Peptic ulcer disease

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PEPTIC ULCER DISEASE

• Dr. W.C. Lwabby (MMed, MD)
• Lecturer Int. Med.Dept

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Learning Objectives

• To define peptic ulcer disease(PUD)
• To describe the pathophysiology of PUD
• To discuss the diagnosis of PUD
• To describe the treatment of PUD

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Gastric Mucosa Secretions
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Hydrochloric Acid Production

• 1. CO2 and Cl- diffuse from the
• blood into the stomach cell.
• 2. CO2 combines with H2O
• to form H2CO3.
• 3. H2CO3 dissociates into
• bicarbonate (HCO3-) and H.
• 4. H combines with Cl- in duct
• of gastric gland to form HCl-.
• 5. An ATP pump is necessary to
• pump the HCl- into the duct
• since the concentration of
• HCl- is about a million times
• more concentrated in the
• duct than in the cytosol of the
• cell.

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Introduction

• The inside of the stomach is bathed in about 2L
  of gastric juice daily.
• Gastric juice is composed of
• Digestive enzymes Concentrated hydrochloric
  acid
• which can readily tear apart the toughest food
  or microorganism
• The gastroduodenal mucosal integrity is
  determined by
• Protective (defensive)
• Damaging (aggressive) factors

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Introduction..

• The Defensive Forces
• Bicarbonate
• Mucus layer
• Mucosal blood flow
• Prostaglandins
• Growth factors

• The Aggressive Forces
• Helicobacter pylori
• HCl acid
• Pepsins
• NSAIDs
• Bile acids
• Ischemia and hypoxia.
• Smoking and alcohol

• When the aggressive factors increase or the
  defensive factors decrease,
• Mucosal damage will result, leading to erosions
  ulcerations.

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Introduction..

• Definition
• Peptic Ulcer
• An ulcer of the alimentary tract mucosa, usually
  in the
• Stomach
• Duodenum
• Lower esophagus( rarely),
• where the mucosa is exposed to the acid gastric
  secretion
• It has to be deep enough to penetrate the
  muscularis mucosa

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Peptic Ulcer Disease
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Pathophysiology

• A peptic ulcer is a mucosal break,
• 3mm or greater in size with depth.
• Two major variants in peptic ulcers are commonly
  encountered in the clinical practice
• Duodenal Ulcer (DU)
• Gastric Ulcer (GU)

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Pathophysiology

• DU results from increased acid load to the
  duodenum due to
• Increased acid secretion because of
• Increased parietal cell mass
• Increased gastrin secretion,
• (e.g. Zollinger-Ellison syndrome, alcohol
  spicy food)
• Decreased inhibition of acid secretion,
• possibly by H. pylori damaging somatostatin-produc
  ing cells in the antrum
• Smoking impairing gastric mucosal healing
• Genetic susceptibility may play a role
• HCO3 secretion is decreased in the duodenum by H.
  pylori inflammation

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Pathophysiology..

• GU results from the break down of gastric mucosa
• Associated with gastritis affecting the body
  the antrum
• The local epithelial damage which occurs because
  of
• Cytokines released from H. pylori
• Abnormal mucus production

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Etiology

• The two most common causes of PUD are
• Helicobacter pylori infection ( 70-80)
• Non-steroidal anti-inflammatory drugs (NSAIDS)
• Other uncommon causes include
• Gastrinoma (Gastrin secreting tumor)
• Stress ulceration (trauma, burns, critical
  illness)
• Vascular insufficiency

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Pathogenesis of H. pylori in PUD

• H. pylori
• Is Gram-negative and spiral
• Has multiple flagella at one end,
• which make it motile,
• allowing it to live deep beneath the mucus layer
  where the pH is close to neutral

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Pathogenesis of H.pylori in PUD.

• Any acidity is buffered by
• Organism's production urease enzyme,
• which catalyzes production of ammonia (NH3) from
  urea raises the pH
• The bacterium stimulates chronic gastritis by
• provoking a local inflammatory response.

