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ULCERATIVE LESIONS OF INTESTINES Dr.Saurav singh Guide:Dr.PM Pagaro

Ulcerative intestine

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ULCERATIVE LESIONS OF INTESTINES

Dr.Saurav singh

Guide:Dr.PM Pagaro

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Overview

Peptic Ulcer Disease Infectious Causes (Typhoid, T.B, Amoebic ulcers) Inflammatory bowel disease (Ulcerative colitis & Crohns disease)

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PEPTIC ULCER DISEASE

DEFINITION A circumscribed ulceration of the

gastrointestinal mucosa occurring in areas exposed to acid and pepsin.

Sites: Duodenum Stomach Oesophagus Gastro-enterostomy stoma Related to ectopic gastric mucosa (e.g. in Meckel’s

diverticulum)

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Epidemiology of PUD

Prevalence about 5-10% Higher prevalence in low socioeconomic

classes and with certain diseases Duodenal ulcer M/F: 3:1 Gastric ulcer equal in both sexes but increases

with age Family history: 3-4 increased risk . Cigarette smoking: ulceration increased Emotional disturbances and Stress: increase

gastric acid secretion

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Etiopathogenesis

H. Pylori: 70% of all cases. Other causes include• NSAIDS• Alcohol• Gastritis• Socioeconomic status• Genetic factors• Stress –shock, sepsis or severe trauma Burns(curling ulcer) Head trauma (cushing ulcer)

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Helicobacter factors in pathogenesis

Some strains are more pathogenic than others. The Cag A (cytotoxic) antigen is one important virulence factor

Human variability also plays a part (e.g. individuals who produce high levels of IL-1b in inflammation get pan gastritis and Gastric ulcer, lower levels associated with antral gastritis and Duodenal ulcer)

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Duodenal Ulcers

duodenal sites are 4x as common as gastric sites most common in middle age

peak 30-50 years Male to female ratio—4:1 Genetic link: 3x more common in 1st degree

relatives more common in patients with blood group O associated with increased serum pepsinogen H. pylori infection common

up to 95% smoking is twice as common

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Gastric Ulcers

common in late middle age incidence increases with age

Male to female ratio—2:1 More common in patients with blood group A Use of NSAIDs - associated with a three- to four-

fold increase in risk of gastric ulcer Less related to H. pylori than duodenal ulcers –

about 80% 10 - 20% of patients with a gastric ulcer have a

concomitant duodenal ulcer

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Symptoms of duodenal ulcer disease:

epigastric pain 2 hours after meal or on a empty stomach or during night

pyrosis

good nutrition

obstipation

seasonal dependence (spring, autumn)

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Symptoms of gastric ulcer disease:

epigastric pain after meal or during meal

upper dyspeptic syndrome – loss of appetite, nauzea, vomiting, flatulence

vomitting brings relief

reduced nutrition

loss of weight

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Complications:

Bleeding Perforation

Penetration

Stenosis

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Diagnosis

Stool for fecal occult blood

Labs: CBC , liver function test, amylase and lipase.

Upper GI Endoscopy: Any pt >50 yrs with new onset of symptoms or those with alarm markings including anemia, weight loss, or GI bleeding.

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Helicobacter pylori detection

Invasive( through endoscopy) Gastric biopsy and

staining culture of Bx specimen Tests using urease

enzyme in Bx specimens Bacterial DNA detection

by PCR Non-invasive:

Urea breath test H.pylori antibodies Stool antigen Salivary antigen

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Staining methods of Helicobacter pylori

Warthin–Starry stain- The Warthin Starry stain (WS) is a silver nitrate based staining method

Leung stain- It is a novel Alcian yellow-toluidine blue (Leung) stain for H.pylori.

Methylene blue

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Biopsy of peptic ulcer:

Biopsy is necessary to distinguish between benign and malignant ulcers.

Biopsy should be taken from the ulcer edge, at least from each quadrant.

Upto 10-12 biopsies may be taken to exclude cancer.

Repeat endoscopy may be necessary if biopsies are negative and there is high index of suspicion.

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Morphology of peptic ulcers

Clean, non-elevated edge

Granulation tissue base (floor)

Underlying fibrosis

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Chronic Gastric Ulcer

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Duodenal ulcer

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Four histological zones are present in a peptic ulcer.

