Peptic Ulcer Disease

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By definition, peptic ulcer disease refers to focal defects in the mucosa of the stomach and duodenum that penetrate the muscularis mucosal layer, resulting in scarring (defects superficial to the muscularis mucosa are erosions and do not cause scarring.

(Quick review of anatomy: the GIT contains four layers. The inner most layer is the mucosa—which includes epithelium, lamina propria, and muscularis mucosa—followed the sub mucosa, muscularis propria, and adventitia.

Helicobacter pylori, previously Campylobacter pylori, is a gram-negative, microaerophilic bacterium found usually in the stomach. It was identified in 1982 by Australian scientists Barry Marshall and Robin Warren, who found that it was present in a person with chronic gastritis and gastric ulcers, conditions not previously believed to have a microbial cause. It is also linked to the development of duodenal ulcers and stomach cancer. More than 50% of the world's population harbor H. pylori in their upper gastrointestinal tract, more common in developing countries. However, over 80% of individuals infected with the bacterium are asymptomatic.)

Etiology

	Duodenal	Gastric
H. Pylori	90%	60%
NSAID	7%	35%
Idiopathic	15%	10%
Physiologic (stress-induced)	<3%	<5%
Zollinger-Ellison Syndrome	<1%	<1%

(Another brief review: Zollinger-Ellison syndrome is a rare condition in which one or more tumors form in your pancreas or the upper part of your small intestine (duodenum). These tumors, called gastrinomas, secrete large amounts of the hormone gastrin, which causes the stomach to produce too much acid.)

Ulcers not related to H. Pylori or NSAIDs are becoming more commonly recognized; these include CMV, cirrhosis of the liver, COPD, chronic renal failure, ischemic and idiopathic causes. Cigarette smoking has been linked to peptic ulcer disease; smoking not only impairs healing but also increases the risk of ulcers, complications, and death. In contrast to popular belief, alcohol consumption damages the gastric mucosa but does not cause ulcers.

Clinical presentation

·      Dyspepsia

o   Most common presentation

o   Only 5% will have ulcers—most have functional disease

o   Can present with complications

§  Bleeding—most common! 10% The bleeding can be severe if from the gastroduodenal artery

§  Perforation (usually from anterior ulcers) 2%

§  Gastric outlet obstruction 2%

§  Posterior inflammation (penetration) 2% and can cause pancreatitis

·      Duodenal ulcers

o   History alone is very similar to that of functional dyspepsia

o   6 classical features

§  Epigastric pain: may localize to tip of xiphoid

§  Burning sensation

§  Develops 1~3 hours after meals

§  Relieved by eating and antacids

§  Interrupts sleep

§  Periodicity (tends to occur in clusters over a week with subsequent periods of remission)

·      Gastric ulcers

o   More atypical symptoms

§  Dull aching pain, often right after eating.

§  Eating will not relieve pain!

§  Dyspepsia or acid reflux

§  Episodes of nausea

§  A noticeable loss of appetite

§  Unplanned weight loss

o   A BIOPSY REQUIRED to rule out malignancy (whereas duodenal ulcers are rarely malignant.)

Investigations

·      Endoscopy (most accurate)

·      Upper GI series

·      H. Pylori tests

·      Fasting serum gastrin measurement if Zollinger-Ellison syndrome suspected—but most common cause of elevated serum gastrin level is atrophic gastritis.

Treatment

·      Specific management depends on etiology

·      Eradicate H pylori if it is present

·      Stop NSAIDs if possible

·      Start proton-pump inhibitors PPI

o   Inhibits parietal cell H+/K+-ATPase pump which secretes acid

o   Will heal most ulcers even if NSAIDs are continued

o   Other medications such as histamine H2-antagonists are less effective

·      Stop smoking

·      No diet modification required but some people have fewer symptoms if they avoid coffee, alcohol, and spices

Management of bleeding peptic ulcers

·      Endoscopy (OGD) to explore upper GI tract

·      IV pantoprazole continuous drip

·      Evaluate risk of rebleeding/continuous bleeding (most ulcers will stop bleeding spontaneously

o   Clinical risk factors: increased age (>60), bleeding diathesis, history of peptic ulcer disease, comorbid disease, hemodynamically unstable (transfusion required)

o   Endoscopic signs of recurrent bleeding are more predictive than clinical risk factors: active bleeding, visible vessel, clots, red spots

o   If high risk, consider ICU admission

H. Pylori-induced peptic ulceration

Pathophysiology

·      H. Pylori are Gram-negative flagellated rod that resides within the gastric mucosa, causing persistent infection and inflammation.

·      Acid secreted by parietal cells (stimulated by vagal acetylcholine, gastrin, histamine) is necessary for most ulcers

·      No satisfactory theories of how H. pylori causes ulcers, but pattern of colonization correlates with outcome

o   Gastritis only in antrum (15% of patients) and high gastric acid are associated duodenal ulcer and may progress to gastric metaplasia of duodenum where ulcer forms.

o   Gastritis through stomach (“pangastritis”—85% of patients) and low gastric acid are associated with stomach ulcer and cancer.

