Gastric Secretion - Prunuske Flashcards
What is the function of the stomach?
- Highly acidic environment provides a line of defense against microorganisms
- Serve as a reservoir for large amounts of food
- Protein digestion through acid hydrolysis and pepsin cleavage
- Fragment bolus into chyme
- Empty contents into the small intestine at a controlled rate to optimize further digestion and absorption
What are the major cell types in the stomach?
- Simple, columnar
- Mucous neck cells => secrete mucus, bicarbonate
- Stem/regenerative
- Parietal (oxyntic) cell => secrete HCl, intrinstic factor, gastroferrin
- Chief cells => secrete pepsinogen
- Endocrine cell
What are the five regions of the stomach with specialized functions?
- Cardia => LES/prevention of reflux
- Fundus and body => Secretion reservoir
- Antrum => Mixing and grinding
- Pylorus => control of emptying
What factors stimulate secretion of gastric acid?
- SIGNALING MOLECULES= Acetylcholine, the neurotransmitter released from vagal fibers and enteric neural excitatory fibers:
- Binds muscarinic receptors on parietal cells
- Gastrin released into the blood by G cells:
- Binds to parietal cells
- Activates ECL cells release of histamine
- Histamine released from ECL cells binds parietal cells
What factors inhibit secretion of gastric acid?
Somatostatin when pH <3
Which of the following: body, antrum, or cardiac would you expect to have longest glands?
- BODY: 70% gland => lots of parietal, chief cells
- cardiac 50% gland- lots of mucous cells
- pyloric 40% gland- mucous cells and enteroendocrine
Where is the hormone gastrin secreted?
Hormone gastrin is secreted from G cells in the antrum, which activates parietal cells in the fundus/corpus to secrete acid.
Would you expect atropine to stimulate or inhibit gastric acid secretion?
Inhibit
(muscarinic antagonist => abolish effects of parasympathetics, stop ACh)
What pumps are involved in ion transport by parietal cells?
- Sodium/Potassium ATPase in basolateral membrane and potassium flows out into the lumen.
- Protons are generated in cytosol via carbonic anhydrase II (C.A. II)
- Proton pump= H+/K+ ATPase pumps protons into the lumen (lots of mitochondria)
- Bicarbonate ions are exported from the basolateral side by vesicular fusion or the chloride/bicarbonate exchanger and enters blood stream creating ALKALINE TIDE
- Cl- moves passively down the electrical gradient when the luminal Cl- channel opens and water follows.
What factors stimulate gastrin release?
- Triggers for Gastrin release from G cells in the antrum:
- Seeing food or stomach distension causes vagal stimulation causing release of Gastrin-releasing peptide
- Aromatic amino acids in the lumen
What factors inhibit gastrin release?
- Somatostatin is secreted from D cells in the antrum when pH <3
What are the four phases of gastric secretion?
- Interdigestive
- Cephalic
- Gastric
- Intestinal
When does the Interdigestive phase of gastric secretion occur?
- Low acid secretion
- D cells secrete somatostatin to maintain low levels of Gastrin
When does the Cephalic phase of gastric secretion occur?
- Dorsal vagal complex integrates input from higher centers (seeing and tasting food) to activate Vagus nerves.
- GRP activates gastrin release and ACh activates ECL and parietal cells.
When does the Gastric phase of gastric secretion occur?
- Distension of the stomach activates vagal afferents and the enteric nervous system.
- Amino acids activate gastrin secretion
- Food raises pH → decreasing somatostatin secretion.
When does the Intestinal phase of gastric secretion occur?
- Introduction of the gastric contents into the small intestine activates duodenal G cell secretion of gastrin.
- Activation of secretin and other enterogastrones
- Neural reflex decreases gastric secretion.
What is required for VitaminB12 absorption in the ileum?
- Intrinsic Factor Glycoprotein
- secreted by parietal cells
- mediates uptake of B12 in ileum
Do PPI’s inhibit the secretion of intrinsic factor?
Protein-pump inhibitor drugs act on parietal cells but do not inhibit secretion of intrinsic factor.
What causes Pernicious Anemia?
- Vitamin B12 deficiency results in pernicious anemia and neurologic deficiencies
- Caused by:
- autoimmune destruction of parietal cells or intrinsic factor
- bypass surgery
- Caused by:
What cells secrete Pepsinogen?
- Chief cells
- Secreted => in response to ACh and gastrin
- Inhibited => by secretin
Besides Pepsinogen, what secretions are released by Chief cells?
Gastric lipase => which releases fatty acids
What is the purpose of the Mucous Gel Layer?
- GASTRIC DIFFUSION BARRIER:
- Surface epithelial cells secrete mucus and bicarbonate in response to PGE2
- pH at surface is 7 and drops to 2 in the lumen
- H+ ions and pepsin crossing the barrier are neutralized by bicarbonate
What is the proposed mechanism of “Stress Ulcers”?
- Catecholamines suppress mucosal bicarbonate secretion
- contributing to gastric irritation and the formation of “stress ulcers”
What causes Zollinger-Ellison Syndrome (gastrinoma)?
- Usually caused by a Gastrin-secreting tumor in the pancreas or small intestine
- Results in excess H+ secretion as well as hyperplasia and hypertrophy of parietal cells
- 95% of patients develop gastric ulcers
What causes Peptic Ulcers Disease?
Hyperacidity => Deterioration of the gastro-mucosal barrier
What microorganism can be attributed to the development of Gastric and Duodenal Ulcers?
Infection => Helicobactor pylori
What is the pathophysiology of GI peptic ulcers?
- Gastrin levels often increased in gastric ulcers since somatostatin inhibition of gastrin during the fasting state is not activated
- may be related to urease activity of H. pylori
- Increased gastrin can cause acid hypersecretion, pepsin secretion, hyperplasia of ECL and Parietal cells and stomach contractions
- Subset of individuals with hypochlorhydria is related to gastritis and destruction of the gastric epithelial cells.
- Inflammatory response to H. pylori or loss of protective factors due to NSAID inhibition of PG synthesis further contributes to ulcer formation.
- Infection and high acidity can spread to duodenum resulting in decreased bicarbonate and duodenal ulcers
What is Achlorhydria?
- REDUCED ACID SECRETION:
- Caused by:
- aging
- gastric resection
- genetic factors
- auto-immune attack of the H+/K+ ATPase
- taking proton pump inhibitor
- infection– atrophic gastritis
- Bacterial overgrowth
- diarrhea
- pneumonia
- Hip fractures
- iron deficient anemia decreased Ca2+ and iron absorption
- Decrease in pepsin activation doesn’t seem to cause problems (no increase in nitrogen excretion)
- Caused by:
