Peptic ulcer disease (PUD)

Summary

Peptic ulcer disease (PUD) refers to the presence of one or more ulcerative lesions in
the stomach or lining of the duodenum. Possible etiologies include infection with the
bacterium Helicobacter pylori (most common), prolonged use of nonsteroidal anti-
inflammatory medicines (possibly in combination with glucocorticoids), conditions
associated with an overproduction of stomach acid (hypersecretory states), and
stress. Epigastric pain is a typical symptom of PUD, however, some patients may
remain asymptomatic. Diagnosis occurs via direct visualization of the ulcer on
esophagogastroduodenoscopy (EGD) and H. pylori detection (via biopsy or non-
invasive testing). The first-line treatment for most peptic ulcers involves H. pylori
eradication via triple therapy (a course of two different antibiotics in combination
with a proton-pump inhibitor) and the withdrawal of offending agents. Antisecretory
drugs (e.g., proton-pump inhibitors, or PPIs), which reduce stomach acid production,
are continued for 4–8 weeks after eradication therapy and may be considered for
maintenance therapy if symptoms recur. Surgical intervention may be necessary in
rare cases, especially if complications such as perforation or massive bleeding occur.
Stomach cancer is an important differential diagnosis and must be ruled out if risk
.factors are present

Epidemiology

Incidence: > 6 million cases annually in the US

.Duodenal ulcers are 3 times more common than gastric ulcers

.Duodenal ulcers occur on average 10–20 years earlier than gastric ulcers

♀ = ♂ :Sex

References:[1][2][3][4][5]

.Epidemiological data refers to the US, unless otherwise specified

Etiology

Risk factors

Chronic gastritis caused by H. pylori, a curved, flagellated gram-negative rod

Duodenal ulcers: up to 90% are due to H. pylori infection

Gastric ulcers: up to 80% are due to H. pylori infection

Chronic gastritis of other etiology

:Long-term use of NSAIDs (e.g., patients with rheumatoid arthritis, SLE, etc.)

.Risk for gastroduodenal ulcers increases 5-fold

NSAID use seems to have a stronger association with gastric ulcers than with
.duodenal ulcers

!Long-term use of NSAIDs plus glucocorticoids: Risk increases 10 to 15-fold

SSRIs

Smoking

Chronic alcohol consumption

.Patients with blood type O have a higher risk for duodenal ulcers

Age > 65 years

Stress (see “Subtypes and variants” below)

:Rare risk factors

Zollinger-Ellison syndrome (can result in duodenal ulcer)

Hyperparathyroidism

References:[2][6][7][8][9][10][11]

Classification

Gastric ulcer: an ulcerative lesion in the stomach lining; typically manifests along the
lesser curvature and the gastric antrum

Duodenal ulcer: an ulcerative lesion located in the duodenum, typically in the first
part (i.e., the duodenal bulb)

Erosive gastritis: acute mucosal inflammation of the stomach that does not extend
beyond the muscularis mucosae

!An atypical location is suspicious for carcinoma

References:[12]

Pathophysiology

Gastric secretions

Parietal cells

Secrete hydrochloric acid (HCl) and intrinsic factor

Stimulated by acetylcholine, histamine, and gastrin

Inhibited by prostaglandins and somatostatin

Mucosal cells

Secrete protective mucus

Stimulated by acetylcholine, prostaglandins, and secretin

Chief cells

Secrete pepsinogen

Stimulated by acetylcholine, gastrin, secretin, and vasoactive intestinal polypeptide

(VIP)

Disturbances

Helicobacter pylori gastritis: increased acid secretion, decreased protective

factors/mucus production

NSAIDs inhibit COX-1 and COX-2 → decrease in PGE2 (normally decreased gastric
acid secretion and increased HCO3- and mucus secretion) → gastric mucosa erosions

Clinical features

Gastric ulcer

Duodenal ulcer

Findings common to both

Dyspepsia: postprandial heaviness, early satiety, and gnawing, aching or burning

epigastric pain

Pain relief with antacids

Potential signs of internal bleeding (anemia, hematemesis, melena)

of patients with PUD are asymptomatic 70% ∼

Stool sample positive for occult blood (see gastrointestinal bleeding)

Pain and eating

Pain increases shortly after eating → weight loss

Pain increases 2–5 hours after eating

Pain on an empty stomach (hunger pain) that is relieved with food intake → weight
gain