Epidemiology

·      H. Pylori is found in about 20% of all Canadians

·      Highest prevalence in those raised during the 1930s

·      Infection most commonly acquired in childhood, presumably by fecal-oral route

·      High prevalence in developing countries, particularly in those of low socioeconomic status (poor sanitation and overcrowding)

Outcome

·      Non-erosive gastritis in 100% of patients but asymptomatic

·      Peptic ulcer in 15% of patients

·      Gastric carcinoma and mucosal associated lymphomatous tissue (MALT) lymphoma in 0.5% of patients

·      Most are asymptomatic but still worthwhile eradicating to lower future risk of peptic ulcer/gastric malignancy and prevent spread to others (mostly children <5 years)

Diagnosis

·      Non-invasive

o   Urea breath test

§  90~100% sensitivity

§  89~100% specificity

§  Can be falsely negative when on PPI therapy

o   Serology

§  88~99% sensitivity

§  89~95% specificity

§  Can remain positive after treatment

·      Invasive (requires endoscopy)

o   Histology

§  93~99% sensitivity

§  95~99% specificity

§  Gold standard!

§  Can be falsely negative when on PPI therapy

o   Rapid urease test (on biopsy)

§  89~98% sensitivity

§  93~100% specificity

§  Rapid

o   Microbiology culture

§  98% sensitivity

§  95~100% specificity

§  Research only

Treatment: H. Pylori eradication

·      Triple therapy for 7~14 days

o   PPI bid + amoxicillin 1g bid + clarithromycin 500mg bid

o   Becoming less successful as prevalence of H. pylori clarithromycin-resistance on the rise

·      Quadruple therapy for 10~14 days now recommended

o   PPI bid + bismuth 525mg qid + tetracycline 500mg qid +metronidazole 250mg qid

·      Levofloxacin can replace metronidazole or tetracycline

·      Sequential therapy

o   5 days of PPI bid + amoxicillin 1g bid

o   6~10 days of PPI bid + clarithromycin 500mg bid, tinidazole 500mg bid (generally substitute with metronidazole as tinidazole is not available in Canada)

·      5~15% are resistant to all known therapies

NSAID-induced ulceration

NSAID use causes gastric mucosal petechiae in virtually all erosions in most people and ulcers in some people (25%); erosions can bleed, but usually only ulcers cause significant clinical problems. Most NSAID ulcers are clinically silent—dyspepsia is as common in patients with ulcers as patients without ulcers; NSAID-induced ulcers characteristically present with complications such as bleeding, perforation, and obstruction. NSAIDs more commonly cause gastric ulcers than duodenal ulcers. NSAID use may exacerbate underlying duodenal ulcer disease.

Pathophysiology

·      Direct: erosions/petechiae are due to local effect of drug on gastric mucosa

·      Indirect: systemic NSAID effect (intravenous NSAID causes ulcers, but not erosions due to inhibition of mucosal cyclooxygenase, leading to decreased synthesis of protective prostaglandins, thus leading to ulcers

Risk factors for NSAID-induced peptic ulcer

·      Previous peptic ulcers or upper GI bleeding

·      Age >65

·      High dose of NSAID/multiple NSAIDs being taken

·      Concomitant corticosteroid use

·      Concomitant cardiovascular disease/other significant disease

Management

·      Prophylactic cytoprotective therapy with PPI is recommended if any of the above risk factors exist concomitantly with ASA/NSAID use

·      Lower NSAID dose or stop all together and replace with acetaminophen

·      Combine NSAID with PPI or misoprostol (less effective) in one tablet

·      Enteric coating of aspirin provides minor benefit since this decreases incidence of erosion, not incidence of ulceration

Stress-induced ulceration

Defined as ulceration or erosion in the upper GI tract of ill patients, usually in ICU (the stress is physiologic not psychologic), stress-induced lesions are most commonly in the fundus of the stomach. The pathophysiology is unclear; it likely involves ischemia and may be cause by CNS disease and acid hypersecretion.

Risk factors include:

·      Mechanical ventilation—most important

·      Anti-coagulation

·      Multi-organ failure

·      Septicemia

·      Severe surgery/trauma

·      CNS injury

·      Burns involving more than 35% of body surface

Curling’s ulcer	Cushing’s ulcer
Acute peptic ulcer of the duodenum resulting as a complication from severe burns when reduced plasma volume leads to ischemia and cell necrosis (sloughing) of the gastric mucosa. Think: BURN from a CURLING iron!	Peptic ulcer produced by elevated intracranial pressure (may be due to stimulation of vagal nuclei secondary to elevated ICP which leads to increased secretion of gastric acid)

Clinical feature is painless upper GI bleeding. Treatment includes prophylaxis with gastric acid suppressants to decrease the risk of upper GI bleeding. PPI most potent but may increase risk of pneumonia; H2 blockers less potent but less likely to cause pneumonia. In active bleeding ulcer the treatment is the same as covered above in peptic ulcer disease but often less successful.

