SM_139b: Peptic Ulcer Disease and H. Pylori

Question 1

3 phases of gastric acid secretion are ____, ____, and ____

Answer 1

3 phases of gastric acid secretion are cephalic, gastric, and intestinal

Question 2

Describe gastric acid secretion

Answer 2

Phases of gastric acid secretion

• Cephalic phase: under cholinergic control (amino acids and peptides)
• Gastric distension after a meal stimulates the release of gastrin
• Release of gastrin by antral G cells (present in pyloric glands) stimulates the parietal cell to secrete HCL through H+/K+ ATPase
• H+/K+ ATPase has three main receptors (histamine, gastrin, ACh) that sitmulate acid resecretion and two (somatostatin and prostaglandin) that inhibit acid secretion through negative feedback)

Question 3

In the pyloric glands in the antrum, G cells ____ and D cells ____

Answer 3

In the pyloric glands in the antrum, G cells secrete gastrin and D cells secrete stomatostatin

• Somatostatin inhibits gastric release

Question 4

In the oxynitic glands in the gastric body and fundus, parietal cells secrete ____, ECL cells secrete ____, chief cells secrete ____, and there are some ____ cells as well

Answer 4

In the oxynitic glands in the gastric body and fundus, parietal cells secrete HCl, ECL cells secrete histamine, chief cells secrete pepsinogen, and there are some D cells (somatostatin) as well

Question 5

Describe parietal cells

Answer 5

Partietal cells

• In oxynitic glands in the gastric body and fundus
• 3 receptors: ACh, gastrin, histamine (H2R)
• H+/K+ pump: pumps out H+ against gradient, site of PPIs (strongest agents to inhibit acid secretion)

Question 6

Describe evidence for role of acid in peptic ulcer disease

Answer 6

Evidence for role of acid in peptic ulcer disease

• Suppressing acid secretion (PPIs, H2R antagonists, and antacids) heals ulcers
• Zollinger-Ellison syndrome nearly always causes ulcers
• No benign ulcers in pernicious anemia (autoimmune gastritis with achlorhydria)

Although most ulcers health with therapy that reduces stomach acid, most recur if anti-secretory therapy is stopped

Question 7

Evidence for the role of H. pylori in peptic ulcer disease includes ____, ____, and ____

Answer 7

Evidence for the role of H. pylori in peptic ulcer disease includes being present in the majority of peptic ulcers in patients not taking NSAIDs, being present before an ulcer develops, and eradication eliminates recurrence and dramatically alters the natural history of peptic ulcer disease

Question 8

H. pylori infection is typically acquired in ____ due to ____, especially ____

Answer 8

H. pylori infection is typically acquired in childhood due to poor sanitary conditions, especially contamination of the water supply

• Transmitted from mother child
• Eradicate with improved sanitation and public health measures
• Nearly universal in developing world, bimodal in developed

Question 9

H. pylori has a ____ reservoir and involves ____ or ____ transmission

Answer 9

H. pylori has a human reservoir and involves fecal-oral or oral-oral transmission transmission

Question 10

H. pylori is uniquely adapted to colonize ____ and causes ____

Answer 10

H. pylori is uniquely adapted to colonize stomach / gastric epithelium and causes gastric metaplasia

• Gastric metaplasia: borders of duodenal ulcer, Meckel’s diverticulum, and Barrett’s esophagus

Question 11

Describe stages of H. pylori infection

Answer 11

Stages of H. pylori infection

1. Flagellated
2. Swims through and attaches to gastric mucosa
3. Multiplies
4. Releases inflammatory mediators and cytokines
5. Damage epitheliums
6. Lymphocyte-predominant gastritis

Question 12

Virulence factors (flagella, urease, adhesions) of H. pylori facilitate ____

Answer 12

Virulence factors (flagella, urease, adhesions) of H. pylori facilitate gastric colonization

Question 13

Describe role of urease for H. pylori

Answer 13

H. pylori urease

1. Urease reacts with gastric acid
2. Prodcues ammonia
3. Buffers H. pylori against bactericidal effects of HCl
4. H. pylori swims to the surface epithelium

Urea breath test is a diagnostic test

Question 14

Describe the mechanism for development of gastric ulcer from H. pylori gastritis

Answer 14

Mechanism for development of gastric ulcer from H. pylori gastritis

1. Preferential damaging effect on gastric D cells
2. Less release of somatostatin by gastric D cells
3. Gastric G cells release more gastrin
4. Increased gastric acid secretion drips into duodenum
5. Over time and with other damaging factors, small foci of gastric metaplasia result
6. H. pylori results from its adaptive habitat in the stomach to a similar niche (gastric metaplasia) in the duodenum
7. Inflammation, damage, and ulcer

Question 15

H. pylori gastritis results in development of peptic ulcer via ____

Answer 15

H. pylori gastritis results in development of peptic ulcer via preferential decrease in somatostatin by gastric D cell

Question 16

Although acid suppression leads to ulcer healing, nearly all ulcers ____

Answer 16

Although acid suppression leads to ulcer healing, nearly all ulcers recur once acid suppression is discontinued

(strongest evidence for critical role of H. pylori in peptic ulcer pathogenesis)

Question 17

Patterns of H. pylori gastritis include ____, ____, and ____

Answer 17

Patterns of H. pylori gastritis include antral predominant gastritis, chronic active pangastritis with some atrophy, and chronic atrophic pangastritis

