33.1 Peptic Ulcer Disease & Gastritis

ABFM Family Medicine Certification Study Guide Exam

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1 Chapter 1: Exam Structure, Blueprint & Clinical Decision-Making

1.1 Exam Blueprint, FMCLA vs. One-Day Exam & Board Scoring 1.2 Clinical Reasoning, Test-Taking Strategy & Ambiguity Management 1.3 Evidence-Based Medicine & Clinical Practice Guidelines in Primary Care

2 Chapter 2: Healthcare Systems, Practice Management & Quality

2.1 Practice Management, Billing, Coding & Documentation 2.2 Quality Improvement, Patient Safety & Diagnostic Stewardship 2.3 Interprofessional Team-Based Care & Care Coordination

3 Chapter 3: Ethics, Law, Biostatistics & Health Equity

3.1 Medical Ethics, Informed Consent & Surrogate Decision-Making 3.2 Biostatistics, Clinical Epidemiology & Diagnostic Test Interpretation 3.3 Social Determinants of Health, Health Equity & Cultural Humility 3.4 Physician Wellness, Burnout Prevention & Professionalism

4 Chapter 4: Lifestyle Counseling & Behavior Change

4.1 Alcohol Use Screening & Brief Intervention 4.2 Illicit Drug & Cannabis Counseling 4.3 Tobacco & Vaping Cessation Counseling

5 Chapter 5: Nutrition, Physical Activity & Chronic Disease Prevention

5.1 Dietary Counseling for Obesity & Chronic Disease Prevention 5.2 Exercise Prescription & Physical Activity Counseling 5.3 Genetic Risk Assessment & Family History Counseling

6 Chapter 6: Routine Adult Immunizations

6.1 ACIP Adult Respiratory Vaccines: Influenza, COVID-19, RSV & Pneumococcal 6.2 ACIP Adult Non-Respiratory Vaccines: Tdap, Shingrix, HPV & Hep B 6.3 Immunizations in Special Populations: Pregnancy, Asplenia & Immunocompromise

7 Chapter 7: Pediatric Health Maintenance & Surveillance

7.1 Newborn Examination & Early Postnatal Care 7.2 Well-Child Care, Developmental Surveillance & Milestones 7.3 Pediatric & Adolescent Screening: Vision, Hearing, Anemia & Lead 7.4 Pediatric Oral Health, Dental Screening & Fluoride

8 Chapter 8: Behavioral Health & Safety Screening

8.1 Primary Care Depression, Anxiety & Behavioral Health Screening 8.2 Domestic Violence, Intimate Partner Violence & Firearm Safety 8.3 Occupational Health & Recreational Safety Counseling

9 Chapter 9: Adult Preventive Screening: Cardiovascular & Metabolic

9.1 Cardiovascular Disease & Hypertension Screening 9.2 Type 2 Diabetes Screening & Prediabetes Risk Stratification 9.3 Abdominal Aortic Aneurysm & Osteoporosis Screening

10 Chapter 10: Adult Cancer Screening: Breast & Gynecologic

10.1 Breast Cancer Screening & Risk-Assessment 10.2 Cervical Cancer Screening & ASCCP Algorithms 10.3 Skin Cancer Clinical Assessment & Counseling

11 Chapter 11: Adult Cancer Screening: Colorectal, Lung & Prostate

11.1 Colorectal Cancer Screening Modalities & Intervals 11.2 Lung Cancer Screening with Low-Dose CT 11.3 Prostate Cancer Screening & Shared Decision-Making

12 Chapter 12: Sexual Health, Infectious Disease Screening & Contraception

12.1 Sexual Health Counseling & Risk-Reduction Strategies 12.2 STI Screening: Chlamydia, Gonorrhea, Syphilis & Trichomoniasis 12.3 Bloodborne Infectious Disease Screening: HIV & Hepatitis C

13 Chapter 13: Reproductive Life Planning, Lactation & Preoperative Care

13.1 Preconception Planning & Comprehensive Contraception Management 13.2 Lactation Support & Breastfeeding Counseling 13.3 Preoperative Medical Evaluation & Pre-Participation Sports Exam

14 Chapter 14: Emergent Cardiovascular Conditions

14.1 Acute Coronary Syndromes & Myocardial Infarction 14.2 Acute Chest Pain Risk Stratification & Triage 14.3 Acute or Critical Valvular Heart Emergencies

15 Chapter 15: Cardiac Arrhythmias, Heart Failure & Hypertensive Crises

15.1 Acute Atrial & Ventricular Arrhythmias 15.2 Acute Decompensated Heart Failure & Cardiogenic Shock 15.3 Hypertensive Emergency & Urgency Management

16 Chapter 16: Vascular & Thromboembolic Emergencies

16.1 Pulmonary Embolism & Deep Vein Thrombosis 16.2 Acute Aortic Syndromes & Peripheral Vascular Emergencies 16.3 Critical Limb Ischemia & Acute Arterial Occlusion

17 Chapter 17: Neurologic Emergencies: Stroke & Altered Consciousness

17.1 Acute Ischemic Stroke & Intracranial Hemorrhage 17.2 Syncope Evaluation & Status Epilepticus 17.3 Acute Delirium, Encephalopathy & Severe Confusion

18 Chapter 18: Neurologic Trauma & Acute Cranial Emergencies

18.1 Concussion, Moderate-to-Severe TBI & Intracranial Injury 18.2 Thunderclap & Acute Severe Secondary Headaches 18.3 Acute Ophthalmologic Emergencies

19 Chapter 19: Acute Abdominal, Pelvic & Gastrointestinal Emergencies

19.1 Acute Abdominal & Pelvic Pain Triage 19.2 Upper & Lower Gastrointestinal Bleeding 19.3 Acute Hepatic Failure, Cholangitis & Severe Jaundice

