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Peptic Ulcer Disease

Peptic Ulcer Disease

Peptic ulcer disease (PUD) refers to the full-thickness ulcerations of duodenal or gastric mucosa Gastric mucosa Lining of the stomach, consisting of an inner epithelium, a middle lamina propria, and an outer muscularis mucosae. The surface cells produce mucus that protects the stomach from attack by digestive acid and enzymes. When the epithelium invaginates into the lamina propria at various region of the stomach (cardia; gastric fundus; and pylorus), different tubular gastric glands are formed. These glands consist of cells that secrete mucus, enzymes, hydrochloric acid, or hormones. Stomach: Anatomy. The ulcerations form when exposure Exposure ABCDE Assessment to acid and digestive enzymes Enzymes Enzymes are complex protein biocatalysts that accelerate chemical reactions without being consumed by them. Due to the body's constant metabolic needs, the absence of enzymes would make life unsustainable, as reactions would occur too slowly without these molecules. Basics of Enzymes overcomes mucosal defense mechanisms Defense mechanisms Defense mechanisms are normal subconscious means of resolving inner conflicts between an individual's subjective moral sense and their thoughts, feelings, or actions. Defense mechanisms serve to protect the self from unpleasant feelings (anxiety, shame, and/or guilt) and are divided into pathologic, immature, mature, neurotic, and other types. Defense Mechanisms. The most common etiologies include Helicobacter Helicobacter Helicobacter pylori is a gram-negative bacterium that causes gastric infection. It is the most well known and clinically significant species of Helicobacter. Transmission is believed to occur by ingestion of contaminated food or water; therefore, a higher prevalence of infection is seen in areas with poor sanitation. Helicobacter pylori ( H. pylori H. pylori A spiral bacterium active as a human gastric pathogen. It is a gram-negative, urease-positive, curved or slightly spiral organism initially isolated in 1982 from patients with lesions of gastritis or peptic ulcers in Western Australia. Helicobacter pylori was originally classified in the genus campylobacter, but RNA sequencing, cellular fatty acid profiles, growth patterns, and other taxonomic characteristics indicate that the micro-organism should be included in the genus Helicobacter. It has been officially transferred to Helicobacter gen. Helicobacter) infection and prolonged use of non-steroidal anti-inflammatory drugs ( NSAIDs NSAIDS Primary vs Secondary Headaches). Patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship may be asymptomatic or may present with abdominal pain Abdominal Pain Acute Abdomen, nausea Nausea An unpleasant sensation in the stomach usually accompanied by the urge to vomit. Common causes are early pregnancy, sea and motion sickness, emotional stress, intense pain, food poisoning, and various enteroviruses. Antiemetics, and early satiety Early Satiety Bariatric Surgery. Peptic ulcer disease typically responds well to medical treatment consisting of H. pylori H. pylori A spiral bacterium active as a human gastric pathogen. It is a gram-negative, urease-positive, curved or slightly spiral organism initially isolated in 1982 from patients with lesions of gastritis or peptic ulcers in Western Australia. Helicobacter pylori was originally classified in the genus campylobacter, but RNA sequencing, cellular fatty acid profiles, growth patterns, and other taxonomic characteristics indicate that the micro-organism should be included in the genus Helicobacter. It has been officially transferred to Helicobacter gen. Helicobacter eradication, eliminating risk factors, and proton pump inhibitors Proton Pump Inhibitors Compounds that inhibit h(+)-k(+)-exchanging ATPase. They are used as anti-ulcer agents and sometimes in place of histamine h2 antagonists for gastroesophageal reflux. Gastric Acid Drugs (PPIs). If left untreated, it can lead to bleeding, perforation Perforation A pathological hole in an organ, blood vessel or other soft part of the body, occurring in the absence of external force. Esophagitis, gastric outlet obstruction Gastric Outlet Obstruction Hypertrophic Pyloric Stenosis, and gastric cancer Gastric cancer Gastric cancer is the 3rd-most common cause of cancer-related deaths worldwide. The majority of cases are from adenocarcinoma. The modifiable risk factors include Helicobacter pylori infection, smoking, and nitrate-rich diets. Gastric Cancer.

Last updated: 8 Jan, 2021

Editorial responsibility: Stanley Oiseth, Lindsay Jones, Evelin Maza

Contents

Overview

Definition

A peptic ulcer is a mucosal defect in the wall of the stomach Stomach The stomach is a muscular sac in the upper left portion of the abdomen that plays a critical role in digestion. The stomach develops from the foregut and connects the esophagus with the duodenum. Structurally, the stomach is C-shaped and forms a greater and lesser curvature and is divided grossly into regions: the cardia, fundus, body, and pylorus. Stomach: Anatomy or duodenum Duodenum The shortest and widest portion of the small intestine adjacent to the pylorus of the stomach. It is named for having the length equal to about the width of 12 fingers. Small Intestine: Anatomy that penetrates the muscularis mucosa.

Epidemiology

  • Incidence Incidence The number of new cases of a given disease during a given period in a specified population. It also is used for the rate at which new events occur in a defined population. It is differentiated from prevalence, which refers to all cases in the population at a given time. Measures of Disease Frequency:
    • Uncomplicated peptic ulcer disease (PUD): 1 case per 1,000 person-years in the general population
    • PUD complications: 0.7 cases per 1,000 person-years in the general population
  • Duodenal ulcers > gastric ulcers (3:1)
  • Affects men and women equally
  • Duodenal ulcers occur, on average, 2 decades earlier than gastric ulcers.
  • PUD rates have been falling over the past few decades.

