Last edited: 8/31/2021

3. GASTRIC SECRETION: THE CEPHALIC & GASTRIC PHASE

Gastric Secretion: The Cephalic & Gastric Phase Medical Editor: Dr. Sofia Suhada M. Uzir

o This is to establish a concentration gradient, where

OUTLINE there will be a lot of sodium outside and a little
sodium in the cell
I) MECHANISM OF HYDROCHLORIC ACID o The potassium that was pumped into the cell can
PRODUCTION drain out of the cell into the lumen passively. But as a
II) CEPHALIC PHASE
result, it’s going to be pumped back into the cell
III) GASTRIC PHASE
IV) THE CONTROL OF GASTRIC CELLS through the proton potassium pump
V) REVIEW QUESTIONS o Omeprazole, which is a drug used in
VI) REFERENCES gastroesophageal reflux disease (GERD), is a
competitive inhibitor which inhibits proton
potassium pump. This inhibits gastric acid
secretion
I) MECHANISM OF HYDROCHLORIC ACID When there is a lot of protons in the cell, some of the
PRODUCTION protons will be pushed out and the sodium that was
pushed out will be going into the cell
There are a lot of mitochondria in the parietal cell which
o This mechanism is to prevent excessive protons in
makes them oxygen dependent
the cell which can make the cell very acidic
As a result of cellular respiration, carbon dioxide will be
produced (A) PROTECTIVE MECHANISM OF THE STOMACH
Hydrochloric acid and proteolytic enzyme pepsin are very
corrosive and can damage the epithelial cells of the
stomach even to a point of digesting the stomach itself
(1) Mucosal barrier
o Protons will go to the lumen through the proton pump
The mucosal barrier prevents the corrosion of the
o The bicarbonate will go out into the blood vessels
stomach
such as the gastric veins, making the blood more
The defects in this barrier contribute to the erosions that
alkali than the gastric artery
may happen as in peptic ulcer diseases
 This is referred as an alkaline tide
(i) Mucous cells
The mucous cells in the stomach secrete molecules that
form the mucosal barrier. The cells include:
o Foveolar cells
o Mucous neck cells

(ii) Secretory molecules

The barrier is made up of:
o Water (95%)
o Electrolytes
 Sodium
 Potassium
o Phospholipids
o Mucin proteins
 It is the most important
 Forms the thick mucosal barrier
o Bicarbonate
 Closer to the apical surface of the cell

(B) PHASES OF GASTRIC ACID SECRETION

Figure 1. Hydrogen and chloride secretion by activated parietal

There are three phases of gastric secretion
cells [Mosby, Elsevier Inc.] o Cephalic
 1/3 of the amount of gastric secretion (gastric juice)
o Gastric
Since bicarbonate, a negative ion, leaves parietal cells,
 2/3 of the amount of gastric acid secretion
another negative ion must come into the cell, which is the
o Intestinal
chloride
o The chloride will travel through the parietal cell only to
get pushed out to the lumen through special channels
o Now, in the lumen, there’s hydrogen ions and
chloride ions → this will form hydrochloric acid
On the cell membrane, there’s sodium-potassium ATPase
which pumps sodium out of the cell and potassium into
the cell

Figure 2. The 2 phases of gastric secretion [Chegg]

GASTRIC SECRETION: The Cephalic & Gastric Phase GASTROINTESTINAL PHYSIOLOGY: Note #3. 1 of 5
 II) CEPHALIC PHASE Remember:
There are dual nerve innervations of the stomach but only
The phase in which there is no food in the stomach one can dominate at a time
The gastric juice is produced before the food enters the o When the sympathetic nervous system is activated ,
stomach to prepare for the food sympathetic nervous system cannot act on parietal and
chief cells
(A) STIMULATION
Note:
Four important stimuli for gastric juice production: Parasympathetic stimulation increase the gastric acid
(1) Site of food release
Sympathetic decrease the gastric release by inhibition of
See the food by the eyes → information from the retina is vagal nerve stimulation
sent to the occipital lobe in the cerebral cortex → travels
to the hypothalamus or the medulla
III) GASTRIC PHASE
(2) The thought of food
The phase in which the food is already in the stomach
May originate from prefrontal cortex → to the
hypothalamus → medulla (A) STIMULATION
(3) Smell of food Important stimuli for gastric juice production include:
The odor/chemicals from the different types of food (1) Distention
triggers the olfactory receptors
Stretch receptors at the muscularis externa of the
stomach is stimulated by the food occupying the stomach
→ this activates different types of reflexes including:

(i) Vagovagal reflex (Figure 2)

