Irritable Bowel Syndrome, Ulcerative

Colitis & Crohn’s Disease

Budi Widodo
Gastrohepatology Division – Internal
medicine Dept
 Definition
• Functional bowel disorder in which abdominal
pain is associated with defecation or change
bowel habit, and featuresof disordered
defecation
 Irritable
Bowel
Syndrome
 Diagnostic
• Rome IV
– Recurrent abdominal pain, on average at least 1
day per week in in the last 3 month associated
with 2 or more of the following
• Related of defecation
• Associated with a change in frequency of stool
• Associated with a change in form (appearance) of stool

Criteria fullfilled for the 3 months with symptom onset at

least 6 months prior to diagnosis
 Subtyping IBS by Predominant Stool
Form
• IBS with constipation (IBS-C)
– Bristol stool scale 1 or 2 > 25% and
– Bristol stool scale 6 or 7 < 25% of bowel movements
• IBS with diarrhoea (IBS-D)
– Bristol stool scale 6 or 7 > 25% and
– Bristol stool scale 1 or 2 < 25% of bowel movements
• Mixed IBS (IBS-M)
– Bristol stool scale 1 or 2 > 25% and
– Bristol stool scale 6 or 7 > 25% of bowel movements
• Unsubtyped IBS – Insufficient abnormality of stool
consistency to meet criteria for IBS-C, D or M
 Pathophysiology
1. Motility abnormalities in the GUT
2. Visceral Hypersensitivity
3. Brain GUT axis
4. Infammation
5. Postinfectious IBS
6. Bacterial overgrowth
7. Food Sensitivity
8. Genetic
9. Psychosocial
 Pathophysiology
• Motility abnormalities in the GUT
– Increase in transit in diarrhoea, slow in constipation
– Stress and meals  increased response in the ileum,
colon, rectum
– High amplitude propagating contractions:
• IBS patient with diarrhea
• IBS patient with pain predominant
– Pharmacological stimulation of gut motility 
reduced gas retention and improvement in symptoms
 Pathophysiology
• Visceral Hypersensitivity
– Increased sensitivity to the normal passage of
gas, fluids and regular contractions in GIT
 Pathophysiology
• Brain GUT axis
– Signals from the brain modulate the gut to
maintain the digestive functions of the body.
– The signals from gut to the brain have a role in
reflex regulation and mood modulation
– Visceral afferent signals from gut reach only to
the brainstem and thalamus and very few are
perceived by the cortex
– Stress and anxiety  perception of painful
events
 Pathophysiology
• Infammation
– Alteration in the immune function
– Elevated level of plasma proinflammatory
interleukins and tumor necrosis factor
– Microscopic inflamation seen in colon and small
bowel
– Lymphocyte infiltration of myenteric plexus,
neuronal degradation, colonic mucosal
lymphocytes and increased nitric oxide
synthetase expression
 Pathophysiology
• Postinfectious IBS
– Develped symptoms of IBS after recovered from
bacterial gastroenteritis
– E coli and campylobacter jejuni are common
pathogens
– Risk factor: female, prolonged episodes
infectious diarrhea and use of antibiotics
 Pathophysiology
• Bacterial overgrowth
– Abnormal breath hydrogen level in IBS after
receiving a test dose of carbohydrate
 Pathophysiology
• Food Sensitivity
– Some patient preceive intolerance to certain foods
– IBS patient have more positive food skin prick test
– FODMAPs (fermentable, oligo, di, monosaccharides
and polyols) get fermented in distal bowel and colon
 cause symptoms
– Increased incidence of flatus, pain, bloating, bleching
and altered bowel habit  fructose intolerance
– May be overlap between celiac and IBS  IBS no
villous atrophy
 Pathophysiology
• Genetic
– Genetic basis is not identified
– Increased incidence in monozygotic twins than
dizygotic twins
 Pathophysiology