Etiology

  • Infection:
    • Helicobacter Helicobacter Helicobacter pylori is a gram-negative bacterium that causes gastric infection. It is the most well known and clinically significant species of Helicobacter. Transmission is believed to occur by ingestion of contaminated food or water; therefore, a higher prevalence of infection is seen in areas with poor sanitation. Helicobacter pylori or H. pylori H. pylori A spiral bacterium active as a human gastric pathogen. It is a gram-negative, urease-positive, curved or slightly spiral organism initially isolated in 1982 from patients with lesions of gastritis or peptic ulcers in Western Australia. Helicobacter pylori was originally classified in the genus campylobacter, but RNA sequencing, cellular fatty acid profiles, growth patterns, and other taxonomic characteristics indicate that the micro-organism should be included in the genus Helicobacter. It has been officially transferred to Helicobacter gen. Helicobacter (most common):
      • 80%–90% duodenal ulcers
      • 70%–80% gastric ulcers
    • Viruses Viruses Minute infectious agents whose genomes are composed of DNA or RNA, but not both. They are characterized by a lack of independent metabolism and the inability to replicate outside living host cells. Virology:
      • Herpes simplex virus Herpes Simplex Virus A group of acute infections caused by herpes simplex virus type 1 or type 2 that is characterized by the development of one or more small fluid-filled vesicles with a raised erythematous base on the skin or mucous membrane. It occurs as a primary infection or recurs due to a reactivation of a latent infection. Encephalitis ( HSV HSV Herpes simplex virus (HSV) is a double-stranded DNA virus belonging to the family Herpesviridae. Herpes simplex virus commonly causes recurrent infections involving the skin and mucosal surfaces, including the mouth, lips, eyes, and genitals. Herpes Simplex Virus 1 and 2)
      • Cytomegalovirus Cytomegalovirus CMV is a ubiquitous double-stranded DNA virus belonging to the Herpesviridae family. CMV infections can be transmitted in bodily fluids, such as blood, saliva, urine, semen, and breast milk. The initial infection is usually asymptomatic in the immunocompetent host, or it can present with symptoms of mononucleosis. Cytomegalovirus (CMV)
    • Rare infections Infections Invasion of the host organism by microorganisms or their toxins or by parasites that can cause pathological conditions or diseases. Chronic Granulomatous Disease:
      • Tuberculosis Tuberculosis Tuberculosis (TB) is an infectious disease caused by Mycobacterium tuberculosis complex bacteria. The bacteria usually attack the lungs but can also damage other parts of the body. Approximately 30% of people around the world are infected with this pathogen, with the majority harboring a latent infection. Tuberculosis spreads through the air when a person with active pulmonary infection coughs or sneezes. Tuberculosis ( TB TB Tuberculosis (TB) is an infectious disease caused by Mycobacterium tuberculosis complex bacteria. The bacteria usually attack the lungs but can also damage other parts of the body. Approximately 30% of people around the world are infected with this pathogen, with the majority harboring a latent infection. Tuberculosis spreads through the air when a person with active pulmonary infection coughs or sneezes. Tuberculosis)
      • Syphilis Syphilis Syphilis is a bacterial infection caused by the spirochete Treponema pallidum pallidum (T. p. pallidum), which is usually spread through sexual contact. Syphilis has 4 clinical stages: primary, secondary, latent, and tertiary. Syphilis
      • Mucormycosis Mucormycosis Mucormycosis is an angioinvasive fungal infection caused by multiple fungi within the order, Mucorales. The fungi are ubiquitous in the environment, but mucormycosis is very rare and almost always occurs in patients who are immunocompromised. Inhalation of fungal spores can cause rhinocerebral or pulmonary mucormycosis, direct inoculation can cause cutaneous mucormycosis, and ingestion can cause gastrointestinal mucormycosis. Mucorales/Mucormycosis
  • Medications:
    • Non-steroidal anti-inflammatory drugs ( NSAIDs NSAIDS Primary vs Secondary Headaches; most common)
    • Medications linked to PUD or risk exacerbated by combination with NSAIDs NSAIDS Primary vs Secondary Headaches:
      • Bisphosphonates Bisphosphonates Bisphosphonates are pyrophosphate analogs most well-known for treating osteoporosis by preventing bone loss. Bisphosphonates end in the suffix “-dronate” or “-dronic acid” (e.g., alendronate, risedronate, pamidronate) and bind to hydroxyapatite crystals in bone, inhibiting osteoclast-induced bone resorption. Bisphosphonates
      • Clopidogrel Clopidogrel A ticlopidine analog and platelet purinergic p2y receptor antagonist that inhibits adenosine diphosphate-mediated platelet aggregation. It is used to prevent thromboembolism in patients with arterial occlusive diseases; myocardial infarction; stroke; or atrial fibrillation. Antiplatelet Drugs
      • Corticosteroids Corticosteroids Chorioretinitis
      • Spironolactone Spironolactone A potassium sparing diuretic that acts by antagonism of aldosterone in the distal renal tubules. It is used mainly in the treatment of refractory edema in patients with congestive heart failure, nephrotic syndrome, or hepatic cirrhosis. Its effects on the endocrine system are utilized in the treatments of hirsutism and acne but they can lead to adverse effects. Potassium-sparing Diuretics
    • Chemotherapy Chemotherapy Osteosarcoma
    • Sirolimus Sirolimus A macrolide compound obtained from streptomyces hygroscopicus that acts by selectively blocking the transcriptional activation of cytokines thereby inhibiting cytokine production. It is bioactive only when bound to immunophilins. Sirolimus is a potent immunosuppressant and possesses both antifungal and antineoplastic properties. Immunosuppressants
    • Mycophenolate Mycophenolate Immunosuppressants mofetil
    • Potassium Potassium An element in the alkali group of metals with an atomic symbol k, atomic number 19, and atomic weight 39. 10. It is the chief cation in the intracellular fluid of muscle and other cells. Potassium ion is a strong electrolyte that plays a significant role in the regulation of fluid volume and maintenance of the water-electrolyte balance. Hyperkalemia chloride Chloride Inorganic compounds derived from hydrochloric acid that contain the Cl- ion. Electrolytes
  • Hormonal:
    • Gastrinoma Gastrinoma A gastrinoma is a tumor that secretes excessive levels of the hormone gastrin and is responsible for Zollinger-Ellison syndrome (ZES). Gastrinomas are frequently associated with multiple endocrine neoplasia 1 (MEN 1) and can arise from the pancreas, stomach, duodenum, jejunum, and/or even from the lymph nodes. Gastrinoma ( Zollinger-Ellison syndrome Zollinger-ellison syndrome A syndrome that is characterized by the triad of severe peptic ulcer, hypersecretion of gastric acid, and gastrin-producing tumors of the pancreas or other tissue (gastrinoma). This syndrome may be sporadic or be associated with multiple endocrine neoplasia type 1. Esophagitis)
    • Antral G-cell hyperplasia Hyperplasia An increase in the number of cells in a tissue or organ without tumor formation. It differs from hypertrophy, which is an increase in bulk without an increase in the number of cells. Cellular Adaptation/hyperfunction ( gastritis Gastritis Gastritis refers to inflammation of the gastric mucosa. Gastritis may occur suddenly (acute gastritis) or slowly over time (chronic gastritis). Gastritis may be asymptomatic or with symptoms, including burning abdominal pain (which either worsens or improves with eating), dyspepsia, nausea, and vomiting. Gastritis)
  • Post-surgical:
    • Antral exclusion
    • Gastric bypass Gastric bypass Surgical procedure in which the stomach is transected high on the body. The resulting small proximal gastric pouch is joined to any parts of the small intestine by an end-to-side surgical anastomosis, depending on the amounts of intestinal surface being bypasses. This procedure is used frequently in the treatment of morbid obesity by limiting the size of functional stomach, food intake, and food absorption. Gastroesophageal Reflux Disease (GERD)
  • Ischemic: cocaine Cocaine An alkaloid ester extracted from the leaves of plants including coca. It is a local anesthetic and vasoconstrictor and is clinically used for that purpose, particularly in the eye, ear, nose, and throat. It also has powerful central nervous system effects similar to the amphetamines and is a drug of abuse. Cocaine, like amphetamines, acts by multiple mechanisms on brain catecholaminergic neurons; the mechanism of its reinforcing effects is thought to involve inhibition of dopamine uptake. Local Anesthetics use
  • Decompensated chronic diseases:
    • Cirrhosis Cirrhosis Cirrhosis is a late stage of hepatic parenchymal necrosis and scarring (fibrosis) most commonly due to hepatitis C infection and alcoholic liver disease. Patients may present with jaundice, ascites, and hepatosplenomegaly. Cirrhosis can also cause complications such as hepatic encephalopathy, portal hypertension, portal vein thrombosis, and hepatorenal syndrome. Cirrhosis
    • Renal failure Renal failure Conditions in which the kidneys perform below the normal level in the ability to remove wastes, concentrate urine, and maintain electrolyte balance; blood pressure; and calcium metabolism. Renal insufficiency can be classified by the degree of kidney damage (as measured by the level of proteinuria) and reduction in glomerular filtration rate. Crush Syndrome
    • Chronic obstructive pulmonary disease Pulmonary disease Diseases involving the respiratory system. Blastomyces/Blastomycosis ( COPD COPD Chronic obstructive pulmonary disease (COPD) is a lung disease characterized by progressive, largely irreversible airflow obstruction. The condition usually presents in middle-aged or elderly persons with a history of cigarette smoking. Signs and symptoms include prolonged expiration, wheezing, diminished breath sounds, progressive dyspnea, and chronic cough. Chronic Obstructive Pulmonary Disease (COPD))
    • Prolonged intensive care unit ( ICU ICU Hospital units providing continuous surveillance and care to acutely ill patients. West Nile Virus) stay for any reason
  • Idiopathic Idiopathic Dermatomyositis
  • Other rare causes:
    • Annular Annular Dermatologic Examination pancreas Pancreas The pancreas lies mostly posterior to the stomach and extends across the posterior abdominal wall from the duodenum on the right to the spleen on the left. This organ has both exocrine and endocrine tissue. Pancreas: Anatomy
    • Sarcoidosis Sarcoidosis Sarcoidosis is a multisystem inflammatory disease that causes noncaseating granulomas. The exact etiology is unknown. Sarcoidosis usually affects the lungs and thoracic lymph nodes, but it can also affect almost every system in the body, including the skin, heart, and eyes, most commonly. Sarcoidosis
    • Crohn’s disease
    • Radiation Radiation Emission or propagation of acoustic waves (sound), electromagnetic energy waves (such as light; radio waves; gamma rays; or x-rays), or a stream of subatomic particles (such as electrons; neutrons; protons; or alpha particles). Osteosarcoma

Risk factors

In many cases, the listed etiologies are not enough to produce PUD. Contributing risk factors to PUD development:

  • Smoking Smoking Willful or deliberate act of inhaling and exhaling smoke from burning substances or agents held by hand. Interstitial Lung Diseases
  • Alcohol
  • Stress (severe illness–related, psychologic)
  • Diet
  • Genetic predisposition
  • Blood types A and O

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Pathophysiology

Anatomic location of ulcers

  • Duodenal ulcer: an ulcer located in the duodenum Duodenum The shortest and widest portion of the small intestine adjacent to the pylorus of the stomach. It is named for having the length equal to about the width of 12 fingers. Small Intestine: Anatomy, typically in the duodenal bulb (1st part)
  • Gastric ulcer: an ulcer in the stomach Stomach The stomach is a muscular sac in the upper left portion of the abdomen that plays a critical role in digestion. The stomach develops from the foregut and connects the esophagus with the duodenum. Structurally, the stomach is C-shaped and forms a greater and lesser curvature and is divided grossly into regions: the cardia, fundus, body, and pylorus. Stomach: Anatomy lining, commonly in the lesser curvature Lesser curvature Stomach: Anatomy of the stomach Stomach The stomach is a muscular sac in the upper left portion of the abdomen that plays a critical role in digestion. The stomach develops from the foregut and connects the esophagus with the duodenum. Structurally, the stomach is C-shaped and forms a greater and lesser curvature and is divided grossly into regions: the cardia, fundus, body, and pylorus. Stomach: Anatomy near the junction of the fundus Fundus The superior portion of the body of the stomach above the level of the cardiac notch. Stomach: Anatomy and antral mucosa (or type I)
Table: Classification of gastric ulcers by location (modified Johnson classification)
Type Location Acid level
I Lesser curve of the stomach Stomach The stomach is a muscular sac in the upper left portion of the abdomen that plays a critical role in digestion. The stomach develops from the foregut and connects the esophagus with the duodenum. Structurally, the stomach is C-shaped and forms a greater and lesser curvature and is divided grossly into regions: the cardia, fundus, body, and pylorus. Stomach: Anatomy at the incisura angularis Low to normal
II Gastric body; coexists with duodenal ulcer Increased
III In the pyloric channel (within 3 cm of pylorus Pylorus The region between the sharp indentation at the lower third of the stomach (incisura angularis) and the junction of the pylorus with the duodenum. Pyloric antral glands contain mucus-secreting cells and gastrin-secreting endocrine cells (g cells). Stomach: Anatomy) Increased
IV Proximal gastroesophageal ulcer Normal
V Anywhere in the stomach Stomach The stomach is a muscular sac in the upper left portion of the abdomen that plays a critical role in digestion. The stomach develops from the foregut and connects the esophagus with the duodenum. Structurally, the stomach is C-shaped and forms a greater and lesser curvature and is divided grossly into regions: the cardia, fundus, body, and pylorus. Stomach: Anatomy ( aspirin Aspirin The prototypical analgesic used in the treatment of mild to moderate pain. It has anti-inflammatory and antipyretic properties and acts as an inhibitor of cyclooxygenase which results in the inhibition of the biosynthesis of prostaglandins. Aspirin also inhibits platelet aggregation and is used in the prevention of arterial and venous thrombosis. Nonsteroidal Antiinflammatory Drugs (NSAIDs)/ NSAID NSAID Nonsteroidal antiinflammatory drugs (NSAIDs) are a class of medications consisting of aspirin, reversible NSAIDs, and selective NSAIDs. NSAIDs are used as antiplatelet, analgesic, antipyretic, and antiinflammatory agents. Nonsteroidal Antiinflammatory Drugs (NSAIDs) induced) Normal
Anatomical components of the stomach

Anatomic components of the stomach Stomach The stomach is a muscular sac in the upper left portion of the abdomen that plays a critical role in digestion. The stomach develops from the foregut and connects the esophagus with the duodenum. Structurally, the stomach is C-shaped and forms a greater and lesser curvature and is divided grossly into regions: the cardia, fundus, body, and pylorus. Stomach: Anatomy

Image by Lecturio.

