Diseases of The Colon

(Focused on IBD and IBS)

Agung F. Sumantri
Departemen Penyakit Dalam
Fakultas Kedokteran UNISBA
How to Diagnose ?

Careful history and physical examination

Diagnostic modalities
 Stool exam with occult blood
 Barium enema
 CT scan
 Virtual colonoscopy
 Video colonoscopy
Normal Colon
Colonic Diseases

Irritable Bowel Syndrome

Inflammatory Bowel Disease
 Chron’s Disease
 Ulcerative Colitis
Diverticular Diseases
Polyps
Colorectal Cancer, etc
Irritable Bowel Syndrome
Irritable Bowel Syndrome

 A functional bowel disorder characterized by

abdominal pain or discomfort and altered bowel
habits in the absence of detectable structural
abnormalities
 10-20% of adults and adolescents have symptoms
c/w IBS, with FEMALE predominance (2-3x as
often as men)
 Commonly first symptoms occur before age 45
7
 World Prevalence of IBS

Canada
UK 22%
13.5% Germany China 23%
12%
France
US 10-20% 9.4% Japan 25%

New
Nigeria
Zealand
Peru 30%
17%
18% Australia
12%

Adapted from Camilleri M, et al. Aliment Pharmacol Ther. 1997;11:3.

8
Muller-Lisners et al. Digestion. 2001;64:200.
Irritable Bowel Syndrome
Rome II diagnostic criteria for IBS

At least 12 weeks, which need NOT be consecutive

(at least 3 days per month), in the preceding 12 weeks
of abdominal discomfort or pain that has two out of
the following three features

 Relieved with defecation; and/or

 Onset associated with change in frequency of stool;
and/or
 Onset associated with a change in form
(appearance) of stool
 IBS: Rome II criteria (1999)

The following symptoms cumulatively support

the diagnosis of IBS:
 abnormal stool frequency;
 abnormal stool form (lumpy/hard or loose/watery
stool);
 abnormal stool passage (straining, urgency, or
feeling of incomplete evacuation);
 passage of mucus;
 bloating or feeling of abdominal distension.

10
Thompson et al, 1999
Rome III – Irritable Bowel Syndrome
Subtyping Irritable Bowel Syndrome (IBS)

 The Rome II committee subclassified IBS on the basis of

expert opinion and attempted to incorporate stool
frequency, stool form, and defecation symptoms.
 In the Rome III the subclassification was revised to be
based solely on stool consistency, which has been
supported by recent studies.
 Subclassification of IBS is important because it would
likely be associated with different treatment choices and
pathophysiologic mechanisms.

http://www.medscape.com/viewarticle/533460
11
 Rome III – Irritable Bowel
Syndrome
Sub typing IBS by Predominant Stool Pattern

Patients with IBS-M have both hard and loose stools over periods of
hours or days, whereas IBS patients with alternating bowel habits
change subtype over periods of weeks and months.

12
Gastroenterology 2006;130:1480-1491
Clinical Features
 Abdominal pain/discomfort
 Prerequisite clinical feature of IBS

 Variable in intensity and location

 Exacerbated by eating or emotional stress

and improved by passage of flatus or stools
 Altered bowel habits
 Most consistent clinical feature in IBS

 Constipation alternating with diarrhea,

usually with one symptom predominating
Clinical Features

 Gas and flatulence

 Impaired transit and tolerance of intestinal
gas loads
 Reflux gas from distal to proximal intestine -
flatulence
 Upper GI symptoms
 25-50% of patients complain of dyspepsia,
heartburn, nausea or vomiting
IBS: Evolving understanding
5-HT mediated visceral
sensitivity and gut motilit

Brain-gut interaction

Visceral hyperalgesia

Abnormal motor function

1950 1960 1970 1980 1990 2000

Drossman et al,
16 1999
 IBS Pathophysiology
Enhanced
Perception

Vagal
Nuclei
5-HT Sympathetic

Altered Visceral
Motility Hypersensitivity

Adapted from Camilleri and Choi. Aliment Pharmacol Ther. 1997;11:3. 17

Approach to the Patient with IBS
IBS NOT IBS
• recurrence of lower • appearance of the disorder
abdominal pain with for the first time in old age
altered bowel habits over a • progressive course from time
period of time without of onset, persistent diarrhea
progressive deterioration after a 48-h fast
• onset of symptoms during • presence of nocturnal
periods of stress diarrhea or steatorrheal
• absence of other systemic stools
symptoms such as fever and
weight loss
• small-volume stool without
any evidence of blood
 The Positive Diagnosis of IBS:
A Symptom-Based Approach

