Transcript PATHLOGY AND PATHOGENESIS OF PEPTIC ULCER

PATHOLOGY AND PATHOGENESIS
OF PEPTIC ULCER
DR. SAMPURNA ROY M.D.
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Ulcers are defined as a breach in the mucosa of the
alimentary tract, which extends through the muscularis
mucosa into the submucosa or deeper.
( An erosion differs from an ulcer in being partial
thickness mucosal defect).
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Peptic ulcers are chronic most often solitary, lesions that
occur in any portion of gastrointestinal tract exposed to
the aggressive action of acid-peptic juices.
Clinical presentation:
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Remitting, relapsing lesion
Most often diagnosed in middle aged to older adults but
may first become evident in young adult life.
Epigastric burning or aching pain.
Pain worse at night and 1 to 3 hours after meal.
Nausea, vomiting, bloating , belching and weight loss
occur.
Complication: Anaemia, hemorrhage, perforation,
obstruction. Malignant formation is rare and related to
underlying gastritis.
Sites of peptic ulcer:
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Duodenum: First portion ( few cms from the pyloric ring).
Anterior wall is more often affected.
Stomach: Usually antrum. Lesser curvature (common) .
Anterior and posterior wall and greater curvature (less
common).
In the margins of a gastroenterostomy (stomal ulcer)
In the duodenum, stomach or jejunum of patients with
Zollinger-Ellison syndrome.
Within or adjacent to a Meckel’s diverticulum that
contains ectopic gastric mucosa.
Pathogenesis of peptic ulcer:
( see diagram )
Peptic ulcers are produced by an imbalance
between the gastro-duodenal mucosal defense
mechanisms and damaging forces of gastric
acid and pepsin, combined with superimposed
injury from environmental or immunologic
agents.
Role of H. Pylori infection in the pathogenesis of peptic
ulcer:
H. pylori infection is present in almost all patients with duodenal
ulcers and 70% cases with gastric ulcers.
Duodenal ulcers - Usually associated with gastritis confined to
the antrum.
Gastric ulcers - Usually associated with pangastritis.
Mechanism:
 H. pylori secretes urease (generates ammonia), protease (breaks
down glycoprotein in the gastric mucus) or phospholipases.
 Bacterial lipopolysaccharide attracts inflammmatory cells to
the mucosa. Neutrophils release myeloperoxide.
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A bacterial platelet-activating factor promotes thrombotic
occlusion of surface capillaries.
 Mucosal damage allows leakage of tissue nutrients in the
surface microenvironment , sustaining the bacillus.
H. Pylori infection in peptic ulceration: (continued)
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Damage of the protective mucosal layer. The epithelial cells are
exposed to the damaging effect of acid-peptic digestion.
Inflammation of the gastric mucosa.
Chronically inflamed mucosa more susceptible to acid- peptic
injury and prone to peptic ulceration.
Ulcers occur at sites of chronic inflammation .
Eg - Antrum
- Junction of antral and body- fundic mucosa (division
between the inflamed antral mucosa and normal acid secreting
mucosa).
Pangastritis - When there is extensive gastritis, the ulcers are
more proximally situated. In elderly patients gastric ulcers are
more proximally situated as there is proximal migration of the
antral-body mucosal junction.
Other factors causing peptic ulcer:
Peptic ulcer caused due to high gastrin level and excess acid
production. Gastrinoma may cause multiple peptic ulceration
as in Zollinger Ellison syndrome. There is increased parietal
cell mass.
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Peptic ulcers caused due to impaired mucosal defense . The
gastric acid and pepsin levels are normal and no H.pylori are
present.
Chronic use of NSAIDs (aspirin) causes suppression of
mucosal prostaglandin and direct irritative topical effect.
Repeated use of corticosteroid in high dose.
Cigarette smoking impair healing and favour recurrences.
Alcoholic cirrhosis.
Personality, psychological stress, ischemia.
Gross features:
Gastric ulcers are usually single well delineated lesion.
 Shape: Round, oval or linear.
 Size: Usually less than 2cm in diameter.
Lesions less than 0.3 cm are likely to be shallow erosions.
Giant ulcers are usually greater than 3cm in diameter.
May also reach upto 10cm (particularly on lesser curvature ).
Mortality rate is higher in these patients.
Size does not differentiate benign from malignant ulcer.
Some carcinomatous ulcers are less than 4cm and 10%
of benign ulcers are more than 4cm .
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Gross features:
Margins:
 Usually level with the surrounding mucosa or slightly
raised.
 The proximal margin has a overhanging border and distal
margin has a sloping border.
 Converging mucosal folds extend to its margin.
 Heaping up of of margin is rare in benign ulcer .
 Prominent marginal nodularity about the ulcer should
suggest the presence of carcinoma .
 Fungal infection can also give a nodular appearance of
the ulcer margin
Gross features:
Depth of penetration :
 Superficial ulcer penetrate the mucosa into the
muscularis mucosae.
 Deeply excavated ulcers having their bases on the
muscularis propria.
 Entire wall is penetrated and the ulcer base is adherant
to the pancreas, omental fat or liver. Free perforation
into peritoneal cavity may occur.
Gross features:
Base of ulcer:
 Smooth and clean (peptic digestion of any exudate).
 Thrombosed or patent blood vessels are evident at
the base.
Surrounding gastric mucosa:
 Puckering of surrounding mucosa. The mucosal fold
radiates from the crater in a spoke- like fashion.
 Edematous and reddened due to gastritis.
Gastric wall:
Scarring involve the entire thickness . Subserosal
fibrosis and inflammation present.
Regional lymphnodes are enlarged.
Biopsy of peptic ulcer:
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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.
Microscopic features
Four distinct layers are present in a peptic ulcer.
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Surface coat of purulent exudate, bacteria and necrotic
debris.
Fibrinoid necrosis.
Granulation tissue.
Fibrosis replacing the muscle wall and extending into
subserosa.
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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Microscopic features:
Healing process
Regenerating epithelium grows over the over the surface,
(any epithelium growing above an area where muscularis
mucosa is interrupted is regarded as regenerating).
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Intestinal metaplasia
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May contain chief and parietal cells (ulcer in the fundus
area)
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Gastritis remains after ulcer has healed. (D/D In erosive
gastritis & stress ulcer, gastritis in adjacent mucosa is
generally absent)
Cellular atypia may be present in ulcers caused by arterial
infusion chemotherapy.
Management
MEDICAL TREATMENT
Eradication of H.pylori (proton pump inhibitor in
combination with antibiotics)
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Acid suppression- Antacid & or H2 blockers
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Cessation of NSAIDS.
Criteria for reduction of the size of ulcer crater.
Reduction of crater size by 50% over 6-8 weeks of
intensive medical management.
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SURGICAL TREATMENT
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Subtotal gastric resection without vagotomy and
drainage (gastroenterostomy or pyloroplasty)
Truncal vagotomy plus antrectomy