Nocturnal pain

of patients 40%–30

of patients 80%–50

Gastric ulcer is associated with pain after light (weight loss) Gorging. Duodenal ulcer
.is associated with relief after massive (weight gain) Desserts

"

Taking NSAIDs can often mask PUD symptoms until complications such as
!hemorrhage and perforation occur

References:[13][14][15][16]

Subtypes and variants

Dieulafoy's lesion

Description: In this rare disease, minor mucosal trauma can lead to major bleeding.
.It is caused by an abnormal submucosal artery

Location: proximal stomach

Clinical presentation: signs of acute upper GI bleeding

Treatment: endoscopic hemostasis (injection therapy, hemoclips, etc.), excision of

the susceptible mucosa

Stress ulcer

.Causes: polytrauma, major surgery, SIRS, kidney failure, etc

Types

Curling ulcer: severe burns → decreased plasma volume → decreased gastric blood
flow → hypoxic tissue injury of stomach surface epithelium → weakening of the
normal mucosal barrier

Cushing ulcer: In patients with brain injury, increased vagal stimulation leads to
.increased production of stomach acid via acetylcholine release

Management: stress ulcer prophylaxis

Nonulcer dyspepsia: Symptoms including bloating, nausea, and belching persisting ≥
.3 months without organic cause (synonym: functional dyspepsia)

Imagine a hot curling iron to remember that Curling ulcers occur in patients with
.severe burns

Imagine a brain resting on a cushion to remember that patients with brain injury can
.develop Cushing ulcers

References:[17][18][19]

Diagnostics

Diagnostic approach

years of age without alarm features: Urea breath test for H. pylori 60 ≤

years of age or presence of ≥ 1 alarm features: EGD with biopsies and rapid 60 >
urease testing for H. pylori

Negative for H. pylori infection and NSAID intake; trial therapy unsuccessful

Measure serum gastrin level at baseline and after secretin stimulation test: high
levels in gastrinoma (Zollinger-Ellison syndrome)

Measure serum calcium and parathyroid hormone: high levels in primary

hyperparathyroidism

Testing for Helicobacter pylori

”See “Helicobacter pylori diagnostics

Esophagogastroduodenoscopy (EGD)

Most accurate test

:Patients > 60 years of age or presence of ≥ 1 alarm features, which include

Certain symptoms: progressive dysphagia, painful swallowing (odynophagia), and/or

persistent vomiting

Signs of active GI bleeding (e.g., melena, unexplained iron-deficiency anemia)

Signs of malignancy (e.g., unintended weight loss, lymphadenopathy, palpable mass)

Family history of upper GI malignancy in a first-degree relative

Jaundice

:Biopsy samples from

. Edge and base of the ulcer (essential to rule out malignancy)

Stomach lining distant from the ulcer (Helicobacter pylori testing for detection of
underlying type B gastritis)

If active bleeding, EGD can be performed for diagnosis and subsequent hemostasis
.treatment (electrocautery) in the same session

Alarm features of PUD include progressive dysphagia, odynophagia, persistent

vomiting, jaundice, signs of GI bleeding, signs of malignancy, and a family history of
!upper GI malignancy

To rule out gastric cancer, patients with stomach ulcers should undergo follow-up
!EGD and histology until the ulcer has healed completely

References:[16][20][21][22][23][24][25]

Treatment

General management of dyspepsia

H. pylori positive → eradication therapy (with antibiotics and a PPI) and supportive
treatment → continue PPIs for 4–8 weeks → follow-up

H. pylori negative → medical acid suppression (with a PPI) and supportive treatment
for 4–8 weeks → follow-up

Medical treatment

Helicobacter pylori eradication therapy (with antibiotics)

Acid suppression: PPIs (most effective), H2 blockers, antacids (mainly used for
symptom relief)

Mucosal protection: misoprostol , sucralfate (both substances are rarely used in

PUD)

Supportive treatment

Discontinue NSAIDs
Restrict alcohol use/smoking/emotional stress

Avoid eating before bedtime

Surgical treatment

With the advent of potent acid suppression in the form of PPIs, surgical intervention
.is rarely needed

Indications

Refractory syndromes despite appropriate medical treatment

If cancer is suspected

Complications that cannot be treated endoscopically (see “Complications” below)

Partial gastrectomy (Billroth)

