The most important contributing factors are H pylori, NSAIDs, acid, and pepsin. Additional aggressive factors include smoking, ethanol, bile acids, aspirin, steroids, and stress.Important protective factors are mucus, bicarbonate, mucosal blood flow, prostaglandins, hydrophobic layer, and epithelial renewal. When an imbalance occurs, Peptic ulcer ds might develop
--H Pylori Causes intense inflammatory and immune response. (Inter leukinL-1, IL-6, TNF, IL-8).it Enhance gastric acid secretion and impairs duodenal bicarbonate production
--------Rapid urease tests are considered the endoscopic diagnostic test of choice. The presence of H pylori in gastric mucosal biopsy specimens is detected by testing for the bacterial product urease. One or more gastric biopsy specimens are placed in the rapid urease test kit. If H pylori are present, bacterial urease converts urea to ammonia, which changes pH and produces a color change
Picture shows Clusters of bacteria on Warthin–Starry staining. WS stains organisms dark brown to black, and the background light golden brown/golden yellow.
The 1st figure shows Hpylori with leung stain…2nd figure shows rod shaped bacilli satained with methylene blue in the gastric pit.
--PETIC ulcer are 4x more common in proximal duodenum then in stomach.they are solitary in more then 80% of patient.classic peptic ulcer is round to oval sharpely punched out defect.this is endoscopic view of peptic ulcer showing….
This is a gross view of a chronic gastric ulcer showingruggae. There is “punched-out” defect with sharp, overhanging margins
Picture shows duodenal peptic ulcer located in first portion of duodenum
Picture shows cross-section of a duodenal ulcer crater with an acute inflammatory exudate
This is picture showing pathogenesis of typhoid fever…
Picture shows circumfential ulceration which is characteristic of intestinal TB
Entamoebahistolytica has a biphasic life cycle, existing in two forms; as an infectious cyst and an amoeboid trophozoite. Transmission is by feco-oral route.
-----------In more severe cases fulminant amoebic colitis develops. Liver involvement is more common in these cases,
-----------------------Muscle coat of the large intestine form a barrier to the penetrating trophozoites which fan out laterally producing a flask-shaped ulcer with narrow neck and broad base.
--------There is little inflammatory response in the early ulcers.
Picture showing amebic colitis,multiple undermined ulcers are present in cecum and ascending colon.
Picture shows Histological cross section of classical flask shaped amoebic ulcer in colonic mucosa
-----------It Refers to two chronic diseases that cause inflammation of the intestines:ulcerative colitis and Crohn's disease.
UC- chemicals in tobacco especially nicotine has a protective effect by increasing the mucus production in the colon and rectum. It also suppresses the immune system and prevents inflammation. But in CD- such chemicals like nicotine, CO, free radicals acts as immunosuppressants on macrophages thus many harmful bacteria cannot be cleared from the gut, they may also lead to restricion in blood flow inside the gut walls thus making intestine more susceptible to develop crohnsds.
The NOD2 gene is expressed mainly in monocyte/macrophage cell lines, where it has a role in host-signaling pathways. One effect is the activation of nuclear factor (NF)-kB Activation leads to production of a wide variety of nonspecific mediators of inflammation like cytokines, growth factors, and metabolites of arachidonic acid and reactive oxygen ultimately lead to tissue destruction
------Inibd Exposure to luminal micro flora triggers an inflammatory response by the cells lining the mucosa, leading to a chronic, destructive immune response.
------------------------ A number of reports suggest a link between Crohnds and early measles infection.
Picture shows chronic form of ulcerative colitis with mucosal ulceration and residual foci of elevated and hyperimic mucosa.
The luminal border is irregular; the colonic crypts have lost their parallel arrangement, and they are branched and budded. The muscularismucosae is hypertrophied.
The luminal border is irregular. Increased inflammatory cells are present within the lamina propria.
Picture showing toxic megacolon.it is complication of ulcerative colitis..