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Effects of H. pylori on gastric Hormones
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Pathogenesis of NSAIDS in PUD

• Symptomatic GI ulceration occurs in 2 - 4 of
  patients treated with NSAIDs for 1 year.
• The effects of aspirin other NSAIDs on the
  gastric mucosa,
• ranges from mucosal hemorrhages to erosions
  acute ulcers
• NSAIDs inhibits the production of prostaglandins
  precursor from membrane fatty acids resulting in
• Decrease mucus HCO3 production
• Decrease mucosal blood flow
• Reduce cell renewal
• The drugs also generate oxygen-free radicals
• Products of the lipoxygenase pathway may
  contribute to ulceration

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Pathogenesis of NSAIDS in PUD

• Gastric acid probably aggravates NSAID-induce
  mucosal injury by
• Converting superficial injury to deeper mucosal
  necrosis
• Interfering with haemostasis platelet
  aggregation
• Impairing ulcer healing
• Users of NSAIDs,
• are at approximately 3 times greater relative
  risk of serious adverse gastrointestinal events
  than non-users

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Clinical Presentation

• Recurrent epigastric pain (the most common
  symptom)
• Burning
• Relieved by food ? DU
• Precipitated by food ? GU
• Relieved by antacids
• Radiate to back (consider penetration)
• Pain may be absent or less characteristic in
  one-third of patients especially in elderly
  patients on NSAIDs

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Clinical Presentation

• Nausea, Vomiting
• Chest discomfort
• Anorexia, weight loss especially in GU
• Hematemesis or melena resulting from Upper GI
  bleeding

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Investigations

• Diagnosis of ulcer
• History
• In most patients routine laboratory tests are
  unhelpful
• Diagnosis of PUD depends mainly on endoscopic and
  radiographic confirmation
• Diagnosis of H. pylori
• Laboratory tests (Stool, breath serology)

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Doudenal Ulcer on Endoscopy

• Normal doudenal bulb

• Doudenal Ulcer

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Diagnosis of H. pylori

• Non-invasive
• C13 or C14 Urea Breath Test
• Stool antigen test
• H. pylori IgG titer (serology)
• Invasive
• Gastric mucosal biopsy from OGD
• Rapid Urease test

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Non-invasive

• C13 or C14 Urea Breath Test

The best test for the detection of an active
infection
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What is the basis of this test?

• Is based on the ability of H. pylori to break
  down urea into carbon dioxide,
• which then is absorbed from the stomach and
  eliminated in the breath.

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How is this breath test done?

• Patients swallow a capsule containing urea made
  from an isotope of carbon.
• If H. pylori is present in the stomach,
• the urea is broken up and turned into carbon
  dioxide.
• The carbon dioxide is absorbed across the lining
  of the stomach and into the blood.
• It then travels in the blood to the lungs,
•  where it is excreted in the breath.
• Samples of exhaled breath are collected,
• the isotopic carbon in the exhaled carbon
  dioxide is measured.

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How are the results of the urea breath test
interpreted?

• If the isotope is detected in the breath,
• it means that H. pylori is present in the
  stomach.
• If the isotope is not found, H. pylori is not
  present.
• When the H. pylori is effectively treated
  (eradicated) by antibiotics,
• the test changes from positive (isotope present)
  to negative (isotope absent).

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Non-invasive

• Serology for H pylori
• Serum Antibodies (IgG) to H pylori
• (Not for active infection)
• Fecal antigen testing
• Test for active HP

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Invasive

• Upper GI endoscopy
• Highly sensitive test
• Patient needs sedation
• Has both diagnostic therapeutic roles
• Diagnostic
• Detect the site and the size of the ulcer,
• even small and superficial ulcer can be detected
• Detect severity of the ulcer like bleeding
• Biopsies can be taken for,
• rapid urease test, histopathology culture

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Rapid urease test ( RUT)

• Gastric biopsy specimens are placed in the rapid
  urease test kit.
• If H pylori are present,
• bacterial urease converts urea to ammonia, which
  changes pH and produces a COLOR change

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• Infection should be considered as present when
  any test is positive
• Both the invasive tests the breath test should
  be negative to establish the absence of
  infection.

