Acid-Peptic Disorders

Question 1

Describe gastric mucosal cells and their products

Answer 1

Parietal cells: acid, intrinsic factor
G cells: gastrin
D cells: somatostatin
ECL cells: histamine
Chief cells: pepsinogen
Surface epithelial and mucus neck cells: Mucus/bicarbonate

Question 2

What stimulates parietal cell secretion? What inhibits it?

Answer 2

Stimulated by histamine, gastrin, vagal stimulation

Inhibition by PGE, PPI, antihistamine, atropine, SS

Question 3

Negative feedback on parietal cell acid secretion comes from what substance?

Answer 3

Somatostatin

Question 4

What is the role of normal mucus layer?

Answer 4

Mucus and bicarbonate prevent autodigestion from acid and pepsin in lumen

Question 5

What are prostaglandin-dependent protective factors (4)

Answer 5

Mucous layer thickness
Decreased pH gradient
Increased bicarbonate secretion
Increased mucosal blood flow

Question 6

What are aggressive factors in peptic ulcers? (4)

Answer 6

Acid
NSAIDs: local effect, COX inhibition
H. Pylori: decreased mucosal protection and increased acid output
Other: steroids, smoking, alf, bile, caffeine

Question 7

Gastric vs. Duodenal ulcers: Clinical presentation

Answer 7

Symptoms: Nausea/vomiting/diffuse pain vs. pinpoint burning pain
Onset: immediately after meals vs. 1-3hr after meals (empty stomach)
Acid: Normal-low vs. normal-high

Question 8

Trend in peptic ulcers in US

Answer 8

Uncomplicated ulcers declining: disappearance of H pylori

BUT complicated ulcer prevalence is unchanged (so increased proportion overall)

Question 9

What is Zollinger Ellison Syndrome?

Answer 9

A gastrin-secreting tumor that leads to fulminant peptic ulcer disease due to gastric acid hypersecretion

Question 10

What are other causes of hypergastrinemia? Appropriate vs. Inappropriate

Answer 10

Appropriate: Drugs (PPIs), atrophic gastritis, H pylori pangastritis, renal failure, vagotomy

Inappropriate: ZES, retained antrum syndrome, antral predominant H pylori (G-cell hyperplasia), intestinal resection, gastric outlet obstruction

Question 11

MEN-1 Syndrome

Answer 11

Autosomal dominant genetic disorder with MENIN mutation
3Ps+ATL
Can cause ZES

Question 12

When should you consider ZES?

Answer 12

Non-NSAID, non H pylori ulcer
Severe peptic disease (multiple recurrent non healing ulcers)
Diarrhea due to hypersecretion
MEN-1 syndrome

Question 13

Idiopathic peptic ulcer disease

Answer 13

Increased BAO (basal acid output), MAO
Not associated with hypergastrinemia

Question 14

Why is H pylori uniquely adapted for survival in stomach? (4)

Answer 14

Urease neutralizes local pH
Attaches directly to host epithelium
Modifies gastric acid secretion to permit maximal survival
Induces inflammation to permit nutrition

Question 15

What is global prevalence of h. pylori?

Answer 15

50%

Question 16

Pathophysiology of H Pylori Gastritis

Answer 16

Person to person transmission
Urease permits non-acidic microenvironment
Flagellae/spiral morphology enables penetration of mucus layer
Enzyme products permit disruption of mucosal barrier
Adherence factors: attachment to mucus cells
Immune response/inflammation causes gastritis
DOES NOT INVADE MUCOSA

Question 17

In what three ways can H pylori affect acid secretion?

Answer 17

Superficial gastritis=decrease in acid secretion from pangastritis (most common)
Antral predominant infection: Huge increase due to duodenal ulcer
Asymptomatic chronic infection: normal range of gastric output

Question 18

Gastrin Hypothesis of H Pylori Duodenal Ulcers

Answer 18

Antral H pylori inhibits somatostatin production: unopposed gastrin release–>gastric acid hyper secretion
Hypersecretion leads to duodenal gastric metaplasia (gastric cells in duodenal bulb) enables colonization in duodenal bulb
Local defenses undermined+hypersecretion=ulceration in duodenum

Question 19

What are sequelae of h. pylori infection?

Answer 19

Chronic gastritis
Duodenal ulcer (90%), gastric ulcer (70%)
Gastric cancer (.5%)
Maltoma (lymphocytic gastritis)
Non-ulcer dyspepsia

Question 20

What is the role of CagA in gastric cancer?

Answer 20

Present in 50-60% of H Pylori
Marker of virulence– associated with increased cytokine release and inflammation
Associated with gastric cancer

Question 21

IL-1B in Gastric Cancer

Answer 21

Polymorphism in IL-1B results in more inflammation–>more susceptible to gastric cancer (more gastritis)

Question 22

NSAIDs-induced mucosal injury

Answer 22

Inhibit both COX1 (constitutive) and COX2

No COX1==>lose prostaglandin-dependent processes: Acid inhibition, altered mucus, blood flow

Question 23

How do you avoid NSAID induced mucosal injury?

Answer 23

COXIBs (selective COXII inhibitors)

Question 24

What is affect of H Pylori on COX?

Answer 24

It induces COXII to reduce acid secretion

Question 25

Effect of H Pylori AND NSAID use?

Answer 25

Higher incidence of ulcers

Question 26

What are other causes of peptic ulcers? (4)

Answer 26

Stress: Curling’s ulcer (burns), Cushing’s ulcer (head trauma)
Chemo
Uremia
Cancer

Question 27

What are causes of non-ulcer dyspepsia?

GI (3) & Non-GO (4)

Answer 27

GI: GERD, gallstones, pancreatitis

Non-GI: Pneumonia, pulmonary embolus, MI, ruptured aortic aneurysm