Gastritis

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Today we discuss another common problem that many people have experienced at one time or another—gastritis! Let’s start with a review of stomach functions:

 Gastritis is defined histologically as inflammation of the stomach mucosa. There are many different causes of gastritis; sometimes one cause can result in different types of gastritis, and sometimes one person can many causes for gastritis.

Updated Sydney Classification of Gastritis (and etiology):

·      Acute gastritis

o   Hemorrhagic/erosive gastritis

§  Alcohol

§  Aspirin/NSAIDs

§  Shock/physiological stress (ICU patients)

o   Helicobacter gastritis

§  H. pylori

·      Chronic gastritis

o   Non-atrophic

§  H. pylori

o   Atrophic

§  H. pylori

§  Dietary

§  Autoimmunity

§  Environmental factors (multi-focal)

o   Chemical

§  NSAIDs

§  Bile

o   Radiation

§  Radiation injury

o   Lymphocytic

§  Celiac disease

§  Drugs

o   Eosinophilic

§  Food allergies

o   Non-infectious granulomatous

§  Crohn’s disease

§  Sarcoidosis

o   Other infectious gastritides

§  Bacteria

§  Viruses

§  Fungi

§  Parasite

§  Tuberculosis

§  Syphilis

In regards to clinical features, non-erosive gastritis is asymptomatic (except in certain causes such as Crohn’s disease) and does not cause pain—making it difficult to diagnose clinically or endoscopically. The diagnosis requires biopsy. Erosive gastritis can cause bleeding (usually without pain; pain only if progresses to ulcers, which is rare) and can be seen endoscopically.

Treatment is determined by etiology specific to the patient. Adjuvant non-pharmacological management includes avoidance of mucosal irritants such as alcohol, NSAIDs, and foods that trigger symptoms.

Case study:

A 76 year-old woman presents to the clinic with generalized weakness and dizziness, so severe that she has had difficulty walking by herself. She reported increasing fatigue and dizziness for the past one week. She denies any chest pain, shortness of breath, palpitations, diarrhea, or black stools.

She does not smoke or drink. She is not on any regular medications but takes some over-the-counter naproxen for joint pain occasionally.

On examination she has pale pink mucosa, orthostatic hypotension, mild epigastric tenderness.

Q: What tests would you order?

A: The following blood tests should be ordered:

·      Complete blood count to assess for anemia, as acute gastritis can cause gastrointestinal bleeding; elevated white cell count may indicate infectious cause

·      Liver and kidney function tests

·      Gallbladder and pancreatic function tests

·      H. pylori serology

Stool occult bloods should be ordered, as well as an endoscopy/colonoscopy to search for a cause of bleeding.

Her hemoglobin is 8 gm/dl and hematocrit 25%. Other routine admission labs are within normal limits. She tested positive for occult stool. Esophogastric endoscopy reveals erosive hemorrhagic gastritis, and a biopsy is performed.

Q: What are the differential diagnoses for this patient?

A: Also consider the following in the differential diagnosis of patients with suspected

•    Acute Complications of Sarcoidosis


•    B-Cell Lymphoma


•    Cholecystitis


•    Crohn’s Disease


•    Gallstones (Cholelithiasis)


•    Gastric Cancer


•    Peptic Ulcer Disease


•    Viral Gastroenteritis

•    Granulomatous gastropathy

Q: What factors may have led to this patient’s bleeding?

A: Although the patient may possibly have H. pylori and associated gastritis, the most common cause of hemorrhagic gastritis in the elderly is medication, especially aspirin and NSAIDs.

Q: Why did this patient not have pain?

A: Elderly patients with NSAID-associated gastric or duodenal damage are often asymptomatic until upper gastrointestinal bleeding or perforation occurs. Bleeding may be gradual, intermittent, and insidious, only showing up on chemical testing.

Q: How should the gastritis be managed?

A: Gastritis induced by NSAIDs without H. pylori infection should be treated with a proton-pump inhibitor or a histamine-2 blocker. NSAID use should be discontinued! If NSAIDs are absolutely necessary, short-acting agents such as ibuprofen, in the lowest possible dose, can be used.

Q: How should her joint pain be managed in the future?

A: Mild joint pain often responds to acetaminophen, and opioid/opioid-like analgesics can be helpful in patients who cannot tolerate NSAIDs. Topical agents such as capsaicin, transdermal lidocaine, and over-the-counter creams containing salicylates or cooling agents like menthol may be useful. Non-pharmacologic therapies such as weight reduction, walking aids, shoe insoles, braces, and prescribed exercises can reduce pain and improve function in some patients. Heat/cold, electrotherapeutics, ultrasound, and acupuncture may also be helpful.