Identify Current Primary Symptoms

 Abdominal pain / discomfort
 Bloating
 Constipation/Diarrhea

Look for ‘Red Flags’ Based on:

 History
 Physical exam
 Laboratory tests

Perform Selected Physical and Diagnostic

Tests to Rule Out Organic Disease

Make a Positive Diagnosis

Adapted from Paterson et al. Can Med Assoc J. 1999;161:154. 27

American Gastroenterological Association. Gastroenterology. 1997;112:2120.
 Identify Red Flags
History Physical
 Unintentional weight loss  Abnormal exams
 Onset in older patient (>50  Rectal bleeding /
years) obstruction
 Family history of cancer or  Positive flexible
IBD sigmoidoscopy or
colonoscopy (>50 years)
Initial labs
  HGB
  WBC
  ESR
 Abnormal chemistry
  TSH Red Flags
Adapted from a technical review. Gastroenterology. 1997;112:2120.
Paterson et al. Can Med Assoc J. 1999;161:154. 28
Camilleri et al. Aliment Pharmacol Ther. 1997;11:3.
The balance of IBS diagnosis

29
Approach to the Patient with IBS
 Young pxs with mild symptoms require minimal
diagnostic evaluation, while older pxs or those with
rapidly progressive symptoms should undergo a
more thorough one
 CBC and sigmoidoscopic examination, stool exam
 In pxs with persistent diarrhea not responding to
anti-diarrhea agents, a sigmoid colon biopsy should
be performed to rule out microscopic colitis
Approach to the Patient with IBS

 In those aged >40 years, an air-contrast barium

enema or colonoscopy should also be performed
 If the main symptoms are diarrhea and increased
gas, the possibility of lactase deficiency should be ruled
out with a hydrogen breath test or with evaluation
after a 3-week lactose-free diet
 Lab features that argue against IBS include anemia,
elevated ESR, presence of leukocytes or blood in
stool, and stool volume >200–300 mL/d
IBS: Further evaluation

 Sigmoidoscopy
 Examination of stool
 Blood studies
 Imaging studies

Drossman, 1997;
33 1999
Irritable Bowel Syndrome
Management
Patient Education (Reassurance)
Dietary Intervention (Fiber)
Pharmacotherapy
 Antispasmodics
 Anti-diarrhea agents
 Prokinetics
Psychotherapy / cognitive and behavior th/
Hypnotherapy
 Drug Treatment of IBS
Abdominal pain/discomfort Bloating and distention
• Antispasmodics • Antiflatulents
• Antidepressants • Antispasmodics
— TCAs/SSRIs • Dietary modification
Abdominal Bloating/
pain/ distention
discomfort

Constipation Altered bowel Diarrhea

• Fiber function • Loperamide
• Laxatives • Cholestyramine
• PEG solutions

None of these medications effectively treat the multiple symptoms of IBS; they may 36
exacerbate individual symptoms (eg, fiber and bloating, antispasmodic, constipation).
Therapeutic Targets for IBS
IBS: Patient's concerns
Can it be
What is IBS? DOCTOR treated?

Where is
Do I have
the toilet?
cancer?

I can’t talk
Can I lead
to anyone
a normal life?
about it

39
Inflammatory Bowel Disease
Contents:

 Introduction
 Epidemiology
 Pathophysiology
 Diagnosis
Signs & Symptoms
Laboratory & Radiology
 Complications
 Treatments
Medical
Surgical
Inflammatory bowel disease

It includes a group of chronic disorders that

cause inflammation or ulceration in large
and small intestines.
Inflammatory Bowel Disease

 Immune-mediated chronic intestinal condition

 2 major types: Ulcerative colitis (UC) and Crohn’s
disease (CD)
 Highest incidence in Europe, the United Kingdom,
and North America
 Urban areas have a higher prevalence of IBD
than rural areas, and high socioeconomic classes
have a higher prevalence than lower
socioeconomic classes
TYPES
Crohn’s disease Ulcerative colitis

