Peptic Ulcer Disease

Background
● The term refers to benign gastric
and duodenal ulcers.

● The etiology and the presence of

complications inform evaluation
and management.
Pathophysiology
● To maintain the normal gastric and duodenal mucosa, there is a balance
between protective forces and aggressive forces.

● Aggressive forces like low gastric pH and peptic enzymes would injure tissue.

● However, protective forces like mucus, bicarbonate, mucosal blood flow which
removes acid, ion pumps, the high regenerative capacity of the mucosal cells
and prostaglandins counteract these forces and defend the tissue

● PUD develops due to an imbalance between protective factors and aggressive

factors in which aggressive factors dominate and damage the gastric or
duodenal mucosa.

● There is a break in the skin or mucous membrane accompanied by surface

tissue being lost and consequently disintegrating. There is also epithelial tissue
necrosis with pus often present.
UNCOMPLICATED PEPTIC
ULCER DISEASE
 Symptoms
➔ It is estimated that 70% of peptic ulcers are asymptomatic
➔ If there are symptoms, symptoms may include:
◆ Gnawing/burning epigastric pain which happens quickly following
meals with a gastric ulcer and approximately 2-3 hours following with
a duodenal ulcer.
◆ Dyspepsia (bloating, belching, fatty food intolerance)
◆ Nausea and vomiting
◆ Early satiety
◆ Heartburn
◆ Loss of appetite and weight loss in severe cases
Differential Diagnosis
● Ascending Cholangitis ● Esophagitis

● Acute Cholecystitis and ● Esophageal Rupture

Biliary Colic
● Gallstones (Cholelithiasis)
● Acute Gastritis
● Gastroesophageal Reflux
● Acute Pancreatitis Disease

● Chronic Gastritis ● Mallory-Weiss Tear

● Acute Coronary Syndrome

● Mesenteric Ischemia
 ● NSAIDs

● H pylori infection

● Lifestyle factors like alcoholism

and smoking

Etiology ● Severe stress

● Hypersecretory states

● Genetic factors
 NSAIDs
● Mechanism of action of this class is to
inhibit the COX-1 and COX-2
pathways.

● Inhibition of the COX-1 pathway,

reduces prostaglandin production,
including PGE2 which are thought to
inhibit gastric acid and pepsin secretion
and stimulate gastric mucus and
gastroduodenal bicarbonate secretion.
 Helicobacter Pylori

➔ A characteristic feature is that it is

urease producing which allows to
survive by neutralizing gastric acidity
and subsequently colonize the lining
of the stomach.
 Lifestyle Factors
➔ Smoking and alcohol use have long
been linked to peptic ulcer disease.

➔ Research has found smoking has a

role in speeding up gastric emptying
and decreasing pancreatic
bicarbonate secretion.

➔ Ethanol can irritate gastric mucosa

and cause nonspecific gastritis.
 Hypersecretory State
➔ Zollinger-Ellison Syndrome

➔ G cells divide uncontrollably to form

gastrinomas

➔ Parietal cells in the stomach secrete

excessive hydrochloric acid

➔ Peptic ulcers form primarily in the

duodenum
 Investigations
➔ Laboratory investigations for uncomplicated peptic ulcer disease are usually vague and
non-specific.

◆ Ordering a CBC, U&E and LFTs help to exclude or rule out complications.

➔ Esophagogastroduodenoscopy/Upper GI endoscopy is the gold standard in diagnosis

uncomplicated peptic ulcer disease.

◆ High sensitivity for gastric and duodenal ulcers

◆ Differentiates benign ulcers from malignant lesions due to ability to perform biopsy
◆ Absolute contraindications would be shock, peritonitis, acute perforation, fulminant
colitis and acute myocardial infarction

➔ Barium contrast radiography can also be ordered but it is NOT diagnostic for peptic ulcer
disease.

◆ Cannot differentiate between benign and malignant ulcers.

◆ Prior gastric surgery or scarring due to chronic inflammation typically yields poor
results.
 Investigations
➔ Testing for H. pylori is guided by whether endoscopy is performed and if patient has been on
previous quadruple therapy

➔ In patients undergoing endoscopy;

◆ Biopsy urease testing (placing gastric biopsy specimens in a reagent containing
urease and pH reagent) is done in patients who have no recent history of undergoing
quadruple therapy

◆ Histopathology can confirm the presence of H. pylori infection if the patient has a
recent history of undergoing quadruple therapy

➔ Non-invasive techniques can also be used

◆ Urea breath test can be performed but is not appropriate in asymptomatic persons and
a negative result does not rule out infection and recent use of antibiotics, bismuth
preparations and PPIs can produce false negatives.