20 Chapter 20: Acute Pulmonary & Airway Emergencies

20.1 Acute Hypoxic Respiratory Failure & ARDS 20.2 Severe Community-Acquired Pneumonia & Empyema 20.3 Acute Severe Epistaxis & Airway Obstruction

21 Chapter 21: Acute Traumatic Injuries & Wound Care

21.1 Major Trauma Resuscitation & Initial Assessment 21.2 Burn Assessment, Inhalation Injury & Resuscitation 21.3 Laceration Management, Complex Wounds & Animal Bites

22 Chapter 22: Acute Orthopedic & Musculoskeletal Emergencies

22.1 Acute Ambulatory Fractures & Initial Splinting 22.2 Compartment Syndrome & Major Orthopedic Trauma 22.3 Septic Arthritis & Acute Microcrystalline Crises

23 Chapter 23: Severe Infections, Sepsis & Systemic Emergencies

23.1 Sepsis, Septic Shock & Initial Fluid Resuscitation 23.2 Necrotizing Soft Tissue Infections & Severe CNS Infections 23.3 Anaphylaxis Diagnosis, Epinephrine Dosing & Airway Protection

24 Chapter 24: Metabolic, Endocrine & Electrolyte Emergencies

24.1 Diabetic Ketoacidosis & Hyperosmolar Hyperglycemic State 24.2 Critical Electrolyte Emergencies: Dyskalemias & Dysnatremias 24.3 Severe Calcium Abnormalities & Acute Adrenal Crisis

25 Chapter 25: Hematologic, Urologic & Dental Emergencies

25.1 Severe Symptomatic Anemias & Coagulopathic Emergencies 25.2 Testicular Torsion, Priapism & Acute Urinary Retention 25.3 Urgent Odontogenic Infections & Dental Trauma

26 Chapter 26: Psychiatric, Behavioral & Obstetric/Gynecologic Emergencies

26.1 Suicidal Ideation, Acute Agitation & Behavioral Emergencies 26.2 Acute Physical & Sexual Assault Care 26.3 Life-Threatening Vaginal Bleeding & Ectopic Pregnancy 26.4 Environmental Heat Stroke & Severe Hypothermia

27 Chapter 27: Acute Head, Neck & Neurologic Symptoms

27.1 Primary Acute Headaches: Migraine, Tension & Cluster 27.2 Concussion & Minor Closed Head Injury Evaluation 27.3 Transient Ischemic Attack Evaluation & ABCD2 Risk Scoring

28 Chapter 28: Acute Cranial Nerves, Hearing & Sensory Symptoms

28.1 Peripheral Neuropathies: Bell's Palsy, Carpal Tunnel & Radiculopathy 28.2 Acute Tinnitus, Sudden Sensorineural Hearing Loss & Cerumen Impaction 28.3 Acute Dizziness, Benign Paroxysmal Positional Vertigo & Vestibular Neuritis

29 Chapter 29: Acute Upper Respiratory Tract Infections

29.1 Acute Viral Rhinosinusitis vs. Bacterial Rhinosinusitis 29.2 Acute Pharyngitis: Group A Streptococcus & Centor Criteria 29.3 Acute Otitis Media, Otitis Externa & Serous Effusion

30 Chapter 30: Acute Lower Respiratory Infections & Cough

30.1 Influenza, COVID-19 & Viral Respiratory Syndromes 30.2 Acute Bronchitis & Lower Respiratory Tract Infections 30.3 Ambulatory Community-Acquired Pneumonia

31 Chapter 31: Allergic, Nasal & Non-Infectious Pulmonary Conditions

31.1 Allergic Rhinitis & Acute Non-Anaphylactic Allergic Reactions 31.2 Acute Dyspnea in Ambulatory Care 31.3 Interstitial Lung Diseases & Sarcoidosis Presentation

32 Chapter 32: Acute Chest, Cardiac & Vascular Symptoms

32.1 Palpitations Evaluation & Arrhythmia Triage in Primary Care 32.2 Deep Vein Thrombosis & Superficial Thrombophlebitis 32.3 Ambulatory Hypotension & Orthostasis Evaluation

33 Chapter 33: Acute Upper Gastrointestinal Conditions

33.1 Peptic Ulcer Disease & Gastritis 33.2 Dysphagia, Esophagitis & Acute Esophageal Disorders 33.3 Acute Nausea, Vomiting & Foodborne Illness

34 Chapter 34: Acute Lower Gastrointestinal Conditions

34.1 Acute Infectious Diarrhea & Gastroenteritis 34.2 Acute Constipation & Functional Bowel Changes 34.3 Ano-Rectal Disorders: Hemorrhoids, Fissures, Abscesses & Pruritus Ani

35 Chapter 35: Inflammatory, Functional & Malabsorptive GI Disorders

35.1 Acute Flares of Inflammatory Bowel Disease 35.2 Irritable Bowel Syndrome: Diagnosis, Subtyping & Management 35.3 Celiac Disease & Malabsorption Syndromes

36 Chapter 36: Acute Abdominal, Hepatic & Biliary Disorders

36.1 Ambulatory Abdominal & Pelvic Pain Triage 36.2 Acute Cholecystitis, Biliary Colic & Pancreatitis 36.3 Acute Liver Injury & Viral Hepatitis

37 Chapter 37: Acute Abdominal Wall, Hernias & Dental Conditions

37.1 Abdominal Wall, Inguinal & Ventral Hernias 37.2 Acute Dental Pain, Odontogenic Abscess & Aphthous Ulcers 37.3 Acute Edema: Unilateral vs. Bilateral Diagnostic Evaluation

