Gastric Secretion - Prunuske Flashcards

1
Q

What is the function of the stomach?

A
  • 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
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2
Q

What are the major cell types in the stomach?

A
  • Simple, columnar
  • Mucous neck cells => secrete mucus, bicarbonate
  • Stem/regenerative
  • Parietal (oxyntic) cell => secrete HCl, intrinstic factor, gastroferrin
  • Chief cells => secrete pepsinogen
  • Endocrine cell
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3
Q

What are the five regions of the stomach with specialized functions?

A
  • Cardia => LES/prevention of reflux
  • Fundus and body => Secretion reservoir
  • Antrum => Mixing and grinding
  • Pylorus => control of emptying
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4
Q

What factors stimulate secretion of gastric acid?

A
  • 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
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5
Q

What factors inhibit secretion of gastric acid?

A

Somatostatin when pH <3

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6
Q

Which of the following: body, antrum, or cardiac would you expect to have longest glands?

A
  • BODY: 70% gland => lots of parietal, chief cells
  • cardiac 50% gland- lots of mucous cells
  • pyloric 40% gland- mucous cells and enteroendocrine
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7
Q

Where is the hormone gastrin secreted?

A

Hormone gastrin is secreted from G cells in the antrum, which activates parietal cells in the fundus/corpus to secrete acid.

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8
Q

Would you expect atropine to stimulate or inhibit gastric acid secretion?

A

Inhibit

(muscarinic antagonist => abolish effects of parasympathetics, stop ACh)

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9
Q

What pumps are involved in ion transport by parietal cells?

A
  • 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.
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10
Q

What factors stimulate gastrin release?

A
  • 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
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11
Q

What factors inhibit gastrin release?

A
  • Somatostatin is secreted from D cells in the antrum when pH <3
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12
Q

What are the four phases of gastric secretion?

A
  1. Interdigestive
  2. Cephalic
  3. Gastric
  4. Intestinal
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13
Q

When does the Interdigestive phase of gastric secretion occur?

A
  • Low acid secretion
    • D cells secrete somatostatin to maintain low levels of Gastrin
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14
Q

When does the Cephalic phase of gastric secretion occur?

A
  • 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.
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15
Q

When does the Gastric phase of gastric secretion occur?

A
  • Distension of the stomach activates vagal afferents and the enteric nervous system.
  • Amino acids activate gastrin secretion
  • Food raises pH → decreasing somatostatin secretion.
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16
Q

When does the Intestinal phase of gastric secretion occur?

A
  • 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.
17
Q

What is required for VitaminB12 absorption in the ileum?

A
  • Intrinsic Factor Glycoprotein
    • secreted by parietal cells
    • mediates uptake of B12 in ileum
18
Q

Do PPI’s inhibit the secretion of intrinsic factor?

A

Protein-pump inhibitor drugs act on parietal cells but do not inhibit secretion of intrinsic factor.

19
Q

What causes Pernicious Anemia?

A
  • Vitamin B12 deficiency results in pernicious anemia and neurologic deficiencies
    • Caused by:
      • autoimmune destruction of parietal cells or intrinsic factor
      • bypass surgery
20
Q

What cells secrete Pepsinogen?

A
  • Chief cells
    • Secreted => in response to ACh and gastrin
    • Inhibited => by secretin
21
Q

Besides Pepsinogen, what secretions are released by Chief cells?

A

Gastric lipase => which releases fatty acids

22
Q

What is the purpose of the Mucous Gel Layer?

A
  • 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
23
Q

What is the proposed mechanism of “Stress Ulcers”?

A
  • Catecholamines suppress mucosal bicarbonate secretion
    • contributing to gastric irritation and the formation of “stress ulcers”
24
Q

What causes Zollinger-Ellison Syndrome (gastrinoma)?

A
  • 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
25
Q

What causes Peptic Ulcers Disease?

A

Hyperacidity => Deterioration of the gastro-mucosal barrier

26
Q

What microorganism can be attributed to the development of Gastric and Duodenal Ulcers?

A

Infection => Helicobactor pylori

27
Q

What is the pathophysiology of GI peptic ulcers?

A
  • 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
28
Q

What is Achlorhydria?

A
  • 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)