are
present, in addition to abundant lymphoid
nodules that often extend through the
muscularis mucosae into the underlying
submucosa. A lymphoid aggregate (LA) arises in the lamina
propria and extends through the muscularis
mucosae (MM) into the submucosa.
 Inflammatory Bowel Disease
• Clinically, inflammatory bowel disease (IBD) is a chronic inflammatory
condition of the intestines that is marked by remission and relapses.

• Inflammatory bowel disease (IBD) is an idiopathic disease caused by a

dysregulated immune response to host intestinal microflora.

• The two major types of inflammatory bowel disease are ulcerative colitis (UC),
which is limited to the colonic mucosa, and Crohn disease (CD), which can
affect any segment of the gastrointestinal tract from the mouth to the anus,
involves "skip lesions," and is transmural.

• Men and women are generally at similar risk for IBD.

• Onset of IBD is highest among adolescents; the peak incidence is between

ages 15 and 25 years. There is a slight second peak in 60s years
• The incidence of IBD is 5-7/100.000, prevalence of IBD is 70-200/100.000
(depending on the country)
 PATHOGENESIS OF INFLAMMATORY
BOWEL DISEASE
• IBD represents a dysregulated mucosal immune response in a genetically
susceptible host to commensal microbial antigens.
• Genetics: Twin and familial studies demonstrate a component of genetic
susceptibility
• Immunologic dysregulation
• Microbiata
• Environmental factors:
– Cigarette smoking increases the risk for Crohn disease but is protective
for ulcerative colitis.
– Diet
 Ulcerative Colitis
• Inflammation in ulcerative colitis is limited to the mucosal layer of the
colon.
• The rectum is virtually always involved, with inflammation extending
proximally in a confluent fashion.
• The extent of proximal involvement is variable.
– Distal type (ulcerative proctitis or rectosigmoiditis)
– Left sided colitis
– Pancolitis (Approximately one third of patients)
– The disease remains confined to the rectum in approximately 25%
of cases, and in the remainder of cases, ulcerative colitis spreads
proximally and contiguously.
– Pancolitis occurs in 10-30% of patients.
– The distal terminal ileum may become inflamed in a superficial
manner, referred to as backwash ileitis.
 Ulcerative Colitis
• Symptoms and signs—depends on the extent and severity of inflammation
• Overt rectal bleeding and tenesmus are virtually universally present and may
be the only symptoms in patients with proctitis alone.
• When the proximal colon is involved, diarrhea and abdominal pain are more
frequent complaints. Nausea and weight loss portend more severe disease.

• Severe abdominal pain or fever suggests fulminant colitis or toxic megacolon.

• Signs of ulcerative colitis include mild abdominal tenderness, often most
localized in the hypogastrium or left lower quadrant. Severe tenderness, fever,
or tachycardia heralds fulminant disease.

• Digital rectal examination may disclose visible red blood. As with Crohn
disease, signs of malnutrition may be evident.

• Toxic megacolon: Medical emergency; patients appear septic, have high fever,
lethargy, chills, and tachycardia, as well as have increasing abdominal pain,
tenderness, distention
 Ulcerative Colitis
• Laboratory findings—anemia and often iron deficiency
• Hypoalbuminemia suggests extensive disease with subsequent colonic protein losses.
• Leukocytosis, thrombocytosis, ESR, and CRP are nonspecific
• Stool : negative for typical bacterial pathogens, C difficile, and ova and parasites.
• fecal leukocytes and fecal lactoferrin, calprotectin .
• Imaging studies—Plain films of the abdomen are useful predominantly in patients with
symptoms of severe or fulminant colitis. Complications such as perforation with free air
and toxic dilatation with a luminal diameter of 5 cm or more.
• Barium enema is less commonly used In ulcerative colitis, the colon typically appears
granular and shortened, perhaps as a consequence of chronic inflammation or fibrosis.
• Colonoscopy allows assessment of the extent of disease and severity of involvement.
• Flexible sigmoidoscopy is a useful tool for disease assessment in the setting of flares of
colitis.
• Biopsy- in both ulcerative colitis and Crohn colitis demonstrate evidence of acute
inflammation, characterized by neutrophilic cryptitis, and chronic inflammation, such as
crypt distortion and a plasmocytic infiltration of the lamina propria.
 Crohn Disease
• The inflammation in Crohn disease is typically transmural.
• Three phenotypes: inflammatory, stricturing, or
perforating disease (the latter including abscesses and
fistulae).
• Unlike ulcerative colitis, Crohn disease may affect any part
of the alimentary canal and may do so in a nonconfluent
(so-called skip lesion) pattern. Nearly half of all patients
with Crohn disease have inflammation localized to the
terminal ileum and cecum
• Perianal disease, including abscesses and fistulae, is
commonly encountered, particularly in conjunction with
terminal ileal disease.
 Localization of Crohn disease within the
gastrointestinal tract