• Psychosocial
– GI symptoms get exacerbated by stress
– Psychiatric and psychological factors coexist in
IBS
 Evaluation
1. Initial evaluation and workup
2. Diagnostic workup symptom based
 Evaluation
• Initial evaluation and workup
– Diagnosis of IBS is symptom based on ROME IV
criteria
– Detail physical and rectal examination will be
helpful to exclude any pre existing condition
– Complete blood counts, blood chemistries, stool
examination and parasites, thyroid functions
tests, antibodies for ceiac sprue and colonoscopy
should be done where indicated
 Evaluation
• Diagnostic workup symptome based
– Constipation predominant and have infrequent
bowel movement then a colon transit study is
suggested
– Patient have a history digital evacuation during
defecation or symptoms suggestive 
obstructive defecation or poor pelvic floor
relaxation
– Anorectal manometry with balloon expulsion
studies can be performed
 Treatment
1. Diet
– Lactose free  lactose intolerance
– Avoided: brocoli, cabbage, brussel sprouts, onions, asparagus, celery,
carrots, raisins, bananas, apricouts, prunes, whole wheat  increase
gas production
– Diet low FODMAPs
2. Fibre
– Soluble or non soluble fibre
– Synthetic fiber (polycarbophil and methylcellulose)  less bloating
– Bulking agents like psylium  help in constipation
3. Others
– Physical activity
– Eat regular and unhurried melas
– Changing social and psycological conditions
Next Chapter
Ulcerative Colitis
 Introduction
• Ulcrative colitis (UC) and Crohn’s Disease (CD):
inflammatory injury to the gastrointestinal
tract may involve certain extraintestinal
manifestation
• UC: affects the rectum and extend proximally
• CD: manifested by focal, asymmetric and
trasmural inflammation of the digestive tract
by granuloma formation
 Ulcerative Colitis
• Clinical feature
– Age: peak between 15 and 30 yo
– Diarrhoea
• Most patients with active disease
• Increased mucosal permeability, reduced Na/K ATPase
pump activity and altered membrane phospholipids
• Rectal symptoms: urgency and tenesmus
• Prcotitis and proctosigmoiditis and constipation (20-
30%)
 Ulcerative Colitis
• Clinical feature
– Rectal bleeding
• Associated with active colitis
• Proctitis: blood streak on surface of hard stool and
mucus
• Proctosigmoiditis: blood usually a mixed with the stool
• When proximal involvement: liquid stool containing
blood, pus, and fecal matter
• Passage of blood clots is unusual  suggests infectious
colitis, haemorrhoids, diverticular disease and
colorectal cancer
 Ulcerative Colitis
• Clinical feature
– Abdominal pain
• Not predominant symptoms
• Severe cramping pain with defecation
• Vague, mild lowr abdominal pain is more common
• Severe attack of the disease  severe abdominal pain
• Cause of pain is unknown  may be due to increased
tension within inflamed colonic wall during muscular
contraction
 Ulcerative COlitis
• Clinical feature
– Systemic symptoms
• Fever, anorexia, nausea
• Hypercatabolism, protein loss, hypoalbuminemia
– Back pain and joint pain
• Extraintestinal manifestation
 Ulcerative Colitis
• Physical Examination
– Patient with mild disease often exhibit no physical sign
– Pallor is secondary to blood loss
– Pedal oedema due to hypoalbuminemia  indicates
involvement of entire colon as well as severe left sided colitis
– Aphthous ulcer/stomatitis is around 10% of cases, episcleritis 5-
8% of cases
– Erythema nodusum 2-4%
– Pyoderma gangrenosum 1%
– Tenderness on sacroiliac joint 12-15%
– Mild tenderness in abdomen
– Digital rectal examination: mucosa may feel velvety and blood
on finger
 Ulcerative Colitis