Billroth I: distal gastrectomy with end-to-end or side-to-end gastroduodenostomy

Billroth II: resection of the distal ⅔ of the stomach with a blind-ending duodenal
stump and end-to-side gastro-jejunostomy. The Billroth I and II methods without a
Brown's anastomosis often lead to bile reflux into the stomach. This may result in
type C gastritis in the region of the anastomosis. The chronic inflammation causes
.atrophic changes and increases the risk of cancer (anastomosis carcinoma)

Vagotomy

References:[14][20][26][27]

Acute management checklist

Start a PPI (e.g., omeprazole ). [28][29]

.Consider alternative therapies (see drugs for peptic ulcer disease)

H. pylori eradication therapy [30][23]

Lifestyle changes: Recommend avoidance of spicy foods and caffeine, remaining

.upright after eating, smoking cessation, and limiting/ceasing alcohol intake

.Discontinue NSAIDs, if possible

Identify and treat complications

Suspected bleeding peptic ulcer: urgent GI consult for consideration of EGD (see
upper gastrointestinal bleed)

Suspected perforation of peptic ulcer: urgent surgery consult for consideration of

exploratory laparotomy
Complications

Bleeding (see gastrointestinal bleeding)

Most common complication of PUD

Located posterior more commonly than anterior

Perforated gastric ulcers of the lesser curvature may cause hemorrhage of the left
.gastric artery

Duodenal ulcers of the posterior wall are more likely to cause massive bleeding
.because of their proximity to the gastroduodenal artery

Gastric/duodenal perforation (see also secondary peritonitis and gastrointestinal

perforation)

Second most common complication of PUD

Located anterior more commonly than posterior

Duodenal ulcers of the anterior wall are more likely to perforate into the abdominal
cavity, causing pneumoperitoneum (free air below the diaphragm) and irritation of
.phrenic nerve (e.g., shoulder pain)

Subhepatic abscess

Etiology: may result from a perforated duodenal or gastric ulcer

Clinical presentation: fever and vomiting (see also “Gastric/duodenal perforation”

above)

Diagnosis: subhepatic gas on abdominal x-ray

Management

Treat underlying cause

IV antibiotics, percutaneous drainage

.See also “Therapy” in pyogenic liver abscess

Gastric outlet obstruction (GOO)

Definition: mechanical obstruction of the pyloric channel or duodenum

Etiology

Malignancy (most common)

PUD

Acute PUD → inflammation and edema

Chronic PUD → scarring and fibrosis

Gastric volvulus
Less common causes that cause strictures in the pyloric channel: Crohn disease,
history of ingestion of a caustic substance, chronic pancreatitis

Clinical presentation

Postprandial, nonbilious vomiting

Succussion splash

Early satiety

Progressive gastric dilation

Weight loss

Diagnosis

Barium swallow

Upper endoscopy (confirmatory test): identification of the gastric pathology

Laboratory tests: hypokalemic hypochloremic metabolic alkalosis

Saline load test

Management

Symptomatic: nasogastric suction, electrolyte and fluid replacement, and parental

nutrition

Definitive: surgery or endoscopic dilation

Fistula formation

Clinical presentation

Increased severity of pain, which is no longer relieved by eating; radiation of pain to

the back

Weight loss, diarrhea

Malignant transformation

Gastric ulcers: high malignant potential (progression to cancer in 5–10% of cases) →

malignancy should be ruled out with biopsy [21]

Duodenal ulcers: usually benign → routine biopsy is not required

Postgastrectomy syndromes

Posterior ulcers are more likely to bleed and anterior ulcers are more likely to
perforate: Postal workers wear Blue collars and should not have an Antisocial
.Personality
References:[27][31][32][33][34][35][36][37][38][39]

.We list the most important complications. The selection is not exhaustive

Prevention

Recurrence prophylaxis

Smoking cessation and avoidance of other offending agents such as alcohol

Reduce coffee consumption

Avoid medications that are associated with the development of ulcers

NSAIDs

Glucocorticoids

SSRIs

Rule out: Zollinger-Ellison syndrome, hyperparathyroidism

Successful H. pylori eradication therapy

Stress ulcer prophylaxis

PPIs or H2 blockers

Indicated in severe organic disease/stress → shock, acidosis, brain trauma, severe

burns, major surgery

Disadvantage of prolonged PPI intake: potentially higher risk of pneumonia and

!gastroenteritis

References:[40]