This slide shows a segment of intestine with Crohn’s disease. This disease does NOT involve bowel in a uniform manner, i.e., there are skip areas. It is a disease, however, in which the affected segments are involved in their entire thickness: mucosa, submucosa, muscularis, and serosa –a transmural involvement
Picture shoeing Cobblestone lesions" usually in terminal ileum and "skip lesions" which are discontinuous areas of inflammation, edema and fibrosis
Crohn colitis demonstrating the "focal active colitis" pattern of injury showing infiltration of chronic inflammatory cells in the lamina propria.
this is a picture showing chronic crohns colitis..the branched crypt is feature of chronicity..
This is a picture showing noncaseatinggranuloma is present in the lamina propria of an uninvolved region of colonic mucosa
This diagram shows Lymphocytic inflitration and the formation of non-caseatinggranuloma.
Picture showing low grade dysplasia with chronic ulcerative colitis.
Cbc-complete blood count
This slide shows differentiating features between ulcerative colitis and crohns ds.1st clinical feature
This diagram shows distribution of lesions in inflammatory bowel disease.the distinction between crohnds and ulcerative colitis is primarily based on morphology.Incrohnds there are skip lesions but in ulcerative colitis there is continuos colon involvement.incrohns ulceration and fissure are seen and in ulcerative there is pseudopolyp are characteristic.
ULCERATIVE LESIONS OF
PEPTIC ULCER DISEASE
A circumscribed ulceration of the
gastrointestinal mucosa occurring in areas
exposed to acid and pepsin.
Related to ectopic gastric mucosa (e.g. in Meckel’s
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
Family history: 3-4 increased risk .
Cigarette smoking: ulceration increased
Emotional disturbances and Stress: increase gastric
H. Pylori: 70% of all cases.
Other causes include
Stress –shock, sepsis or severe trauma
Head trauma (cushing ulcer)
Helicobacter factors in
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-1 in inflammation get pan
gastritis and Gastric ulcer, lower levels associated with
antral gastritis and Duodenal ulcer)
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
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
10 - 20% of patients with a gastric ulcer have a
concomitant duodenal ulcer
Symptoms of duodenal ulcer
epigastric pain 2 hours after meal or on a empty
stomach or during night
seasonal dependence (spring, autumn)
Symptoms of gastric ulcer disease:
epigastric pain after meal or during meal
upper dyspeptic syndrome – loss of appetite, nauzea,
vomitting brings relief
loss of weight
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.
Helicobacter pylori detection
Gastric biopsy and
culture of Bx specimen
Tests using urease
enzyme in Bx
Bacterial DNA detection
Urea breath test
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.
Biopsy of peptic ulcer:
Biopsy is necessary to distinguish between benign and
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.
Morphology of peptic ulcers
Four histological zones
are present in a peptic
Thickening of vessels caused by subendothelial fibrous
Hypertrophy of nerve bundles.
Mucosa surrounding the ulcer is pyloric type.
Necrotic surface shows superimposed infection by
In case of H. pylori infection following features are
at the ulcer edge : loss of apical portion of cells,
dropout of epithelial cells,
erosion, cellular tufts.
Regenerating epithelium grows over the surface.
May contain chief and parietal cells (ulcer in the
Gastritis remains after ulcer has healed.
Cellular atypia may be present.
Neoplasm of the stomach
Nonulcer dyspepsia (also called functional dyspepsia)
MI—not to be missed if having chest pain
Natural history of PUD
PUD is a chronic episodic disease with relapses and
If left untreated, 30-40 % of ulcers heal within 8
Recurrence rate without treatment is 70% during first
year and 90% within 2 years.
Complications develop in 20% of PUD
Acute enteric infectious disease
caused by Salmonella typhi (S.Typhi).
Clinical features : prolonged fever, Relative bradycardia,
apathetic facial expressions, roseola, splenomegaly,
Can lead to intestinal perforation, intestinal hemorrhage
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).
enter spleen, liver and bone marrow (reticulo-endothelial
further proliferation occurs
A lot of bacteria enter blood again causing secondary
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
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
2. Gastrointestinal Tuberculosis
Abdominal tuberculosis is usually secondary to pulmonary
The ileocecal region is the most common area of involvement in
the gastrointestinal tract due to the abundance of lymphoid
The natural course of gastrointestinal tuberculosis may be
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
Urine routine - to detect diabetes mellitus
Plain X-ray of the abdomen
Laparoscopic biopsy of tubercles found in the
peritoneum or other parts
3. AMOEBIC ULCER
The causative organism is parasitic protozoan, called
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
Mouth - Cyst ingested
Excyst to trophozoite
Passed in stool
Invades gut mucosa – cyst formation
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
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
The base of the ulcer is covered by grey - white exudate.