• Investigation
– Biochemistry
• Low Hb
• Elevated leucocyte and platelet
• Low albumin serum
• C reactive protein (CRP) normal in one-fourth patient with active
UC
– Stool examination
• To role out Cl. difficile infection
• Diagnosis of fecal leucocytes
• Fecal calprotectin (FC):
– neutrophilic marker of inflammation and is elevated in infectious and
inflammatory colitis
– Marker fo disease activity and to assess response to therapy and relaps
– High level FC correlate with endoscopically severe disease
 Ulcerative Colitis
• Investigation
– Colonoscopy
• Sigmoidoscopy is enough to diagnose
• Inflammation began in the rectum and extends
proximally without skiping areas
• Ileitis 10-20%
• Early sign: superficial erosion, hyperemia and loss of
vascularity
• Granular (small rough grain size mass of tissue
containing blood vessels and fibroblast), friable and
ulcerated mucosa
Endoscopy showing superficial erosions and loss of vascularity
indicates early UC
Friable, ulcerated mucosa in severe UC
 Ulcerative Colitis
• Investigation
– Plain X-ray abdomen
• Plain abdominal radiographs may be normal or show edematous,
irregular margin, thickening colonic wall, some times dilated
colonic segmen
– Barium enema
• Rarely used to diagnose IBD
• Double contrast enema is safe in mild to moderately active disease
• Helpful to evaluated possible strictures of the bowel
• Characteristics feature
– Fine granular mucosa, irregularity thickened mucosa, superfisial and deep
ulceration, oedematous and thickened hasutral folds, shortening of
colon, presence of pseudopolyps, widening of pre-sacral space (.1 cm)
 Ulcerative Colitis
• Investigation
– Other modalities
• CT colonography (virtul coloscopy)  sensitivity 69-84%
• MR colonography: show increased wall thickeness and increasd
enhancement
– Histophatology
• Disruption of glandular architecture and an inflammatory infiltrate
• Inflammation at the crypt epithelium lining the base of the
mucosa
• Acute cryptitis is the earliest histological finding due to migration
PMN leukocytes from basal crypt
– Serologic Marker
• Prevalence of perinuclear anti neutrophil cytoplasmic antibody
(pANCA) 50-60%
 Ulcerative Colitis
• Classification disease severity
– Various classification in patient with UC  based
on symptoms, extend and severityof the disease
and colonoscopy finding
• True love and Witt’s criteria
• Mayo score for UC activity
• Proposed America College of Gastroenterology UC
Activity index
 Truelove and Witt’s
Mild Stool frequency less than 4 times per day
with or without blood, with no systemic
distrubances and a normal ESR
Moderate More than 4 times per day stool frequency
with minimal systemic distrubances
Severe Stool frequency more than 6 times per day
with evidence of systemic distrubances and
elevated ESR > 30
 Mayo score for UC activity
Pamameter Sub score (0-3)
Stool frequency 0 = normal numberstools
1 = 1-2 stools more than normal
2 = 3-4 stools more than normal
3 = 5 0r more stools more than normal
Rectal bleeding 0 = no blood seen
1 = streak of blood with stool less than one half of the time
2 = obvious blood with stool most of time
3 = blood alone passed without stool
Finding on endoscopy 0 = normal or incative disease
1 = mild disease (erythema, decreased vascular pattern and mild
frability)
2 = moderate disease (marked erythema lack of vascular pattern,
friability and erosions)
3 = severe disease (spontaneous bleeding and ulcerations)
Physicians’ global 0 = normal
assessment 1 = mild disease
2 = moderate disease
3 = severe disease
 UCEIS Mayo Endoscopic
Score Score Features
0 0 Normal