Pathophysiology

  • Stomach Stomach The stomach is a muscular sac in the upper left portion of the abdomen that plays a critical role in digestion. The stomach develops from the foregut and connects the esophagus with the duodenum. Structurally, the stomach is C-shaped and forms a greater and lesser curvature and is divided grossly into regions: the cardia, fundus, body, and pylorus. Stomach: Anatomy and duodenum Duodenum The shortest and widest portion of the small intestine adjacent to the pylorus of the stomach. It is named for having the length equal to about the width of 12 fingers. Small Intestine: Anatomy: 
    • Normally exposed to a toxic environment (acid + pepsin Pepsin Pepsin breaks down proteins into proteoses, peptones, and large polypeptides. Proteins and Peptides)
    • Imbalance between offending agents and defense mechanisms Defense mechanisms Defense mechanisms are normal subconscious means of resolving inner conflicts between an individual’s subjective moral sense and their thoughts, feelings, or actions. Defense mechanisms serve to protect the self from unpleasant feelings (anxiety, shame, and/or guilt) and are divided into pathologic, immature, mature, neurotic, and other types. Defense Mechanisms leads to PUD.
  • Defense preventing mucosal injury:
    • Mucus- bicarbonate Bicarbonate Inorganic salts that contain the -HCO3 radical. They are an important factor in determining the ph of the blood and the concentration of bicarbonate ions is regulated by the kidney. Levels in the blood are an index of the alkali reserve or buffering capacity. Electrolytes-phospholipid layer
    • Epithelial layer (repair of which is regulated by prostaglandins Prostaglandins A group of compounds derived from unsaturated 20-carbon fatty acids, primarily arachidonic acid, via the cyclooxygenase pathway. They are extremely potent mediators of a diverse group of physiological processes. Eicosanoids)
    • Subepithelial Subepithelial Membranoproliferative Glomerulonephritis defense (mucosal blood flow Flow Blood flows through the heart, arteries, capillaries, and veins in a closed, continuous circuit. Flow is the movement of volume per unit of time. Flow is affected by the pressure gradient and the resistance fluid encounters between 2 points. Vascular resistance is the opposition to flow, which is caused primarily by blood friction against vessel walls. Vascular Resistance, Flow, and Mean Arterial Pressure for supply of nutrients and oxygen, disposal of noxious agents)
  • Mechanisms by offending agents:
    • Increased gastric acid Gastric acid Hydrochloric acid present in gastric juice. Gastroesophageal Reflux Disease (GERD) secretion Secretion Coagulation Studies:
      • H. pylori H. pylori A spiral bacterium active as a human gastric pathogen. It is a gram-negative, urease-positive, curved or slightly spiral organism initially isolated in 1982 from patients with lesions of gastritis or peptic ulcers in Western Australia. Helicobacter pylori was originally classified in the genus campylobacter, but RNA sequencing, cellular fatty acid profiles, growth patterns, and other taxonomic characteristics indicate that the micro-organism should be included in the genus Helicobacter. It has been officially transferred to Helicobacter gen. Helicobacter gastritis Gastritis Gastritis refers to inflammation of the gastric mucosa. Gastritis may occur suddenly (acute gastritis) or slowly over time (chronic gastritis). Gastritis may be asymptomatic or with symptoms, including burning abdominal pain (which either worsens or improves with eating), dyspepsia, nausea, and vomiting. Gastritis or inflammation Inflammation Inflammation is a complex set of responses to infection and injury involving leukocytes as the principal cellular mediators in the body’s defense against pathogenic organisms. Inflammation is also seen as a response to tissue injury in the process of wound healing. The 5 cardinal signs of inflammation are pain, heat, redness, swelling, and loss of function. Inflammation: ↑ gastric acid Gastric acid Hydrochloric acid present in gastric juice. Gastroesophageal Reflux Disease (GERD), inhibits somatostatin Somatostatin A 14-amino acid peptide named for its ability to inhibit pituitary growth hormone release, also called somatotropin release-inhibiting factor. It is expressed in the central and peripheral nervous systems, the gut, and other organs. SRIF can also inhibit the release of thyroid-stimulating hormone; prolactin; insulin; and glucagon besides acting as a neurotransmitter and neuromodulator. In a number of species including humans, there is an additional form of somatostatin, srif-28 with a 14-amino acid extension at the n-terminal. Gastrointestinal Secretions, ↓ mucus
      • NSAID NSAID Nonsteroidal antiinflammatory drugs (NSAIDs) are a class of medications consisting of aspirin, reversible NSAIDs, and selective NSAIDs. NSAIDs are used as antiplatelet, analgesic, antipyretic, and antiinflammatory agents. Nonsteroidal Antiinflammatory Drugs (NSAIDs) inhibition of COX 1 COX 1 A constitutively-expressed subtype of prostaglandin-endoperoxide synthase. It plays an important role in many cellular processes. Antiplatelet Drugs → ↓ prostaglandin (↓ mucus, ↓ mucosal blood flow Flow Blood flows through the heart, arteries, capillaries, and veins in a closed, continuous circuit. Flow is the movement of volume per unit of time. Flow is affected by the pressure gradient and the resistance fluid encounters between 2 points. Vascular resistance is the opposition to flow, which is caused primarily by blood friction against vessel walls. Vascular Resistance, Flow, and Mean Arterial Pressure, ↓ epithelial proliferation) 
      • NSAID NSAID Nonsteroidal antiinflammatory drugs (NSAIDs) are a class of medications consisting of aspirin, reversible NSAIDs, and selective NSAIDs. NSAIDs are used as antiplatelet, analgesic, antipyretic, and antiinflammatory agents. Nonsteroidal Antiinflammatory Drugs (NSAIDs) inhibition of COX 2 COX 2 An inducibly-expressed subtype of prostaglandin-endoperoxide synthase. It plays an important role in many cellular processes and inflammation. It is the target of cox 2 inhibitors. Antiplatelet Drugs → delays healing
    • Impaired duodenal bicarbonate Bicarbonate Inorganic salts that contain the -HCO3 radical. They are an important factor in determining the ph of the blood and the concentration of bicarbonate ions is regulated by the kidney. Levels in the blood are an index of the alkali reserve or buffering capacity. Electrolytes secretion Secretion Coagulation Studies (in patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship with duodenal ulcers)
    • Effects of other etiologies or risk factors:
      • Smoking Smoking Willful or deliberate act of inhaling and exhaling smoke from burning substances or agents held by hand. Interstitial Lung Diseases → ↑ acid secretion Secretion Coagulation Studies, ↓ prostaglandin
      • Zollinger-Ellison syndrome Zollinger-ellison syndrome A syndrome that is characterized by the triad of severe peptic ulcer, hypersecretion of gastric acid, and gastrin-producing tumors of the pancreas or other tissue (gastrinoma). This syndrome may be sporadic or be associated with multiple endocrine neoplasia type 1. Esophagitis ( gastrinoma Gastrinoma A gastrinoma is a tumor that secretes excessive levels of the hormone gastrin and is responsible for Zollinger-Ellison syndrome (ZES). Gastrinomas are frequently associated with multiple endocrine neoplasia 1 (MEN 1) and can arise from the pancreas, stomach, duodenum, jejunum, and/or even from the lymph nodes. Gastrinoma) → ↑ gastrin Gastrin A family of gastrointestinal peptide hormones that excite the secretion of gastric juice. They may also occur in the central nervous system where they are presumed to be neurotransmitters. Gastrointestinal Secretions
      • Brain Brain The part of central nervous system that is contained within the skull (cranium). Arising from the neural tube, the embryonic brain is comprised of three major parts including prosencephalon (the forebrain); mesencephalon (the midbrain); and rhombencephalon (the hindbrain). The developed brain consists of cerebrum; cerebellum; and other structures in the brain stem. Nervous System: Anatomy, Structure, and Classification injury increases intracranial pressure Intracranial Pressure Idiopathic Intracranial Hypertension, overstimulates vagus nerve Vagus nerve The 10th cranial nerve. The vagus is a mixed nerve which contains somatic afferents (from skin in back of the ear and the external auditory meatus), visceral afferents (from the pharynx, larynx, thorax, and abdomen), parasympathetic efferents (to the thorax and abdomen), and efferents to striated muscle (of the larynx and pharynx). Pharynx: Anatomy → ↑ gastric acid Gastric acid Hydrochloric acid present in gastric juice. Gastroesophageal Reflux Disease (GERD) (Cushing’s ulcer)
      • Burn injury (stress) → reduced volume, cell necrosis Necrosis The death of cells in an organ or tissue due to disease, injury or failure of the blood supply. Ischemic Cell Damage → gastric mucosal sloughing → impaired barrier (Curling’s ulcer)
Peptic ulcer disease

Development of PUD in the stomach Stomach The stomach is a muscular sac in the upper left portion of the abdomen that plays a critical role in digestion. The stomach develops from the foregut and connects the esophagus with the duodenum. Structurally, the stomach is C-shaped and forms a greater and lesser curvature and is divided grossly into regions: the cardia, fundus, body, and pylorus. Stomach: Anatomy and duodenum Duodenum The shortest and widest portion of the small intestine adjacent to the pylorus of the stomach. It is named for having the length equal to about the width of 12 fingers. Small Intestine: Anatomy

Image by Lecturio.
  • Pathophysiology of peptic ulcer disease

    Helicobacter Helicobacter Helicobacter pylori is a gram-negative bacterium that causes gastric infection. It is the most well known and clinically significant species of Helicobacter. Transmission is believed to occur by ingestion of contaminated food or water; therefore, a higher prevalence of infection is seen in areas with poor sanitation. Helicobacter pylori infection decreases mucus production and increases the risk of ulcer formation.

