Physiology of Acid Secretion Flashcards
Which gastric cells secrete somatostatin?
D cells.
What is the function of enterochromaffin-like cells in the stomach?
Secretion of histamine.
How is the function of D cells regulated?
Decreasing pH in the lumen of the stomach stimulates the secretion of somatostatin.
How is the function of G cells regulated?
Somatostatin inhibits the secretion of gastrin.
How is the function of ECL cells regulated?
(1) somatostatin inhibits the release of histamine.
(2) ACh from vagal nerve innervation and gastrin stimulate the release of histamine.
How is the function of parietal cells regulated?
ACh from vagal nerve innervation, gastrin and histamine stimulate the secretion of HCl.
What are the aggressive factors for acid peptic disease?
(1) acid
(2) NSAIDs
(3) H. pylori
(4) smoking, steroids, alcohol, caffeine, bile, pepsin
What are defensive factors against acid peptic disease?
(1) mucus
(2) bicarbonate
(3) blood flow (delivery of O2 and mediators)
(4) cell regeneration
(5) prostaglandins
How do the symptoms of duodenal and gastric ulcers differ?
D: burning, pinpoint epigastric pain
G: diffuse epigastric pain, nausea, vomiting, weight loss
How do the onsets of duodenal and gastric ulcers differ?
D: 1-3 hrs after meals, empty stomach, relieved by food or antacids
G: immediately after meals, aggravated by food
How do the gastric acid levels in duodenal and gastric ulcers differ?
D: normal to high
G: normal to low
What is Zollinger-Ellison syndrome?
A fulminant peptic ulcer disease caused by a gastrinoma, a non-beta islet cell tumor that secretes gastrin. It is either sporadic or associated with MEN-1.
What is the hallmark of ZES?
Inappropriate hypergastrinemia.
What are causes of appropriate hypergastrinemia?
(1) PPIs and H2-receptor antagonists
(2) atrophic gastritis
(3) H. pylori pangastritis
(4) chronic renal failure
(5) vagotomy
What are causes of inappropriate hypergastrinemia?
(1) ZES
(2) retained antrum syndrome
(3) antral H. pylori infection
(4) massive intestinal resection
(5) gastric outlet obstruction
When should you consider ZES?
(1) severe peptic disease
(2) before anti-ulcer surgery
(3) Dx of MEN-1 syndrome
(4) non-NSAID, non-H. pylori ulcers
How does the parietal cell mass differ in duodenal and gastric ulcers?
D: elevated
G: normal to low
How is H. pylori adapted to infection and survival in the stomach?
(1) urease: creation of a non-acidic microenvironment by secreting ammonium.
(2) flagella and spiral morphology: penetration of mucus layer.
(3) proteases and phospholipase: disruption of mucosal barrier.
(4) adherence factors: exclusive attachment to mucus-secreting cells.
(5) non-invasion of mucosa: avoidance of immune response.
What is the Gastrin Hypothesis for H. pylori duodenal ulcers?
(1) Antral infection inhibits somatostatin release, leading to unopposed gastrin secretion.
(2) Hypergastrinemia leads to elevated acid secretion.
(3) Duodenal gastric metaplasia permits colonization of duodenal bulb.
(4) Undermined local defenses and acid hypersecretion leads to ulcers.
What are the spectrum of disorders following an H. pylori infection?
(1) chronic gastritis
(2) duodenal ulcers
(3) gastric ulcers
(4) gastric cancer
(5) maltoma
What are some environmental factors for developing gastric cancer?
(1) nitroso compounds and salt
(2) smoking
(3) low vitamin C
What is CagA?
It is a marker of virulence for H. pylori, though the role of the protein is unknown. It is associated with greater inflammation (elevated IL-1, IL-2, IL-8) and gastric cancer.
J: This peptic ulcer is caused by ischemia and necrosis of the gastric mucosa after severe burns.
What is Curling’s ulcer.
J: This peptic ulcer is caused by vagal stimulation from increased intracranial pressure after a head injury.
What is Cushing’s ulcer.
What is in the ddx for ulcer-like pain and dyspepsia?
(1) peptic ulcer
(2) GERD
(3) gallstones
(4) pancreatitis
(5) pneumonia
(6) pulmonary embolus
(7) MI
(8) ruptured aortic aneurysm
What functions are associated with COX1?
It is constitutively active and performs in some housekeeping activities:
(1) aggregation of platelets
(2) cytoprotection of the stomach (mucus, bicarbonate)
(3) blood flow to the kidney
(4) vessel dilatation
What functions are associated with COX2?
It’s activity is inducible and it contributes to the inflammatory response.
What are the cytoprotective effects of prostaglandins?
(1) increased mucus
(2) increased bicarbonate
(3) increased submucosal blood flow
(4) some direct action in reducing acid secretion
Simply, how does the action of coxibs differ from NSAIDs?
Coxibs only inhibit COX2, sparing COX1.
What is the MoA of NSAIDs?
They inhibit COX enzymes, lessening the inflammatory response. ( However it is the inhibition of COX1 specifically that leads to peptic ulcers.)
