Ulcerative intestine
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Transcript of Ulcerative intestine
ULCERATIVE LESIONS OF INTESTINES
Dr.Saurav singh
Guide:Dr.PM Pagaro
Overview
Peptic Ulcer Disease Infectious Causes (Typhoid, T.B, Amoebic ulcers) Inflammatory bowel disease (Ulcerative colitis & Crohns disease)
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)
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
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)
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)
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
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
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)
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
Complications:
Bleeding Perforation
Penetration
Stenosis
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.
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
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
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.
Morphology of peptic ulcers
Clean, non-elevated edge
Granulation tissue base (floor)
Underlying fibrosis
Chronic Gastric Ulcer
Duodenal ulcer
Four histological zones are present in a peptic ulcer.
1. Necrotic zone
2. Nonspecific acute inflammation
3. Granulation tissue
4. Fibrosis
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.
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.
Morphology of duodenal ulcer
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
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
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
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
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).
enter spleen, liver and bone marrow (reticulo-
endothelial system)
further proliferation occurs
A lot of bacteria enter blood again causing
secondary bacteremia.
Recovery
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
Peyers patches
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 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.
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.
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
Intestinal tuberculosis.
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.
Life cycle
Mouth - Cyst ingested
Invades gut mucosa – cyst formation
Cyst
Passed in stool Excyst to trophozoite
Trophozoite
Amoebic disease
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
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.
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.
“ 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.”
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.
Crohn’s disease
• In 1913 Dr Dalziel described transmural intestinal inflammation in 13 autopsied patients.
• In 1930 Burril Crohn described TERMINAL ILEITIS first .
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
PATHOGENESIS
I. GENETIC PREDISPOSITION.
II. INFECTIOUS CAUSES.
III. ABNORMAL HOST IMMUNOREACTIVITY.
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.
• 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.
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
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.
• 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.
•
Implicated pathogens include Mycobacterium paratuberculosis Paramyxovirus Listeria monocytogenes Helicobacter hepaticus.
.
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.
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
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
Ulcerative colitis – clinical presentation
The major symptoms of UC are:
- diarrhea
- rectal bleeding
- tenesmus
- passage of mucus
- crampy abdominal pain
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)
Acute form with marked hyperemia
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
Broad based ulceration of the mucosa in distal colon or throughout its length
Pseudopolyps in
Ulcerative colitis
Ulcerative colitis
featuring crypt
abscesses
Chronic ulcerative colitis in remission
Ulcerative colitis in an active phase.
Ulcerative colitis - complications
Hemorrhage Perforation Stricture Toxic megacolon (transverse colon with a
diameter of more than 5 to 6 cm with loss of haustration)
Toxic Megacolon
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
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%
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
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
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
Skip lesion of crohns disease
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
SEGMENTAL
INVOLVEMENT WITH
TRANSMURAL
SPREAD
TYPICAL
COBBLESTONE
APPEARANCE
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.
Crohn colitis
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
The branched crypt
A - Mucosal Granuloma eroding a crypt of lieberkhun and initiating crypt abscess formation.
B - Crypt obliterated by Granuloma formation
• 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.
Crohn
disease
of the
colon.
Submucosal nonnecrotizing granulomas
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)
Extraintestinal manifestations of IBD
Iritis Episcleritis Arthritis Skin involvement Pericholangitis Sclerosing cholangitis
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
Gross :
Thick mucosa with finely nodular or velvety
surface configuration.
Lesion polypoid , elevated , nodular or villous
formation.
M/E :
Adenocarcinoma with varying degree of
differentiation .
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
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
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
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
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%
REFERENCES
Robbins and Cotran.
Surgical Pathology – Rosai and Ackerman’s.
Sternburg.
Harrison’s Textbook of Internal Medicine.
Internet