    Image: “Figure 24.20” by OpenStax (credit top left photo: modification of work by “Santhosh Thomas”/YouTube; credit top right photo: modification of work by Moriya M, Uehara A, Okumura T, Miyamoto M, and Kohgo Y). License: CC BY 4.0.

Clinical Presentation

Asymptomatic

  • 70% of PUD patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship
  • Older adults
  • Patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship taking NSAIDs NSAIDS Primary vs Secondary Headaches
  • Complication(s) (bleeding or perforation Perforation A pathological hole in an organ, blood vessel or other soft part of the body, occurring in the absence of external force. Esophagitis) may be the 1st clinical presentation Presentation The position or orientation of the fetus at near term or during obstetric labor, determined by its relation to the spine of the mother and the birth canal. The normal position is a vertical, cephalic presentation with the fetal vertex flexed on the neck. Normal and Abnormal Labor without antecedent symptoms.

Symptomatic

  • Abdominal pain Abdominal Pain Acute Abdomen:
    • Epigastric with radiation Radiation Emission or propagation of acoustic waves (sound), electromagnetic energy waves (such as light; radio waves; gamma rays; or x-rays), or a stream of subatomic particles (such as electrons; neutrons; protons; or alpha particles). Osteosarcoma to left or right upper quadrants
    • Sometimes radiates to the back
    • Classic duodenal ulcer pain Pain An unpleasant sensation induced by noxious stimuli which are detected by nerve endings of nociceptive neurons. Pain: Types and Pathways: 2–5 hours after eating and at night (when acid is secreted without food)
    • Sometimes exacerbated by eating (pyloric channel ulcers)
  • Other symptoms:
    • Nausea Nausea An unpleasant sensation in the stomach usually accompanied by the urge to vomit. Common causes are early pregnancy, sea and motion sickness, emotional stress, intense pain, food poisoning, and various enteroviruses. Antiemetics/ vomiting Vomiting The forcible expulsion of the contents of the stomach through the mouth. Hypokalemia
    • Early satiety Early Satiety Bariatric Surgery
    • Postprandial fullness/ bloating Bloating Constipation
    • Belching

Related videos

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Peptic Ulcer Disease

Diagnosis

History

Review of common risk factors:

  • NSAID NSAID Nonsteroidal antiinflammatory drugs (NSAIDs) are a class of medications consisting of aspirin, reversible NSAIDs, and selective NSAIDs. NSAIDs are used as antiplatelet, analgesic, antipyretic, and antiinflammatory agents. Nonsteroidal Antiinflammatory Drugs (NSAIDs)/ aspirin Aspirin The prototypical analgesic used in the treatment of mild to moderate pain. It has anti-inflammatory and antipyretic properties and acts as an inhibitor of cyclooxygenase which results in the inhibition of the biosynthesis of prostaglandins. Aspirin also inhibits platelet aggregation and is used in the prevention of arterial and venous thrombosis. Nonsteroidal Antiinflammatory Drugs (NSAIDs) use
  • Concomitant use of high-risk medications
  • Underlying chronic disease
  • Prior gastric surgery or radiation Radiation Emission or propagation of acoustic waves (sound), electromagnetic energy waves (such as light; radio waves; gamma rays; or x-rays), or a stream of subatomic particles (such as electrons; neutrons; protons; or alpha particles). Osteosarcoma

Laboratory studies

  • Anemia Anemia Anemia is a condition in which individuals have low Hb levels, which can arise from various causes. Anemia is accompanied by a reduced number of RBCs and may manifest with fatigue, shortness of breath, pallor, and weakness. Subtypes are classified by the size of RBCs, chronicity, and etiology. Anemia: Overview and Types (occult bleeding and/or iron Iron A metallic element with atomic symbol fe, atomic number 26, and atomic weight 55. 85. It is an essential constituent of hemoglobins; cytochromes; and iron-binding proteins. It plays a role in cellular redox reactions and in the transport of oxygen. Trace Elements malabsorption Malabsorption General term for a group of malnutrition syndromes caused by failure of normal intestinal absorption of nutrients. Malabsorption and Maldigestion)
  • High fasting gastrin Gastrin A family of gastrointestinal peptide hormones that excite the secretion of gastric juice. They may also occur in the central nervous system where they are presumed to be neurotransmitters. Gastrointestinal Secretions levels (if Zollinger-Ellison syndrome Zollinger-ellison syndrome A syndrome that is characterized by the triad of severe peptic ulcer, hypersecretion of gastric acid, and gastrin-producing tumors of the pancreas or other tissue (gastrinoma). This syndrome may be sporadic or be associated with multiple endocrine neoplasia type 1. Esophagitis is suspected)

Esophagogastroduodenoscopy (EGD)

  • Most accurate diagnostic test
  • Findings:
    • Gastric ulcer: 
      • Usually solitary discrete mucosal lesions, with punched-out smooth base
      • Benign Benign Fibroadenoma lesions have smooth, rounded edges (as opposed to irregular edges noted in malignant lesions).
      • Typically in lesser curvature Lesser curvature Stomach: Anatomy
    • Duodenal ulcer:
      • Small breaks in the mucosa, often < 1 cm
      • Noted usually in the 1st part of the duodenum Duodenum The shortest and widest portion of the small intestine adjacent to the pylorus of the stomach. It is named for having the length equal to about the width of 12 fingers. Small Intestine: Anatomy
  • Indications for biopsy Biopsy Removal and pathologic examination of specimens from the living body. Ewing Sarcoma:
    • Suspected malignancy Malignancy Hemothorax (ulcerated mass Mass Three-dimensional lesion that occupies a space within the breast Imaging of the Breast, irregular margins, abnormal mucosal folds)
    • Any gastric ulcer in areas with a high incidence Incidence The number of new cases of a given disease during a given period in a specified population. It also is used for the rate at which new events occur in a defined population. It is differentiated from prevalence, which refers to all cases in the population at a given time. Measures of Disease Frequency of gastric cancer Gastric cancer Gastric cancer is the 3rd-most common cause of cancer-related deaths worldwide. The majority of cases are from adenocarcinoma. The modifiable risk factors include Helicobacter pylori infection, smoking, and nitrate-rich diets. Gastric Cancer
    • If unusual etiology is suspected (e.g., sarcoidosis Sarcoidosis Sarcoidosis is a multisystem inflammatory disease that causes noncaseating granulomas. The exact etiology is unknown. Sarcoidosis usually affects the lungs and thoracic lymph nodes, but it can also affect almost every system in the body, including the skin, heart, and eyes, most commonly. Sarcoidosis)
    • Gastric mucosal biopsy Biopsy Removal and pathologic examination of specimens from the living body. Ewing Sarcoma of antrum and body (in addition to the ulcer itself) for H. pylori H. pylori A spiral bacterium active as a human gastric pathogen. It is a gram-negative, urease-positive, curved or slightly spiral organism initially isolated in 1982 from patients with lesions of gastritis or peptic ulcers in Western Australia. Helicobacter pylori was originally classified in the genus campylobacter, but RNA sequencing, cellular fatty acid profiles, growth patterns, and other taxonomic characteristics indicate that the micro-organism should be included in the genus Helicobacter. It has been officially transferred to Helicobacter gen. Helicobacter detection
Endoscopy of ulcerative lesions

Endoscopic view of duodenal (left) and gastric (right) ulcerative lesions

Image: “F0002” by the Department of Surgery, King Fahad Specialist Hospital, Dammam, Saudi Arabia. License: CC BY 2.0, and Image: “F1” by the Department of Psychosomatic Internal Medicine, Health Sciences University of Hokkaido, Japan. License: CC BY 2.0, edited by Lecturio.

