PEPTIC ULCERPEPTIC ULCER

Ulcers are defined as a breach in the mucosa of the Ulcers are defined as a breach in the mucosa of the alimentary tract, which extends through the muscularis alimentary tract, which extends through the muscularis mucosa into the submucosa or deepermucosa into the submucosa or deeper..

( (An erosion differs from an ulcer in being partial thickness An erosion differs from an ulcer in being partial thickness mucosal defectmucosal defect.).)

Peptic ulcers are chronic most often solitary, lesions that Peptic ulcers are chronic most often solitary, lesions that occur in any portion of gastrointestinal tract exposed to occur in any portion of gastrointestinal tract exposed to the aggressive action of acid-peptic juicesthe aggressive action of acid-peptic juices..

DEFINITIONDEFINITION

Imbalance between Imbalance between aggressive & aggressive & protective factorsprotective factors

Aggressive factorsAggressive factors

Gastric acidGastric acid

Proteolytic enzymeProteolytic enzyme

Protective factorsProtective factors

Mucosal layerMucosal layer

Bicarbonate secretionBicarbonate secretion

ProstaglandinsProstaglandins

Gastric physiologyGastric physiologyAcid secretionAcid secretion

* *The human stomach contains about 1 billion parietal cellsThe human stomach contains about 1 billion parietal cells * *These are located in the walls of the midsection of the oxyntic These are located in the walls of the midsection of the oxyntic

glandsglands * *Oxyntic glands are the secretory glands of the gastric mucosaOxyntic glands are the secretory glands of the gastric mucosa

* *Oxyntic glands also contin chief, mucous, endocrine, and Oxyntic glands also contin chief, mucous, endocrine, and somatostatin cellssomatostatin cells

* *There are three primary pathways that stimulate gastric acid There are three primary pathways that stimulate gastric acid secretionsecretion

11 ) )The neurocrine pathway which delivers transmitters such as The neurocrine pathway which delivers transmitters such as acetylcholine post-ganglionic nerves on the stomach wallacetylcholine post-ganglionic nerves on the stomach wall

22 ) )The endocrine pathway which releases hormones such as gastrinThe endocrine pathway which releases hormones such as gastrin 33 ) )The paracrine pathway which releases histamineThe paracrine pathway which releases histamine

* *These pathways are interdependentThese pathways are interdependent

* *Once pH is <3.5, pepsinogen is converted to Once pH is <3.5, pepsinogen is converted to the active proteolytic enzyme pepsinthe active proteolytic enzyme pepsin

Pathogenesis of peptic ulcerPathogenesis of peptic ulcer::

Peptic ulcers are produced by an imbalance Peptic ulcers are produced by an imbalance between the gastro-duodenal mucosal between the gastro-duodenal mucosal defense mechanisms and damaging defense mechanisms and damaging forces of gastric acid and pepsin, forces of gastric acid and pepsin, combined with superimposed injury from combined with superimposed injury from environmental or immunologic agentsenvironmental or immunologic agents..

Imbalance Imbalance )Aggressive/Defensive )Aggressive/Defensive Factors(Factors(

Aggressive FactorsAggressive Factors * *H. pyloriH. pylori

* *Acid SecretionAcid Secretion * *Pepsinogen SecretionPepsinogen Secretion

* *NSAIDSNSAIDS * *Cigarette smokingCigarette smoking * *Corticosteroid useCorticosteroid use

Defensive FactorsDefensive Factors

* * Mucus ProductionMucus Production * *Bicarbonate ProductionBicarbonate Production

* *Mucosal blood flow - more important in the Mucosal blood flow - more important in the development of stress ulcerdevelopment of stress ulcer

* *High epithelial cell turnoverHigh epithelial cell turnover

* *Prostaglandins )PGE2( - stimulate mucus and Prostaglandins )PGE2( - stimulate mucus and bicarbonate production, and blood flowbicarbonate production, and blood flow

Clinical presentationClinical presentation::

Remitting, relapsing lesionRemitting, relapsing lesionMost often diagnosed in middle aged to older Most often diagnosed in middle aged to older adults but may first become evident in young adults but may first become evident in young adult lifeadult life..

Epigastric burning or aching pain. PyrosisEpigastric burning or aching pain. Pyrosis Pain worse at night and 1 to 3 hours after mealPain worse at night and 1 to 3 hours after meal.. Nausea, vomiting, bloating , belching and weight Nausea, vomiting, bloating , belching and weight

loss occurloss occur.. Complication: Anaemia, hemorrhage, perforation, Complication: Anaemia, hemorrhage, perforation,

obstruction. Malignant formation is rare and obstruction. Malignant formation is rare and related to underlying gastritisrelated to underlying gastritis..

Sites of peptic ulcerSites of peptic ulcer::

Duodenum: First portion ) few cms from the pyloric Duodenum: First portion ) few cms from the pyloric ring(. Anterior wall is more often affectedring(. Anterior wall is more often affected..

