PEPTIC ULCER DISEASE Flashcards
What is an ulcer?
A break through in the lining of the mucosa with appreciable depth at endoscopy.
What are erosions?
Superficial breaks in the mucosa that do not have perceptible depth.
What is a peptic ulcer?
Includes ulcers and erosions in the stomach and duodenum, involving mucosal integrity disruption and resulting in local defects due to active inflammation.
What does pepsin do?
Causes mucosal breaks regardless of the cause of the inciting agent.
What does the epithelial lining of the stomach contain?
Rugae or folds with microscopic gastric pits branching into 4 or 5 gastric glands.
What are gastric glands and what varies?
Gastric glands’ makeup varies with anatomical location.
What is the gastric cardia?
Comprises less than 5% of the gastric gland area and contains mucous and endocrine cells.
Where are most gastric glands found?
75% are found in oxyntic mucosa and contain mucous neck, parietal, chief, endocrine, enterochromaffin, and enterochromaffin-like (ECL) cells.
What are pyloric glands and where are they found?
Similar to the cardia, they contain mucous and endocrine cells, and are found in the antrum of the stomach.
Where are parietal (oxyntic) cells found?
In the neck or isthmus of the oxyntic gland.
What happens to parietal cells in the resting state?
They contain prominent cytoplasmic tubulovesicles and short microvilli along the apical surface; H+ K+-ATPase is expressed in the tubulovesicle membrane.
What happens to parietal cells in the stimulated state?
Microvilli in the canaliculi lengthen, and the tubulovesicle membrane moves to the apical portion, forming a dense network of long microvilli.
What is the pre-epithelial barrier in the gastroduodenal defense system?
It is the most superficial barrier, composed of a mucus-bicarbonate-phospholipid bilayer.
What does mucus in the stomach contain?
Mainly water (95%) and a mixture of phospholipids and glycoproteins (mucin).
What role does the mucus gel play in protection?
Impeding diffusion of ions (e.g., hydrogen ion) and molecules (e.g., pepsin).
What is the role of bicarbonate in gastric protection?
It forms a pH gradient from 1-2 at the gastric luminal surface to 6-7 along the epithelial surface, stabilizing clots in ulcers.
What are the components of the epithelial barrier in gastric protection?
Mucus production, ionic transporters for intracellular pH maintenance, and intracellular tight junctions.
What is the purpose of heat shock proteins in the stomach?
They prevent protein denaturation and protect cells from increased temperature, cytotoxic agents, and oxidative stress.
What is restitution in gastric epithelial defense?
The process by which gastric epithelial cells migrate to restore a damaged region if the pre-epithelial barrier is breached.
What conditions are necessary for restitution?
Uninterrupted blood flow and an alkaline pH in the surrounding environment.
Why are ICU patients prone to develop stress-related mucosal injuries?
Due to ischemia and reduced blood flow to the GI tract during states like hypotension and shock.
What is the subepithelial defense layer?
The deeper mucosal layer with a microvascular system supporting mucosal defense.
What does the subepithelial layer provide?
HCO3 for acid neutralization, micronutrient supply, oxygen, and removal of toxic by-products.
What local factors in the stomach promote blood flow?
Nitric oxide (NO), hydrogen sulfide, and prostacyclin, which cause vasodilation of the microcirculation.
What is the central role of prostaglandins in gastric epithelial defense?
Prostaglandins regulate the release of mucosal bicarbonate and mucus, inhibit parietal cell secretion, and maintain mucosal blood flow and epithelial restitution.
What enzyme is the rate-limiting factor in prostaglandin synthesis?
Cyclooxygenase (COX), present in two isoforms: COX-1 and COX-2.
Which COX enzyme is involved in housekeeping functions and found in the stomach, kidney, platelets, and endothelium?
COX-1
What are the functions of COX-2?
COX-2 mediates inflammation, mitogenesis, bone formation, and other inflammatory functions.
Name four non-specific NSAIDs that inhibit both COX-1 and COX-2.
Ibuprofen, Naproxen, Naloxone, and Diclofenac
How does nitric oxide contribute to gastric mucosal defense?
Nitric oxide stimulates gastric mucus production, increases mucosal blood flow, and maintains epithelial cell barrier function.
What are the principal gastric secretory products that can induce mucosal injury?
HCl and pepsinogen
When are basal acid production levels highest and lowest?
Highest at night and lowest in the morning hours.
What initiates the cephalic phase of gastric acid secretion?
The thought, sight, or smell of food, stimulating acid secretion via the vagus nerve.
Which hormone provides negative feedback inhibition of gastric acid secretion?
Somatostatin
What cell type releases somatostatin in response to HCl?
D cells in the gastric mucosa
What is the role of somatostatin in gastric acid inhibition?
Somatostatin inhibits acid production by acting directly on parietal cells and indirectly by reducing histamine, ghrelin, and gastrin release.
What are the three main receptors on parietal cells that stimulate acid secretion?