◆ Stool antigen assay can be performed and is a cost effective method. Recent use of
antibiotics, bismuth preparations and PPIs can produce false negatives.
Management
➔ Non-operative management is recommended for uncomplicated PUD.

➔ NSAID Ulcers can be treated with Omeprazole 20-40 mg PO daily or

Lansoprazole 15-30 mg PO daily and misoprostol 100-200 mcg po
QID

➔ H. pylori infection include 10-14 days of quadruple therapy (bismuth,

a proton pump inhibitor like omeprazole, tetracycline, and a
nitroimidazole) or 7-14 days of triple therapy (PPI, amoxicillin, and
clarithromycin).

➔ Surveillance is also required with Upper GI Endoscopy performed 6-8

weeks after initial diagnosis to document healing of the ulcer and rule
out malignant transformation.
Complications
● Refractory ulcers

● Bleeding

● Perforation

● Penetration

● Obstruction

● Malignancy
 Bleeding
● Bleeding can be described as either
chronic, slow bleeding or rapid,
life-threatening hemorrhage.

● Bleeding occurs most often at ulcers in

the proximal duodenum/duodenal bulb at
the posterior wall.

● Patients can present with previously

listed symptoms and melena (black, tarry
stool or hematemesis/coffee-ground
emesis. Less commonly presents with
hematochezia (fresh blood with or mixed
with stool), massive bleeds and
orthostatic hypotension may be present.
Hemodynamic Instability
➔ In bleeding PUD, assessment of hemodynamic
stability and need for resuscitation is the first step.

➔ Adequate IV access, volume resuscitation, central

venous line for monitoring and in the case of massive
bleeds, blood transfusion are part of the initial
management of a hemodynamically unstable person.

➔ Supportive care such as supplementary oxygen via a

nasal cannula or face mask and no oral intake may
also play a role.
 Treatment
● Bleeding can be classified according to the Forrest Classification into active
bleeding, signs of recent bleeding and lesions without bleeding with
subclassifications within each category.

● With respect to the endoscopy, different methods are described in literature like
injection therapy, thermocoagulation, hemoclips, fibrin sealant, etc. The most
commonly used methods are thermocoagulation therapy or hemoclips due to
their relatively lower risk for recurrence of bleeding after endoscopy.

● If there have been two failed attempts at achieving hemostasis then surgery can
be the next step. Surgery for bleeding peptic ulcer disease involves oversewing
of the ulcer plus truncal vagotomy and pyloroplasty.

● Acid-suppression therapy using PPIs is effective for reducing the risk for
recurrence of peptic ulcer bleeding.
 Perforation
● 2-10% patients with PUD will be
complicated by perforation.

● Perforation occurs most commonly at

ulcers on the anterior wall of the
duodenum.

● Patients presents with tachycardia,

sudden, severe, diffuse abdominal
pain and abdominal rigidity on
examination.
Perforation
● Initial management involves IV fluid therapy, no oral intake, and broad-spectrum
antibiotics.

● In perforated gastric ulcers, surgical intervention depends on the type. In type 1 ulcers,
an antrectomy (resection of 35% of the distal stomach) and Billroth II reconstruction is
preferred. For type II and type III, antrectomy and vagotomy is preferred. In older
patients and generally unfit patients, wedge resections or patch closures may be
performed.

● In small perforated duodenal ulcers, a piece of omentum is taken and used for surgical
closure (Graham patch). This usually can be performed with generally good results for
older patients and generally unfit patients (shock, medical comorbidities or peritoneal
contamination). Additionally in ulcers close to pylorus, a truncal vagotomy with
pyloroplasty can also be performed.

● In larger ulcers over 2 cm or complex perforated duodenal ulcers, open closure is

preferred to laparoscopy. This allows for Kocherization/anterior and leftward mobilization
of the second part (C loop) of the duodenum after incision of the parietal peritoneum on
its right aspect.
 Penetration
● Peptic ulcers which penetrate through
the duodenal or gastric wall without a
free perforation or leakage of luminal
contents into the peritoneal cavity.

● Pain associated is more intense, lasts

longer and radiates to lower thoracic or
upper lumbar spine area.