Tests for H. pylori H. pylori A spiral bacterium active as a human gastric pathogen. It is a gram-negative, urease-positive, curved or slightly spiral organism initially isolated in 1982 from patients with lesions of gastritis or peptic ulcers in Western Australia. Helicobacter pylori was originally classified in the genus campylobacter, but RNA sequencing, cellular fatty acid profiles, growth patterns, and other taxonomic characteristics indicate that the micro-organism should be included in the genus Helicobacter. It has been officially transferred to Helicobacter gen. Helicobacter

  • Non-invasive:
    • Stool antigen Antigen Substances that are recognized by the immune system and induce an immune reaction. Vaccination assay: 
      • For initial diagnosis
      • To confirm eradication
    • Urea breath test Urea breath test Gastritis: 
      • Patient is given radioactively labeled urea Urea A compound formed in the liver from ammonia produced by the deamination of amino acids. It is the principal end product of protein catabolism and constitutes about one half of the total urinary solids. Urea Cycle orally.
      • Urease Urease An enzyme that catalyzes the conversion of urea and water to carbon dioxide and ammonia. Nocardia/Nocardiosis produced by H. pylori H. pylori A spiral bacterium active as a human gastric pathogen. It is a gram-negative, urease-positive, curved or slightly spiral organism initially isolated in 1982 from patients with lesions of gastritis or peptic ulcers in Western Australia. Helicobacter pylori was originally classified in the genus campylobacter, but RNA sequencing, cellular fatty acid profiles, growth patterns, and other taxonomic characteristics indicate that the micro-organism should be included in the genus Helicobacter. It has been officially transferred to Helicobacter gen. Helicobacter splits urea Urea A compound formed in the liver from ammonia produced by the deamination of amino acids. It is the principal end product of protein catabolism and constitutes about one half of the total urinary solids. Urea Cycle and liberates CO2.
      • Radioactive CO2 is detected in the breath.
    • Serology Serology The study of serum, especially of antigen-antibody reactions in vitro. Yellow Fever Virus:
      • Detection of serum IgG IgG The major immunoglobulin isotype class in normal human serum. There are several isotype subclasses of igg, for example, igg1, igg2a, and igg2b. Hypersensitivity Pneumonitis against H. pylori H. pylori A spiral bacterium active as a human gastric pathogen. It is a gram-negative, urease-positive, curved or slightly spiral organism initially isolated in 1982 from patients with lesions of gastritis or peptic ulcers in Western Australia. Helicobacter pylori was originally classified in the genus campylobacter, but RNA sequencing, cellular fatty acid profiles, growth patterns, and other taxonomic characteristics indicate that the micro-organism should be included in the genus Helicobacter. It has been officially transferred to Helicobacter gen. Helicobacter
      • Low accuracy
      • IgG IgG The major immunoglobulin isotype class in normal human serum. There are several isotype subclasses of igg, for example, igg1, igg2a, and igg2b. Hypersensitivity Pneumonitis remains positive after eradication.
  • Invasive (require sampling of gastric mucosa Gastric mucosa Lining of the stomach, consisting of an inner epithelium, a middle lamina propria, and an outer muscularis mucosae. The surface cells produce mucus that protects the stomach from attack by digestive acid and enzymes. When the epithelium invaginates into the lamina propria at various region of the stomach (cardia; gastric fundus; and pylorus), different tubular gastric glands are formed. These glands consist of cells that secrete mucus, enzymes, hydrochloric acid, or hormones. Stomach: Anatomy):
    • Biopsy Biopsy Removal and pathologic examination of specimens from the living body. Ewing Sarcoma urease Urease An enzyme that catalyzes the conversion of urea and water to carbon dioxide and ammonia. Nocardia/Nocardiosis test: 
      • Urease Urease An enzyme that catalyzes the conversion of urea and water to carbon dioxide and ammonia. Nocardia/Nocardiosis produced by H. pylori H. pylori A spiral bacterium active as a human gastric pathogen. It is a gram-negative, urease-positive, curved or slightly spiral organism initially isolated in 1982 from patients with lesions of gastritis or peptic ulcers in Western Australia. Helicobacter pylori was originally classified in the genus campylobacter, but RNA sequencing, cellular fatty acid profiles, growth patterns, and other taxonomic characteristics indicate that the micro-organism should be included in the genus Helicobacter. It has been officially transferred to Helicobacter gen. Helicobacter liberates ammonia Ammonia A colorless alkaline gas. It is formed in the body during decomposition of organic materials during a large number of metabolically important reactions. Note that the aqueous form of ammonia is referred to as ammonium hydroxide. Acid-Base Balance from urea Urea A compound formed in the liver from ammonia produced by the deamination of amino acids. It is the principal end product of protein catabolism and constitutes about one half of the total urinary solids. Urea Cycle.
      • Alkaline pH pH The quantitative measurement of the acidity or basicity of a solution. Acid-Base Balance changes color of a pH pH The quantitative measurement of the acidity or basicity of a solution. Acid-Base Balance reagent.
    • Histology: 
      • Accuracy improved by stains (immunohistochemical, Giemsa stains)
      • Curved, flagellated gram-negative rods are seen.
    • Bacterial culture and sensitivity Sensitivity Binary classification measures to assess test results. Sensitivity or recall rate is the proportion of true positives. Blotting Techniques

Related videos

6:20
Peptic Ulcer Disease (PUD) with Case

Management

Risk factor modification

Medications

  • H. pylori H. pylori A spiral bacterium active as a human gastric pathogen. It is a gram-negative, urease-positive, curved or slightly spiral organism initially isolated in 1982 from patients with lesions of gastritis or peptic ulcers in Western Australia. Helicobacter pylori was originally classified in the genus campylobacter, but RNA sequencing, cellular fatty acid profiles, growth patterns, and other taxonomic characteristics indicate that the micro-organism should be included in the genus Helicobacter. It has been officially transferred to Helicobacter gen. Helicobacter eradication:
    • A combination of an antibiotic regimen and proton pump inhibitors Proton Pump Inhibitors Compounds that inhibit h(+)-k(+)-exchanging ATPase. They are used as anti-ulcer agents and sometimes in place of histamine h2 antagonists for gastroesophageal reflux. Gastric Acid Drugs (PPIs):
      • Triple therapy: PPI + clarithromycin Clarithromycin A semisynthetic macrolide antibiotic derived from erythromycin that is active against a variety of microorganisms. It can inhibit protein synthesis in bacteria by reversibly binding to the 50s ribosomal subunits. This inhibits the translocation of aminoacyl transfer-RNA and prevents peptide chain elongation. Macrolides and Ketolides + amoxicillin Amoxicillin A broad-spectrum semisynthetic antibiotic similar to ampicillin except that its resistance to gastric acid permits higher serum levels with oral administration. Penicillins or metronidazole Metronidazole A nitroimidazole used to treat amebiasis; vaginitis; trichomonas infections; giardiasis; anaerobic bacteria; and treponemal infections. Pyogenic Liver Abscess
      • Bismuth-containing quadruple therapy: PPI + bismuth + tetracycline Tetracycline A naphthacene antibiotic that inhibits amino Acyl tRNA binding during protein synthesis. Drug-induced Liver Injury + metronidazole Metronidazole A nitroimidazole used to treat amebiasis; vaginitis; trichomonas infections; giardiasis; anaerobic bacteria; and treponemal infections. Pyogenic Liver Abscess
    • Confirm H. pylori H. pylori A spiral bacterium active as a human gastric pathogen. It is a gram-negative, urease-positive, curved or slightly spiral organism initially isolated in 1982 from patients with lesions of gastritis or peptic ulcers in Western Australia. Helicobacter pylori was originally classified in the genus campylobacter, but RNA sequencing, cellular fatty acid profiles, growth patterns, and other taxonomic characteristics indicate that the micro-organism should be included in the genus Helicobacter. It has been officially transferred to Helicobacter gen. Helicobacter eradication after treatment.
  • PPIs:
    • Uncomplicated ulcers: 
      • Given for 2 weeks (plus antibiotic treatment for H. pylori H. pylori A spiral bacterium active as a human gastric pathogen. It is a gram-negative, urease-positive, curved or slightly spiral organism initially isolated in 1982 from patients with lesions of gastritis or peptic ulcers in Western Australia. Helicobacter pylori was originally classified in the genus campylobacter, but RNA sequencing, cellular fatty acid profiles, growth patterns, and other taxonomic characteristics indicate that the micro-organism should be included in the genus Helicobacter. It has been officially transferred to Helicobacter gen. Helicobacter if positive)
      • Longer if the patient has indications for maintenance therapy
    • Complicated ulcers (bleeding, penetration Penetration X-rays, obstruction, or perforation Perforation A pathological hole in an organ, blood vessel or other soft part of the body, occurring in the absence of external force. Esophagitis):
      • Duodenal ulcer: 4–8 weeks
      • Gastric ulcer: 8–12 weeks (confirmation of ulcer healing needed)
      • Longer if the patient has indications for maintenance therapy
    • Maintenance therapy:
      • If NSAIDs NSAIDS Primary vs Secondary Headaches or aspirin Aspirin The prototypical analgesic used in the treatment of mild to moderate pain. It has anti-inflammatory and antipyretic properties and acts as an inhibitor of cyclooxygenase which results in the inhibition of the biosynthesis of prostaglandins. Aspirin also inhibits platelet aggregation and is used in the prevention of arterial and venous thrombosis. Nonsteroidal Antiinflammatory Drugs (NSAIDs) need to be continued
      • Giant ulcer (> 2 cm)
      • H. pylori H. pylori A spiral bacterium active as a human gastric pathogen. It is a gram-negative, urease-positive, curved or slightly spiral organism initially isolated in 1982 from patients with lesions of gastritis or peptic ulcers in Western Australia. Helicobacter pylori was originally classified in the genus campylobacter, but RNA sequencing, cellular fatty acid profiles, growth patterns, and other taxonomic characteristics indicate that the micro-organism should be included in the genus Helicobacter. It has been officially transferred to Helicobacter gen. Helicobacter negative, NSAID NSAID Nonsteroidal antiinflammatory drugs (NSAIDs) are a class of medications consisting of aspirin, reversible NSAIDs, and selective NSAIDs. NSAIDs are used as antiplatelet, analgesic, antipyretic, and antiinflammatory agents. Nonsteroidal Antiinflammatory Drugs (NSAIDs)-negative ulcers
      • Recurrent PUD (> 2/year)