1. Necrotic zone

2. Nonspecific acute inflammation

3. Granulation tissue

4. Fibrosis

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Microscopic features

Thickening of vessels caused by subendothelial fibrous

proliferation. Hypertrophy of nerve bundles. Mucosa surrounding the ulcer is pyloric type. Necrotic surface shows superimposed infection by

candida albicans. In case of H. pylori infection following features are

noted at the ulcer edge : loss of apical portion of cells, dropout of epithelial cells, erosion, cellular tufts.

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Healing process- Regenerating epithelium grows over the

surface. Intestinal metaplasia May contain chief and parietal cells (ulcer in

the fundus area) Gastritis remains after ulcer has healed. Cellular atypia may be present.

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Morphology of duodenal ulcer

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Differential Diagnosis

Neoplasm of the stomach Pancreatitis Pancreatic cancer Diverticulitis Nonulcer dyspepsia (also called functional

dyspepsia) Cholecystitis Gastritis GERD MI—not to be missed if having chest pain

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Natural history of PUD

PUD is a chronic episodic disease with relapses and remissions.

If left untreated, 30-40 % of ulcers heal within 8 weeks.

Recurrence rate without treatment is 70% during first year and 90% within 2 years.

Complications develop in 20% of PUD

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Infectious causes

1. TYPHOID

Acute enteric infectious disease

caused by Salmonella typhi (S.Typhi).

Clinical features : prolonged fever, Relative

bradycardia, apathetic facial expressions, roseola,

splenomegaly, hepatomegaly, leukopenia.

Can lead to intestinal perforation, intestinal

hemorrhage

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S.Typhi.

stomach

Lower ileum

peyer's patches &mesenteric lymph nodes

thoracic

duct

1st bacteremia(Incubation stage)

10-14d

(mononuclear phagocytes )

2nd bacteremia

liver、 spleen、 gall、

BM ,ectearly stage

(1-3W)

LN Proliferate,swell necrosis

defervescence stage

( 3-4w)

Bac. In gall

Bac. In feces

S.Typhi eliminatedconvalvescence stage

(4-5w)

Enterorrhagia,intestinal

perforation

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Pathogenesis The amount of bacilli infection (>105bacteria)

Bacteria ingested orally Stomach barrier (some Eliminated) Enters the small intestine Penetrate the mucus layer Enter mononuclear phagocytes of ileal peyer's patches

and mesenteric lymph nodes Proliferate in mononuclear phagocytes

spread to blood causing primary bacteremia (Incubation period).

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enter spleen, liver and bone marrow (reticulo-

endothelial system)

further proliferation occurs

A lot of bacteria enter blood again causing

secondary bacteremia.

Recovery

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Proliferation of RES (reticuloendothelial system ) Specific changes in lymphoid tissues and

mesenteric lymph nodes."typhoid nodules“ Most characteristic lesion:

Ulceration of mucosa in the region of the Peyer’s patches of the small intestine

PATHOLOGY

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Peyers patches

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Major findings in lower ileum

Hyperplasia stage(1st week):

swelling lymphoid tissue and proliferation of macrophages.

Necrosis stage(2nd week): necrosis of swelling lymph nodes or solitary follicles.

Ulceration stage(3rd week):

Oval ulcer with its long axis parallel to the small intestine , this results from sloughing and shedding of necrotic lymphoid tissue in the peyers patches leading to intestinal hemorrhage, perforation .

Stage of healing (from 4th week):

healing of ulcer, no cicatrices and no contraction

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2. Gastrointestinal Tuberculosis Abdominal tuberculosis is usually secondary to

pulmonary tuberculosis Sites:

The ileocecal region is the most common area of involvement in the gastrointestinal tract due to the abundance of lymphoid tissue.

The natural course of gastrointestinal tuberculosis may be

• Ulcerative• hypertrophic or • ulcer hypertrophic.

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Clinical presentation Abdominal pain mimicking peptic ulcer disease

with stomach or duodenal infection;

Malabsorption with infection of the small intestine;

Pain, diarrhea, or hematochezia with infection of the colon.