38 Chapter 38: Acute Infectious Dermatoses

38.1 Bacterial Skin Infections: Impetigo, Cellulitis & Cutaneous Abscesses 38.2 Fungal Skin Infections: Tinea Corporis, Cruris, Pedis & Onychomycosis 38.3 Viral Cutaneous Infections: Herpes Simplex, Zoster & Molluscum Contagiosum

39 Chapter 39: Inflammatory, Allergic & Autoimmune Dermatoses

39.1 Atopic Dermatitis, Contact Dermatitis & Eczematous Flares 39.2 Non-Infectious Rashes: Urticaria, Drug Eruptions & Erythema Multiforme 39.3 Cutaneous Malignancies & Premalignant Lesions: AK, BCC, SCC & Melanoma

40 Chapter 40: Acute Shoulder, Elbow & Upper Extremity Injuries

40.1 Rotator Cuff Pathology, Tendinopathy & Shoulder Impingement 40.2 Lateral & Medial Epicondylitis, Olecranon Bursitis & Elbow Sprains 40.3 Wrist & Hand Soft-Tissue Injuries: De Quervain, TFCC & Finger Sprains

41 Chapter 41: Acute Knee, Ankle & Lower Extremity Injuries

41.1 Meniscal Tears, Ligamentous Knee Injuries & Patellofemoral Pain 41.2 Ankle Sprains, Ottawa Ankle Rules & Achilles Tendinopathy 41.3 Plantar Fasciitis, Shin Splints & Overuse Syndromes

42 Chapter 42: Acute Ambulatory Fractures & Dislocations

42.1 Distal Radius, Scaphoid & Common Upper Extremity Fractures 42.2 Metatarsal, Clavicle & Common Lower Extremity Fractures 42.3 Joint Dislocation Management: Nursemaid's Elbow & Shoulder Subluxation

43 Chapter 43: Acute Axial Musculoskeletal Pain & Falls

43.1 Acute Low Back Pain: Red Flags, Strain & Disc Herniation 43.2 Acute Cervical Strain, Whiplash & Axial Neck Pain 43.3 Evaluation of Falls in Ambulatory & Older Patients

44 Chapter 44: Acute Inflammatory Arthropathies & Generalized Pain

44.1 Acute Inflammatory Arthritis & Spondyloarthropathies 44.2 Myalgias, Rhabdomyolysis & Post-Viral Pain Syndromes 44.3 Acute Non-Headache Pain Management Strategies

45 Chapter 45: Acute Renal, Urinary & Genitourinary Conditions

45.1 Uncomplicated UTI, Pyelonephritis & Acute Urethritis 45.2 Hematuria Workup & Glomerulonephritis 45.3 Nephrolithiasis & Acute Urinary Tract Obstruction

46 Chapter 46: Acute Male Genitourinary & Prostatic Conditions

46.1 Acute Prostatitis, Epididymitis & Orchitis 46.2 Acute Scrotal Pain: Torsion vs Appendage, BPH & Male Genital Emergencies 46.3 Acute Urinary Retention & Incontinence Evaluation

47 Chapter 47: Acute Women's Health & Early Pregnancy Care

47.1 Early Pregnancy Diagnosis, Dating & Initial Complications 47.2 Abnormal Uterine Bleeding & Acute Menstrual Disorders 47.3 Premenstrual Syndrome & Premenstrual Dysphoric Disorder

48 Chapter 48: Breast Disorders, STIs & Pediatric Elimination

48.1 Palpable Breast Mass, Mastitis & Nipple Discharge 48.2 Sexually Transmitted Infections: Diagnosis, Staging & CDC Guidelines 48.3 Pediatric Enuresis & Encopresis

49 Chapter 49: Systemic Signs, Metabolic Dysregulation & Miscellaneous Infections

49.1 Acute Fever, Sepsis Screening & FUO in Primary Care 49.2 Acute Hyperglycemia & Symptomatic Hypoglycemia 49.3 Electrolyte Abnormalities: Mild-to-Moderate Disturbances 49.4 Vector-Borne, Tick-Borne & Rickettsial Illnesses

50 Chapter 50: Chronic Cardiovascular Diseases: Hypertension & Ischemia

50.1 Essential Hypertension Management: 2025 AHA/ACC Guideline & JNC Strategies 50.2 Chronic Coronary Artery Disease & Post-MI Secondary Prevention 50.3 Chronic Heart Failure: HFrEF, HFpEF & Quadruple GDMT

51 Chapter 51: Chronic Vascular, Valvular & Dyslipidemic Diseases

51.1 Peripheral Arterial Disease & Claudication 51.2 Chronic Valvular Heart Disease & Murmur Evaluation 51.3 Lipid Disorders & ASCVD Risk-Based Statin Therapy

52 Chapter 52: Chronic Respiratory Diseases: Asthma & COPD

52.1 Chronic Asthma Management: GINA Stepwise SMART Therapy 52.2 Chronic Obstructive Pulmonary Disease: GOLD Recommendations 52.3 Solitary Pulmonary Nodule Evaluation & Fleischner Society Criteria

53 Chapter 53: Chronic Metabolic Diseases: Diabetes Mellitus

53.1 Type 2 Diabetes Management: ADA Pharmacotherapy Algorithms 53.2 Type 1 Diabetes: Basal-Bolus Insulin, CGMs & Diabetic Complications 53.3 Diabetic Microvascular & Macrovascular Disease Surveillance

54 Chapter 54: Obesity, Nutrition & Metabolic Bone Diseases

54.1 Medical & Behavioral Management of Obesity & Incretin Mimetics 54.2 Osteoporosis & Metabolic Bone Disease: DEXA, FRAX & Antiresorptives 54.3 Nutritional Deficiencies: Vitamin D, B12, Iron & Malnutrition