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PUD Complications

• Bleeding Upper GI bleeding
• Perforation-Peritonitis
• Gastric outlet or duodenal obstruction
• Chronic anemia

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Treatment Goals

• Rapid relief of symptoms
• Healing of ulcer
• Preventing ulcer recurrences
• Reducing ulcer-related complications
• Reduce the morbidity (including the need for
  endoscopic therapy or surgery)
• Reduce the mortality

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General Strategy

• Treat complications aggressively if present
• Determine the etiology of ulcer
• Discontinue NSAID use if possible
• Eradicate H. pylori infection if present or
  strongly suspected,
• even if other risk factors (e.g., NSAID use) are
  also present)
• Smoking cessation should be encouraged

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Drugs Therapy

• H2-Receptors antagonists bd for 6-8 weeks, can
  heal DU 90.
• Proton pump inhibitors
• Cyto-protective agents
• Prostaglandin agonists
• Antacids
• Antibiotics for H. pylori eradication

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H2-Receptors AntagonistsAgents

• Cimetidine 800mg OD or 400mg BID
• Ranitidine 300mg OD or 150mg BID
• Famotidine 40mg OD or 20mg BID
• Nizatidine 300mg OD or 150mg BID
• Should be taken for 6-8 weeks

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Proton Pump Inhibitors (PPIs)

• Omeprazole 20mg
• Lansoprazole 30mg
• Pantoprazole 40mg
• Rabeprazole 20mg
• Esomeprazole 40mg

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Antacids

• Antacids contain either
• Sodium-bicarbonate
• Aluminum-hydroxide
• Magnesium-hydroxide
• Calcium carbonate
• Require large neutralizing capacity,
• a single dose of 156 meq antacid given 1 hr
  after meal effectively neutralize gastric acid
  for 2 hr,
• a second dose given 3 hr after eating maintains
  the effect for over 4 hr after the meal

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H. Pylori Eradication Therapy

• Until recently,
• the recommended duration of therapy for H.pylori
  eradication was 10 -14 days
• There are number of recent studies evaluated
  one-, five-, seven-day regimens
• Regimens for eradication of H. pylori infection ar
  e typically chosen empirically,
• on the basis of regional bacterial resistance
  patterns, local recommendations, and drug
  availability.
• They include
• Triple therapy
• Nonbismuth quadruple therapy
• Bismuth-based therapy
• Levofloxacin-containing therapy
• Second-line therapy
• Rescue or third-line therapy

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Triple therapy

• Remains an option for first-line therapy in areas
  of low clarithromycin resistance (lt15)
• Consists of the following
• Proton pump inhibitor (PPI) (eg, omeprazole 20 mg
  BID, lansoprazole 30 mg BID)
• Clarithromycin 500 mg BID  (first-line) or
  metronidazole 500 mg BID (when clarithromycin
  resistance is increasing) 
• Amoxicillin 1000 mg BID or metronidazole  (if not
  already selected)
• 14 days is the optimal duration of triple therapy

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Nonbismuth quadruple therapy

• May be given sequentially or concomitantly.
• Sequential therapy
• Is superior to standard triple therapy
• Consists of the following
• PPI plus amoxicillin for 5-7 days then
• PPI plus 2 other antibiotics for the next 5-7
  days,
• clarithromycin and metronidazole are the
  antibiotics usually chosen
• Concomitant therapy
• consists of the following
• PPI plus
• Amoxicillin plus
• Clarithromycin plus
• Metronidazole

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Heligo Kit

• Heligo Kit contains
• Clarithromycin, Lansoprazole, and Tinidazole as
  active ingredients.
• It improves the patient's condition by performing
  the following functions
• Killing bacteria and reducing the infection.
• Inhibiting the protein's production in bacteria
  to stop the bacterial growth.
• Decreasing the amount of acid made in the stomach

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• Patients with Peptic ulcers usually require,
• 3 to 4 weeks further treatment with a proton
  pump inhibitors after eradication therapy.
• The effectiveness of treatment should be assessed
  symptomatically.
• If symptoms persist,
• a C13 urea breath test or stool test for H.
  pylori should be performed to check eradication.

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REFERENCES

• Brian R, Walker N, Stuart H. Davdsons Principle
  and Practice of Medicine 22nd Edition. Peptic
  ulcer disease, pg 872-879.
• KASPER F,HAUSER LONGO. HARRISONS PRINCIPLES OF
  INTERNAL MEDICINE 19th Edition. Peptic ulcer
  disease and related disorders pg 2438-2452.

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• THANK YOU