Stomach: Usually antrum. Lesser curvature Stomach: Usually antrum. Lesser curvature )common( . Anterior and posterior wall and )common( . Anterior and posterior wall and

greater curvature )less common(greater curvature )less common( . .In the margins of a gastroenterostomy )stomal In the margins of a gastroenterostomy )stomal ulcer(ulcer(In the duodenum, stomach or jejunum of patients In the duodenum, stomach or jejunum of patients

with Zollinger-Ellison syndromewith Zollinger-Ellison syndrome . .Within or adjacent to a Meckel’s diverticulum that Within or adjacent to a Meckel’s diverticulum that

contains ectopic gastric mucosacontains ectopic gastric mucosa . .

H.PyloriH.Pylori

Role ofRole of H. Pylori infection in the pathogenesis of peptic H. Pylori infection in the pathogenesis of peptic ulcerulcer::

H. pylori infection is present in almost all patients with duodenal H. pylori infection is present in almost all patients with duodenal ulcers and 70% cases with gastric ulcersulcers and 70% cases with gastric ulcers..

Duodenal ulcers - Usually associated with gastritis confined to Duodenal ulcers - Usually associated with gastritis confined to the antrumthe antrum..

Gastric ulcers - Usually associated with pangastritisGastric ulcers - Usually associated with pangastritis.. MechanismMechanism::

H. pylori secretes urease (generates ammonia), protease (breaks H. pylori secretes urease (generates ammonia), protease (breaks down glycoprotein in the gastric mucus) or phospholipasesdown glycoprotein in the gastric mucus) or phospholipases . .

Bacterial lipopolysaccharide attracts inflammmatory cells to the Bacterial lipopolysaccharide attracts inflammmatory cells to the mucosa. Neutrophils release myeloperoxidemucosa. Neutrophils release myeloperoxide..

A bacterial platelet-activating factor promotes thrombotic A bacterial platelet-activating factor promotes thrombotic occlusion of surface capillariesocclusion of surface capillaries..Mucosal damage allows leakage of tissue nutrients in the surface Mucosal damage allows leakage of tissue nutrients in the surface microenvironment , sustaining the bacillusmicroenvironment , sustaining the bacillus..

H. Pylori infection in peptic ulceration: (continued)H. Pylori infection in peptic ulceration: (continued)

Damage of the protective mucosal layer. The epithelial cells are Damage of the protective mucosal layer. The epithelial cells are exposed to the damaging effect of acid-peptic digestionexposed to the damaging effect of acid-peptic digestion..Inflammation of the gastric mucosaInflammation of the gastric mucosa..Chronically inflamed mucosa more susceptible to acid- peptic Chronically inflamed mucosa more susceptible to acid- peptic injury and prone to peptic ulcerationinjury and prone to peptic ulceration..

Ulcers occur at sites of chronic inflammationUlcers occur at sites of chronic inflammation. . Eg - AntrumEg - Antrum

- - Junction of antral and body- fundic mucosa (division Junction of antral and body- fundic mucosa (division between the inflamed antral mucosa and normal acid secreting between the inflamed antral mucosa and normal acid secreting mucosa)mucosa)..

Pangastritis - When there is extensive gastritis, the ulcers are Pangastritis - When there is extensive gastritis, the ulcers are more proximally situated. In elderly patients gastric ulcers are more proximally situated. In elderly patients gastric ulcers are more proximally situated as there is proximal migration of the more proximally situated as there is proximal migration of the antral-body mucosal junctionantral-body mucosal junction . .

Other factors causing peptic ulcerOther factors causing peptic ulcer::

Peptic ulcer caused due to Peptic ulcer caused due to high gastrin level and excess acidhigh gastrin level and excess acid productionproduction. Gastrinoma may cause multiple peptic ulceration . Gastrinoma may cause multiple peptic ulceration as in Zollinger Ellison syndrome. There is increased parietal as in Zollinger Ellison syndrome. There is increased parietal cell masscell mass..

Peptic ulcers caused due to Peptic ulcers caused due to impaired mucosal defenseimpaired mucosal defense . The . The gastric acid and pepsin levels are normalgastric acid and pepsin levels are normal and and no H.pylorino H.pylori are are presentpresent..Chronic use of NSAIDs (aspirin) causes suppression of mucosal Chronic use of NSAIDs (aspirin) causes suppression of mucosal prostaglandin and direct irritative topical effectprostaglandin and direct irritative topical effect..

Repeated use of corticosteroid in high doseRepeated use of corticosteroid in high dose.. Cigarette smoking impair healing and favour recurrencesCigarette smoking impair healing and favour recurrences..

Alcoholic cirrhosisAlcoholic cirrhosis.. Personality, psychological stress, ischemiaPersonality, psychological stress, ischemia..

