PATHLOGY AND PATHOGENESIS OF PEPTIC ULCER

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PATHLOGY AND PATHOGENESIS OF PEPTIC ULCER Powered By Docstoc
					PEPTIC ULCER
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).

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.
               DEFINITION

                     Aggressive factors
                     Gastric acid
                     Proteolytic enzyme
Imbalance between    Protective factors
aggressive &         Mucosal layer
protective factors
                     Bicarbonate secretion
                     Prostaglandins
                Gastric physiology
                 Acid secretion
* The human stomach contains about 1 billion parietal cells
* These are located in the walls of the midsection of the oxyntic
glands
* Oxyntic glands are the secretory glands of the gastric mucosa
* Oxyntic glands also contin chief, mucous, endocrine, and
somatostatin cells
* There are three primary pathways that stimulate gastric acid
secretion
1) The neurocrine pathway which delivers transmitters such as
acetylcholine post-ganglionic nerves on the stomach wall
2) The endocrine pathway which releases hormones such as gastrin
3) The paracrine pathway which releases histamine
* These pathways are interdependent
* Once pH is <3.5, pepsinogen is converted to
the active proteolytic enzyme pepsin
Pathogenesis of peptic ulcer:
 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.
   Imbalance (Aggressive/Defensive
                         Factors)

Aggressive Factors
* H. pylori
* Acid Secretion
* Pepsinogen Secretion
* NSAIDS
* Cigarette smoking
* Corticosteroid use
Defensive Factors
* Mucus Production
* Bicarbonate Production
* Mucosal blood flow - more important in the
development of stress ulcer
* High epithelial cell turnover
* Prostaglandins (PGE2) - stimulate mucus and
bicarbonate production, and blood flow
             Clinical presentation:

 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. Pyrosis
 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:

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.
H.Pylori
 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.
 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)



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.

   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.
Diagnostic Test and Procedures

a) Routine
* Routine lab tests are not useful in establishing the diagnosis
of uncomplicated PUD
* Hct, HgB, and stool hemoccult are useful to detect bleeding
b) H.pylori test
Histology
Culture
Biopsy/gram stain
Biopsy/CLO test
Urea breath test
Serology
           Diagnosis

   Breath Test: 
 Carbon 14 Urea
Test (see picture)

      Blood Test 




     Endoscopy 
                    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 .
                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.
Endoscopy
              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.
                Microscopic features

Four distinct layers are present in a peptic ulcer.
Surface coat of purulent exudate, bacteria and necrotic
debris.
Fibrinoid necrosis.
Granulation tissue.
Fibrosis replacing the muscle wall and extending into
subserosa.
                  Management
MEDICAL TREATMENT
a) Antisceretory/Anti-acid Agents
1) H2-blockers
2) Proton-pump inhibitors
3) Antacids
b) Cytoprotectives
1) Misoprostil
2) Sucralfate
c) H. pylori Agents
Eradication of H.pylori (proton pump inhibitor in
combination with antibiotics)
 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.
 Endoscopic
SURGICAL TREATMENT
              Differentials
Mesenteric ischemia
Angina pectoris
Biliary colic
Pancreatitis
              Complication
Hemorrhage
Perforation
Penetration
Obstruction
Malignancy

				
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posted:12/19/2011
language:English
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