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Investigations

Blood routine Urine routine - to detect diabetes mellitus Plain X-ray of the abdomen Laparoscopy Laparoscopic biopsy of tubercles found in the

peritoneum or other parts Barium studies

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Intestinal tuberculosis.  

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3. AMOEBIC ULCER

The causative organism is parasitic protozoan, called Entamoeba histolytica.

Site: It usually involves caecum and ascending colon  followed by sigmoid colon, rectum, and appendix. In severe cases the entire colon is involved.

The spectrum of colitis in amoebiasis ranges from mucosal thickening, to multiple cyst formation, to diffuse Inflammation / oedema, to necrosis and perforation of colonic wall.

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Life cycle

Mouth - Cyst ingested

Invades gut mucosa – cyst formation

Cyst

Passed in stool Excyst to trophozoite

Trophozoite

Amoebic disease

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Clinical presentation

• Gradual onset of bloody diarrhoea• Abdominal pain and tenderness.• Leucocytes and pus may be present in stool. • Fever present in <40% of patients.• Weight loss and anorexia can be present. • Local inflammatory masses, amoebomas, may

cause obstructive symptoms

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Gross features: Begin as small foci of necrosis that progress to ulcers. 

In the early stages the colonic ulcers have a narrow neck and thus appear as small nodules

As the ulcers enlarge they always retain their undermined base but the ulcerated area of the mucosa becomes larger.

The base of the ulcer is covered by grey - white exudate. There is always undenuded mucosa between the ulcers.

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Microscopic features: The ulcer is typically 'flask- shaped' and the broad 

base is composed of fibrin and cellular debris. A sharp line divides the necrotic and viable mucosa Trophozoites are found on the surface of the ulcers, in

the exudate and in the crater. They are frequently found in the submucosa,

muscularis propria, serosa.

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“ IBD is a set of chronic inflammatory conditions resulting from inappropriate and persistent activation of the mucosal immune system ,driven by the presence of normal intestinal flora.”

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HISTORY

ULCERATIVE COLITIS• First officially described by Wilks and Moxon in

1875.• Before this discovery , all the diarrheal diseases

were believed to be caused by infectious agents and bacteria.

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Crohn’s disease

• In 1913 Dr Dalziel described transmural intestinal inflammation in 13 autopsied patients.

• In 1930 Burril Crohn described TERMINAL ILEITIS first .

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Epidemiology of IBDUlcerative colitis Crohn’s disease

Incidence (US) 11/100 000 7/100 000

Age of onset 15-30 & 60-80 15-30 & 60-80

Male:female ratio 1:1 1.1-1.8:1

Smoking May prevent disease

May cause disease

Oral contraceptive No increased risk Relative risk

Appendectomy Not protective Protective

Monozygotic twins 8% concordance 67% concordance

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PATHOGENESIS

I. GENETIC PREDISPOSITION.

II. INFECTIOUS CAUSES.

III. ABNORMAL HOST IMMUNOREACTIVITY.

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GENETIC

• Genome wide scanning with microsatellite DNA markers has identified several genetic sites as being potentially associated with UC or CD.

• Significant linkages have been reported on chromosomes 1, 3, 6, 7, 12, 14, 16, and 19.

• One of the clearest linkages is for IBD-1, a susceptibility locus in the pericentromeric region of chromosome 16.

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• Detailed analysis has resulted in the identification of the nucleotide-binding oligomerization domain 2 (NOD2) gene and protein.

• NOD2 is also known as caspase activation and recruitment domain 15 (CARD15).

• This is a polymorphic gene, the product of which is involved in the innate immune system.

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NOD2 PROTEIN EXPRESSED IN macrophages / monocytes

FUNCTION AS AN INTRACELLULAR RECEPTOR MICROBES

TRIGGER NF- kB pathway

CYTOKINES AND OTHER PROTEINS

INNATE IMMUNE DEFENSE MECHANISM

NOD2 gene mutation

DOWN REGULATION OF INNATE IMMUNITY LEADS TO INFLAMMATORY BOWEL

DISEASES

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Abnormal host immunoreactivity

IBD is characterized by immunoregulatory defects in the mucosa, which appear to be associated with microbial exposure.

A number of theories have been advanced concerning the pathogenesis of this process:

- dysfunctional immune host response to normal luminal component

- infection with a specific pathogen

- defective mucosal barrier to luminal antigens.

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• It is hypothesized that exposure to commensal bacteria down-regulates the inflammatory genes and blocks activation of the NF-kB pathway, thus inhibiting the inflammatory immune response of the gut to the microbes and food antigens to which it is constantly exposed.

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Implicated pathogens include Mycobacterium paratuberculosis Paramyxovirus Listeria monocytogenes Helicobacter hepaticus.

.

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Defective barrier function

IBD is associated with increased permeability of the epithelial lining of the gut resulting in continuous stimulation of the mucosal immune system.

Luminal bacteria appear to intensify the permeability defect further, establishing a self-sustaining cycle of mucosal inflammation that allows for uptake and translocation of bacteria.

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Ulcerative colitis

Is an inflammatory disease involving only the large intestine.

The inner lining or mucosa of the intestine becomes inflamed and develops ulcers.

Always starts in rectum and is continuous until some proximal part of the colon.

Involves the mucosa and submucosa

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sites

40-50% of patients have disease limited to the rectum and rectosigmoid

30-40% of patients have disease extending beyond the sigmoid

20% of patients have a total colitis Proximal spread occurs in continuity without

areas of uninvolved mucosa

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Ulcerative colitis – clinical presentation

The major symptoms of UC are:

- diarrhea

- rectal bleeding

- tenesmus

- passage of mucus

- crampy abdominal pain

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Ulcerative colitis – macroscopic features

Mucosa is :

- erythematous, has a granular surface that looks like a sand paper

In more severe diseases:

- hemorrhagic, edematous and ulcerated

In fulminant disease a toxic colitis or a toxic megacolon may develop ( wall become very thin and mucosa is severly ulcerated)

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Acute form with marked hyperemia

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Ulcerative colitis – microscopic features

Process is limited to the mucosa and submucosa with deeper layer unaffected

Two major histologic features:

- the crypt architecture of the colon is distorted

- some patients have basal plasma cells and multiple basal lymphoid aggregates

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Broad based ulceration of the mucosa in distal colon or throughout its length

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Pseudopolyps in

Ulcerative colitis

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Ulcerative colitis

featuring crypt

abscesses

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Chronic ulcerative colitis in remission

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Ulcerative colitis in an active phase.

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Ulcerative colitis - complications

Hemorrhage Perforation Stricture Toxic megacolon (transverse colon with a

diameter of more than 5 to 6 cm with loss of haustration)

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Toxic Megacolon

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Crohn’s disease (CD)

Also referred to as granulomatous or regional enteritis, granulomatous ileitis, ileocolitis

Can have non-continuous pattern-”skip lesions”, with areas of severe inflammation with intervening normal mucosa

Most frequently affects distal third of small intestine and the colon

Affects all layers of the affected bowel

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sites

Can affect any part of GI tract from the mouth to the anus

30-40% of patients have small bowel disease alone

40-55% of patients have both small and large intestines disease

15-25% of patients have colitis alone

In 75% of patients with small intestinal disease the terminal ileum in involved in 90%

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Crohn’s disease – sign and symptoms

Ileocolitis - right lower quadrant pain and diarhhea - palpable mass, fever and leucocytosis - pain is colickly and relieved by defecation

Jejunoileitis - inflammatory disease is associated with loss of

digestive and absorptive surface

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Crohn’s disease – sign and symptoms Colitis and perianal disease - low grade fever, malaise, diarrhea, crampy

abdominal pain, sometimes hematochezia - pain is caused by passage of fecal material

through narrowed and inflamed segments of large bowel

Gastroduodenal disease - nausea, vomiting, epigastric pain - second portion of duodenum is more commonly

involved than the bulb

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Crohn’s disease – macroscopic features

CD is a transmural process

CD is segmental with skip areas in the midst of diseased intestine

In one –third of patients with CD perirectal fistulas, fissures, abscesses, anal stenosis are present

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Skip lesion of crohns disease

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Crohn’s disease – macroscopic features

mild disease is characterized by: aphtous or small superficial ulcerations

In more active disease: stellate ulcerations fuse longitudinally and

transversely to demarcate island of mucosa that are histologically normal

Cobblestone appearance is characteristic of CD

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SEGMENTAL

INVOLVEMENT WITH

TRANSMURAL

SPREAD

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TYPICAL

COBBLESTONE

APPEARANCE

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M/E : Mucosal inflammation Mucosa normal and retain mucus. Well-defined focus of inflammatory cells

surrounded by non inflammed and normal mucosa

As the disease establish , neutrophils infiltrate isolated crypts – abscess – ultimate destruction.

