Cecil's Chap 37
Wednesday, January 30, 2013
1:29 PM
Diseases of the Stomach and Duodenum (Ending at complications of peptic ulcer disease)
 By storing large quantities of food, the stomach allows intermittent feeding.
 Gastroduodenal Anatomy
o The lower esophageal sphincter (LES) at the end of the esophagus, prevents gastric contents
from refluxing into the esophagus.
o The fundus projects upward above the cardia and is the most superior part of the stomach
in contact with the left hemidiaphragm and the spleen.
o The body of the stomach is characterized by longitudinal folds called rugae.
o The mucosa, or inner lining, is formed by columnar epithelium.
o The third tissue layer, the muscularis propria, has an inner oblique, middle circular, and
outer longitudinal smooth muscle layer.
o The anterior and posterior trunks of the vagus nerve provide parasympathetic innervation
while the celiac plexus provides sympathetics.
o Oxyntic or acid-producing region of the stomach is found in the fundus and body.
 Chief cells secrete pepsinogen.
 Enterochromaffin-like endocrine cells (ECL cells) secrete histamine.
o The first part of the duodenum has a smooth, featureless luminal surface while the
remainder has plica circualris.
o The duodenal mucosa has columnar cells surrounded by crypts of Lieberkuhn.
o The submucosa includes Brunner Glands that produce bicarbonate rich secretions involved
in acid neutralizaiton.
 Gastroduodenal Mucosal Secretions and Protective Factors
o Gastric acid also prevents the development of enteric colonization and systemic infections.
o Parietal cells in the oxyntic glands of the fundus and body are stimulated to secrete acid in
three different ways
 Neurocrine through vagal release of acetylcholine acting on muscarinic M3 receptors.
 Paracrine through the release of histamine from mast cells and ECL cells in stomach
acting on histamine-2 receptors to activate adenylate cyclase, increasing cAMP.
 Endocrine through Gastrin release from antral G cells to stimulate both histamine
from ECL cells and acid from parietal cells.
o A negative feedback loop governs both gastrin release and acid secretion, preventing
postprandial acid hypersecretion.
o Somatostatin, produced by D cells in the body and fundus, inhibits release of gastrin and
possibly histamine/acid secretion.
 Gastroduodenal Motor Physiology
o Stomach has two functional compartments
 Proximal stomach (fundus and proximal third) act as reservoir for recently ingested
food.
 Smooth muscle allows for gastric accommodation.
 Distal stomach grinds, mixes, and sieves food.
 Produces high-amplitude contractions originating from the pacemaker region if
the midportion of the greater curvature.
o

During fasting, the migrating motor complex (MMC) clears the stomach and small intestine
of undigested food, mucus, and sloughed epithelial cells.
 Starts in stomach and works downward for 84-112 minutes.
o Liquids empty from the stomach relatively linearly whereas solids are propelled forward by
gastric contractions toward the antrum.
Gastritis
o Clinical Presentation: Three Most Common Causes
 Helicobacter Pylori
 Curved, flagellated, gram-negative rods.
 Most common worldwide microbial infection.
 Colonization more common in lower socioeconomic strata compared with other
groups.
 Factors important in the ability to colonize include
 Motility
 Production of urease
 Bacterial adherence
 Ammonia generated from urea by H. pylori neutralizes acid, creating a more
hospitable climate in which the bacteria can survive.
 Tissue injury mediated by production of lipopolysaccharide, leukocyte-activating
factors, and CagA and VacA proteins associated with cytotoxic effects,
inflammation, and cytokine activation.
 Factors that may influence outcomes of infection are
 Host response
 Environmental factors
 Age at time of infection
 Patients with H. pylori infection, severe atrophic gastritis, corpus-predominant
gastritis, or both, along with intestinal metaplasia, have increased risk of
intestinal-type gastric cancer.
 Flat, localized, nonbulky lesions of the distal stomach are associated with
greater rates of cure after antibiotic therapy.
 NSAIDS
 One of the most widely used classes of drug.
 Dual-injury hypothesis
 NSAIDS have direct toxic effects on gastroduodenal mucosa
 Have indirect effects through active hepatic metabolites and decreased
synthesis of mucosal prostaglandins.
 Prostaglandin inhibition leads to reduction in epithelial mucus, decreased
secretion of bicarb, impaired mucosal blood flow, reduced epithelial
proliferation, and decreased mucosal resistance to injury.
 Prostaglandins derived from arachidonic acid, which comes from cell
membrane phospholipids by action of phospholipase A2.
 This is catalyzed by cyclo-oxygenase (COX)
 COX1 is mostly a housekeeping enzyme while COX2 can be induced by
inflammatory stimuli and mitogens in different tissues.
 NSAIDS mainly work through inhibition of COX2.
 Injury from NSAIDS include subepithelial hemorrhages, erosions, and
ulcerations.