 Extends into the deeper

layers of the intestinal wall,
and may affect the mouth,
esophagus, stomach, and
small intestine.
 Transmural inflammation
and skip lesions.
 In 50% cases -ileocolic,30%
ileal and 20% -colic region.
 Regional enteritis
 causes ulceration and
inflammation of the inner
lining of the colon and
rectum.
 It is usually in the form of
characteristic ulcers or
open sores.
Epidemiology
Ulcerative colitis Crohn’s

Incidence / 1 lac. 2.2-14.3 3.1-14.6

Age of onset 15-30, 60-80

Ethnicity Jewish

Male: Female 1:1 1.1-1.8 : 1

Smoking May prevent Causative

Oral contraceptives No risk 1.4 odds ratio

Appedicectomy Protective Not

Monozygotic 6% 58%

Dizygotic 0% 4%
Etiopathogenesis

 Exact cause is unknown.

 Genetic factors
 Immunological factors
 Microbial factors
 Psychosocial factors
Etiopathogenesis
Genetic Considerations

 The diseases and the genetic risk factors that

are shared with IBD include rheumatoid
arthritis (TNFAIP3), psoriasis (IL23R,IL12B),
ankylosing spondylitis (IL23R), type 1 diabetes
mellitus (IL10,PTPN2), asthma (ORMDL3), and
systemic lupus erythematosus (TNFAIP3,IL10)
Pathogenesis of IBD
Tolerance

Acute Injury

Environmental
trigger
Normal Complete Healing
Gut (Infection, NSAID,
other)

Genetically
Tolerance- Acute Inflammation Susceptible
controlled Host
↓ Immunoregulation,
inflammation
failure of repair or
bacterial clearance

Chronic Inflammation
American Gastroenterological Association Institute, Bethesda, MD.
Sartor RB. Nat Clin Pract Gastroenterol Hepatol. 2006;3:390-407.
Pathology

Macrocopic features
 Ulcerative colitis
 Usually involves rectum & extends
proximally to involve all or part of colon.
 Spread is in continuity.
 May be limited colitis( proctitis &
proctosigmoiditis)
 in total colitis there is back wash ileitis
(lumpy-bumpy appearance)
Ulcerative Colitis – Macroscopic
Features
Ulcerative colitis

pseudopoly
Ulcer ps
Microscopic features

 Crypts atrophy & irregularity

 Superficial erosion
 Diffuse mixed inflammation
 Basal lymphoplasmacytosis
Ulcerative Colitis – Microscopic Features
Diffuse
inflammation

Crypt
distortion
Macroscopic features

 Crohn’s disease
 Can affect any part of GIT
 Transmural
 Segmental with skip lesions
 Cobblestone appearance
 Creeping fat- adhesions & fistula
Crohn’s Disease – Macroscopic Features
Microscopic features

 Aphthous ulcerations
 Focal crypt abscesses
 Granuloma-pathognomic
 Submucosal or subserosal lymphoid
aggregates
 Transmural with fissure formation
Crohn’s Disease – Microscopic
Features
 Aphthous
ulcer

Granuloma
Only GALS can be Crohn’s!

G – Granulomas
AL – All Layers and All Levels
S – Skip lesions
Macroscopic Features

UC CD
Rectal involvement  
Pseudopolyps  
Toxic megacolon  
Skip lesions  
Perirectal fistulas,  
fissures, abscesses, and
anal stenosis
Transmural involvement  
Clinical features UC

 Ulcerative colitis
 Diarrhea
 Rectal bleeding
 Tenesmus
 Passage of mucus
 Crampy abdominal pain
 Physical signs
 Proctitis – Tender anal canal & blood on
rectal examination
 Extensive disease-tenderness on
palpation of colon
 Toxic colitis-severe pain & bleeding
 If perforation-signs of peritonitis
 Clinical Severity of UC

Mild Moderate Severe Fulminant

Bowel movement <4 >6 >10

Blood in stool Intermittent Frequent Continuous

Temperature Normal >37.5° >37.5°

Pulse Normal >90 bpm >90 bpm

Intermediate
<75% normal Transfusion
Hemoglobin Normal
rate required
ESR <30 mm/hour >30 mm/hour >30 mm/hour
Abdominal
Abdominal
Clinical signs distension and
tenderness
tenderness
1. Truelove SC, et al. Br Med J. 1955;2:1041-1045.
2. Sandborn WJ. Curr Treat Options Gastroenterol.1999;2:113-118.
Diagnosis

