Peptic Ulcer Disease

Peptic Ulcer Disease KhalaylehHarbi

Definition • PUD is a disease of multiple etiology that characteristic of local gastric or duodenal damage and ulceration

Epidemiology • The annual incidence in USA 1.8% or 500.000 new cases per year. • There are 4 million ulcer recurrences yearly. • More than 15.000 operation for PUD performed yearly. • About 4000 patient die from complication of their PUD yearly

Pathogenesis • Disbalance between aggressive factors and defenisive factors cause ulcer • Protective factor (defensive) – mucous bicarbonate secretion ,blood flow, grwoth factors, cell renewal, endogenous prostaglandine • Damaging(aggressive ) factors-HCL secretion, ethanol, smoking, reflux of bile, NSAID, hypoxia, HP

cause • 1. H.PYLORI infection (most common cause) • 2.NSAID (second most common cause) • 3.stress • 4. incrased pepsin and acid secretion

Role of HP • 90% of duodenal ulcer and 70% of gastric ulcer are associated with H.Pylori infection • H.Pylori is a gram-negative rod with 6 flagella.

HP • HP is a chronic infection that found worldwide • Person is infected, usually in childhood. • Developing countries have a higher rate of HP infection.

HP infection varies with racial and ethnic group- in USA white tend to have lowest rates of infection, African American rates of infection at each age is doubled those of white. • This difference in prevalence is related to lower socioeconomic status during childhood.

Rout of transmission • HP infection in one household member is associated with greater chance of infection in other members. • This mean that infection is transmitted person- to- person route and acquired early in life

HP • HP resides in gastric type epithelium within or beneath the mucus layer which is protect it from acid and antibiotic. • It shape and flagella aid it movement within through the mucus layer • HP produce variety of enzymes that help it adapt to hostile environment

HP • HP most potent producer of urease • Urease an enzyme that split urea into ammonia and bicarbonate creating an alkaline microenvironment in the sitting of acidic gastric milieu • This facilitate DS in laboratory test

Mechanism of gastric injury by HP • 1. production of toxic product to case local tissue injury • 2. induction of local mucosal immune response • 3. increased gastrin levels with a resultant increase in acid secretion.

1.Toxic product -local injury • HP locally produce toxic product include: * breakdown product from urease activity (ammonia). * cytotoxins : - a mucinase that degrades mucus and glycoprotein's , phospholipases that damage epithelial and mucus cells * platelet-activating factor-known to cause mucusal injury and thrombosis in microcalcification

2. Local Immune Injury d/t HP • HP known to case local inflammatory reaction in gastric mucusa and to produce chemotactic factors that attract neutrophils and monocytes • Activated monocytes and neutrophils in turn produce a number of proinflamatory cytokines and reactive oxygen metabolites

3.Gastrine and HP • In patient with HP infection basal and stimulated gastrine level are increased secondry to reduction in antral D cells caused by infection with HP. • HP-infected patient with duodenal ulcer did have a marked increase in acid secretion

HP and other GI disorder • HP is present in most case of chronic gastritis • HP most gastric cancer patient show evidence of past HP infection. • There is strong association between mucosa-associated lymphoid tissue( MALT) lymphoma and HP infection • Eradication of HP infection cause regression of these MALT lymphoma

Gastritis and PUD • PUD strongly associated with antral gastritis. • All patient with PUD have histologic evidence of antral gastritis (95%) • The only patient with gastric ulcer and no gastritis those ingesting aspirin or NSAID • 25% of patient with NSAID- associated ulcer have evidence of antral gastritis.

PUD and NSAID

after HP infection NSAID is the most common cause of PUD. • Risk of complication and bleeding in patient taking NSAID is increased with age >60 , patient having prior GI event or use of steroid and anticoagulant

Epidemiology of PUD and NSAID • 3 million people in USA take daily NSAID • 1 in 10patient taking NSAID have an acute ulcer • 2%-4% of NSAID user have GI complication each year • More than 3000 death and 25000 hospitalization per year are attributed to NSAID induced GI complication

NSAID injury • NSAID can cause acute gastroduodenal injury or chronic. • Acute injury occur within 2 week of use and range from hyperemia to erosion • Chronic injury occur after month of use and range from erosion to ulceration

Characteristic of NSAID ulcer • NSAID ulcer more frequently found in stomach whereas HP- ulcer found in duodenum • Chronic active gastritis always associated with HP and not found in NSAID associated ulcer • When NSAID is stopped the ulcer not recur but HP – associated ulcer recurrence is 50%-80% in 1 year unless the organism is eradicated

DU pathophisiology • Is a disease of multiple ethiology • Absolute requirement: acid and pepsin secretion in combination of H.Pylori infection or NSAIDs ingestion • Secretor abnormalities such as : bicarbonate secretion, nocturnal acid secretion, daytime acid secretion • DU associated with parietal cell number

Pathophysiology of gastric ulcer • GU may occur anywhere in stomach • GU rarely develop before age of 40, peak incidence 55-60 years • Predispose condition: age>40, sex f:m 2:1, ingestion of barrier breaking drug (aspirin), abnormalities in acid and pepsin secretion, gastric stasis, delayed gastric emptying, coexisting DU, duodenal gastric reflux of bile, infection with HP, smoking, alcohol intake

TYPE I of GU • Account for 60% of GU • Occur within 1.5cm of the histologic transition zone between the fundic and andantral mucosa (in the lesser curvature near the incisura) • Are not associated with excessive acid secretion • Not associated with DU or prepyloric ,pyloric mucosal abnormalities • Malignancy are major concern

