Peptic Ulcer Disease - Gastrointestinal

Snapshot

A 65-year-old-male presents with complaints of epigastric pain and belching, which improves when he eats food but gets worse within a few hours after his meal. The pain is described as stabbing, intermittent, and concentrated at the epigastric region. He noticed a 5-lb. weight loss over the past 3 months and a dark color to his stools. Calcium carbonate seems to help with the pain.

Introduction

Clinical definition
- characterized by erosion and defects in the mucosal lining of the stomach, duodenum, and sometimes the lower esophagus that persists as a function of the acid or peptic activity in gastric juice
  - gastric ulcers describe ulcers occurring at the stomach
  - duodenal ulcers describe ulcers occurring at the duodenum
- duodenal ulcers
  - abdominal pain is relieved with food intake
  - the majority (90%) of cases are secondary to Helicobacter pylori
  - lower risk of malignancy
- gastric ulcers
  - abdominal pain is exacerbated with food intake
  - the leading causes are H. pylori followed by nonsteroidal anti-inflammatory drugs (NSAIDs) use
  - higher risk of malignancy
Epidemiology
- demographics
  - ulcer incidence increases with age
  - H. pylori is the predominant cause of peptic ulcer disease (PUD) worldwide
  - increasing prevalence of NSAID-related PUD due to widespread use of aspirin and NSAID
- risk factors
  - NSAIDs
  - smoking
  - stress
  - age
Pathogenesis
- development of ulcers is secondary to the disruption of normal protective mechanisms of the gastric mucosa (e.g., bicarbonate)
- H. pylori
  - secretion of urease creates an alkaline environment which allows for the survival of the bacteria
  - inflammatory cytokines inhibit parietal cell acid secretion causing gastric ulcers
  - at the pyloric antrum, somatostatin production is reduced and gastric production is increased, leading to metaplasia of the duodenal cells and causing duodenal ulcers
- NSAIDs
  - mechanism of action blocks the function of cyclooxygenase-1 (COX-1), which is essential for the production of prostaglandins that stimulates the secretion of mucous that protects the gastric mucosa
  - also inhibits stomach mucosa cell proliferation and mucosal blood flow
- other causes
  - stress from serious illness
  - gastric ischemia
  - metabolic disturbances
  - vasculitis
  - gastrinoma (Zollinger-Ellison syndrome)
Associated conditions
- Zollinger-Ellison syndrome
  - suspect in patients with refractory duodenal ulcers
- Behcet disease
- Crohn disease

Painful sores or ulcers in the lining of the stomach or duodenum
- breach in the mucosa with extension into the submucosa or deeper
Occurs when gastric acid secretion outweighs mucosal defenses
- most commonly due to decreased mucosal barrier
  - NSAIDs
  - H. pylori
  - smoking
- less commonly due to acid hypersecretion
  - such as gastrinoma (Zollinger-Ellison syndrome)

Presentation

Symptoms
- abdominal pain
  - most commonly at the upper quadrants
- belching
- vomiting
- weight loss
- poor appetite
- bloating
- hematemesis
- melena
Physical exam
- abdominal tenderness
- peritoneal signs if perforation

Imaging

Esophagogastroduodenoscopy (EGD)
- gold standard of diagnosis
- indicated in patients who show no symptom improvement following few weeks of treatment
- allows for direct visual identification and allows for evaluation of the location and severity of the disease
- biopsy is important for the differentiation between benign ulcers and malignancy
Abdominal and chest radiographs
- may be useful in detecting pneumoperitoneum secondary to perforation
- positive findings include air-fluid levels with bowel dilation or free air

Studies

Urease breath test
- best initial test
- noninvasive and allows for the detection of H. pylori infection
Complete blood count
- often normal

Differential

Gastric malignancy
- differentiating factors
  - lesions will appear different on endoscopy and will be confirmed via biopsy
Chronic pancreatitis
- differentiating factors
  - may have characteristic disease history and will present with calcifications on abdominal imaging

Treatment

Management depends on disease etiology and severity
Lifestyle
- discontinue smoking and NSAIDs
H. pylori induced PUD
- clarithromycin, amoxicillin, and pantoprazole for 7-14 days
- clarithromycin, amoxicillin, pantoprazole, and metronidazole for 7-14 days
NSAID-induced PUD
- stop NSAID use
- introduce proton pump inhibitor (PPI) use
Bleeding ulcers
- resuscitation with IV fluids and/or blood products
- IV PPI
- endoscopic therapy with either cautery, endoclip, or epinephrine injection
Surgery
- indicated in patients with perforated ulcer and/or hemorrhage
  - requires IV antibiotics and PPI prior to repair
- other indications include PUD refractory to medical therapy and Zollinger-Ellison syndrome

Complications

Bleeding
Perforation
- manage with broad spectrum antibitoics, PPI, and emergency surgery
Obstruction
Malignancy

