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GIT&NUT L1 Physio

Secretory functions of the stomach

The gastric mucosa contains gastric glands responsible for gastric secretion.
-In the cardiac and pyloric regions : glands secrete mucus.
-In the fundus and body glands contain:
 Parietal (Oxyntic) cells: secrete HCL and intrinsic factor.
 Chief (Peptic) cells: secrete pepsinogen.
 Mucus neck cells: secrete mucus.
 Enterochromaffin (ECL) like cells: secrete histamine.
-In the antrum glands contain:
 G cells: secrete gastrin hormone.
 D cells: secrete somatostatin hormone.
 Mucus cells: secrete mucus.

Gastric secretion:
Volume: about 2L/ d. pH: highly acidic (about 2).
Contents:
1) Water (most of the gastric juice volume).
2) Inorganic constituents: Na+, K+, Ca2+, Mg2+
3) Hydrochloric acid (HCL).
4) Organic constituents: Enzymes as pepsinogen, gelatinase & gastric lipase.
Intrinsic factor and Mucus.

1- Hydrochloric acid
Mechanism of HCL secretion:
HCL is formed by oxyntic cells through an active process. Oxyntic cell contain large
number of mitochondria (40% of cell volume) and a system of canaliculi communicating
with the lumen of the gastric glands. HCL is formed at the membrane of these canaliculi,
so the cytoplasm isn’t destroyed by this
strong acid.

H⁺ and cl⁻ are actively secreted by the

oxyntic cells as follow:

 H⁺ is secreted into the lumen by

primary active transport in exchange
for K⁺ through H⁺-K⁺ ATPase pump
(proton pump) at the luminal
membrane.

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GIT&NUT L1 Physio

 The transported K⁺ passively leaks back into the lumen through luminal K⁺ channels (i.e the
K+ is being recycled between the cell and the lumen).

 The secreted H⁺ is derived from the breakdown of H2O into H⁺ &OH⁻. OH⁻is neutralized by
another H⁺ derived from H2CO3.

 H2CO3 is generated within the cell from combination of CO2⁺ water under the effect of
carbonic anhydrase enzyme (CAE). CO2 is either metabolically produced by the cell or
diffuses from plasma.

 Cl⁻is secreted by secondary active transport in exchange with HCO3⁻ through Cl⁻ ,HCO3⁻
exchanger in the basolateral membrane, driven by the HCO3⁻ concentration gradient.

 Cl ⁻entered from the cell diffuses out of the cell down its electrochemical gradient through
a luminal Cl⁻ channel into the lumen.

 Water diffuses out of the cell into the lumen by osmosis.

 Postprandial alkaline tide:

When gastric secretion increase after meal, excess HCO3⁻ is added to the blood, so the
pH of the blood is elevated, this effect is called the postprandial alkaline tide.

Control of HCL secretion:

a- Stimulating factors: (3 Stimulants)
1) Acetyl choline: secreted by cholinergic neurons, it acts on M3 receptors by increasing
intracellular Ca2⁺.
2) Histamine: secreted by ECL and acts in a paracrine manner on H2 receptors by increasing
intracellular c-AMP.
3) Gastrin hormone: secreted by G cells, it reaches the stomach via blood, it has
 Direct action: by increasing intracellular Ca2⁺.
 Indirect action: Stimulate histamine release (the main mechanism).
These stimuli bind with their receptors on the parietal cells → release second messengers
(Ca2+ &CAMP) → transfer the H⁺,K⁺ ATPase from intracellular
vesicles → luminal membrane & increase their number.
b- Inhibiting factors:
1) Prostaglandin E2: by decreasing C-AMP.
2) Somatostatin: acts in a paracrine manner, either directly by
decreasing C-AMP in oxyntic cells or indirectly by inhibiting
gastrin and histamine release.
3) Excess HCL: decrease pH less than 2 → stimulate release of
somatostatin. i.e HCL inhibit its own secretio(autoregulation).

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GIT&NUT L1 Physio

Functions of HCL:
1-It kills most ingested bacteria (leading to sterilization of the stomach).
2- Dissolving food particles changing them into chyme.
3- Activation of pepsinogen into pepsin.
4- Provides an optimum pH for pepsin action (2-3.5).
5- It helps absorption of iron by converting Fe+++ → Fe++ and calcium by preventing
precipitation of calcium salts.
6- It stimulates bile flow and pancreatic secretions.

2-Gastric enzymes:
Pepsinogen:
 It is secreted by peptic (chief) cells. The release of which
is stimulated by the substances that stimulate HCL secretion.

 They are inactive and become activated into pepsin by HCL,

in addition to the formed pepsin further activate pepsinogen
(autoactivation).

 Pepsins are proteolytic enzymes which start protein digestion, however it is incomplete
digestion as it result in polypeptides and peptones.

 It needs a highly acidic medium for its action (optimum pH 2-3.5).

Gelatinase: Liquefies gelatin.

