·
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 HCO3-
o
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 fromantral G cells reaches parietal cells by systemic circulation
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)
o
Outlet
obstruction (tumor, scarring)
o
Diabetic
neuropathy or vagotomy
·
Accelerated
emptying
o
Dumping
Syndrome
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