There is always undenuded mucosa between the ulcers.
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
― IBD is a set of
activation of the
system ,driven by
the presence of
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.
In 1913 Dr Dalziel described transmural intestinal
inflammation in 13 autopsied patients.
In 1930 Burril Crohn described TERMINAL
ILEITIS first .
Epidemiology of IBD
Ulcerative colitis Crohn’s disease
Age of onset
15-30 & 60-80
15-30 & 60-80
May cause disease
Oral contraceptive No increased risk Relative risk
Monozygotic twins 8% concordance
ABNORMAL HOST IMMUNOREACTIVITY.
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.
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.
EXPRESSED IN macrophages / monocytes
FUNCTION AS AN INTRACELLULAR RECEPTOR
TRIGGER NF- kB pathway
CYTOKINES AND OTHER PROTEINS
INNATE IMMUNE DEFENSE MECHANISM
DOWN REGULATION OF INNATE IMMUNITY
LEADS TO INFLAMMATORY BOWEL
Abnormal host immunoreactivity
IBD is characterized by immunoregulatory defects in the
mucosa, which appear to be associated with microbial
A number of theories have been advanced concerning the
pathogenesis of this process:
- dysfunctional immune host response to
- infection with a specific pathogen
- defective mucosal barrier to luminal antigens.
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
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.
Is an inflammatory disease involving only the large
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
40-50% of patients have disease limited to the rectum
30-40% of patients have disease extending beyond the
20% of patients have a total colitis
Proximal spread occurs in continuity without areas of
Ulcerative colitis – clinical presentation
The major symptoms of UC are:
- rectal bleeding
- passage of mucus
- crampy abdominal pain
Ulcerative colitis – macroscopic
Mucosa is :
- erythematous, has a granular surface that looks like a
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
Ulcerative colitis – microscopic
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
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
Most frequently affects distal third of small intestine
and the colon
Affects all layers of the affected bowel
Can affect any part of GI tract from the mouth to the
30-40% of patients have small bowel disease alone
40-55% of patients have both small and large intestines
15-25% of patients have colitis alone
In 75% of patients with small intestinal disease the
terminal ileum in involved in 90%
Crohn’s disease – sign and
- right lower quadrant pain and diarhhea
- palpable mass, fever and leucocytosis
- pain is colickly and relieved by defecation
- inflammatory disease is associated with loss of digestive
and absorptive surface
Crohn’s disease – sign and
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
- nausea, vomiting, epigastric pain
- second portion of duodenum is more commonly involved
than the bulb
Crohn’s disease – macroscopic
CD is a transmural process
CD is segmental with skip areas in the midst of diseased
In one –third of patients with CD perirectal fistulas,
fissures, abscesses, anal stenosis are present
Crohn’s disease – macroscopic
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
Cobblestone appearance is characteristic of CD
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.
A - Mucosal
eroding a crypt of
B - Crypt
Non Caseating Granuloma-in ½ cases , Sarcoid
Granuloma in all tissue layers.
In diseased segments muscularis mucosa exhibits
thickening, irregularity's leads to
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
• Duration of disease 10 yrs or more
• Pancolonic involvement
• Continuous progressive disease
• Severe initial onset
• Associated liver disease
Thick mucosa with finely nodular or velvety surface
Lesion polypoid , elevated , nodular or villous formation.
Adenocarcinoma with varying degree of
Always accompanied by dysplastic changes .
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.
Lab Findings in IBD
Anemia is common due to blood loss or
Leukocytosis & thrombocytosis also common
ESR typically elevated; monitors disease activity
Abnormal LFTs may represent pericholangitis or
Low serum albumin (protein-losing enteropathy)
suggests extensive colitis
75%, fissures, fistulas,
Response to steroid
Result of surgery
Sparing of rectum
Involvement of ileum
May be present
Longitudinal and transverse
Distribution of involvement
May be extreme
Present in 60%
Robbins and Cotran.
Surgical Pathology – Rosai and Ackerman’s.
Harrison’s Textbook of Internal Medicine.