TYPE II of GU • About 15% • Are located in the body of stomach in combination with a duodenal ulcer • Associated with excess acid secretion

TYPE III of GU • About 20% • Located in the preylorus • Are associated with excess of acid secretion

TYPE IV of GU • ABOUT 10% • Occur hiegh in the lesser curvature near the gasroesophageal junction • Are not associated with excessive acid secretion

clinical feature • Abdominal midepigastric pain. • Pain is well localized • Tolerable and relieve by food in DU and exagerated by food in GU • Pain irradiation to back suggest pentration to pancreas • Other magnifestation: perforation, bleeding, obstruction

Perforation • About 5% of the time ulcer perforated into free peritoneal cavity and elicit chemical peritonitis. • The patient recall the exact time of onset of pain. • Pain accompanied by fever, tachycardia, dehydration and ileus.

Perforation • Examination reveal: tenderness, rigidity and rebound • Diagnosis is established by free air in upright chest X-Ray underneath the diaphragm. • Treatment is operative after fluid resuscitation

Bleeding • The most common cause of death with PUD is bleeding in those who have medical problems or are older than 60 years • In DU bleeding usually from GDA • Most case of massive GI bleeding are DU following penetration of ulcer in GDA • Bleeding can manifests as melena or bloody vomiting

Obstruction • Active inflamation of duodenum can cause mechanical obstruction and functional gastric outlet obstruction • Delayed gastric emptying lead to nausea and vomiting • Can lead to hypochloremic hypokalemic metabolic alkalosis secondry to loss of gastric juice and H+, CL-, K

Zollinger –Ellison Syndrome • ZES clinical triade: 1 .Gastric acid hyper secretion 2. Severe PUD 3. Non-b islet cell tumors • ZES are known to produce gastrin and called gastrinomas

ZES • ZES usually localized to the head of pancreas, duodenal wall or regional LN. • ½ of ZES are multiple • 2/3 of ZES are malignant • ¼ of ZES are associated with MEN1

ZES • Clinically- abdominal pain and PUD in 80% of case. • ½ of patient have diarrhea secondary to increase gastric acid secretion (Gastrin stimulation secretion of acid) • Weight loss and steatorrhea occur secondary to decreased duodenal and jeujenal PH and inactivation of lipase • Esophagitis is common

When consider ZES • In a ptient with recurrent or intractable PUD despite eradication of H.Pylori. • In patient with multiple or atypically located ulcer. • PUD associated with significant diarrhea • PUD associated with symptom of MEN1: hyperparthyroidism • Patient with other pancreatic endocrine tumors • Large gastric rugae in endoscopy

How to diagnose ZES • Elevated serum gastrin > 200 pg/ml, value >1000 is diagnostic • Secretin test: give secretine 2u/kg and measure serum gastrin before and after gastrin administration evrey5 minute for 30 minute: an increase of serum gastrin of greater than 200pg/ml above basal level is specific for gastrinoma.

Diagnosis of PUD

History and physical examination. • Laboratory to R/O other condition: CBC, Liver chimistry, cre, elecgtrolytes, amylase • Serum Gastrin in refractory ulcer • Chest- X-ray- to rule out perforation • Endoscopy or contrast radiography • H.pylori testing

H.Pylori testing • Serology- HP ilicites a local as a systemic immunoglonulin G mediated immune response that can measured by ELISA • Serology is test of choice when endoscopy is not indicated • Sensitivity 90% • Limitation: the test remain high for year or more thus cannot used to assess eradication

Urease breath test • Carbon- labeled urea breath test • Based in ability of HP to hydrolyze urea to ammonia and bicarbonate • Patient ingest 14C or 13C Isotope after carbone ingestion urea metabolized to ammonia and bicarbonate if HP present

Urease breath test • The bicarbonate is excreted in the breath as labeled carbon dioxide • Negative result occur if the test done early after treatment , , 4 weak. • Is the method of choice to documment erradication, • Test not expensive

Rapid urease assay • The urease catalize urea to ammonia and bicarbonate creating an alkaline environment • This environment can measured by PH indicator • Endoscopy is performed and gastric mucosal biopsied to perform the test • Sensitivity 90%, specificity 98%.

Diagnosis of HP by histology • Endoscopy performed and biopsy obtained • Diagnosis is by visualization of HP by hematoxyline and eosin stain • Sensitivity is 90%, specificity is 99% • HP can cultured – diagnosis required 3-5 days and expensive, sensitivity 80%, specificity is 99%

Upper GI radiography • The barium is demonstrated within the ulcer crater which is round or oval and may or may not surrounded by edema • With single contrast 50% of ulcer may be missed • With double contrast 80-90% of ulcer carter can be detected • Can asses the depth and penetration • Limitation- cannot r/o malignancy

Endoscopy • The most reliable method of diagnosis • Ability to diagnose malignancy • Benign ulcer have smooth ulcer base • Malignant ulcer associated with mass and protrude into the lumen or have fold surrounding the ulcer carter • Biopsy can performed with endoscopy .

Treatment Medical management

The goals of treatment 1.symptom need to be relieved 2.The ulcer need to be healed 3. Recurrence must be prevented • The antisecretory agent achieve the first 2 goals • With NSAIDs related ulcer discontinuation of NSAIDs achieve the 3 goal • Eradication of HP achieve the 3 goal

Peptic Ulcer Disease