• Location and Frequency (%)

– Ileocolonic : 35 (26–48)
– Small bowel only: 28 (11–48)
– Colon only: 32 (19–51)
– Gastroduodenal: 1–4 (★)
– Perianal: 18 (14–20) (★)

★
Typically in conjunction with disease elsewhere
 Crohn Disease
Symptoms and signs:
• Recurring and periods of remission.
• Abdominal pain and diarrhea are the most typical symptoms (nonbloody diarrhea).
• Fever and weight loss are common.
• Mass in the right lower abdominal quadrant may be present in CD.
• As a general rule, the location and phenotype of disease (inflammatory, stricturing, or
perforating), along with the severity of inflammation, dictate a patient’s symptoms and
signs.
• Complications from fistulizing disease are common.
• Extraintestinal manifestations
• Signs of Crohn disease include abdominal tenderness, most classically in the right lower
quadrant. Temporal wasting and cachexia indicate significant malnutrition. Typical
symptoms of small bowel obstruction (distention, tympany, high-pitched bowel sounds)
may be present in stenosing disease. Perianal and cutaneous fistulae are readily
identified on a careful perineal and skin examination.
 Crohn Disease
• Laboratory findings—No single laboratory test is diagnostic or specific for Crohn disease.
• Patients are typically at least mildly anemic, often with iron deficiency. Leukocytosis and
thrombocytosis are common and typically reflect systemic inflammation.
• Protein-losing enterocolitis or in malnutrition.
• Malabsorption due to inflammation, bacterial overgrowth, or surgical resection may lead to
diminished levels of various minerals (serum calcium, magnesium) and vitamins (B12, D, and folate).
• C-reactive protein (CRP)—and, to a lesser extent, erythrocyte sedimentation rate (ESR)—are
nonspecific markers of inflammation that are frequently elevated in Crohn disease.
• Stool studies may reveal excess fat, indicative of malabsorption, or fecal leukocytes, indicative of gut
inflammation.
• Calprotectin is a calcium- and zinc-binding protein, which for practical purposes can be considered
to be neutrophil-specific, although low levels are found in other phagocytic cells. Calprotectin
accounts for approximately 60% of total soluble proteins in the cytosol fraction of neutrophils.
• Fecal lactoferrin has shown early promise as a marker of disease activity. LF is an iron binding
glycoprotein. It is present in various secretory fluids, such as milk, saliva, tears, and nasal
secretions]LF is a component of the innate immune system, with antimicrobial activity as a
bactericide and fungicide, as well as being a major constituent of neutrophil granules that is
released during apoptosis. æDuring intestinal inflammation polymorphonuclear neutrophils infiltrate
the mucosa, increasing LF concentration in feces proportional to neutrophil translocation to the GI
tract.
• Perinuclear antineutrophil cytoplasmic antibodies (ANCA), anti-Saccharomyces cerevisiae antibodies
(ASCA)
• Stool studies should be negative for infectious pathogens
 Crohn Disease
• Imaging studies—Standard abdominal plain films are useful for detecting obstructive
disease and megacolon,
• Small bowel series are useful for imaging small bowel mucosal disease, including
strictures, ulcerations, and fistulae.
• Enteroclysis, although more sensitive, is limited by patient discomfort, increased
radiation exposure, and its technically demanding nature.
• Barium enema remains an option for imaging colonic disease, especially to help
delineate obstructive or fistulizing disease
• Computed tomography (CT) of the abdomen and pelvis has revolutionized the imaging
of Crohn disease by allowing imaging of the bowel wall itself, as well as extraluminal
disease such as abscesses or inflammatory masses.
• MRI over CT lie in superior imaging of the pelvis and lack of ionizing radiation.
• Colonoscopy remains a mainstay in the assessment of Crohn disease, as it allows direct
visualization of the bowel mucosa and sampling of tissue. Ileal ulceration and skip
lesions help distinguish Crohn disease from ulcerative colitis.
• Capsul enteroscopy If there is no obstructive lesion
• Enteroscopy
• Biopsy- Noncaseating granulomas and transmural disease both are highly specific to
Crohn diseas but only 30% of the specimens
Ulcerative colitis Crohn’s colitis
Common extraintestinal manifestations of
inflammatory bowel disease
Differential Diagnosis inflammatory bowel disease.
 ASCA and pANCA
• pANCA (Anti-neutrophil cytoplasmic antibody) Nuclear histone
1 of polymorphonuclear leukocytes10%-15%(CD) 60%-70%(UC)

