Pathophysiology - Exam 4: Part 1 Upper GI

• Esophageal Disorders


  • Gastroesophageal reflux disease (GERD)
  • Heart burn on a plate
• Esophagus


  • Receives food from pharynx
  • Peristalsis (sequential waves of muscle contraction) moves food into the stomach
  • Upper and lower ends act as sphincters
  • Upper: prevents air from entering
  • Lower: prevents gastric reflux into the esophagus -lower esophageal sphincter (LES)
• Dysphagia


  • Subjective difficulty in swallowing
  • Inability to initiate swallowing
  • Sensation that the swallowed solid or liquid "stick" in the esophagus
• Pathophysiology of Dysphagia


  • Neuromuscular incoordination
  • Altered peristalsis
  • Lower esophageal sphincter (LES) dysfunction
• Dysphagia


  1. Neuromuscular Coordination: Problem with transport of bolus down the body of esophagus

  2. Altered peristaltic activity

  3. Esophageal motor dysfunction

  4. Mechanical Obstruction: Tumors, strictures, diverticular herniation

  5. Lower esophageal sphincter (LES) dysfunction: Problem in bolus entry into the stomach

  6. Atresia

  7. Fistula

  8. CN V, VII, IX, X, and XII

  9. Achalasia
• Gastroesophageal reflux disease (GERD)


  • Backflow of gastric contents into esophagus through lower esophageal sphincter (LES)
  • Inflammation caused by reflux of highly acidic material
  • Progression can lead to ulceration, fibrotic scarring, strictures, Barrett esophagus
• GERD


  • Clinical manifestations: Heartburn, regurgitation, chest pain, and dysphagia due to reflux esophagitis (Inflammation due to highly acidic refluxed material)
  • Heartburn (acid reflux) more common after meals and when lying down. Many patients with GERD are awakened from sleep by heartburn
  • Complications include Esophageal stricture, Barrett esophagus (risk for cancer due to cellular changes), Pulmonary symptoms (cough, asthma, laryngitis) due to reflux into respiratory passages
• GERD Risk factors


  • Any factor that alters function of LES or increases intraabdominal pressure
  • Fatty foods, caffeine, alcohol, smoking, sleep position or obesity
  • Drugs: progesterone-containing drugs (Oral contraceptives), narcotics, benzodiazepines, calcium-channel blockers and theophyilline
  • Pregnancy
  • Hiatal hernia
  • Helicobacter pylori contribution to GERD is not clear
• Hiatal Hernia


  • Defect in diaphragm when a portion of the stomach passes through the diaphragmatic opening into the thorax
  • Sliding hernia (most common): Portion of stomach and gastroesophageal junction slip up into thorax above diaphragm
  • Paraesophageal hernia (rolling): Part of greater curvature of stomach rolls through the diaphragmatic defect
• Hiatal Hernia Risk factors

  • Increases with age and increased intraabdominal pressure
  • Hiatal hernias occur more often in women, people who are overweight, and people older than 50
• Hiatal Hernia


  • Clinical manifestations: Predisposed to GERD (heartburn, chest pain, dysphagia)
  • May or may not require treatment
  • Ulcerations of stomach mucosa possible
  • Incarceration of stomach can be life threatening (rare)
• Cells of the Stomach

  • Mucous cells
  • Parietal Cell – HCL, Intrinsic factor
  • Chief cell – pepsinogen / pepsin
  • Mucous cell – alkaline mucus
• Food remains in the stomach approx. 3 hr.
• Parietal cells


  • Secrete Hydrochloric Acid (HCL)
  • Secretion of intrinsic factor (vit B12 absorption)
• Chief cells


  • Secrete pepsinogen/ pepsin (break down proteins)
• Mucus Cells


  • Alkaline mucus protects lining
• D cells


  • Release somatostatin which suppresses PNS
• Enterochromaffin-like cells (ELC)


  • in mucosa -secretes histamine in response to PNS stimulation (ACH)
• Gastrin (from G cells)


  • Stimulates parietal cells to produce HCL
• Cells of the Stomach

  • Parietal cells: Secrete Hydrochloric Acid (HCL), Secretion of intrinsic factor
  • Chief cells: Secrete pepsinogen pepsin (break down proteins)
  • G cells (in gastric pit): Secretes gastrin which acts on parietal cells to produce more acid
  • HCL: Gastrin stimulates ELC cells in gastric mucosa to release histamine – binds H2 receptor on parietal cells and secretes acid
  • Mucus Cells: Alkaline mucus protects lining
• Protective Factors for Mucosa


  • Impermeable epithelial cell surface (tight junctions and hydrophobic lipid layer) prevents acids from entering underlying tissue
  • Mucus and bicarb produced by cells that line gastric mucosal and gastric pits
  • Prostaglandins and nitric oxide: protect GI mucosa by increasing bicarb, improving blood flow and increasing mucus production
  • Epithelial repair: renewed every 3-4 days and protects mucosa
• Destructive Factors to Mucosa