Repeat endoscopy Endoscopy Procedures of applying endoscopes for disease diagnosis and treatment. Endoscopy involves passing an optical instrument through a small incision in the skin i.e., percutaneous; or through a natural orifice and along natural body pathways such as the digestive tract; and/or through an incision in the wall of a tubular structure or organ, i.e. Transluminal, to examine or perform surgery on the interior parts of the body. Gastroesophageal Reflux Disease (GERD)

  • Duodenal ulcers:
    • Usually not necessary
    • If symptoms persist with treatment > 4 weeks
    • If evidence of ongoing bleeding
  • Gastric ulcers:
    • Persistent symptoms despite 8–12 weeks of medical therapy
    • Unclear etiology
    • Giant ulcer (> 2 cm)
    • Ulcer was suspicious for malignancy Malignancy Hemothorax on the 1st endoscopy Endoscopy Procedures of applying endoscopes for disease diagnosis and treatment. Endoscopy involves passing an optical instrument through a small incision in the skin i.e., percutaneous; or through a natural orifice and along natural body pathways such as the digestive tract; and/or through an incision in the wall of a tubular structure or organ, i.e. Transluminal, to examine or perform surgery on the interior parts of the body. Gastroesophageal Reflux Disease (GERD) (even with negative biopsy Biopsy Removal and pathologic examination of specimens from the living body. Ewing Sarcoma).
    • Evidence of ongoing bleeding
    • Failure to eradicate H. pylori H. pylori A spiral bacterium active as a human gastric pathogen. It is a gram-negative, urease-positive, curved or slightly spiral organism initially isolated in 1982 from patients with lesions of gastritis or peptic ulcers in Western Australia. Helicobacter pylori was originally classified in the genus campylobacter, but RNA sequencing, cellular fatty acid profiles, growth patterns, and other taxonomic characteristics indicate that the micro-organism should be included in the genus Helicobacter. It has been officially transferred to Helicobacter gen. Helicobacter infection
    • Risk factors for gastric cancer Gastric cancer Gastric cancer is the 3rd-most common cause of cancer-related deaths worldwide. The majority of cases are from adenocarcinoma. The modifiable risk factors include Helicobacter pylori infection, smoking, and nitrate-rich diets. Gastric Cancer:
      • Age > 50
      • H. pylori H. pylori A spiral bacterium active as a human gastric pathogen. It is a gram-negative, urease-positive, curved or slightly spiral organism initially isolated in 1982 from patients with lesions of gastritis or peptic ulcers in Western Australia. Helicobacter pylori was originally classified in the genus campylobacter, but RNA sequencing, cellular fatty acid profiles, growth patterns, and other taxonomic characteristics indicate that the micro-organism should be included in the genus Helicobacter. It has been officially transferred to Helicobacter gen. Helicobacter
      • Family history Family History Adult Health Maintenance
      • Immigrants from endemic areas (Japan, Korea)
      • Gastric atrophy Atrophy Decrease in the size of a cell, tissue, organ, or multiple organs, associated with a variety of pathological conditions such as abnormal cellular changes, ischemia, malnutrition, or hormonal changes. Cellular Adaptation, metaplasia Metaplasia A condition in which there is a change of one adult cell type to another similar adult cell type. Cellular Adaptation/ dysplasia Dysplasia Cellular Adaptation, adenoma

Surgical treatment

  • Uncommon because medical therapy is very effective
  • Indications for surgery:
    • Management of complications:
    • PUD refractory to medical management
    • Non- compliance Compliance Distensibility measure of a chamber such as the lungs (lung compliance) or bladder. Compliance is expressed as a change in volume per unit change in pressure. Veins: Histology or intolerable side effects of medications
  • Surgical principles:
  • Procedures:
    • Highly selective vagotomy: Only the vagal branches stimulating acid secretion Secretion Coagulation Studies are transected.
    • Vagotomy and drainage (pyloroplasty or gastrojejunostomy)
    • Procedures involving partial stomach Stomach The stomach is a muscular sac in the upper left portion of the abdomen that plays a critical role in digestion. The stomach develops from the foregut and connects the esophagus with the duodenum. Structurally, the stomach is C-shaped and forms a greater and lesser curvature and is divided grossly into regions: the cardia, fundus, body, and pylorus. Stomach: Anatomy resection:
      • Vagotomy and antrectomy: removes the acid-producing portion of the stomach Stomach The stomach is a muscular sac in the upper left portion of the abdomen that plays a critical role in digestion. The stomach develops from the foregut and connects the esophagus with the duodenum. Structurally, the stomach is C-shaped and forms a greater and lesser curvature and is divided grossly into regions: the cardia, fundus, body, and pylorus. Stomach: Anatomy
      • Partial gastrectomy: removes the portion of the stomach Stomach The stomach is a muscular sac in the upper left portion of the abdomen that plays a critical role in digestion. The stomach develops from the foregut and connects the esophagus with the duodenum. Structurally, the stomach is C-shaped and forms a greater and lesser curvature and is divided grossly into regions: the cardia, fundus, body, and pylorus. Stomach: Anatomy containing the gastric ulcer
      • Reconstruction needed for a partial gastrectomy: by gastroduodenal (Billroth I) or gastrojejunal (Billroth II) anastomosis

Complications

Gastrointestinal bleeding Gastrointestinal bleeding Gastrointestinal bleeding (GIB) is a symptom of multiple diseases within the gastrointestinal (GI) tract. Gastrointestinal bleeding is designated as upper or lower based on the etiology’s location to the ligament of Treitz. Depending on the location of the bleeding, the patient may present with hematemesis (vomiting blood), melena (black, tarry stool), or hematochezia (fresh blood in stools). Gastrointestinal Bleeding

  • Patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship present with hematemesis Hematemesis Vomiting of blood that is either fresh bright red, or older ‘coffee-ground’ in character. It generally indicates bleeding of the upper gastrointestinal tract. Mallory-Weiss Syndrome (Mallory-Weiss Tear) and/or melena Melena The black, tarry, foul-smelling feces that contain degraded blood. Gastrointestinal Bleeding.
  • May be chronic/low grade and present as anemia Anemia Anemia is a condition in which individuals have low Hb levels, which can arise from various causes. Anemia is accompanied by a reduced number of RBCs and may manifest with fatigue, shortness of breath, pallor, and weakness. Subtypes are classified by the size of RBCs, chronicity, and etiology. Anemia: Overview and Types
  • Acute bleeding is usually approached with endoscopic intervention.
  • Dieulafoy lesion: vascular malformation in the stomach Stomach The stomach is a muscular sac in the upper left portion of the abdomen that plays a critical role in digestion. The stomach develops from the foregut and connects the esophagus with the duodenum. Structurally, the stomach is C-shaped and forms a greater and lesser curvature and is divided grossly into regions: the cardia, fundus, body, and pylorus. Stomach: Anatomy (submucosa) that ulcerates and causes massive bleeding
  • Surgery may be required if unable to achieve control endoscopically.

Perforation Perforation A pathological hole in an organ, blood vessel or other soft part of the body, occurring in the absence of external force. Esophagitis

  • Sudden onset of severe diffuse abdominal pain Abdominal Pain Acute Abdomen, peritonitis Peritonitis Inflammation of the peritoneum lining the abdominal cavity as the result of infectious, autoimmune, or chemical processes. Primary peritonitis is due to infection of the peritoneal cavity via hematogenous or lymphatic spread and without intra-abdominal source. Secondary peritonitis arises from the abdominal cavity itself through rupture or abscess of intra-abdominal organs. Penetrating Abdominal Injury, tachycardia Tachycardia Abnormally rapid heartbeat, usually with a heart rate above 100 beats per minute for adults. Tachycardia accompanied by disturbance in the cardiac depolarization (cardiac arrhythmia) is called tachyarrhythmia. Sepsis in Children
  • Emergent surgery is required.