• ASCA Mannan in the cell wall of bakers’ yeast 60%-70%(CD)

10%-15%(UC)
• Anti-Saccharomyces cerevisiae antibody (ASCA), an anti-glycan
antibody, is an antibody against mannan on the cell wall surface of
baker’s yeast (S. cerevisiae).
 IBD Complications
• Crohn disease frequently causes complications from penetrating and stenosing disease,
including perforation, abscess, fistulae, and obstruction.
• Active small bowel disease or extensive small bowel resection may lead to
complications from malabsorption
• Malabsorption of fatty acids predisposes patients with Crohn disease to renal calculi.
Calcium readily binds unabsorbed fatty acids, allowing oxalate to be taken up by the
bowel in greater quantity. Subsequent renal excretion of this excess oxalate promotes
the precipitation of calcium oxalate calculi.
• Severe, life-threatening hemorrhage occurs rarely.
• Toxic megacolon with subsequent infarction and perforation (early diagnosis and
treatment is critical)
• Colorectal cancer (CRC) is the most feared long-term complication for ulcerative colitis.
Risk factors include duration and extent of disease, severity of inflammation, family
history of CRC, and concomitant primary sclerosing cholangitis (PSC). Early age of onset
has been suggested to be a risk factor. The excess risk of CRC appears after 8–10 years
of disease. Hence, a screening colonoscopy is recommended after 8 years for patients
with extensive colitis, with surveillance examinations every 1–2 years.
• Crohn colitis confers a risk of CRC comparable to that of ulcerative colitis.
• Pouchitis
• PSC patients carry a high risk for cholangiocarcinoma.
 THERAPY
• The two goals of therapy are the achievement of remission (induction) and
the prevention of disease flares (maintenance). Note that a top-down
approach, with earlier introduction of biologics and immunomodulators, is
frequently advocated to forestall complications.

• The medical approach for patients with IBD is both symptomatic care (ie,
relief of symptoms) and mucosal healing following a stepwise approach to
medication, with escalation of the medical regimen until a response is
achieved. The concept of deep mucosal healing, particularly in Crohn disease,
is becoming increasingly advocated. There are several studies, primarily
involving anti-TNF agents (and occasionally immune modifiers); that have
shown that the elimination of inflammation (as demonstrated by endoscopic
and histologic criteria) results in a decrease in the rate of surgery, the use of
corticosteroids, and the rate of hospitalization.

• This supports the use of immune-modifying agents (mercaptopurine or

azathioprine) or one of the anti-TNF agents earlier in the course of IBD.
Medical management of inflammatory bowel disease.
5-ASA ， 5-aminosalisylic acid; CD ， Crohn's disease; U C ， ulcerative colitis
Indications for surgery in IBD