55 Chapter 55: Chronic Endocrine Disorders

55.1 Primary & Subclinical Hypothyroidism, Hyperthyroidism & Nodules 55.2 Adrenal Disorders: Addison's Disease & Cushing's Syndrome 55.3 Hypercalcemia, Hyperparathyroidism & Pituitary Disorders

56 Chapter 56: Chronic Kidney Disease & Venous Disorders

56.1 Chronic Kidney Disease: KDIGO Staging & Renoprotective Therapy 56.2 Chronic Venous Insufficiency, Stasis Dermatitis & Lymphedema 56.3 Chronic Electrolyte & Acid-Base Management in CKD

57 Chapter 57: Chronic Gastrointestinal & Hepatic Diseases

57.1 Gastroesophageal Reflux Disease, Barrett's Esophagus & Dyspepsia 57.2 Chronic Liver Disease: MASLD/NAFLD, Cirrhosis & Portal Hypertension 57.3 Viral Hepatitis B & C: Long-Term Monitoring & DAA Therapy

58 Chapter 58: Colorectal Surveillance & Chronic Pancreaticobiliary Care

58.1 Post-Polypectomy Colorectal Polyp Surveillance Guidelines 58.2 Chronic Pancreatitis & Exocrine Pancreatic Insufficiency 58.3 Chronic Nausea, Gastroparesis & Functional GI Disorders

59 Chapter 59: Chronic Musculoskeletal & Rheumatologic Disorders

59.1 Osteoarthritis: Hip, Knee & Hand Management 59.2 Spinal Conditions: Spinal Stenosis, Spondylolisthesis & Compression Fractures 59.3 Chronic Myopathies & Fibromyalgia Syndrome

60 Chapter 60: Chronic Neurologic & Neurodegenerative Disorders

60.1 Dementia: Alzheimer's, Vascular & Lewy Body Disease 60.2 Parkinson's Disease & Essential Tremor 60.3 Epilepsy: Chronic Antiseizure Medications & Post-Stroke Care

61 Chapter 61: Chronic Peripheral Nerves, Pain & Sensory Disorders

61.1 Diabetic & Chronic Peripheral Neuropathies 61.2 Chronic Pain Syndromes & Chronic Daily Headaches 61.3 Chronic Tinnitus, Presbycusis & Persistent Dizziness

62 Chapter 62: Chronic Psychiatric Disorders

62.1 Major Depressive Disorder & Generalized Anxiety Disorder 62.2 Bipolar Disorder: Maintenance Pharmacotherapy & Lithium Monitoring 62.3 Adult & Pediatric Attention-Deficit/Hyperactivity Disorder

63 Chapter 63: Chronic Behavioral Health & Neurodevelopmental Conditions

63.1 Chronic Behavioral Conditions: PTSD, OCD & Somatization 63.2 Autism Spectrum Disorder & Intellectual Disabilities 63.3 Eating Disorders: Anorexia Nervosa, Bulimia & Binge Eating

64 Chapter 64: Chronic Substance Use Disorders & Tobacco Cessation

64.1 Alcohol Use Disorder: Pharmacotherapy & Relapse Prevention 64.2 Opioid & Stimulant Use Disorders: MOUD & Harm Reduction 64.3 Longitudinal Tobacco Cessation Pharmacotherapy

65 Chapter 65: Chronic Dermatologic Conditions

65.1 Acne Vulgaris, Rosacea & Seborrheic Dermatitis 65.2 Chronic Plaque Psoriasis & Biologic Therapies 65.3 Chronic Eczema, Hidradenitis Suppurativa & Cutaneous Lupus

66 Chapter 66: Chronic Reproductive, Infectious & Geriatric Special Care

66.1 Chronic Menstrual Disorders, Infertility & Sexual Dysfunction 66.2 Menopause Management & Hormone Replacement Therapy 66.3 Chronic HIV Infection Management & Primary Care Integration 66.4 Gender-Affirming Primary Care & Hormone Therapy 66.5 Advance Care Planning, Palliative Care & End-of-Life Symptom Control

67 Chapter 67: Continuity Care: Sleep, Fatigue, Cancer, Pregnancy & the Adult Preventive Visit

67.1 Chronic Insomnia & Obstructive Sleep Apnea 67.2 Chronic Malaise, Fatigue & ME/CFS 67.3 Primary Care During Cancer Treatment & Survivorship 67.4 Routine Prenatal Care & Longitudinal Pregnancy Management 67.5 The Periodic Adult Health Examination & Medicare Annual Wellness Visit

33.1 Peptic Ulcer Disease & Gastritis

Key Takeaways Explain This Topic AI

Peptic ulcer disease (PUD) manifests with distinct chronobiologic pain patterns: duodenal ulcers (90-95% H. pylori-associated) classically present with epigastric burning relieved by food or antacids that recurs 2 to 3 hours postprandially or awakens the patient nocturnally; gastric ulcers (60-70% H. pylori, 30-40% NSAID-associated) present with epigastric pain worsened immediately by food, driving anorexia and weight loss, and harbor intrinsic malignant potential.

Upper endoscopy (EGD) is indicated as the mandatory initial diagnostic investigation in dyspepsia for any patient aged ≥60 years (ACG/CAG guidelines) or at any age in the presence of alarm features: progressive dysphagia, odynophagia, unexplained weight loss (>10%), persistent vomiting, palpable epigastric mass or lymphadenopathy, iron deficiency anemia, or overt gastrointestinal bleeding.

Active Helicobacter pylori testing mandates either a laboratory stool antigen test (SAT) or a 13C-urea breath test (UBT); proton pump inhibitors (PPIs) must be discontinued for at least 1 to 2 weeks, and bismuth compounds and systemic antibiotics held for at least 4 weeks prior to testing to prevent false-negative results. Serologic IgG antibody testing is non-recommended due to its inability to distinguish active from resolved infection.