Histamine (H2), Gastrin (cholecystokinin 2/gastrin receptor), and Acetylcholine (muscarinic, M3)
Which enzyme controls the acid-secreting pump (H+, K+-ATPase)?
The H+, K+-ATPase enzyme, regulated by signaling pathways from histamine, gastrin, and acetylcholine receptors.
Why are proton pump inhibitors (PPIs) effective acid suppressants?
PPIs block the H+, K+-ATPase pump, which is the main generator of H+ ions for acid secretion.
What is the primary function of chief cells in the stomach?
Chief cells synthesize and secrete pepsinogen, the inactive precursor of pepsin.
What is the optimal pH for pepsin activity?
pH < 2
What are the principal risk factors for peptic ulcer disease (PUD)?
H. pylori infection and NSAID use
Which drug class increases the odds of gastrointestinal bleeding 5-6x?
NSAIDs
Name three substances or conditions that contribute to mucosal ischemia in the GI tract.
Cocaine, methamphetamine, and bisphosphonates
How does smoking affect peptic ulcer disease in H. pylori-infected patients?
Smoking increases the risk of PUD in H. pylori-infected patients.
List some other risk factors for PUD aside from H. pylori and NSAID use.
Older age, COPD, chronic renal insufficiency, coronary heart disease, and stress.
What are some pathogens that can cause ulcers aside from H. pylori?
Cytomegalovirus and Herpes simplex virus
Name a few drugs or toxins, other than NSAIDs, that can cause ulcers.
Bisphosphonates, chemotherapy, clopidogrel, crack cocaine, and glucocorticoids (when combined with NSAIDs)
List a few miscellaneous causes of ulcers not related to H. pylori or NSAIDs.
Radiation therapy, Crohn’s disease, ischemia, and eosinophilic infiltration.
Principal agents in peptic ulcer disease
Gastric acid and Pepsin
What physiologic role do gastric acid and pepsin play?
Protein digestion; absorption of iron, calcium, magnesium, and Vitamin B12
Effect of H. pylori predominant gastritis
Reduced somatostatin in the antrum, increased basal and meal-stimulated acid secretion
Acid secretion in duodenal ulcer vs gastric ulcer
Duodenal ulcer: increased acid secretion; Gastric ulcer: normal or decreased acid production
Gastric mucosa defense mechanisms
Gastric surface epithelium, mucus/phospholipid and bicarbonate barrier, epithelial cell renewal and regeneration, mucosal blood flow, alkaline tide, prostaglandin production
Role of prostaglandin in gastric mucosa
Stimulates mucus, bicarbonate, and phospholipid production
Effect of COX1 inhibition
Reduces prostaglandin synthesis, compromising gastric mucosa integrity
NSAIDs effect on COX enzymes
Inhibit both COX 1 and COX 2, which contributes to gastric injury
Non-H. pylori causes of peptic ulcers
Crohn’s disease, Lymphoma, Gastrin-secreting tumors, Systemic Mastocytosis
Location of duodenal ulcers
D1/First portion of duodenum (>95%)
Typical characteristics of benign duodenal ulcers
Usually < 1 cm, sharply demarcated, high recurrence without H. pylori eradication
Reduction in duodenal ulcer recurrence post H. pylori eradication
> 80% reduction
Why biopsy gastric ulcers upon discovery
Potential malignancy
Histopathology of NSAID-related gastric ulcers
Foveolar hyperplasia, lamina propria edema, epithelial regeneration, absence of H. pylori
Peak incidence age for gastric ulcers
6th decade
Primary causes of duodenal ulcers
H. pylori and NSAID-induced injuries
Acid production in gastric vs duodenal ulcers
Gastric ulcer: normal or decreased acid; Duodenal ulcer: increased acid secretion
Helicobacter pylori characteristics
Gram-negative, microaerophilic rod, spiral shape, unipolar flagella, urease production
Helicobacter pylori’s diagnostic feature
Urease enzyme hydrolyzes urea to ammonia and CO2
Risk factors for H. pylori infection
Low socioeconomic status, less education, birth or residence in developing country, crowding, unsanitary conditions
Modes of H. pylori transmission
Person-to-person (oral-oral, fecal-oral, gastro-oral), contaminated water
Interplay determining H. pylori-induced gastrointestinal disease
Bacterial and host factors
Virulence factors associated with H. pylori
y-glutamyl transpeptidase (GGT), cagA, vacA, adhesins
Role of cag-PAI in H. pylori pathogenicity
Encodes CagA and other factors increasing risk of PUD, premalignant lesions, gastric cancer
H. pylori’s effect on gastric epithelial cells
Apoptosis due to interaction with T cells and pro-inflammatory cytokines
Result of antral-predominant gastritis from H. pylori
Duodenal ulcer formation or asymptomatic infection
Potential outcomes of chronic corpus-predominant atrophic gastritis
Gastric ulcer, intestinal metaplasia, dysplasia, and potential gastric cancer