Gastric lipase: act on triglycerides resulting in fatty acids and Monoglycerides.(minor
role in fat digestion).

3- Intrinsic factor:
A glycoprotein secreted by oxyntic cells and play an essential role in vitamin B12
absorption in the terminal ileum. Its absence lead to pernicious anemia.

4- Mucus:
There are 2 types of mucus:
a- Soluble (thin) mucus:
Produced by cardiac, pyloric, antral as well as mucus neck cells in the gastric
glands in the body and fundus. It lubricates the chyme and protect the mucosa.
b- Insoluble (thick) mucus:
Thick, alkaline mucus secreted by surface epithelial cell. It forms flexible gel layer
(1.5 mm thick) that coats the gastric mucosa, also these surface epithelial cells secret HCO3-
which is being trapped in the mucus gel, providing protection against HCL and pepsin and also
contributes for food lubrication.
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GIT&NUT L1 Physio

Phases of gastric secretion:

The secretion of gastric juice passes in 3 phases; cephalic, gastric and intestinal.
Cephalic phase (cephalic =head):
 It occurs before food reaches the stomach. It accounts for 1/3 of gastric secretion.
 It is mediated through both conditioned and unconditioned reflexes i.e neural mechanism,
they stimulate vagal nucleus and the vagal stimulation. Vagal fibers terminate at the
neurons of the enteric nervous system, the axon of which stimulate:
a) The oxyntic, peptic and ECL cells by releasing acetyl choline.
Or b) G cells by releasing gastrin releasing peptide (GRP) which release gastrin
hormone.

Gastric phase:
-It occurs when the food actually reaches the stomach. It accounts for 2/3 of gastric secretion.
The stimuli are:
- Distention of the stomach with food.
-Protein (the most potent stimulus).
- Caffeine and alcohol.
-It is mediated by nervous and hormonal mechanisms:
 Nervous mechanism: mechanical and chemical stimulation of the gastric mucosa
initiates impulses that are either: transported in afferent vagal fibers →vagal nucleus
→efferent vagal fibers to the stomach (long vago-vagal reflex).
Or initiates short local enteric reflex.
 Hormonal mechanism: mediated through gastrin hormone secretion. Gastrin
secretion occurs mainly due to and the local enteric reflex (the main) and the
vago-vagal reflex.

(Vago-vagal reflex) (Local enteric reflex)

N.B Caffeine and alcohol stimulates the secretion of highly acidic gastric juice, even
when no food is present. Thus, they should be avoided by persons with peptic ulcers
and hyperacidity.

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GIT&NUT L1 Physio

Intestinal phase:
Occurs in response to chyme when it reach the duodenum. It is formed of an excitatory
(weak) component and inhibitory (powerful) component.

Excitatory component of the intestinal phase: (minor role)

Products of protein digestion in the duodenum, stimulate secretion of intestinal gastrin→
increase acid and pepsin secretion.

Inhibitory component of the intestinal phase: (major role)

Acidity, presence of fat, osmolarity changes (hypo or hyperosmolarity) and distention of the
duodenum inhibit gastric secretion via:
 Nervous mechanism: enterogastric reflex (inhibitory reflex) through which oxyntic and
peptic cells are inhibited.
 Hormonal mechanisms: (Enterogastrones)
Due to release of several hormones (secreted by special cells in the mucosa of duodenum
and jejunum) that inhibit gastric secretion, such hormones include; Cholecystokinin (CCK)
(the most important), Secretin and glucose dependent insulinotropic polypeptide (GIP).

Gastric mucosal barrier

The gastric mucosa is protected from damage by HCL and autodigestion by pepsin
through the following mechanisms:
1- The surface epithelium secrete the insoluble mucus that forms the flexible gel layer, due to
the tapped HCO3-the pH ranges from 2 at the luminal side and 6-7 at the surface of epithelial
cells. main way
2- The tight junctions between the mucosal cells prevent HCL from penetrating between them.
3- The luminal membrane of the mucosal cells is impermeable to H+.
4- There is an active transport mechanism of H+ from the mucosal surface to the gastric lumen.
5- Prostaglandins (secreted by surface mucus cells) strengthen the membrane of the gastric
mucosa by stimulating mucus and HCO3- secretion.
6- Continuous regeneration of the gastric mucosa.

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GIT&NUT L1 Physio

Peptic ulcer
Lost (eroded) area of gastric mucosa caused by autodigestion by gastric juice.
Causes:
a- Breakdown of gastric mucosal barrier:
By alcohol, aspirin and bacterial infection (helicobacter pylori), resulting in diffusion of H+
from the lumen → increase intracellularly and destroy the cell metabolic function resulting in
mucosal ulcer.
b- Excess HCL secretion in case of:
(Zollinger -Ellison syndrome) caused by gastrinomas (tumors that secrete gastrin)
that develop in stomach, duodenum and more commonly in pancreas.

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