Penetration Penetration X-rays

  • Walled-off perforation Perforation A pathological hole in an organ, blood vessel or other soft part of the body, occurring in the absence of external force. Esophagitis or perforation Perforation A pathological hole in an organ, blood vessel or other soft part of the body, occurring in the absence of external force. Esophagitis into the retroperitoneal Retroperitoneal Peritoneum: Anatomy space
  • Symptoms not as pronounced as with a free perforation Perforation A pathological hole in an organ, blood vessel or other soft part of the body, occurring in the absence of external force. Esophagitis; subacute onset
  • Often results in an abscess Abscess Accumulation of purulent material in tissues, organs, or circumscribed spaces, usually associated with signs of infection. Chronic Granulomatous Disease formation or fistulas to the surrounding organs ( colon Colon The large intestines constitute the last portion of the digestive system. The large intestine consists of the cecum, appendix, colon (with ascending, transverse, descending, and sigmoid segments), rectum, and anal canal. The primary function of the colon is to remove water and compact the stool prior to expulsion from the body via the rectum and anal canal. Colon, Cecum, and Appendix: Anatomy, biliary tree Biliary tree The bile ducts and the gallbladder. Gallbladder and Biliary Tract: Anatomy, blood vessels)

Gastric outlet obstruction Gastric Outlet Obstruction Hypertrophic Pyloric Stenosis

  • Mechanical obstruction Mechanical Obstruction Any impairment, arrest, or reversal of the normal flow of intestinal contents toward the anal canal. Imaging of the Intestines from peri-pyloric inflammation Inflammation Inflammation is a complex set of responses to infection and injury involving leukocytes as the principal cellular mediators in the body’s defense against pathogenic organisms. Inflammation is also seen as a response to tissue injury in the process of wound healing. The 5 cardinal signs of inflammation are pain, heat, redness, swelling, and loss of function. Inflammation and scarring Scarring Inflammation
  • 1st-line treatment is H. pylori H. pylori A spiral bacterium active as a human gastric pathogen. It is a gram-negative, urease-positive, curved or slightly spiral organism initially isolated in 1982 from patients with lesions of gastritis or peptic ulcers in Western Australia. Helicobacter pylori was originally classified in the genus campylobacter, but RNA sequencing, cellular fatty acid profiles, growth patterns, and other taxonomic characteristics indicate that the micro-organism should be included in the genus Helicobacter. It has been officially transferred to Helicobacter gen. Helicobacter eradication and PPIs.
  • Endoscopic dilation for failure of medical management
  • Surgery as a last resort

Gastric cancer Gastric cancer Gastric cancer is the 3rd-most common cause of cancer-related deaths worldwide. The majority of cases are from adenocarcinoma. The modifiable risk factors include Helicobacter pylori infection, smoking, and nitrate-rich diets. Gastric Cancer

  • Adenocarcinoma
  • MALToma MALToma Extranodal marginal zone lymphoma (EMZL) of mucosa-associated lymphoid tissue (also called MALToma, MALT lymphoma, and pseudolymphoma) is a group of non-Hodgkin’s lymphomas that have historically been grouped together because they appear to arise from postgerminal center marginal zone B cells and share a similar immunophenotype. MALT Lymphoma ( mucosa-associated lymphoid tissue Mucosa-associated lymphoid tissue Colon, Cecum, and Appendix: Anatomy)
  • Both associated with chronic H. pylori H. pylori A spiral bacterium active as a human gastric pathogen. It is a gram-negative, urease-positive, curved or slightly spiral organism initially isolated in 1982 from patients with lesions of gastritis or peptic ulcers in Western Australia. Helicobacter pylori was originally classified in the genus campylobacter, but RNA sequencing, cellular fatty acid profiles, growth patterns, and other taxonomic characteristics indicate that the micro-organism should be included in the genus Helicobacter. It has been officially transferred to Helicobacter gen. Helicobacter infection and atrophic gastritis Atrophic gastritis Gastritis with atrophy of the gastric mucosa, the gastric parietal cells, and the mucosal glands leading to achlorhydria. Atrophic gastritis usually progresses from chronic gastritis. Gastritis
Edg findings of a peptic ulcer

A: esophagogastroduodenoscopy of an open gastric ulcer with exposed vessel
B: gastric ulcer without active bleeding

Image: “F1” by the Department of Psychosomatic Internal Medicine, Health Sciences University of Hokkaido, Japan. License: CC BY 2.0.