The American College of Gastroenterology (ACG) recommends 14-day Bismuth Quadruple Therapy (Standard-dose PPI BID + Bismuth subsalicylate 300-524 mg QID + Metronidazole 500 mg TID-QID + Tetracycline 500 mg QID) as the preferred first-line empiric regimen due to North American clarithromycin resistance exceeding 15% to 20%; clarithromycin triple therapy is restricted exclusively to patients with no prior macrolide exposure in areas of documented clarithromycin resistance <15%.

Mandatory confirmation of H. pylori eradication must be documented in all treated patients using UBT or stool antigen performed at least 4 weeks post-treatment completion (and off PPIs for ≥1-2 weeks); refractory or recurrent multi-site/atypical peptic ulcers warrant evaluation for Zollinger-Ellison syndrome (gastrinoma) via fasting serum gastrin (>1,000 pg/mL with gastric pH <2.0).

Last updated: September 2026

Peptic Ulcer Disease: Pathophysiology & Etiology

Peptic ulcer disease (PUD) is a mucosal defect in the stomach or duodenum that penetrates through the muscularis mucosae into the deeper layers of the gastrointestinal wall, driven by an imbalance between aggressive luminal factors (gastric acid, pepsin) and mucosal defensive mechanisms (mucus-bicarbonate barrier, mucosal blood flow, epithelial cellular regeneration, and endogenous prostaglandins).

Endogenous Mucosal Defense vs. Luminal Aggressors

Mucosal Defensive Barrier :

Pre-epithelial : The mucus-gel layer enriched with bicarbonate secreted by surface foveolar cells, creating an alkaline microenvironment (pH ~7.0) at the epithelial surface despite a luminal pH of 1.0 to 2.0.

Epithelial : Tight junctions between gastric epithelial cells preventing back-diffusion of hydrogen ions; rapid cell turnover and restitution mediated by restitution peptides and epidermal growth factors.

Sub-epithelial : Microvascular mucosal blood flow that rapidly removes back-diffused acid, delivers oxygen, bicarbonate, and nutrients, and supports tissue repair.

Endogenous Prostaglandins (PGE2 and PGI2) : Synthesized in gastric mucosa via cyclooxygenase-1 (COX-1) and cyclooxygenase-2 (COX-2) enzymes. Prostaglandins stimulate mucus and bicarbonate secretion, inhibit acid secretion by parietal cells via Gi protein-coupled receptors, promote mucosal vasodilation, and stimulate epithelial renewal.

Major Etiologies of Peptic Ulcer Disease

Helicobacter pylori Infection :

Microaerophilic, Gram-negative, flagellated curved rod that colonizes the human gastric antrum and body.

Urease Activity : H. pylori produces copious urease, which hydrolyzes gastric luminal urea into carbon dioxide (CO2) and ammonia (NH3). Ammonia buffers local gastric acid, enabling bacterial survival, while exerting direct cytotoxicity on gastric foveolar cells.

Virulence Factors :

CagA (Cytotoxin-Associated Gene A) : Translocated into host gastric epithelial cells via a Type IV secretion system, causing cytoskeletal rearrangements, cellular elongation (the "hummingbird" phenotype), disruption of tight junctions, and intense IL-8 secretion with mucosal neutrophil infiltration.

VacA (Vacuolating Cytotoxin A) : Induces cellular vacuolization, alters mitochondrial membrane permeability, triggers epithelial apoptosis, and inhibits T-lymphocyte activation.

Antral-Predominant vs. Corpus-Predominant Gastritis :

Antral-predominant gastritis : Decreased somatostatin release from D cells leads to unchecked G-cell gastrin secretion ( hypergastrinemia ), stimulating parietal cells to hypersecrete hydrochloric acid, overwhelming duodenal bicarbonate defenses and producing duodenal ulcers .

Corpus-predominant (pangastritis) : Direct mucosal destruction and progressive atrophy of acid-secreting parietal cells result in hypochlorhydria, mucosal atrophy, intestinal metaplasia, and gastric ulcers , dramatically raising the risk of gastric adenocarcinoma and gastric mucosa-associated lymphoid tissue ( MALT ) lymphoma.

Non-Steroidal Anti-Inflammatory Drugs (NSAIDs) & Aspirin :

NSAIDs represent the second major cause of PUD. Mechanism involves both systemic and topical mucosal injury:

Systemic Inhibition of COX-1 : Blocks mucosal synthesis of cytoprotective prostaglandin E2 (PGE2) and prostacyclin (PGI2), resulting in decreased bicarbonate and mucus secretion, reduced mucosal blood flow, and increased acid secretion.

Topical Caustic Effect ("Ion Trapping") : NSAIDs are weak organic acids (pKa 3-5) that remain non-ionized in acidic gastric juice, freely diffusing across the lipid membrane of gastric epithelial cells. Once inside neutral intracellular cytoplasm (pH 7.4), they ionize into charged anions and protons, becoming trapped intracellularly, disrupting mitochondrial oxidative phosphorylation and compromising membrane integrity.

Other Etiologies & Risk Factors :

Cigarette Smoking : Impairs mucosal blood flow, inhibits pancreatic bicarbonate secretion, impairs ulcer healing, and accelerates ulcer recurrence.

Severe Physiological Stress (Stress Ulcers) : Seen in critically ill ICU patients (Curling ulcers associated with severe extensive burns; Cushing ulcers associated with elevated intracranial pressure or severe head trauma triggering intense vagal hyperstimulation and massive acid hypersecretion).

Hypersecretory States : Zollinger-Ellison syndrome (gastrinoma), systemic mastocytosis (massive histamine release).

Medication Interactions : Concurrent systemic corticosteroids, anticoagulants, antiplatelet agents (clopidogrel), and SSRIs markedly potentiate NSAID-induced gastrointestinal ulceration and bleeding.