1-3 1 Erythema,
decreased vascular
pattern, mild
friability

4-6 2 Marked erythema,

absent vascular
pattern, friability,
erosions
7-8 3 Spontaneous
bleeding,
ulceration

UC endoscopic Index Severity score and partial Mayo Score

 Proposed America College of Gastroenterology
UC Activity index
Remission Mild Moderate-severe Fulminant
Stool (no /d) Formed stool <4 >6 >10
Blood None Intermitten Frequent Continous
Urgency None Mild, occasional Often Continous
Haemoglobin Normal Normal > 75% of normal Transfusion
required
ESR < 30 < 30 > 30 > 30
CRP Normal Elevated Elevated Elevated
FC < 150-200 > 150-200 > 150-200 > 150-200
Endoscopy 0-1 1 2-3 3
(mayo sub score)
UCEIS (UC 0-1 2-4 5-6 7-8
endoscopic Index
of Severity)
 Ulcerative Colitis
• Site of involvement in UC
– Proctosigmoiditis: 40-50%
– Left sided colitis: 30-40%
– Pancolitis: 20%

• Extraintestinal manifestation
– Erythema nodusum - Pyoderma gangrenosum
– Sweet’s syndrome - Episcleritis, anterior uveitis
– Acute arthropathy - Sarcoilitis
– Ankylosing spondylitis - Thromboebolism
– Primary sclerosing cholangitis
– Apthous ulcer, sore tongue, stomatitis
 Ulcerative Colitis
• Complication of UC
– Haemorrhage
– Perforation
– Toxic megacolon
– Stricture with or without cancer
– Colorectal cancer
 Ulcerative Colitis
• Management
– Induction and maintenance of remission in patient
with active UC
– Maintain adequate nutrition and to improve
quality of live
 Ulcerative Colitis
• Management
– Various drugs are avaiable that induce as well as
maintain the remission
• Aminosalicylates
• Glucocorticoids – not used to maintain remission
• Immunomodulator
• Biological treatment
 Ulcerative Colitis
• Management
– Aminosalicylates
• Decreases T cell proliferation
• Decreases presentation of atigen to T cells
• Decreases neutrophils and acrophages adhesion
• Decreases IL-1 and TNF
• Down regulation of NF-kB
• Free radical scavengers
 Ulcerative Colitis
• Management
– Glucocorticoids – not used to maintain remission
• Numerous anti inflammatory and immunosuppresive
effect
• Inhibition of expression of proinflammatory cytokines,
adhesion molecules and leukotrienes
• Inhibits elastase, clollagenese and nitric oxide synthase
• Downregulation of NFkB and induction of inhibitory kB
• Reduces neutrophilic phagocytic activity
 Ulcerative Colitis
• Management
– Immunomodulator
• Traditionally have been used in corticosteroid
dependent or refractory
• Agents are
– Thiopurine
– Cylosporine
– Tacrolimus
 Ulcerative Colitis
• Management
– Biological treatment
• Effective anti-TNF class agents to induced and maintain
remmision
• The agents are:
– Infliximab
– Adalimumab
– Golimumab
Next Chapter
Crohn’s Disease
 Crohn’s Disease
• Introduction
– Manifested by focal, asymetric and transmural
inflammation of the digestive tract that may, or may
not, be accompained by granuloma formation
– Inflamation of CD is patchier (focal), may be
transmural and can involve any segmen of the
gastrointestinal tract form mouth to anus
– Transmural nature of CD lead to stricture and fistulae
– Histological finding of noncaseating granulomas is a
hallmark of CD but these lessions are identified about
30% patients
 Crohn’s Disease
• Clinical features
– Diarrhoea
• Increased mucosal permeability due to mucosal inflamation
• imbalance in the luminal concentration of bile acids and bacterial overgrowth
behind stricture
– Abdominal pain
• Streching of receptors in the bowel wall as the food bolus passes through
narrow segment
– Weight loss and malnutrition
• Intestinal malabsorption secondary to diseased
• Protein loss through exudation of inflamed bowel, folate malabsorption,
hypercatabolic state, poor intake
– Anorexia
• Associated with TNF-a and delayed gastric emtying
– Fever
• Secondary to leukotrienes like IL-1, IL-6, TNF a
 Crohn’s Disease
• Physical Examination
– Anaemia
• Vitamin B12, iron and folate deficiency
• Inhibit erythropoetin production
– Sign of malabsorption syndrome
– Aphthous ulcer in the mouth
– Skin lesions
– Eyes: episcleritis, scleritis or uveitis
– Musculoskeletal
• Waxing and waning type of join pain
• Knee and ankle are the most common joins involved