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Crohn colitis

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Chronic mucosal damage:

Architectural distortion manifested as villous blunting.

Crypts exhibit irregularities and branching. Crypt destruction leads to atrophy Gastric antral type or paneth cell metaplasia

occur

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The branched crypt

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A - Mucosal Granuloma eroding a crypt of lieberkhun and initiating crypt abscess formation.

B - Crypt obliterated by Granuloma formation

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• Non Caseating Granuloma-in ½ cases , Sarcoid

like, Granuloma in all tissue layers.

Others:

• In diseased segments muscularis mucosa exhibits

reduplication , thickening, irregularity's leads to

strictures.

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Crohn

disease

of the

colon.

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Submucosal nonnecrotizing granulomas

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Complications of Crohn's Disease:

Perianal fistulas

Perianal skin ulceration Increased incidence of gall and kidney stones (due

to malabsorption of fats and bile salts)

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Extraintestinal manifestations of IBD

Iritis Episcleritis Arthritis Skin involvement Pericholangitis Sclerosing cholangitis

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Risk of Malignancy in IBD

In Crohn’s disease, increased risk of cancer of the affected areas is seen

In ulcerative colitis, 8-10 years after initial diagnosis, there is a steady, significant increased risk of developing cancer Prognostic factors increasing malignancy risk in UC:

• Duration of disease 10 yrs or more• Pancolonic involvement• Continuous progressive disease• Severe initial onset• Associated liver disease

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Gross :

Thick mucosa with finely nodular or velvety

surface configuration.

Lesion polypoid , elevated , nodular or villous

formation.

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M/E :

Adenocarcinoma with varying degree of

differentiation .

Always accompanied by dysplastic

changes .

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Evaluation of Dysplasia

1 - Negative for Dysplasia.

2 - Indefinite for Dysplasia,probably Negative.

3 - Indefinite for Dysplasia, Unknown.

4 - Indefinite for Dysplasia,probably Positive.

5 - Positive for Dysplasia,Low Grade.

6 - Positive for Dysplasia,High Grade.

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Lab Findings in IBD

CBC’s: Anemia is common due to blood loss or

malabsorption Leukocytosis & thrombocytosis also

common ESR typically elevated; monitors disease

activity Abnormal LFTs may represent pericholangitis

or sclerosing cholangitis Low serum albumin (protein-losing

enteropathy) suggests extensive colitis

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Features UC CD

Clinical

Rectal Bleeding Common Inconspicuous

Abdominal mass Practically never 10-15%

Abdominal pain Left sided Right sided

Sigmoidoscopy Abnormal 95% Abnormal <50%

Free perforation 12% 04%

Colon CA 2 % Rare

Anal complications Minor 75%, fissures, fistulas, ulceration

Response to steroid 75% 25%

Result of surgery Good Fair

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Features UC CD

Radiographic

Sparing of rectum Exceptional 90%

Involvement of ileum Rare Common

Strictures Absent Present

Skip areas Absent Common

Internal fistula Absent May be present

Longitudinal and transverse ulcers

Exceptional Common

Fissuring Absent Common

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Features UC CD

Morphologic

Distribution of involvement

Diffuse Focal

Mucosal atrophy Marked Minimal

Cytoplasmic Mucin Diminished Preserved

Lymphoid aggregates Rare Common

Edema Minimal Marked

Hyperemia May be extreme Minimal

Granulomas Absent Present in 60%

Fissuring Absent Present

Crypt abscesses Common Rare

Rectal involvement Practically always 50%

Ileal involvement Minimal 50%

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REFERENCES

Robbins and Cotran.

Surgical Pathology – Rosai and Ackerman’s.

Sternburg.

Harrison’s Textbook of Internal Medicine.

Internet

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