Duodenal vs. Gastric Ulcers: Clinical & Diagnostic Distinction

Careful chronobiologic history and risk assessment differentiate duodenal from gastric ulcerations:

• Clinical Characteristic Duodenal Ulcer (DU) Gastric Ulcer (GU)
• Peak Age of Onset 30 to 55 years (younger cohort) 55 to 70 years (older cohort)
• Helicobacter pylori Association 90% to 95% 60% to 70%
• NSAID Association 2% to 5% 30% to 40%
• Gastric Acid Secretion Elevated or hypernormal acid production Normal to decreased (hypochlorhydria)

Anatomic Localization Duodenal bulb (first portion; anterior wall perforates, posterior wall bleeds) Lesser curvature of the stomach at incisura angularis / antrum

Pain Timing & Food Relationship Relieved by food or antacids ; pain recurs 2 to 3 hours postprandially as acid enters duodenum Exacerbated immediately by food intake (within 15-30 min) due to distention and acid secretion

Nocturnal Symptoms Frequent (awakes patient at 1 to 3 AM) when unbuffered nocturnal acid peaks Infrequent nocturnal pain

Nutritional Impact & Weight Weight gain or stability (patients eat frequently to relieve pain) Weight loss and anorexia (food avoidance due to postprandial distress)

Malignant Potential Virtually 0% (almost always benign) 4% to 5% harbor occult adenocarcinoma

Biopsy & Endoscopic Surveillance Biopsy not routinely required; no routine surveillance EGD needed Mandatory 4-quadrant biopsy at index EGD; repeat surveillance EGD at 8 to 12 weeks to document complete healing

Important

Anatomic Complication Pearls for Board Exams :

Anterior duodenal ulcers are in direct contact with the peritoneal cavity; perforation causes sudden catastrophic peritonitis and pneumoperitoneum (free air under the diaphragm).

Posterior duodenal ulcers erode directly into the gastroduodenal artery , precipitating massive, life-threatening upper gastrointestinal hemorrhage.

Gastric ulcers along the lesser curvature can erode directly into the left gastric artery .

Dyspepsia Evaluation & Upper Endoscopy (EGD) Indications

Dyspepsia is defined as one or more postprandial symptoms: postprandial fullness, early satiety, and epigastric pain or burning. The Joint Guidelines of the American College of Gastroenterology (ACG) and Canadian Association of Gastroenterology (CAG) establish clear management pathways based on age and alarm features.

Guideline-Directed Indications for Upper Endoscopy (EGD)

Age ≥60 Years :

All patients aged 60 years or older presenting with new-onset or persistent dyspepsia must undergo prompt diagnostic esophagogastroduodenoscopy (EGD) , regardless of whether alarm features are present, due to the high baseline incidence of upper gastrointestinal malignancy in this demographic.

Alarm Features ("Red Flags") at Any Age :

The presence of any alarm feature warrants immediate EGD, irrespective of patient age:

• Progressive dysphagia (difficulty swallowing) or odynophagia (painful swallowing);
• Unintentional, unexplained weight loss (>10% of baseline body weight);
• Persistent, intractable vomiting ;
• Evidence of gastrointestinal bleeding (hematemesis, "coffee-ground" emesis, melena, hematochezia);
• Unexplained iron deficiency anemia (microcytic hypochromic indices, low ferritin);

Palpable epigastric abdominal mass or lymphadenopathy (Virchow node [left supraclavicular], Sister Mary Joseph nodule [periumbilical], Irish node [left anterior axillary]);

Family history of upper gastrointestinal tract malignancy in a first-degree relative.

Patients Aged <60 Years Without Alarm Features :

In younger patients without alarm signs, invasive endoscopy is not initially recommended. The preferred approach is non-invasive testing for Helicobacter pylori ("test-and-treat" strategy). If testing is positive, eradicate the infection. If testing is negative or symptoms persist after proven eradication, initiate an empiric trial of once-daily proton pump inhibitor (PPI) therapy for 4 to 8 weeks.

Endoscopic Biopsy Protocol for Gastric Ulcers

Mandatory Biopsy : Because benign gastric ulcers and malignant ulcerated gastric adenocarcinomas can appear macroscopically indistinguishable on endoscopy, all gastric ulcers must be biopsied at index EGD.

Sydney Protocol : Minimum of 4 to 6 quadrant biopsies taken from the raised, rolled ulcer margins and the base to exclude malignancy, plus antral and corpus mucosal biopsies for H. pylori.

Surveillance Endoscopy : All patients with gastric ulcers must undergo repeat surveillance EGD 8 to 12 weeks after completion of acid suppression therapy to verify complete histologic and endoscopic ulcer healing. Failure of a gastric ulcer to heal completely after 8 to 12 weeks of high-dose PPI therapy strongly suggests occult malignancy and mandates repeat deep biopsies or surgical wedge resection.

Diagnostic Testing for Helicobacter pylori

Diagnostic tests are divided into non-invasive active tests, non-invasive non-active serology, and endoscopic invasive tests. Testing should only be performed if the clinician intends to treat positive results. H. PYLORI DIAGNOSTIC WORKUP

• Patient with Suspected PUD / Dyspepsia
• │
• ┌──────────────────────┴──────────────────────┐
• ▼ ▼
• Age >=60 OR Alarm Signs Age <60, No Alarm Signs
• │ │
• ▼ ▼
• DIAGNOSTIC EGD + BIOPSY NON-INVASIVE ACTIVE TEST
• Rapid Urease Test (CLOtest) • Stool Antigen Test (SAT) OR
• Histology (Giemsa / W-Starry) • 13C-Urea Breath Test (UBT)
• Rule out malignancy • MUST HOLD PPI x 1-2 weeks
• MUST HOLD Antibiotics/Bismuth x 4 wk

• NEVER USE SEROLOGY (IgG EIA)!