 Crohn’s Disease
• Physical Examination
– Abdominal examination:
• May normal
• Distension and signs of intestinal obstruction
• Hepatomegaly seen in 10% patient
– Digital rectal examination
• 24% CD patien have perianal lession:
– Fissure 25%
– Fistula 15-35%
– Ulcer, stenosis, abscess
• Perianal tenderness, blood on the finger, palpation of
pseudopolyp
 Crohn’s Disease
• Investigation
– Biochemistry
• Low Hb
• Leucocytosis in case of active disease
• Low serum albumin
– Colonoscopy
• Variable and changes with disease activity and duration
• Spare the rectum to ileum
• Skip lesions
• Aphthous ulcer
Colonoscopy showing deep ulceration
 Crohn’s Disease
• Investigation
– Plain radiograph and Barium series
• Plan radiograph: bowel dilatation, obstruction,
perforation and wall thickening
• Barium series: choice for determining the extend of the
involvement of small bowel
• Deep transverse and longitudinal ulcer separated by
oedematous mucosa gives cobble stone appearance
• String sign: narrowed terminal ileum secondary to
oedema, inflammation and spasm
 Crohn’s Disease
• Investigation
– CT Scan abdomen and MRI
• Thickening of owel wall, skip lesion on CT, perienteric
inflammation, fistula formation
• Fibrofatty proliferation of mesentery and increased
vascularity of mesentery
• Accurate modality for fistula, sinus tract and abscess
• If mesenteric node > 1 cm suspect malignancy
• Comb sign: hypervascular mesentery (mesenteric fat
penetrate muscularis propia of segmen bowel)
 Crohn’s Disease
• Investigation
– Histology
• Focal intestinal inflammation
• Inflammation is not defined by the directionality of the
crypt epithelium and may involve any portion of
intestinal mucoa
• Retention of globet cell mucin
• Prsence of sarcoid like non-caseating granulomas
 Crohn’s Disease
• Investigation
– Fecal and serology
• Anti Saccharomyces cerevisae (ASCA) reported 50-60%
• Fecal calprotectin seem in UC
 Endoscopic diffrentiation
Ulcerative Colitis Crohn’s Disease
Rectum is involved Rectum usually spared
No skip lesion Skip lesion seen
Normal appearing terminal ileum Ulceration in terminal ileum
Fistulae are not seen Fistulas are seen
Loss of vascular marking Aphthous ulcer
Mucosal granularity Linier or serpiginous ulcer
Cobblestone mucosa is not common Cobblestone mucosa
 Crohn’s Disease
• Montreal classification
– Age at diagnosis
• A1 : < 16 yo
• A2 : 17-40 yo
• A3 : > 40 yo
– Location
• L1 : Ileum (30%)
• L2 : Colon (20-25%)
• L3 : Ileocolonic (40%)
• L4 : Upper GI (5-10%)
– Behaviour
• B1 : non-cicatrizing/non fistulazing
• B2 : Stricturing
• B3 : Penetrating
• P : Perianal disease modifier
 Crohn’s Disease
• Complication
– Abscess
• 20%
• Intraabdominal abscess  most tipically the terminal
ileum
– Fistulae
• 20-40%
– Obstructuion
• Many cases of long standing disease
 Crohn’s Disease
• Treatment
– Nutritional management
– Medical treatment
– Biological therapy
– Surgical management
 Crohn’s Disease
• Treatment
– Nutritional management
• Goals: treating nutritional deficiency or reducing
inflammation
• Deficiencies of specific nutrients  suplementation
• Complex carbohydrates
• Elemental diets: consist of amino acids,
monosaccharide, vitamins, minerals, essential fatty acid
 Crohn’s Disease
• Treatment
– Medical treatment
• Aminosalicylates
• Corticosteroid
• Immunomodulator
• Thiopurines
 Crohn’s Disease
• Treatment
– Biological therapy
• TNF a inhibitor
– Infliximab
– Adalimumab
– Certolizumab Pegol
– Golimumab
• Inhibitor of lymphocyte trafficking
– a-4 b-7 integrims antagonizes – natalizumab, vedolizumab
– Anti sense to ICAM-1
– Antibody to a-4 b-7 antibody
• Inhibitors of Th 1 response
– Anti IL-2 antibody
– Anti INF g antibody
– IL-10
– Nati IL-2 receptor antibody – daclizumab, basiliximab
• Anti CD4 antibody
• JAK inhibitors – Tofacitinib, Filgotinib
 Crohn’s Disease
• Treatment
– Surgical management
• For complications CD – one third of patient
• To preserve length and functional of intestine
• Not for curative
• Indication:
– Medically intractable fistula
– Intra abdominal abscess
– Intestinal obstruction
– Toxic megacolon
– Haemorrhage
– Cancer
Thank
You