 Laboratory tests
 Endoscopy
 Radiography
 Biopsy
Laboratory tests

 Hemogram
 C-reactive protein is increased
 ESR is increased
 Platelet count-increased
 Hemoglobin-decreased
 Fecal Calponectin levels correlate with
histological inflammation,predict relapses
&detect pouchitis
Barium enema

 Fine mucosal granularity

 Superficial ulcers seen
 Collar button ulcers
 Pipe stem appearance-
loss of haustrations
 Narrow & short colon-
ribbon contour colon
Endoscopic features
 Mild disease- erythema & sand paper
appearance(fine granularity)
 Moderate-marked erythema,coarse
granularity,contact bleeding & no ulceration
 Severe- spontaneous bleeding, edematous &
ulcerated(collar button ulcer).
 Long standing-epithelial regeneration so
pseudopolyps , mucosal atrophy &
disorientation leads to a precancerous condition.
 Fulminant disease-Toxic colitis/megacolon
Extra intestinal manifestations
Extraintestinal Manifestations

 Dermatologic
 Rheumatologic
 Ocular
 Hepatobiliary
 Urologic
 Metabolic bone disorders
 Thromboembolic disorders
 Others
Extraintestinal Manifestations:
A PIE SAC
 Aphthous ulcers
 Pyoderma gangrenosum
 Iritis
 Erythema nodosum
 Sclerosing cholangitis
 Arthritis
 Clubbing of fingertips
Clinical features CD

 Ileal Crohn’s Disease

 Abdominal pain
 Diarrhea
 Weight loss
 Low grade fever
 Jejunoileitis disease
 Malabsorption
 Steatorrhea
Colitis and perianal disease
 Bloody diarrohea
 Passage of mucus
 Lethargy
 Malaise
 Anorexia
 Weight loss
Diagnosis

 Laboratory tests
 Endoscopy
 Radiography
 Biopsy
 CT enterography
Laboratory tests

 CRP-elevated
 ESR-elevated
 Anemia
 Leukocytosis
 hypoalbuminemia
Barium enema

String
sign
Colonoscopy
CT enterography

 Mural hyperenhancement
 Stratification
 Engorged vasa recta
 Perienteric inflammatory
changes
Clinical Features of UC vs CD
Endoscopic and Radiographic
Features of UC vs CD
Treatment of IBD
Treatment
Lifestyle changes
Drugs

 5-ASA (aminosalycilates) agents

 Glucocorticoids
 Antibiotics
 Immunosuppresants
 Biological therapy
5-ASA Agents

Mainstay of therapy for mild to moderate UC is

Sulfasalazine and other 5-ASA agents. Limited
role in inducing remission in CD.
 Topical Action of 5-ASA: Extent of
Disease Impacts Formulation Choice
Distribution of 5-ASA Preparations
Oral
• Varies by agent: may be released in the
distal/terminal ileum, or colon1

Liquid Enemas
• May reach the splenic flexure2-4
• Do not frequently concentrate in the rectum3

Suppositories
• Reach the upper rectum2,5
(15-20 cm beyond the anal verge)

1. Sandborn WJ, et al. Aliment Pharmacol Ther. 2003;17:29-42; 2. Regueiro M, et al. Inflamm Bowel Dis. 2006;12:972–978; 3. Van
Bodegraven AA,
et al. Aliment Pharmacol Ther. 1996; 10:327-332; 4. Chapman NJ, et al. Mayo Clin Proc. 1992;62:245-248; 5. Williams CN, et al. Dig Dis Sci.
1987;32:71S-75S.
Glucocorticoids

 Anti inflammatory agents for moderate to

severe relapses (UC abd CD).
 Inhibition of inflammatory pathways
 Prednisone-40-60mg/day, that is
unresponsive to 5-ASA therapy
 Parenteral: hydrocortisone, 300 mg/d, or
methylprednisolone, 40–60 mg/d
 No role in maintainence therapy
Antibiotics