Question 18

____ type of H. pylori gastritis is associated with increased risk of cancer

Answer 18

Chronic atrophic pangastritis type of H. pylori gastritis is associated with increased risk of cancer

Question 19

Describe the patterns of H. pylori gastritis

Answer 19

H. pylori gastritis patterns

• Localized antral predominant gastritis (duodenal ulcer): acid secretion -> damaging D cells -> decreased somatostatin release
• Diffuse chronic active gastritis with some atrophy (gastric ulcer): continued mucosal damage from H. pylori
• Diffuse atrophic gastritis (intestinal metaplasia -> gastric cancer): chronic and persistant inflammation

Question 20

Most patients with H. pylori gastritis are ____ but can present with ____, ____, and rarely ____

Answer 20

Most patients with H. pylori gastritis are asymptomatic but can present with dyspepsia, peptic ulcer, and rarely gastric cancer

Question 21

Describe diagnosis of H. pylori gastritis

Answer 21

H. pylori gastritis diagnosis

• Serologic testing (IgG): detects exposure to organism and cannot distinguish current from previous infection
• Fecal antigen testing and urea breath test: determine current infection

Question 22

____ test for H. pylori gastritis takes advantage of ability of H. pylori to produce urease

Answer 22

Urea breath test for H. pylori gastritis takes advantage of ability of H. pylori to produce urease

Question 23

Acid suppression from PPIs like omeprazole can ____, resulting in ____

Answer 23

Acid suppression from PPIs like omeprazole can limit growth of H. pylori, resulting in false negatives for non-serologic tests

(testing shoiuld be done after several weeks without infection)

Question 24

Eradication of H. pylori requires ____

Answer 24

Eradication of H. pylori requires sophisticated and prolonged course of antibiotics

(antibiotic resistance is a huge issue)

Question 25

Chronic use (4-6 weeks) of NSAIDs can cause ____

Answer 25

Chronic use of NSAIDs (4-6 weeks) can cause gastric or duodenal ulcer

Question 26

NSAID-induced ulcer is most commonly ____ but may present with ____

Answer 26

NSAID-induced ulcer is most commonly asymptomatic but may present with GI bleeding

Question 27

Describe the types of NSAID induced ulcers

Answer 27

NSAID induced ulcers

• Low pKa of NSAIDs and low pH of stomach -> NSAID induces a back diffusion of H+ into cells -> more damage -> short-lived -> cells heal
• Acid suppression with PPIs and use of COX-2-selective NSAIDs which do not inhibit gastro protective prostaglandins

Question 28

The less serious mechanism of NSAID induced ulcer involves ____

Answer 28

The less serious mechanism of NSAID induced ulcer involves NSAID induced back diffusion of H+ into cells due to low pKa of NSAIDs and low pH of the stomach, causing more damage

(short-lived injury, cells health quickly)

Question 29

The more serious mechanism of NSAIDs occur with ____

Answer 29

The more serious mechanism of NSAIDs occur with acid suppression with PPIs and use of COX-2-selective NSAIDs which do not inhibit gastroprotective prostaglandins

Question 30

Describe strategies to mitigate NSAID induced ulcers

Answer 30

Strategies to mitigate NSAID induced ulcers

• Use of oral prostaglandins (misoprostol)
• Acid suppression with PPIs and selective use of NSAIDs which do not inhibit production of constitutive prostaglandins (may carry risk of cardio toxicity through increase thromboxane generation)

Question 31

____ results from an autonomously gastrin producing tumor

Answer 31

Zollinger Ellison syndrome results from an autonomously gastrin producing tumor

Question 32

Describe pathogenesis of Zollinger-Ellison syndrome

Answer 32

Zollinger-Ellison syndrome

1. Autonomously gastrin producing tumor
2. Gastrin not inhibited by the usual negative feedback
3. Excessive amounts of acid produced and result in intractable ulcers (can be in unusual locations like distal duodenum or jejunum)
4. Trophic effects of gastrin on parietal cell causes hyperplasia and enlarged gastric folds
5. Excessive amounts of acid that reach small itntestine denatures pancreatic enzymes -> maldigestion of fat and chronic diarrhea

Question 33

Zollinger-Ellison syndrome may be part of ____, which includes hyperparathyroidism and pituitary tumors

Answer 33

Zollinger-Ellison syndrome may be part of Multiple Endocrine Neoplasia Type I, which includes hyperparathyroidism and pituitary tumors

Question 34

Diagnosis of Zollinger-Ellison syndrome is made by ____

Answer 34

Diagnosis of Zollinger-Ellison syndrome is made by measuring fasting serum gastrin (above 1000 pg/ml as long as achlorhydria is ruled out)

Question 35

Patient has serum gastrin above 1000 pg/mL and achlorhydria. Is this Zollinger-Ellison syndrome?

Answer 35

Patient has serum gastrin above 1000 pg/mL and achlorhydria. Is this Zollinger-Ellison syndrome?

NO - achlorhydria occurs in pernicious anemia and autoimmune gastritis, but NOT Zollinger-Ellison syndrome

Question 36

Zollinger-Ellison syndrome is managed with ____

Answer 36

Zollinger-Ellison syndrome is managed with high dose PPIs

(imaging studies can localize, endoscopic ultrasound useful for small tumor, tumors often not localized)