STOMACH
 Functions
o Storage of ingested meal
o Inhibition of bacterial growth
o Mixing contents of stomach
o Physical breakdown of food into small particles, some components
solubilized
o Regulates reate of emptying into small intestine
o Provides intrinsic factor for vitamin B12 absorption
 Body of stomach
o Structure of gastric gland
 Mucus epithelial cells and overlying mucus contribute to gastric
mucosal barrier
 Parietal cells secrete hydrochloric acid and intrinsic fact
 In fundus and body
 Chief cells produce and secrete pepsinogen
 Fundus, body, and antrum
 ECL cells synthesis and release histamine
 Do not contact gland lumen
 Mucus neck cells include stem cells which divide, differentiate and
move up and down the gland in normal cellular turnover
 Endocrine cells
 Somatostatin and ghrelin from fundus
 Gastrin and somatostatin from antrum
 Secretion of HCl by Parietal Cells
o CO2 diffuses into parietal cells from plasma or is produced by cellular
metabolism
o Hydrated to H2CO3 via carbonic anhydrase and dissociates to H and
HCO3o At apical membrane H+ is transported out of the cell in exchange for K+
by H+/K+ ATPase
 ATPase is a target for proton pump inhibitors
 Activated in the acid environment of the gastric gland
 At rest, most are within the cell in inactive form and with
stimulation of parietal cells they fuse to luminal membrane
 Activation includes Gastrin, ACh, and histamine
 Activation shows potentiation of response
o Cl- exits passives through a Cl- channel
 Integrated control of Gastric Acid secretion
o Vagus acts directly on parietal cells and indirectly by effects on gastrin
and histamine release
o Histamine released from ECL cells reaches parietal cells by local diffusion
o Gastrin released from antral G cells reaches parietal cells by systemic
circulation
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o Inhibitory regulators include somatostatin released from D cells in the
antrum and body of the stomach, prostagladin from surface cells and
intestinal hormones collectively termed “enterogastrone”
Pepsin
o Proteolytic enzyme secreted by chief cells as an inactive precursor,
pepsinogen
o Release stimulated by vagal nerve and by presence of acid in stomach
o Activated by peptide cleavage at acid pH
o Initiates digestion of protein
 Endopeptidase acting on internal peptide bonds
 Products are large peptides called peptones (potent stimulators of
gastrin and CCK release)
Intrinsic Factor
o Glycoprotein which binds Vitamin B12
o Produced by Parietal cells
o After binding B12 its binds receptors on ileal absorptive cells and is
internalized by endocytosis
o Absent in pernicious anemia
Gastric Mucosal Barrier
o Protection against acid and pepsin
o Includes:
 Prominent mucous layer
 Bicarbonate secreted by surface cells which sets up a pH gradient
 Tight junctions between epithelial cells
 Surfactant like molecules secreted by mucosal cells
 Gastric mucosal blood flow which rapidly removes any
penetrating acid
Gastric Motility
o Proximal: Receptive relaxation as stomach fills (fundus)
o Distal: propulsive mixing and grinding (antrum)
 Only particles smaller than 1 mm can exit through the pylorus
 Peristalsis initiated by pacemaker cells
 Muscular contraction is brought about by action potentials
occurring when the smooth muscle cells depolarize below
threshold
 Increased by vagal or gastrin stimulation
 Decreased by vagotomy or sympathetic stimulation
o Pylorus regulates outflow
 Regulated to prevent overload in intestine and allow optimal
digestion
 Increases in fatty acids, acidity, osmolarity, volume, and amino
acids in the intestine leads to the release of CCK and secretrin
which inhibits stomach emptying
 Disorders
 Delayed emptying (helped via use of prokinetic agents)
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o Outlet obstruction (tumor, scarring)
o Diabetic neuropathy or vagotomy
Accelerated emptying
o Dumping Syndrome