 No role in active/quienscent UC, Pouchitis

in 1/3 of UC patients post colectomy
 Metronidazole is effective in active
inflammatory,fistulous & perianal CD.
 Dose-15-20mg/kg/day in 3 divided doses.
 Ciprofloxacin
 Rifaximin
Immunosuppresants

 Thiopurines
 Azathioprine
 6-mercaptopurin
 Methotrexate
 Cyclosporine
 Tacrolimus
Cyclosporine

 Preventing clonal expansion of T cell subsets

 Use
Steroid sparing
Active and chronic disease
 Side effects
Tremor, paraesthesiae, malaise, headache,
gingival hyperplasia, hirsutism Major: renal
impairment, infections, neurotoxicity
Biological therapy

 Anti-TNF therapies
 Natalizumab
Standard Medical Management
of UC
Standard Medical Management
of CD
Surgery
THANK YOU!
Questions?
References
1. ^ Baumgart DC, Carding SR (2007). "Inflammatory bowel disease: cause and immunobiology.". The Lancet 369 (9573):
1627–40. doi:10.1016/S0140-6736(07)60750-8. PMID 17499605.
2. ^ a b Baumgart DC, Sandborn WJ (2007). "Inflammatory bowel disease: clinical aspects and established and evolving
therapies.". The Lancet 369 (9573): 1641–57. doi:10.1016/S0140-6736(07)60751-X. PMID 17499606.
3. ^ Xavier RJ, Podolsky DK (2007). "Unravelling the pathogenesis of inflammatory bowel disease.". Nature 448 (7152):
427–34. doi:10.1038/nature06005. PMID 17653185.
4. ^ "Crohn's & Colitis Foundation of America".
5. ^ Elson, CO; Cong, Y; Weaver, CT; Schoeb, TR; Mcclanahan, TK; Fick, RB; Kastelein, RA (2007). "Monoclonal Anti–
Interleukin 23 Reverses Active Colitis in a T Cell–Mediated Model in Mice". Gastroenterology 132 (7): 2359.
doi:10.1053/j.gastro.2007.03.104. PMID 17570211.
6. ^ a b c d e f internetmedicin.se > Inflammatorisk tarmsjukdom, kronisk, IBD By Robert Löfberg. Retrieved Oct 2010
Translate.
7. ^ a b c d Hanauer, Stephen B.; William Sandborn (2001-03-01). "Management of Crohn's disease in adults" (PDF).
American Journal of Gastroenterology 96 (3): 635–43. doi:10.1111/j.1572-0241.2001.03671.x. PMID 11280528.
Retrieved 2009-11-07.
8. ^ a b c Kornbluth, Asher; David B. Sachar (July 2004). "Ulcerative colitis practice guidelines in adults (update): American
College of Gastroenterology, Practice Parameters Committee" (PDF). American Journal of Gastroenterology 99 (7):
1371–85. doi:10.1111/j.1572-0241.2004.40036.x. PMID 15233681. Archived from the original on April 6, 2008.
Retrieved 2009-11-07.
9. ^ Broomé, Ulrika; Annika Bergquist (February 2006). "Primary sclerosing cholangitis, inflammatory bowel disease, and
colon cancer". Seminars in Liver Disease 26 (1): 31–41. doi:10.1055/s-2006-933561. PMID 16496231.
10. ^ Shepherd, NA. (August 2002). "Granulomas in the diagnosis of intestinal Crohn's disease: a myth exploded?".
Histopathology 41 (2): 166–8. doi:10.1046/j.1365-2559.2002.01441.x. PMID 12147095.
11. ^ Mahadeva, U.; Martin, JP.; Patel, NK.; Price, AB. (July 2002). "Granulomatous ulcerative colitis: a re-appraisal of the
mucosal granuloma in the distinction of Crohn's disease from ulcerative colitis.". Histopathology 41 (1): 50–5.
doi:10.1046/j.1365-2559.2002.01416.x. PMID 12121237.
12. ^ a b c Pages 152-156 (Section: Inflammatory bowel disease(IBD)) in:Elizabeth D Agabegi; Agabegi, Steven S. (2008).
Step-Up to Medicine (Step-Up Series). Hagerstwon, MD: Lippincott Williams & Wilkins. ISBN 0-7817-7153-6.