  • Aspirin, NSAIDs: Directly cytotoxic to endothelial cells and destroy barrier, ↓ mucus, inhibit prostaglandin synthesis (COX-1 pathways), ↓ renewal of gastric mucus
  • Helicobacter pylori: colonize mucus secreting epithelial cells and disrupt barrier by producing enzymes which degrade mucin (glycoprotein constituent of mucus), mostly infects antrum (close to duodenum), Inflammation, more gastrin, destroy D cells, stimulated more PNS (vagal nerve), Increases acid
• • Acetaminophen is not an NSAID
  • HCL acid will enter the mucosa and injure underlying tissue if mucosal barrier is not intact
  • ↑ Vagus nerve stimulation causes parietal cells to release HCL (particularly when fasting and at night)

  Stress and spicy foods do not cause PUD but they can make the symptoms worse.
• Gastritis


  • Gastritis is inflammation of the lining of the stomach (mucosa)
  • Acute and Chronic
  • Damage includes: Mucosal hemorrhages, Anemia, Vitamin B12 deficiency (Intrinsic factor needed for B12 absorption), Pernicious anemia results
• Causes of Gastritis


  • Alcohol consumption
  • Long-term use of nonsteroidal anti-inflammatory (NSAID) drugs
  • Helicobacter pylori infection
  • Trauma
  • Surgery
  • Infection
  • Gastric banding surgery for weight loss
• Types of Gastritis


  • Acute: Drugs (NSAIDS inhibit prostaglandin synthesis), chemicals, H.Pylori
  • Chronic: Chronic inflammation, mucosal atrophy and epithelial metaplasia, Often caused by: H. pylori infection, Autoimmune gastritis
• Symptoms of Gastritis


  • Abdominal pain - Vague abdominal discomfort, epigastric tenderness and bleeding
  • Indigestion
  • Bloating
  • Nausea
  • Vomiting
  • Pernicious anemia
• Treatment of Gastritis


  • Antacids
  • Proton pump inhibitors
  • Antibiotics
  • Vitamin B12 supplementation via: Injection, Nasal spray, High oral doses
• Peptic Ulcer Disease (PUD)

  • A break or ulceration in the protective mucosal lining of the lower esophagus, stomach or duodenum
  • Ulcers develop when mucosal protective factors are overcome by erosive factors
  • Most common causes are NSAIDs and H Pylori
  • Most common in stomach and duodenum
• Causes of gastritis


  • Long-term use of nonsteroidal anti-inflammatory (NSAID) drugs
  • Helicobacter pylori infection
  • Trauma
  • Surgery
  • Infection
  • Gastric banding surgery for weight loss
• Acute gastritis


  • Caused by drugs (NSAIDs inhibit prostaglandin synthesis), chemicals, H.Pylori
  • Symptoms include vague abdominal discomfort, epigastric tenderness and bleeding
  • Healing within a few days if discontinue injurious agent
• Chronic gastritis


  • Chronic inflammation, mucosal atrophy and epithelial metaplasia
  • Often caused by H. pylori infection or autoimmune gastritis
• Symptoms of gastritis


  • Abdominal pain - Vague abdominal discomfort, epigastric tenderness and bleeding
  • Indigestion
  • Bloating
  • Nausea
  • Vomiting
  • Pernicious anemia
• Treatments for gastritis


  • Antacids
  • Proton pump inhibitors
  • Antibiotics
  • Vitamin B12 supplementation via injection or nasal spray or high oral doses
• Peptic Ulcer Disease (PUD)

  • A break or ulceration in the protective mucosal lining of the lower esophagus, stomach or duodenum
  • Ulcers develop when mucosal protective factors are overcome by erosive factors
• Risk factors for peptic ulcer disease

  • Infection with Helicobacter pylori (H pylori)
  • Chronic use of nonsteroidal anti-inflammatory drugs (NSAIDs)
  • Alcohol
  • Smoking
  • Advanced age
  • Chronic diseases (emphysema, rheumatoid arthritis, cirrhosis, obesity and diabetes)
• Helicobacter Pylori


  • Gram negative spiral bacterium
  • Prevalence: ~2/3 of the world's population is infected
  • Asymptomatic in ~70% of cases
  • Infection underlies gastric and duodenal ulcer and gastric cancer
  • Immune response is activation of T and B cells and release of neutrophils - inflammatory cytokines
  • Inflammation and immune response promote mucosal ulcerations or prevent healing of injured tissue
• Duodenal ulcer


  • Most common type of peptic ulcer
  • Acid and pepsin concentrations in the duodenum penetrate the mucosal barrier causing ulceration
• Gastric ulcer


  Disrupted mucosa followed by inflammatory process
• Stress ulcer


  • An acute form of peptic ulcer that tends to accompany the physiologic stress of severe illness or major trauma
  • Usually multiple sites of ulceration
  • Ischemic - develop within hours of an event such as hemorrhage, trauma, burns, shock, sepsis