Long reflex arc
Stretch receptors are coupled with afferent fibers of
(4) Taste of food cranial nerve 10 (vagus nerve) which is a sensory nerve
Taste buds on the tongue picks up different types of taste → sends signals to nervous system
chemicals → sends the information down the cranial The efferent nerves which reach the stomach sends
nerves signals away from the nervous system
o Anterior 2/3 of tongue → carried by facial nerve Stretching of the stomach stimulates the vagus nerves
o Posterior 1/3 of tongue → Glossopharyngeal nerve
o Posterior aspect of pharynx → Vagus nerve
How gastric stimuli influence gastric secretion:
o Stimulation of cerebral cortex neurons

 Cardia
 Fundus
 Corpus/ body
 Antrum
 Pylorus, which is where the sphincter is located Figure 3. Neural regulation of gastric acid secretion in the
o Vagus nerve stimulates the parietal and chief cells to gastric phase of the meal is mediated by the vagus nerve
make hydrochloric acid and pepsinogen → [Mosby, Elsevier Inc.]
pepsinogen at an optimal pH of 1.8-3.5 can be
activated to a digestive enzyme known as pepsin

(B) INHIBITION (ii) Submucosal plexus

Anything that activates sympathetic nervous system Short reflex arc
inhibits the gastric secretion Submucosal plexus, which are neurons in submucosa
o Stress can stimulate different types of cells of the stomach →
o Emotional upset this includes parietal and chief cells → this then increase
This is achieved through: the hydrochloric acid and pepsin production
o Stimulation of sympathetic preganglionic fibers in the
spinal cord (T1-L2)
(iii) Myenteric plexus
Short reflex arc
Concerns with the contractility and motility of the stomach

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 (2) Partially digested proteins (B) INHIBITION
Directly related to pH (1) Sympathetic nervous system
o Proteins are buffers which has specific sequences
o Amino acids which make up the protein have negative Sympathetic nervous system is the primary inhibitor of
charges that can tie up protons gastric secretion
o When there’s a lot of proteins o Stress
o Emotional upset
o Anxiety
o Depression
o This is achieved through:
Enteroendocrine G cells in the gastric glands of the  Stimulation of sympathetic preganglionic fibers in
antrum → responds to partially digestive proteins the spinal cord (T1-L2)
Increase in the partially digestive proteins in the gastric
mucosa stimulates enteroendocrine G cells → this
secretes gastrin hormone → which travels through the
blood:

(i) It reaches the parietal cells

Bind to cholecystokinin type 2 (CCK 2) receptor, which is (2) Somatostatin
a natural peptide on parietal cell Stimulus
o Really low pH/high amounts of protons intraluminal
(lumen of the stomach)

Mechanism
o Antral D-cell in the antrum of the stomach which is a
chemoreceptor and a hormone, detects the high
concentration of the proton
Remember, parietal cells also make intrinsic factor
o Important for absorbing vitamin B12

(ii) Reaches the chief cell

Which can be found throughout the stomach
Gastrin binds onto cholecystokinin type 1 (CCK1) o Gastrin that was initially responsible for stimulation of
receptor on the chief cell pepsin and proton secretion will be inhibited

Pepsinogen can be converted to pepsin (active proteolytic

form)
o At the N-terminus peptide, there’s a specific sequence
in which when there’s a proper concentration of
protons, optimally pH around 1.8-3.5 can stimulate
conversion of pepsinogen to pepsin
o Hence, hydrochloric acid is needed to activate this

Figure 4. Feedback regulation of gastric acid secretion by

release of somatostatin and its action on G cells in the gastric
antrum [Mosby, Elsevier Inc.]

GASTRIC SECRETION: The Cephalic & Gastric Phase GASTROINTESTINAL PHYSIOLOGY: Note #3. 3 of 5
 IV) THE CONTROL OF GASTRIC CELLS Inhibited by:

(A) ANTRAL CELLS OF THE STOMACH

(i) Prostaglandin
Vagus nerve Specifically, PGE2, binds EP3 receptor
o Vagus nerve can act directly on the antral D-cells and
G-cells
Remember: (ii) Somatostatin
o D-cells release somatostatin which is an inhibitory
Binds to SST receptor
mechanism
o G-cells release gastrin which increase pepsin and
hydrochloric acid secretion
(1) D-cells
Acetylcholine (parasympathetic nervous system), which is
(2) Chief cell
released by the vagus nerve binds to the M3 receptor on
the antral D-cells Stimulated by:

(i) Gastrin
Gastrin can also inhibit the D-cells from releasing Binds to cholecystokinin type 1 (CCK1) receptor on the
somatostatin by binding to the CK2 receptor chief cell → stimulate vesicles in the chief cell to fuse with
the cell membrane → exocytosis like pocket with
(2) G-cells pepsinogen molecules
Gastrin releasing peptide (GRP) or also called Bombesin (ii) Histamine
molecule which is also released by the vagus nerve can
also bind to the receptor on the G-cell and stimulate it Binds to H2 receptor