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Differential Diagnosis

  • Gastroesophageal reflux disease Gastroesophageal Reflux Disease Gastroesophageal reflux disease (GERD) occurs when the stomach acid frequently flows back into the esophagus. This backwash (acid reflux) can irritate the lining of the esophagus, causing symptoms such as retrosternal burning pain (heartburn). Gastroesophageal Reflux Disease (GERD) ( GERD GERD Gastroesophageal reflux disease (GERD) occurs when the stomach acid frequently flows back into the esophagus. This backwash (acid reflux) can irritate the lining of the esophagus, causing symptoms such as retrosternal burning pain (heartburn). Gastroesophageal Reflux Disease (GERD)): can present with recurrent regurgitation Regurgitation Gastroesophageal Reflux Disease (GERD), epigastric/substernal burning, indigestion, belching. The disease process involves an inappropriate relaxation of the lower esophageal sphincter Lower Esophageal Sphincter Esophagus: Anatomy. Gastroesophageal reflux disease Gastroesophageal Reflux Disease Gastroesophageal reflux disease (GERD) occurs when the stomach acid frequently flows back into the esophagus. This backwash (acid reflux) can irritate the lining of the esophagus, causing symptoms such as retrosternal burning pain (heartburn). Gastroesophageal Reflux Disease (GERD) can lead to mucosal damage of the lower esophagus Esophagus The esophagus is a muscular tube-shaped organ of around 25 centimeters in length that connects the pharynx to the stomach. The organ extends from approximately the 6th cervical vertebra to the 11th thoracic vertebra and can be divided grossly into 3 parts: the cervical part, the thoracic part, and the abdominal part. Esophagus: Anatomy from exposure Exposure ABCDE Assessment to gastric acid Gastric acid Hydrochloric acid present in gastric juice. Gastroesophageal Reflux Disease (GERD).  
  • Gastric cancer Gastric cancer Gastric cancer is the 3rd-most common cause of cancer-related deaths worldwide. The majority of cases are from adenocarcinoma. The modifiable risk factors include Helicobacter pylori infection, smoking, and nitrate-rich diets. Gastric Cancer: can be asymptomatic in the early stages but typically presents with bloating Bloating Constipation, early satiety Early Satiety Bariatric Surgery, dysphagia Dysphagia Dysphagia is the subjective sensation of difficulty swallowing. Symptoms can range from a complete inability to swallow, to the sensation of solids or liquids becoming “stuck.” Dysphagia is classified as either oropharyngeal or esophageal, with esophageal dysphagia having 2 sub-types: functional and mechanical. Dysphagia, weight loss Weight loss Decrease in existing body weight. Bariatric Surgery, and cancer-related fatigue Fatigue The state of weariness following a period of exertion, mental or physical, characterized by a decreased capacity for work and reduced efficiency to respond to stimuli. Fibromyalgia. Diagnosis is made by endoscopy Endoscopy Procedures of applying endoscopes for disease diagnosis and treatment. Endoscopy involves passing an optical instrument through a small incision in the skin i.e., percutaneous; or through a natural orifice and along natural body pathways such as the digestive tract; and/or through an incision in the wall of a tubular structure or organ, i.e. Transluminal, to examine or perform surgery on the interior parts of the body. Gastroesophageal Reflux Disease (GERD) with biopsy Biopsy Removal and pathologic examination of specimens from the living body. Ewing Sarcoma.
  • Gastritis Gastritis Gastritis refers to inflammation of the gastric mucosa. Gastritis may occur suddenly (acute gastritis) or slowly over time (chronic gastritis). Gastritis may be asymptomatic or with symptoms, including burning abdominal pain (which either worsens or improves with eating), dyspepsia, nausea, and vomiting. Gastritis: inflammation Inflammation Inflammation is a complex set of responses to infection and injury involving leukocytes as the principal cellular mediators in the body’s defense against pathogenic organisms. Inflammation is also seen as a response to tissue injury in the process of wound healing. The 5 cardinal signs of inflammation are pain, heat, redness, swelling, and loss of function. Inflammation of the gastric mucosa Gastric mucosa Lining of the stomach, consisting of an inner epithelium, a middle lamina propria, and an outer muscularis mucosae. The surface cells produce mucus that protects the stomach from attack by digestive acid and enzymes. When the epithelium invaginates into the lamina propria at various region of the stomach (cardia; gastric fundus; and pylorus), different tubular gastric glands are formed. These glands consist of cells that secrete mucus, enzymes, hydrochloric acid, or hormones. Stomach: Anatomy. H. pylori H. pylori A spiral bacterium active as a human gastric pathogen. It is a gram-negative, urease-positive, curved or slightly spiral organism initially isolated in 1982 from patients with lesions of gastritis or peptic ulcers in Western Australia. Helicobacter pylori was originally classified in the genus campylobacter, but RNA sequencing, cellular fatty acid profiles, growth patterns, and other taxonomic characteristics indicate that the micro-organism should be included in the genus Helicobacter. It has been officially transferred to Helicobacter gen. Helicobacter infection is also the most common culprit. Gastritis Gastritis Gastritis refers to inflammation of the gastric mucosa. Gastritis may occur suddenly (acute gastritis) or slowly over time (chronic gastritis). Gastritis may be asymptomatic or with symptoms, including burning abdominal pain (which either worsens or improves with eating), dyspepsia, nausea, and vomiting. Gastritis may coexist with PUD and presents with epigastric pain Epigastric pain Mallory-Weiss Syndrome (Mallory-Weiss Tear), nausea Nausea An unpleasant sensation in the stomach usually accompanied by the urge to vomit. Common causes are early pregnancy, sea and motion sickness, emotional stress, intense pain, food poisoning, and various enteroviruses. Antiemetics, and dyspepsia Dyspepsia Impaired digestion, especially after eating. Lactose Intolerance. Endoscopy Endoscopy Procedures of applying endoscopes for disease diagnosis and treatment. Endoscopy involves passing an optical instrument through a small incision in the skin i.e., percutaneous; or through a natural orifice and along natural body pathways such as the digestive tract; and/or through an incision in the wall of a tubular structure or organ, i.e. Transluminal, to examine or perform surgery on the interior parts of the body. Gastroesophageal Reflux Disease (GERD) may show mucosal irritation/ atrophy Atrophy Decrease in the size of a cell, tissue, organ, or multiple organs, associated with a variety of pathological conditions such as abnormal cellular changes, ischemia, malnutrition, or hormonal changes. Cellular Adaptation, but no full-thickness ulceration Ulceration Corneal Abrasions, Erosion, and Ulcers.
  • Cholecystitis Cholecystitis Cholecystitis is the inflammation of the gallbladder (GB) usually caused by the obstruction of the cystic duct (acute cholecystitis). Mechanical irritation by gallstones can also produce chronic GB inflammation. Cholecystitis is one of the most common complications of cholelithiasis but inflammation without gallstones can occur in a minority of patients. Cholecystitis/ cholelithiasis Cholelithiasis Cholelithiasis (gallstones) is the presence of stones in the gallbladder. Most gallstones are cholesterol stones, while the rest are composed of bilirubin (pigment stones) and other mixed components. Patients are commonly asymptomatic but may present with biliary colic (intermittent pain in the right upper quadrant). Cholelithiasis: gallstones Gallstones Cholelithiasis (gallstones) is the presence of stones in the gallbladder. Most gallstones are cholesterol stones, while the rest are composed of bilirubin (pigment stones) and other mixed components. Patients are commonly asymptomatic but may present with biliary colic (intermittent pain in the right upper quadrant). Cholelithiasis obstructing the cystic duct Cystic duct The duct that is connected to the gallbladder and allows the emptying of bile into the common bile duct. Cholecystitis with or without associated inflammation Inflammation Inflammation is a complex set of responses to infection and injury involving leukocytes as the principal cellular mediators in the body’s defense against pathogenic organisms. Inflammation is also seen as a response to tissue injury in the process of wound healing. The 5 cardinal signs of inflammation are pain, heat, redness, swelling, and loss of function. Inflammation of the gallbladder Gallbladder The gallbladder is a pear-shaped sac, located directly beneath the liver, that sits on top of the superior part of the duodenum. The primary functions of the gallbladder include concentrating and storing up to 50 mL of bile. Gallbladder and Biliary Tract: Anatomy. The common presentation Presentation The position or orientation of the fetus at near term or during obstetric labor, determined by its relation to the spine of the mother and the birth canal. The normal position is a vertical, cephalic presentation with the fetal vertex flexed on the neck. Normal and Abnormal Labor is the right upper quadrant Right upper quadrant Anterior Abdominal Wall: Anatomy and epigastric pain Epigastric pain Mallory-Weiss Syndrome (Mallory-Weiss Tear), nausea Nausea An unpleasant sensation in the stomach usually accompanied by the urge to vomit. Common causes are early pregnancy, sea and motion sickness, emotional stress, intense pain, food poisoning, and various enteroviruses. Antiemetics, and vomiting Vomiting The forcible expulsion of the contents of the stomach through the mouth. Hypokalemia. Frequently associated with right upper quadrant Right upper quadrant Anterior Abdominal Wall: Anatomy or subcostal tenderness. Diagnosis is made by ultrasound.
  • Viral gastroenteritis Gastroenteritis Gastroenteritis is inflammation of the stomach and intestines, commonly caused by infections from bacteria, viruses, or parasites. Transmission may be foodborne, fecal-oral, or through animal contact. Common clinical features include abdominal pain, diarrhea, vomiting, fever, and dehydration. Gastroenteritis: acute self-limited illness associated with diffuse abdominal pain Abdominal Pain Acute Abdomen, vomiting Vomiting The forcible expulsion of the contents of the stomach through the mouth. Hypokalemia, and diarrhea Diarrhea Diarrhea is defined as ≥ 3 watery or loose stools in a 24-hour period. There are a multitude of etiologies, which can be classified based on the underlying mechanism of disease. The duration of symptoms (acute or chronic) and characteristics of the stools (e.g., watery, bloody, steatorrheic, mucoid) can help guide further diagnostic evaluation. Diarrhea. May also be associated with fever Fever Fever is defined as a measured body temperature of at least 38°C (100.4°F). Fever is caused by circulating endogenous and/or exogenous pyrogens that increase levels of prostaglandin E2 in the hypothalamus. Fever is commonly associated with chills, rigors, sweating, and flushing of the skin. Fever.  Watery diarrhea Watery diarrhea Rotavirus is a characteristic feature.
  • Pancreatitis Pancreatitis Inflammation of the pancreas. Pancreatitis is classified as acute unless there are computed tomographic or endoscopic retrograde cholangiopancreatographic findings of chronic pancreatitis. The two most common forms of acute pancreatitis are alcoholic pancreatitis and gallstone pancreatitis. Acute Pancreatitis: inflammation Inflammation Inflammation is a complex set of responses to infection and injury involving leukocytes as the principal cellular mediators in the body’s defense against pathogenic organisms. Inflammation is also seen as a response to tissue injury in the process of wound healing. The 5 cardinal signs of inflammation are pain, heat, redness, swelling, and loss of function. Inflammation of the pancreas Pancreas The pancreas lies mostly posterior to the stomach and extends across the posterior abdominal wall from the duodenum on the right to the spleen on the left. This organ has both exocrine and endocrine tissue. Pancreas: Anatomy. Pancreatitis Pancreatitis Inflammation of the pancreas. Pancreatitis is classified as acute unless there are computed tomographic or endoscopic retrograde cholangiopancreatographic findings of chronic pancreatitis. The two most common forms of acute pancreatitis are alcoholic pancreatitis and gallstone pancreatitis. Acute Pancreatitis can be acute or chronic, and usually presents with epigastric pain Epigastric pain Mallory-Weiss Syndrome (Mallory-Weiss Tear) radiating to the back, nausea Nausea An unpleasant sensation in the stomach usually accompanied by the urge to vomit. Common causes are early pregnancy, sea and motion sickness, emotional stress, intense pain, food poisoning, and various enteroviruses. Antiemetics, vomiting Vomiting The forcible expulsion of the contents of the stomach through the mouth. Hypokalemia, and bloating Bloating Constipation. Blood tests will show elevated amylase Amylase A group of amylolytic enzymes that cleave starch, glycogen, and related alpha-1, 4-glucans. Digestion and Absorption and lipase Lipase An enzyme of the hydrolase class that catalyzes the reaction of triacylglycerol and water to yield diacylglycerol and a fatty acid anion. It is produced by glands on the tongue and by the pancreas and initiates the digestion of dietary fats. Malabsorption and Maldigestion.
  • Acute coronary syndrome: presents with chest pain Chest Pain Chest pain is one of the most common and challenging complaints that may present in an inpatient and outpatient setting. The differential diagnosis of chest pain is large and includes cardiac, gastrointestinal, pulmonary, musculoskeletal, and psychiatric etiologies. Chest Pain, which is usually described as pressure across the precordium that may radiate to the neck Neck The part of a human or animal body connecting the head to the rest of the body. Peritonsillar Abscess, shoulder, jaw Jaw The jaw is made up of the mandible, which comprises the lower jaw, and the maxilla, which comprises the upper jaw. The mandible articulates with the temporal bone via the temporomandibular joint (TMJ). The 4 muscles of mastication produce the movements of the TMJ to ensure the efficient chewing of food. Jaw and Temporomandibular Joint: Anatomy, back, upper abdomen, or either arm Arm The arm, or “upper arm” in common usage, is the region of the upper limb that extends from the shoulder to the elbow joint and connects inferiorly to the forearm through the cubital fossa. It is divided into 2 fascial compartments (anterior and posterior). Arm: Anatomy. Acute coronary syndrome can sometimes present as mostly substernal/ epigastric pain Epigastric pain Mallory-Weiss Syndrome (Mallory-Weiss Tear), and it is important to maintain a high index of suspicion. An electrocardiogram Electrocardiogram An electrocardiogram (ECG) is a graphic representation of the electrical activity of the heart plotted against time. Adhesive electrodes are affixed to the skin surface allowing measurement of cardiac impulses from many angles. The ECG provides 3-dimensional information about the conduction system of the heart, the myocardium, and other cardiac structures. Electrocardiogram (ECG) will show changes due to myocardial ischemia Myocardial ischemia A disorder of cardiac function caused by insufficient blood flow to the muscle tissue of the heart. The decreased blood flow may be due to narrowing of the coronary arteries (coronary artery disease), to obstruction by a thrombus (coronary thrombosis), or less commonly, to diffuse narrowing of arterioles and other small vessels within the heart. Coronary Heart Disease/infarction.

References

  1. Vakil, N.B. (2020). Peptic ulcer disease: Clinical manifestations and diagnosis. Retrieved 27 November 2020, from https://www.uptodate.com/contents/peptic-ulcer-disease-clinical-manifestations-and-diagnosis?search=peptic%20ulcer%20disease&source=search_result&selectedTitle=2~150&usage_type=default&display_rank=2
  2. Vakil, N.B. (2020). Peptic ulcer disease: Epidemiology, etiology, and pathogenesis. Retrieved 27 November 2020, from https://www.uptodate.com/contents/peptic-ulcer-disease-epidemiology-etiology-and-pathogenesis?search=peptic%20ulcer%20disease&source=search_result&selectedTitle=5~150&usage_type=default&display_rank=5
  3. Vakil, N.B. (2020). Peptic ulcer disease: Treatment and secondary prevention. Retrieved 27 November 2020, from https://www.uptodate.com/contents/peptic-ulcer-disease-treatment-and-secondary-prevention?search=peptic%20ulcer%20disease&source=search_result&selectedTitle=1~150&usage_type=default&display_rank=1
  4. Vakil, N.B. (2020). Overview of complications of peptic ulcer disease. Retrieved 27 November 2020, from https://www.uptodate.com/contents/overview-of-complications-of-peptic-ulcer-disease?search=peptic%20ulcer%20disease&source=search_result&selectedTitle=4~150&usage_type=default&display_rank=4
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