Comparison of H. pylori Diagnostic Modalities

Diagnostic Test Category Sensitivity / Specificity Pre-Test Washout Requirements Clinical Pearls & Exam Rules

13C- or 14C-Urea Breath Test (UBT) Non-Invasive Active Test >95% / >95% Hold PPIs for 1-2 weeks; hold antibiotics and bismuth for 4 weeks Ingested labeled urea is cleaved by bacterial urease into labeled CO2, exhaled and measured via mass spectrometry. Excellent for initial diagnosis and test-of-cure .

Fecal Stool Antigen Test (SAT) Non-Invasive Active Test >95% / >95% Hold PPIs for 1-2 weeks; hold antibiotics and bismuth for 4 weeks Monoclonal enzyme immunoassay (EIA) detecting active bacterial shedding. Highly reliable, cost-effective, and validated for test-of-cure . Unformed/diarrheal stool can cause false negatives.

Serum IgG Serology (ELISA) Non-Invasive Non-Active 80% / 70% None STRICTLY NOT RECOMMENDED / DEPRECATED . Circulating IgG antibodies remain positive for months to years following eradication; cannot distinguish active from past resolved infection.

Rapid Urease Test (CLOtest) Endoscopic Invasive 90-95% / 95-98% Hold PPIs 1-2 wk; hold antibiotics/bismuth 4 wk Biopsy placed into urea broth with phenol red indicator. Bacterial urease generates ammonia, raising pH and causing rapid color change (yellow to magenta). False negatives occur with recent PPI use.

Endoscopic Mucosal Histology Endoscopic Invasive >95% / >98% Decreased sensitivity with recent PPI use Gold standard pathologic evaluation using special stains (Warthin-Starry silver, Giemsa, or immunohistochemistry). Detects gastritis grade, atrophy, intestinal metaplasia, and MALT lymphoma.

Warning

Crucial Pre-Test Washout Rules to Prevent False Negatives :

Proton Pump Inhibitors (PPIs) suppress bacterial metabolic activity and reduce bacterial density, causing false-negative UBT, stool antigen, and CLOtest results. PPIs must be stopped for at least 1 to 2 weeks prior to active testing.

Bismuth compounds and systemic antibiotics suppress H. pylori numbers and must be stopped for at least 4 weeks prior to testing.

Safe symptomatic alternatives : H2-receptor antagonists (famotidine) and antacids do not interfere with urease-based tests and can be used up to 24 to 48 hours before testing.

ACG Guideline-Directed Eradication Regimens

Historically, clarithromycin-based triple therapy (PPI + clarithromycin + amoxicillin) was the standard regimen. However, extensive nationwide surveillance has demonstrated North American clarithromycin resistance rates between 20% and 30%, resulting in treatment failure rates exceeding 30% to 40%. Consequently, clinical practice guidelines from the ACG have dethroned triple therapy as the empiric choice.

ACG First-Line Regimens

Regimen Medications & Specific Dosages Administration Schedule Duration Clinical Context & Rationale

Bismuth Quadruple Therapy (PREFERRED FIRST-LINE) • Standard-dose PPI (e.g., Omeprazole 20 mg, Lansoprazole 30 mg, Pantoprazole 40 mg, Esomeprazole 40 mg); • Bismuth subsalicylate 300 to 524 mg; • Metronidazole 500 mg; • Tetracycline hydrochloride 500 mg • PPI: Twice daily (BID, before breakfast & dinner); • Bismuth: Four times daily (QID, with meals & bedtime); • Metronidazole: TID or QID (with meals & bedtime); • Tetracycline: QID (with meals & bedtime) 14 Days Preferred first-line empiric therapy for all patients , regardless of penicillin allergy. Achieves >85-90% eradication. Overcomes metronidazole resistance through bismuth-tetracycline synergy.

Clarithromycin Triple Therapy (RESTRICTED) • Standard-dose PPI BID; • Clarithromycin 500 mg BID; • Amoxicillin 1,000 mg BID (or Metronidazole 500 mg TID if penicillin-allergic) BID before meals 14 Days Acceptable ONLY IF : Local clarithromycin resistance is documented to be <15% AND the patient has never had prior macrolide exposure (for any indication).

Concomitant Non-Bismuth Quadruple Therapy • Standard-dose PPI BID; • Amoxicillin 1,000 mg BID; • Clarithromycin 500 mg BID; • Metronidazole 500 mg BID BID with meals 14 Days Alternative four-drug non-bismuth regimen when bismuth quadruple components are unavailable. High pill burden.

Potassium-Competitive Acid Blocker (P-CAB) Dual / Triple Therapy • Vonoprazan 20 mg BID; • Amoxicillin 1,000 mg TID (Dual); OR; • Vonoprazan 20 mg BID + Amoxicillin 1,000 mg BID + Clarithromycin 500 mg BID (Triple) BID or TID 14 Days Vonoprazan provides superior, rapid, acid-stable pH suppression (>6.0) without CYP2C19 dependency. FDA-approved and highly effective.

Patient Counseling & Adverse Effects

Bismuth Subsalicylate : Causes harmless, temporary black discoloration of the tongue and stool (bismuth sulfide precipitation); patients must be reassured this is not melena. Tinnitus can occur from salicylate toxicity.

Metronidazole : Severe disulfiram-like ethanol intolerance (nausea, violent vomiting, flushing, tachycardia); patients must strictly avoid all alcohol during therapy and for 72 hours following completion. Causes metallic dysgeusia.

Tetracycline : Pill esophagitis, cutaneous photosensitivity, gastrointestinal distress. Strictly contraindicated in children <8 years and during pregnancy/lactation due to permanent dental staining and bone growth inhibition.