Erosions are small and superficial while ulcerations are large and
deep, most frequently affecting the antrum.
 Stress-Related Gastric Mucosal Damage
 Events like shock, hypotension, and catecholamine release are associated with
reduced blood flow and mucosal ichemia.
 Epithelial turnover, mucus, and bicarb mechanisms are altered along with
increasing cytokines and free radicals.
 These things combine to reduce the mucosal resistance to injury, resulting
in ulceration and bleeding.
o Treatment
 Aggressive volume resuscitation, control of sepsis, and adequate oxygenation.
 Pharmacologic agents use three main mechanisms
 Acid neutralization
 Use of antacids works but causes diarrhea, hypermagnesemia, and
alkalemia.
 Takes up too much nurse time to administer.
 Mucosal protection
 Sucralfate increases blood flow but causes constipation and aluminum
toxicity in patients with chronic renal failure.
 Inhibition of gastric acid secretion
 Histamine-2 (H2) receptor antagonists reduce stress bleeding but have
side effects of CNS toxicity
 Proton Pump Inhibitors block the H+/K+ ATPase.
o Other Causes of Gastritis
 Autoimmune Atrophic Gastritis:
 Associated with autoantibody formation
 Characterized by chronic inflammation, gradual atrophy of glands, and loss of
parietal cells.
 Loss of parietal cells results in achlorydia, vitB12 deficiency, and megaloblastic
anemia.
 Lymphocytic Gastritis
 Mononuclear infiltration of T cells, antral predominant.
 Eosinophilic Gastritis
 Esosinophilic infiltration of antral stomach
 Manifests with delayed gastric emptying or anemia from chronic blood loss.
 Menetrier Disease
 Giant gastric folds in the fundus and body of stomach
 Hypochlorydia and hypoalbuminemia commonly see.
 In children is caused by CMV.
 Gastric Infections typically seen in immunocompromised patients in settings of HIV,
chemotherapy, and organ transplant.
Peptic Ulcer Disease
o Mucosal defects of the GI mucosa of stomach or duodenum.
o Incidence of PUD is decreasing in young age groups and increasing in groups older than 65.
 Likely related to decrease in H pylori infection and increased use of NSAIDS in older
populations.
 Most important risk factors for PUD is infection with H pylori and use of NSAIDS.
o Pathophysiologic Factors

Postprandial acid secretion regulated by gastrin release, which is controlled via
negative feedback by somatostatin from antral D cells.
 Acid is not the only factor involved in pathogenesis of peptic ulcers.
 Maintenance of protective mucosal barrier including mucus and bicarb
secretion, mucosal blood flow, cell restitution and repair, and changes in local
immune factors.
 Imbalance between defensive and aggressive factors.
 Individuals with H pylori infection have lower numbers of somatostatinsecreting D cells, which decreases the response to luminal acidification.
 NSAIDS decrease prostaglandins which decreases mucosal protection.
o Clinical Presentation
 Asymptomatic iron deficiency to abdominal pain, obstruction, perforation, and
hemorrhage.
 Abdominal pain is usually epigastric and is usually described as a dull ache but may be
sharp or burning.
 Nocturnal pain and pain relief with milk or antacids are common with duodenal ulcers
and can occur with gastric ulcers.
 Nausea and vomiting are common with peptic ulcers, slightly more common with
gastric ulcers.
 Weight loss frequently reported with peptic ulcers.
o Diagnosis
 Imaging studies of the GI tract are required to confirm the presence of peptic ulcers.
 Endoscopy is usually preferred since it allows characterizing the ulcer, sampling to
exclude malignancy, assessment of H pylori infection, and delivery of endoscopic
therapy.
o Diagnostic Tests for H Pylori
 Eradication of H pylori associated with reduction in ulcer recurrence.
 Immunoglobin G serologic testing is the noninvasive test of choice in the UNTREATED
patient.
 Not useful to document cure of the infection since antibodies can stay in the
body and thus give positive results due to past exposure and not necessarily
current infection.
 Urea Breath test is more accurate than serologic tests, although more expensive and
less widely available.
 Noninvasive test of choice to DOCUMENT successful H pylori eradication.
 If endoscopy is performed, the rapid urease test is used and has high sensitivity and
specificity equivalent to histologic analysis.
 Gastric Biopsy should be taken from both the antrum and the corpus because the
bacteria are not uniformly distributed throughout the stomach.
Pharmacologic agents used to treat Gastritis work by three main mechanisms. Which of the following is
NOT one of the three?
a. Acid neutralization
b. Mucosal Protection
c. Inhibition of Acid Secretion
d. Increased bicarbonate-rich secretions