Blood, Plasma, Serum	Reference Range
ALT	8-20 U/L
Amylase, serum	25-125 U/L
AST	8-20 U/L
Bilirubin, serum (adult) Total // Direct	0.1-1.0 mg/dL // 0.0-0.3 mg/dL
Calcium, serum (Ca²⁺)	8.4-10.2 mg/dL
Cholesterol, serum	Rec: < 200 mg/dL
Cortisol, serum	0800 h: 5-23 μg/dL //1600 h: 3-15 μg/dL 2000 h: ≤ 50% of 0800 h
Creatine kinase, serum	Male: 25-90 U/L Female: 10-70 U/L
Creatinine, serum	0.6-1.2 mg/dL
Electrolytes, serum
Sodium (Na⁺)	136-145 mEq/L
Chloride (Cl^-)	95-105 mEq/L
Potassium (K⁺)	3.5-5.0 mEq/L
Bicarbonate (HCO₃^-)	22-28 mEq/L
Magnesium (Mg²⁺)	1.5-2.0 mEq/L
Estriol, total, serum (in pregnancy)
24-28 wks // 32-36 wks	30-170 ng/mL // 60-280 ng/mL
28-32 wk // 36-40 wks	40-220 ng/mL // 80-350 ng/mL
Ferritin, serum	Male: 15-200 ng/mL Female: 12-150 ng/mL
Follicle-stimulating hormone, serum/plasma	Male: 4-25 mIU/mL Female: premenopause: 4-30 mIU/mL midcycle peak: 10-90 mIU/mL postmenopause: 40-250
pH	7.35-7.45
PCO₂	33-45 mmHg
PO₂	75-105 mmHg
Glucose, serum	Fasting: 70-110 mg/dL 2-h postprandial:<120 mg/dL
Growth hormone - arginine stimulation	Fasting: <5 ng/mL Provocative stimuli: > 7ng/mL
Immunoglobulins, serum
IgA	76-390 mg/dL
IgE	0-380 IU/mL
IgG	650-1500 mg/dL
IgM	40-345 mg/dL
Iron	50-170 μg/dL
Lactate dehydrogenase, serum	45-90 U/L
Luteinizing hormone, serum/plasma	Male: 6-23 mIU/mL Female: follicular phase: 5-30 mIU/mL midcycle: 75-150 mIU/mL postmenopause 30-200 mIU/mL
Osmolality, serum	275-295 mOsmol/kd H₂O
Parathyroid hormone, serume, N-terminal	230-630 pg/mL
Phosphatase (alkaline), serum (p-NPP at 30° C)	20-70 U/L
Phosphorus (inorganic), serum	3.0-4.5 mg/dL
Prolactin, serum (hPRL)	< 20 ng/mL
Proteins, serum

Hematologic	Reference Range
Bleeding time	2-7 minutes
Erythrocyte count	Male: 4.3-5.9 million/mm³ Female: 3.5-5.5 million mm³
Erythrocyte sedimentation rate (Westergren)	Male: 0-15 mm/h Female: 0-20 mm/h
Hematocrit	Male: 41%-53% Female: 36%-46%
Hemoglobin A1c	≤ 6 %
Hemoglobin, blood	Male: 13.5-17.5 g/dL Female: 12.0-16.0 g/dL
Hemoglobin, plasma	1-4 mg/dL
Leukocyte count and differential
Leukocyte count	4,500-11,000/mm³
Segmented neutrophils	54%-62%
Bands	3%-5%
Eosinophils	1%-3%
Basophils	0%-0.75%
Lymphocytes	25%-33%
Monocytes	3%-7%
Mean corpuscular hemoglobin	25.4-34.6 pg/cell
Mean corpuscular hemoglobin concentration	31%-36% Hb/cell
Mean corpuscular volume	80-100 μm³
Partial thromboplastin time (activated)	25-40 seconds
Platelet count	150,000-400,000/mm³
Prothrombin time	11-15 seconds
Reticulocyte count	0.5%-1.5% of red cells
Thrombin time	< 2 seconds deviation from control
Volume
Plasma	Male: 25-43 mL/kg Female: 28-45 mL/kg
Red cell	Male: 20-36 mL/kg Female: 19-31 mL/kg

Cerebrospinal Fluid	Reference Range
Cell count	0-5/mm³
Chloride	118-132 mEq/L
Gamma globulin	3%-12% total proteins
Glucose	40-70 mg/dL
Pressure	70-180 mm H₂O
Proteins, total	< 40 mg/dL

Sweat	Reference Range
Chloride	0-35 mmol/L
Urine
Calcium	100-300 mg/24 h
Chloride	Varies with intake
Creatinine clearance	Male: 97-137 mL/min Female: 88-128 mL/min
Estriol, total (in pregnancy)
30 wks	6-18 mg/24 h
35 wks	9-28 mg/24 h
40 wks	13-42 mg/24 h
17-Hydroxycorticosteroids	Male: 3.0-10.0 mg/24 h Female: 2.0-8.0 mg/24 h
17-Ketosteroids, total	Male: 8-20 mg/24 h Female: 6-15 mg/24 h
Osmolality	50-1400 mOsmol/kg H₂O
Oxalate	8-40 μg/mL
Potassium	Varies with diet
Proteins, total	< 150 mg/24 h
Sodium	Varies with diet
Uric acid	Varies with diet
Body Mass Index (BMI)	Adult: 19-25 kg/m²