Mandatory Confirmation of Eradication (Test-of-Cure)

Rule : Every patient treated for Helicobacter pylori infection must undergo a formal test-of-cure to confirm bacterial clearance.

Timing : Perform test-of-cure at least 4 weeks after completion of antibiotic therapy AND at least 1 to 2 weeks after stopping PPI therapy .

Test Modality : Use either the 13C-urea breath test or laboratory-based stool antigen test (or repeat mucosal biopsy if undergoing surveillance EGD for a gastric ulcer). Serum antibody testing must never be used.

NSAID-Associated Ulcer Prevention & Risk Stratification

Chronic NSAID use confers a four- to five-fold increased risk of upper gastrointestinal ulceration and bleeding. Clinicians must risk-stratify patients prior to initiating long-term NSAID therapy.

Gastrointestinal Risk Stratification for NSAID Therapy

High Risk : History of a prior complicated ulcer (perforation, obstruction, bleeding); OR multiple (>2) moderate risk factors.

Moderate Risk : Age ≥65 years; high-dose NSAID therapy; concurrent use of aspirin, systemic corticosteroids, or anticoagulants (warfarin, DOACs); history of an uncomplicated peptic ulcer.

Low Risk : Age <65 years with no risk factors.

Prevention Strategies

Proton Pump Inhibitor Co-Therapy : Standard-dose PPI once daily co-prescribed with the NSAID significantly reduces both gastric and duodenal ulcer recurrence and bleeding complications.

COX-2 Selective Inhibitors (Celecoxib) : Selectively inhibits inducible COX-2 while sparing constitutive mucosal COX-1, reducing endoscopic ulcer incidence by 50% compared to non-selective NSAIDs. However, celecoxib confers increased cardiovascular thrombotic risk (myocardial infarction, stroke) at higher doses and does not eliminate ulcer risk when combined with low-dose aspirin.

Misoprostol (Cytotec) :

Synthetic prostaglandin E1 (PGE1) analog that directly replaces deficient mucosal prostaglandins, stimulating bicarbonate and mucus secretion and maintaining mucosal blood flow.

Dosing : 200 mcg PO four times daily with food.

Adverse Effects : High incidence of dose-dependent crampy abdominal pain and explosive diarrhea (seen in 20% to 30% of patients), which severely limits adherence.

Black Box Warning : Strictly contraindicated in women of childbearing potential and pregnancy due to potent uterotonic properties causing uterine contractions, vaginal bleeding, and spontaneous abortion .

Zollinger-Ellison Syndrome (ZES / Gastrinoma)

Zollinger-Ellison syndrome is a clinical syndrome caused by a gastrin-secreting neuroendocrine tumor ( gastrinoma ), characterized by severe gastric acid hypersecretion resulting in refractory peptic ulcer disease and chronic secretory diarrhea.

Epidemiology & Clinical Manifestations

Epidemiology : 75% to 80% are sporadic neuroendocrine tumors; 20% to 25% occur in association with Multiple Endocrine Neoplasia Type 1 (MEN1) syndrome (triad of parathyroid adenomas, pituitary adenomas, and pancreatic neuroendocrine tumors).

Localization : Over 70% of gastrinomas arise within the anatomic "gastrinoma triangle" bounded by the junction of the cystic duct and common bile duct superiorly, the junction of the second and third portions of the duodenum inferiorly, and the neck and body of the pancreas medially.

Hallmark Clinical Presentations :

Refractory, persistent, or rapidly recurrent peptic ulcer disease despite guideline-directed PPI therapy and confirmed H. pylori eradication;

• Multiple peptic ulcers occurring simultaneously;
• Ulcers located in atypical anatomic sites : the distal duodenum (post-bulbar) or proximal jejunum ;

Peptic ulcer disease accompanied by severe, chronic watery secretory diarrhea (large volumes of hydrochloric acid overwhelm duodenal neutralization, denaturing pancreatic enzymes and inactivating pancreatic lipase, causing acid-induced malabsorption and secretory enteropathy; diarrhea completely resolves with high-dose gastric acid suppression).

Diagnostic Evaluation Algorithm

Fasting Serum Gastrin (FSG) :

The initial screening test of choice. Must be measured while fasting and ideally with the patient off PPI therapy for at least 1 to 2 weeks (or on H2-blockers):

FSG >1,000 pg/mL (normal <100 pg/mL) combined with a gastric pH <2.0 is virtually pathognomonic for Zollinger-Ellison syndrome.

Caveat : Documenting gastric pH <2.0 is mandatory to distinguish gastrinoma from secondary hypergastrinemia caused by achlorhydria (such as autoimmune atrophic gastritis or chronic PPI suppression, where lack of acid eliminates negative feedback on G cells).

Secretin Stimulation Test (Confirmatory for Borderline Cases) :

Indicated when fasting serum gastrin is non-diagnostically elevated between 110 and 1,000 pg/mL with gastric pH <2.0.

Intravenous secretin (2 clinical units/kg) is administered, and serum gastrin levels are measured at 2, 5, 10, 15, and 30 minutes.

Diagnostic Response : In normal parietal cells, secretin inhibits gastrin release. In gastrinoma cells, secretin stimulates secretin receptors, causing a paradoxical rise in serum gastrin of >120 pg/mL over baseline (confirms Zollinger-Ellison syndrome).

Tumor Localization :

Somatostatin Receptor PET/CT (68Ga-DOTATATE PET/CT) : The gold standard imaging modality with >90% sensitivity for identifying primary gastrinomas and metastatic hepatic lesions.

Endoscopic Ultrasound (EUS) is highly sensitive for identifying tiny pancreatic and duodenal wall tumors.

Loading diagram... Clinical Diagnostic & Therapeutic Algorithm for Dyspepsia, PUD & H. Pylori