● Conservative management is preferred

as most fistulas close spontaneously
however if a patient is unresponsive to
conservative management, surgery
should be considered.
 Obstruction
● Gastric outlet obstruction can occur because
of ulceration at the the pyloric channel or
duodenum or because of malignancy.

● Patient may present with early satiety, weight

loss, postprandial, nonbilious vomiting,
succussion splash among others.

● Initial management includes parenteral

nutrition, electrolyte fluid replacement and
nasogastric suction

● Endoscopic balloon dilation provides transient

relief but repeated procedures increase risk
for perforation

● An antrectomy is generally performed but

vagotomy and drainage can be alternative.
 Malignancy
➔ A risk factor for malignancy is H. pylori infection.

➔ Suspicion warranted in a persistent non-healing peptic ulcer where

twice-daily antisecretory therapy with a PPI for 24 weeks has been
done. Additionally, other modifiable factors like medication
noncompliance, NSAID use, and H. pylori infection have been
corrected

➔ Tumor staging is important in determining the extent of disease.

◆ Chest and abdominal CT scans determines if there is

metastatic disease, which contraindicates gastrectomy.
◆ Preoperative endoscopic evaluation assesses the location
of the tumor and its proximity to the gastroesophageal
junction.

➔ Total gastrectomy is preferred for proximal (upper third) lesions and

distal gastrectomy or subtotal gastrectomy plus resection of adjacent
lymph nodes is preferred for lesions in the distal stomach.
 Refractory Ulcers
● Ulcers with a diameter greater than 5 mm which have
been endoscopically proven and do not heal after
treatment with a proton pump inhibitor for 8-12
weeks.

● Recurrence depends on the success of eradication of

H. pylori infection, size of ulcer and non-compliance
to stopping use of NSAIDs.

● The first step would be to increase once daily dosing

to twice daily dosing of antisecretory therapy. After 12
weeks, an upper GI endoscopy with biopsy should be
repeated.

● Surgical management is rare and is only performed

after a 24 week, twice-daily antisecretory therapy
where modifiable factors have been corrected has
failed. Even in these cases, the type of surgery varies
on a case by case basis.
References
● AMBOSS GmbH. (2023, October 17). Peptic ulcer disease - knowledge @ amboss. amboss.com.
https://www.amboss.com/us/knowledge/peptic-ulcer-disease
● BS Anand, M. (2022, July 13). Peptic ulcer disease. Background, Anatomy, Pathophysiology.
https://emedicine.medscape.com/article/181753-overview
● Ferzoco, S. J. (2022, August 4). Surgical management of peptic ulcer disease. UpToDate.
https://www.uptodate.com/contents/peptic-ulcer-disease-clinical-manifestations-and-diagnosis
● Gossage, J. A., Bultitude, M., Corbett, S. A., Burnand, K. M., Lahiri, R., Burnand, K. G., & Browse, N. L.
(2021). Browse’s introduction to the symptoms & signs of surgical disease. CRC Press.
● Saltzman, J. R. (2023, October 25). Overview of the treatment of bleeding peptic ulcers. UpToDate.
https://www.uptodate.com/contents/peptic-ulcer-disease-clinical-manifestations-and-diagnosis
● Vakil, N. B. (2022, July 19). Peptic ulcer disease: Clinical manifestations and diagnosis. UpToDate.
https://www.uptodate.com/contents/peptic-ulcer-disease-clinical-manifestations-and-diagnosis
● Vakil, N. B. (2022, August 8). Peptic ulcer disease: Treatment and secondary prevention. UpToDate.
https://www.uptodate.com/contents/peptic-ulcer-disease-clinical-manifestations-and-diagnosis
● Vakil, N. B. (2022, July 20). Peptic ulcer disease: Epidemiology, etiology, and pathogenesis. UpToDate.
https://www.uptodate.com/contents/peptic-ulcer-disease-clinical-manifestations-and-diagnosis
● Vakil, N. B. (2022, September 6). Overview of complications of peptic ulcer disease. UpToDate.
https://www.uptodate.com/contents/peptic-ulcer-disease-clinical-manifestations-and-diagnosis
● Vakil, N. B. (2023, February 20). Approach to refractory peptic ulcer disease. UpToDate.
https://www.uptodate.com/contents/peptic-ulcer-disease-clinical-manifestations-and-diagnosis