Diagnostic Test and ProceduresDiagnostic Test and Procedures

a( Routinea( Routine * * Routine lab tests are not useful in establishing the diagnosis Routine lab tests are not useful in establishing the diagnosis

of uncomplicated PUDof uncomplicated PUD * * Hct, HgB, and stool hemoccult are useful to detect bleedingHct, HgB, and stool hemoccult are useful to detect bleeding

b( b( H.pyloriH.pylori test test HistologyHistology

CultureCulture Biopsy/gram stainBiopsy/gram stain

Biopsy/CLO testBiopsy/CLO test

Urea breath testUrea breath test

SerologySerology

DiagnosisDiagnosis

Breath Test: Breath Test: Carbon 14 Urea Carbon 14 Urea

Test )see picture(Test )see picture(

Blood TestBlood Test

EndoscopyEndoscopy

Gross featuresGross features::

Gastric ulcers are usually single well delineated lesionGastric ulcers are usually single well delineated lesion..

Shape:Shape: Round, oval or linear Round, oval or linear..

Size:Size: Usually less than 2cm in diameter Usually less than 2cm in diameter..

Lesions less than 0.3 cm are likely to be shallow erosionsLesions less than 0.3 cm are likely to be shallow erosions..

Giant ulcers are usually greater than 3cm in diameterGiant ulcers are usually greater than 3cm in diameter . .

May also reach upto 10cm )particularly on lesser curvature (May also reach upto 10cm )particularly on lesser curvature (..

Mortality rate is higher in these patientsMortality rate is higher in these patients..

Size does not differentiate benign from malignant ulcerSize does not differentiate benign from malignant ulcer..

Some carcinomatous ulcers are less than 4cm and 10%Some carcinomatous ulcers are less than 4cm and 10%

of benign ulcers are more than 4cmof benign ulcers are more than 4cm. .

Gross featuresGross features : :

Depth of penetrationDepth of penetration: : Superficial ulcer penetrate the mucosa into the Superficial ulcer penetrate the mucosa into the

muscularis mucosaemuscularis mucosae.. Deeply excavated ulcers having their bases on Deeply excavated ulcers having their bases on

the muscularis propriathe muscularis propria.. Entire wall is penetrated and the ulcer base is Entire wall is penetrated and the ulcer base is

adherantadherant to the pancreas, omental fat or liver. Free to the pancreas, omental fat or liver. Free

perforation into peritoneal cavity may occurperforation into peritoneal cavity may occur..

EndoscopyEndoscopy

Biopsy of peptic ulcerBiopsy of peptic ulcer::

Biopsy is necessary to distinguish between benign and Biopsy is necessary to distinguish between benign and malignant ulcersmalignant ulcers..

Biopsy should be taken from the ulcer edge, at least from Biopsy should be taken from the ulcer edge, at least from each quadranteach quadrant..

Upto 10-12 biopsies may be taken to exclude cancerUpto 10-12 biopsies may be taken to exclude cancer..

Repeat endoscopy may be necessary if biopsies are Repeat endoscopy may be necessary if biopsies are negative and there is high index of suspicionnegative and there is high index of suspicion..

Microscopic featuresMicroscopic features

Four distinct layers are present in a peptic ulcerFour distinct layers are present in a peptic ulcer..

Surface coat of purulent exudate, bacteria and necrotic Surface coat of purulent exudate, bacteria and necrotic debrisdebris..

Fibrinoid necrosisFibrinoid necrosis..

Granulation tissueGranulation tissue..

Fibrosis replacing the muscle wall and extending into Fibrosis replacing the muscle wall and extending into subserosasubserosa..

ManagementManagement

MEDICAL TREATMENTMEDICAL TREATMENT

a) Antisceretory/Anti-acid Agentsa) Antisceretory/Anti-acid Agents 11 ( (H2-blockersH2-blockers

22 ( (Proton-pump inhibitorsProton-pump inhibitors

33 ( (AntacidsAntacids

b) Cytoprotectivesb) Cytoprotectives 11 ( (MisoprostilMisoprostil

22 ( (SucralfateSucralfate

c) c) H. pyloriH. pylori Agents Agents

Eradication of H.pylori )proton pump inhibitor in Eradication of H.pylori )proton pump inhibitor in combination with antibiotics(combination with antibiotics(

Cessation of NSAIDSCessation of NSAIDS.. Criteria for reduction of the size of ulcer craterCriteria for reduction of the size of ulcer crater..

Reduction of crater size by 50% over 6-8 weeks of Reduction of crater size by 50% over 6-8 weeks of intensive medical managementintensive medical management..

EndoscopicEndoscopic SURGICAL TREATMENTSURGICAL TREATMENT

DifferentialsDifferentials

Mesenteric ischemiaMesenteric ischemia

Angina pectorisAngina pectoris

Biliary colicBiliary colic

PancreatitisPancreatitis

ComplicationComplication

HemorrhageHemorrhage

PerforationPerforation

PenetrationPenetration

ObstructionObstruction

MalignancyMalignancy