Acid-Peptic Disorders Flashcards
Describe gastric mucosal cells and their products
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
What stimulates parietal cell secretion? What inhibits it?
Stimulated by histamine, gastrin, vagal stimulation
Inhibition by PGE, PPI, antihistamine, atropine, SS
Negative feedback on parietal cell acid secretion comes from what substance?
Somatostatin
What is the role of normal mucus layer?
Mucus and bicarbonate prevent autodigestion from acid and pepsin in lumen
What are prostaglandin-dependent protective factors (4)
Mucous layer thickness
Decreased pH gradient
Increased bicarbonate secretion
Increased mucosal blood flow
What are aggressive factors in peptic ulcers? (4)
Acid
NSAIDs: local effect, COX inhibition
H. Pylori: decreased mucosal protection and increased acid output
Other: steroids, smoking, alf, bile, caffeine
Gastric vs. Duodenal ulcers: Clinical presentation
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
Trend in peptic ulcers in US
Uncomplicated ulcers declining: disappearance of H pylori
BUT complicated ulcer prevalence is unchanged (so increased proportion overall)
What is Zollinger Ellison Syndrome?
A gastrin-secreting tumor that leads to fulminant peptic ulcer disease due to gastric acid hypersecretion
What are other causes of hypergastrinemia? Appropriate vs. Inappropriate
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
MEN-1 Syndrome
Autosomal dominant genetic disorder with MENIN mutation
3Ps+ATL
Can cause ZES
When should you consider ZES?
Non-NSAID, non H pylori ulcer
Severe peptic disease (multiple recurrent non healing ulcers)
Diarrhea due to hypersecretion
MEN-1 syndrome
Idiopathic peptic ulcer disease
Increased BAO (basal acid output), MAO Not associated with hypergastrinemia
Why is H pylori uniquely adapted for survival in stomach? (4)
Urease neutralizes local pH
Attaches directly to host epithelium
Modifies gastric acid secretion to permit maximal survival
Induces inflammation to permit nutrition
What is global prevalence of h. pylori?
50%
Pathophysiology of H Pylori Gastritis
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
In what three ways can H pylori affect acid secretion?
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
Gastrin Hypothesis of H Pylori Duodenal Ulcers
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
What are sequelae of h. pylori infection?
Chronic gastritis Duodenal ulcer (90%), gastric ulcer (70%) Gastric cancer (.5%) Maltoma (lymphocytic gastritis) Non-ulcer dyspepsia
What is the role of CagA in gastric cancer?
Present in 50-60% of H Pylori
Marker of virulence– associated with increased cytokine release and inflammation
Associated with gastric cancer
IL-1B in Gastric Cancer
Polymorphism in IL-1B results in more inflammation–>more susceptible to gastric cancer (more gastritis)
NSAIDs-induced mucosal injury
Inhibit both COX1 (constitutive) and COX2
No COX1==>lose prostaglandin-dependent processes: Acid inhibition, altered mucus, blood flow
How do you avoid NSAID induced mucosal injury?
COXIBs (selective COXII inhibitors)
What is affect of H Pylori on COX?
It induces COXII to reduce acid secretion
Effect of H Pylori AND NSAID use?
Higher incidence of ulcers
What are other causes of peptic ulcers? (4)
Stress: Curling’s ulcer (burns), Cushing’s ulcer (head trauma)
Chemo
Uremia
Cancer
What are causes of non-ulcer dyspepsia?
GI (3) & Non-GO (4)
GI: GERD, gallstones, pancreatitis
Non-GI: Pneumonia, pulmonary embolus, MI, ruptured aortic aneurysm