(B) CORPUS/BODY CELLS OF THE STOMACH (iii) Acetylcholine

(1) Parietal Cells binds to M3 receptor → increase intracellular calcium
concentration → stimulate pepsinogen secretion
Stimulated by:
(iv) Secretin
(i) Gastrin
Secreted from the S-cells of the duodenum which
Binds to cholecystokinin type 2 (CCK 2) receptor, which is
responds to acidic or fatty chyme
a natural peptide
Stimulate through an unknown mechanism which helps
in the release of pepsinogen
(3) Enterochromaffin like cells (ECL)
Secrete histamines → stimulate hydrochloric acid and
pepsinogen secretion
Can respond to certain chemicals including:
(ii) Acetylcholine (i) Acetylcholine
Binds to muscarinic type 3 (M3) receptor
Bind on the M3 receptor → stimulate the release of
histamine

(ii) Gastrin
(iii) Histamine Helps stimulate in the release of histamine
Binds to H2 receptor (iii) Somatostatin
It comes from the corpus (body) D-cells, not the antral D-
cells
Inhibits the release of histamine
(4) D-cells
Stimulation of M3 receptor which is specifically sensitive
to acetylcholine

Figure 5. Stimulators of parietal cells [Mosby, Elsevier Inc.]

4 of 5 GASTROINTESTINAL PHYSIOLOGY: Note #3. GASTRIC SECRETION: The Cephalic & Gastric Phase
 V) REVIEW QUESTIONS d. During fasting periods
Mucous presents on the surface of the mucosa of
Stimulation of gastrointestinal secretion include: the stomach, small and large intestine is:
a. Chemical stimuli a. Resistant to enzymes secreted into the lumen of the
b. Tactile stimulation gastrointestinal tract
c. Distension b. Alkaline, and thus a poor buffer for alkaline foods
d. A and B c. A non-amphoteric protein
e. All are correct d. Easily removed from the surface of the stomach by
the gastric secretions during the gastric phase of
The Secretion of gastrin cease(stop): digestion
a. When the stomach is distended by meal
b. When the pH of the gastric content is decreased CHECK YOUR ANSWERS
below 2
c. If the fundic mucosa is anaesthetized VI) REFERENCES
d. If the vagus is stimulate ● MCQ digestion [Quiz]
http://www1.mans.edu.eg/facmed/dept/physiology/pdf/digestion.pdf
● Berne and Levy Physiology, 6th ed; 28.The Gastric Phase of the
Secretin: Integrated Response to a Meal; Mosby Elsevier Inc. [digital images]
a. Is a GIT hormone secreted from the pylorus https://doctorlib.info/physiology/physiology/28.html
b. Is secreted as a result of vagus nerve stimulation ● Chegg Digestive System. The 2 phases of gastric acid secretion
[digital image] https://www.chegg.com/flashcards/nurs-208-
c. Stimulates gastric secretion
digestive-system-8a732b50-4c5e-4c65-a051-6998cc486d41/deck
d. Is released as a result of contact of acid chyme to
the duodenal mucosa

Concerning the gastrin, the followings are true

except:
a. It is a polypeptide hormone secreted in several
chemical forms
b. Its release is stimulated by gastric distension and
inhibited by presence of excess acid in pyloric
antrum
c. It stimulates insulin secretion from pancreas
d. It Is released only during gastric phase of gastric
secretion and increase the secretion of only the
oxyntic cells

All the followings are correct about gastrin except:

a. Its secretion is increased by secretin//
b. It is stimulated by distension of antrum
c. It is stimulated by insulin induced hypoglycemia

The cephalic phase of gastric secretion :

a. Occurs when food reach the stomach.
b. Is not accompanied by release of GRP
c. Is controlled by the vagi nerves
d. Is not blocked by injection of atropine.
e. Constitutes about one 1⁄2 of the gastric juice
secreted on eating.

Gastric HCL secretion :

a. Is a passive process that occurs in all parts of the
stomach
b. Is stimulated by somatostatin, cimetidine &
pirenzepine
c. Is inhibited by histamine, gastrin & acetylcholine
d. Plays a significant rule in iron absorption

90-Pepsin, secreted by the gastric mucosa:

a. Continues to act in the neutral medium of the
duodenum
b. Is proteolytic on the mucosal surface, in the alkaline
medium provided by the mucus secreted by the
surface cells of the stomach
c. Is synthesized within the chief cells
d. Does not increased in concentration in response to
the mental stimuli found in the cephalic phase of
gastric digestion

Under the normal conditions, the bulk of gastric

secretions are produces:
a. Before the food is ingested and while the pleasure of
its ingestion is anticipated
b. While the food stays in the stomach
c. After the food has entered the duodenum

GASTRIC SECRETION: The Cephalic & Gastric Phase GASTROINTESTINAL PHYSIOLOGY: Note #3. 5 of 5