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

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

3. 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)

5. 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

6. 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)

8. 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-1 in inflammation get pan
gastritis and Gastric ulcer, lower levels associated with
antral gastritis and Duodenal ulcer)

9. 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

10. 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

11. 
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)

12. 
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

13. 
Complications:

Bleeding

Perforation

Penetration

Stenosis

14. 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.

15. 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

16. 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

19. 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.

20. Morphology of peptic ulcers



Clean, non-elevated
edge
Granulation tissue
base (floor)
Underlying fibrosis

21. Chronic
Gastric
Ulcer

22. Duodenal
ulcer

23. 
1.
2.
3.
4.
Four histological zones
are present in a peptic
ulcer.
Necrotic zone
Nonspecific acute
inflammation
Granulation tissue
Fibrosis

24. 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.


25. 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.

26. Morpholog
y of
duoden
al ulcer

27. 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

28. 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

29. 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

30. S.Typhi.
2nd bacteremia
liver、spleen、gall、
BM ,ect
early stage
(1-3W）
stomach
(mono
Bac. In gall
nuclea
r
phago
cytes )
Bac. In
feces
Lower
ileum
S.Typhi eliminated
convalvescence stage
(4-5w)
peyer's patches &
mesenteric lymph nodes
LN Proliferate,swell
necrosis
defervescence stage
Enterorrhagia,i
ntestinal
perforation
（3-4w）
thoracic
duct
1st bacteremia
(Incubation stage)
10-14d

31. 
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).

32. 
enter spleen, liver and bone marrow (reticulo-endothelial
system)
further proliferation occurs

A lot of bacteria enter blood again causing secondary
bacteremia.

Recovery

33. PATHOLOGY
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


34. Peyers
patches

35. 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

36. 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.

37. 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.

38. 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

39. Intestinal tuberculosis.

40. 
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.

41. Life cycle
Mouth - Cyst ingested
Excyst to trophozoite
Passed in stool
Amoebic disease
Cyst
Trophozoite
Invades gut mucosa – cyst formation

42. 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

43. 



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.

44. 
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.




47. ― 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.‖

48. 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.

49. Crohn’s disease
•
In 1913 Dr Dalziel described transmural intestinal
inflammation in 13 autopsied patients.
•
In 1930 Burril Crohn described TERMINAL
ILEITIS first .

50. Epidemiology of IBD
Ulcerative 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
Smoking
1:1
May prevent
disease
1.1-1.8:1
May cause disease
Oral contraceptive No increased risk Relative risk
Appendectomy
Not protective
Monozygotic twins 8% concordance
Protective
67% concordance

51. PATHOGENESIS
I.
GENETIC PREDISPOSITION.
II.
INFECTIOUS CAUSES.
III.
ABNORMAL HOST IMMUNOREACTIVITY.

52. 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.

53. •
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.

54. NOD2 PROTEIN
EXPRESSED IN macrophages / monocytes
FUNCTION AS AN INTRACELLULAR RECEPTOR
MICROBES
TRIGGER NF- kB pathway
NOD2 gene
mutation
CYTOKINES AND OTHER PROTEINS
INNATE IMMUNE DEFENSE MECHANISM
DOWN REGULATION OF INNATE IMMUNITY
LEADS TO INFLAMMATORY BOWEL

55. 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.

56. •
•
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.

57. 




.
Implicated pathogens include
Mycobacterium paratuberculosis
Paramyxovirus
Listeria monocytogenes
Helicobacter hepaticus.

58. 
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.

59. 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

60. 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

61. Ulcerative colitis – clinical presentation
The major symptoms of UC are:
- diarrhea
- rectal bleeding
- tenesmus
- passage of mucus
- crampy abdominal pain


62. 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)

63. Acute form with
marked
hyperemia

64. 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


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

66. Pseudopolyps in
Ulcerative colitis

67. Ulcerative colitis
featuring crypt
abscesses

68. Chronic
ulcerative
colitis in
remission

69. Ulcerativ
e colitis
in an
active
phase.

70. Ulcerative colitis - complications




Hemorrhage
Perforation
Stricture
Toxic megacolon (transverse colon with a diameter of
more than 5 to 6 cm with loss of haustration)

71. Toxic Megacolon

72. 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

73. 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%

74. 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


75. 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


76. 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

77. Skip
lesion of
crohns
disease

78. 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

80. SEGMENTAL
INVOLVEMENT
WITH
TRANSMURAL
SPREAD

81. TYPICAL
COBBLESTONE
APPEARANCE

82. 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.

83. Crohn
colitis

84. 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

85. The branched
crypt

86. A - Mucosal
Granuloma
eroding a crypt of
lieberkhun and
initiating crypt
abscess
formation.
B - Crypt
obliterated by
Granuloma
formation

87. •
Non Caseating Granuloma-in ½ cases , Sarcoid
Granuloma in all tissue layers.
Others:
•
In diseased segments muscularis mucosa exhibits
reduplication ,
strictures.
thickening, irregularity's leads to
like,

88. Crohn
disease of
the colon.

89. Submucosal
nonnecrotizi
ng
granulomas

90. 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)

91. Extraintestinal manifestations of IBD






Iritis
Episcleritis
Arthritis
Skin involvement
Pericholangitis
Sclerosing cholangitis

92. 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

93. Gross :

Thick mucosa with finely nodular or velvety surface
configuration.

Lesion polypoid , elevated , nodular or villous formation.

94. M/E :

Adenocarcinoma with varying degree of
differentiation .

Always accompanied by dysplastic changes .

95. 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.

99. 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

100. Features
UC
CD
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
Clinical

101. Features
UC
CD
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
Radiographic

102. Features
UC
CD
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%
Morphologic

104. REFERENCES

Robbins and Cotran.

Surgical Pathology – Rosai and Ackerman’s.

Sternburg.

Harrison’s Textbook of Internal Medicine.

Internet