By: Abduljabbar Hamid Jabbar

University of Baghdad-College Of Medicine

M. B. Ch. B
By: Abduljabbar Hamid Jabbar
University of Baghdad-College Of Medicine
M. B. Ch. B
The stomach: The stomach can be divided into a. the fundus, b. the body, and c. the antrum.

Physiologically the fundus functions mainly as part of the body. The lining epithelium of the stomach mucosa is a simple
columnar epithelium composed entirely of mucous cells.

They produce a cloudy, protective two-layer coat of alkaline mucus in which the surface layer consists of viscous,
insoluble mucus that traps a layer of bicarbonate-rich fluid beneath it.

This otherwise smooth lining is dotted with millions of deep gastric pits, which lead into tubular gastric glands that produce
the stomach secretion called gastric juice.
1. Storage: Is mediated by the process of receptive relaxation
of the stomach until the food can be delivered to the small
intestine at the proper time. Normally, when food enters the
stomach a vago-vagal reflex greatly reduces the tone in the
muscular wall of the body of the stomach (active relaxation
of smooth muscles, vagally mediated, Nitric oxide is the
neurotransmitter thought to mediate receptive relaxation at
the smooth muscle cell) so that the wall can bulge
progressively outward accommodating greater and greater
quantities of food up to a limit of about 1 liter.

Stomach accommodation depends exclusively upon an

intact vago-vagal reflex. If vagal innervation is interrupted,
then intra-gastric pressure increases. This is a potential
cause of vomiting due to the inability of the proximal
stomach smooth muscle to undergo receptive relaxation.

2. Mixing and propelling of food: When the stomach is filled,

weak peristaltic and segmentation (mixing) contractions
move toward the antrum along the stomach wall, propelling
and mixing food with gastric juice until it forms a semifluid
mixture called chyme. This is due to distension of the
stomach which elicit vagovagal reflex
3. Emptying: Slow emptying of chyme from the stomach into the small intestine at a rate suitable for proper
digestion and absorption by the small intestine. The degree of constriction of the pyloric sphincter and the
intensity of antral peristaltic wave (mediated by myenteric reflexes) can be varied according to signals both,
from the stomach and from duodenum. The antral peristaltic waves provide a pumping action and are
frequently called the pyloric pump.

The stomach is a poor absorptive area of the gastrointestinal tract because it lacks the typical villus type of
absorptive membrane, and also because the junctions between the epithelial cells are tight junctions. Only a
few highly lipid-soluble substances, such as alcohol and some drugs like aspirin can be absorbed in small
quantities.
Regulation of gastric emptying (pyloric pump): Gastric emptying is a key control point in the gastrointestinal
tract to ensure the orderly delivery of nutrients in a form that can be digested and to give appropriate signals
of fullness (satiety).

Gastroparesis (“weak stomach”) is a common complication of poorly controlled diabetes mellitus and
significantly slows gastric emptying. The rate at which the stomach empties is regulated by signals both from
the stomach and duodenum. These signals will be discussed later in association with the factors that affect
gastric secretion. Gastric emptying takes about 3 hours and very closely regulated so that nutrient absorption
is maximized and H+ in the duodenum has time to be neutralized.
Gastric secretions aid in the breakdown of food into small
particles and continue the process of digestion which had begun
by the salivary enzymes. About 2 L / day of gastric secretions are
produced. The stomach mucosa contains two main types of
gastric glands

[A] Gastric glands which are located in the fundus and the body of
the stomach. They contain three types of secretory cells:

1. Mucus secreting cells which secretes mucus.

2. Parietal (oxyntic) cells which secrete intrinsic factor and HCl.

3. Peptic (chief) cells which secrete pepsinogen, the precursor for

the proteolytic enzyme pepsin.

4. Enteroendocrine cells (or enterochromaffin-like cells, ECL cell)

release a variety of chemical messengers directly into the
interstitial fluid of the mucosa of the stomach. Some of these are
histamine, serotonin, and somatostatin.
[B] Pyloric glands which are located in the antral and pyloric
regions of the stomach. They contain:
G cells and some mucous cells, G cells are responsible for the
release of the hormone gastrin.
D cells, which release somatostatin, a hormone that inhibits the
release of gastrin
Gastric intrinsic factor secretion: A substance called intrinsic factor is secreted by the oxyntic cells, and it is essential for
absorption of vitamin B12 in the ileum. If the acid producing cells of the stomach are destroyed as it occurs in chronic
gastritis, the person develops achlorhydria and pernicious anaemia because of failure of maturation of the RBC in the
absence of vitamins B12.

Although intrinsic factor is secreted by the oxyntic cells of the gastric mucosa, binding to cobalamin occurs in the
duodenum. The vitamin B12-intrinsic factor complex is propelled along the small intestine to the terminal ileum, where
specific transporters located on the enterocyte microvilli bind the vitamin B12-intrinsic factor complex. Binding requires
calcium and is optimal at pH 6.6. Absorption is an active transport process.
Gastric HCl secretion: HCl is secreted into the parietal cell canaliculi by the following steps :

[1] CO2 diffuses from blood to inside the parietal cells.

[2] Within the parietal cells, carbonic acid is formed from the reaction: CO2 + H2O H2CO3.
The formation of H2CO3 from CO2 is catalyzed by the enzyme carbonic anhydrase.

[3] HCO3 – diffuses back into the plasma in exchange for Cl- , thus providing Cl for the initial
step in the secretory process. As HCO3 – is added to the venous blood, the pH of the blood
drained from the stomach increases (alkaline tide). The active transport process is begun by
the transport of Cl ion into the canaliculi that open to the lumen of the stomach.

[4] The H+ that is supplied by the dissociation of carbonic acid into H+ and HCO3 - within the
parietal cells is exchanged for K+ by the H+ -K + -ATPase pump (proton pump).

[5] Chloride ions diffuse with the charged H+ .

[6] Water enters the canaliculi down the osmotic gradient created by the movement of HCl into
the canaliculi.
Most of the HCl that is secreted into the stomach is neutralized and reabsorbed within the small intestine.
However, if the gastric contents are lost before they enter the small intestine as in case of vomiting, sever
alkalosis may ensue. The pH of the parietal cell secretion can be as low as 0.8 (or almost 4 million times as
great as the H+ concentration of plasma).

Parietal cells bear receptors for three potent stimulators of acid secretion, reflecting a triad of neural,
paracrine and endocrine control:

Acetylcholine (muscarinic type receptor) Gastrin Histamine (H2 type receptor)

A variety of substances are capable of reducing gastric acid secretion including:

Prostaglandin E2 (PGE2),
Several peptides hormones, including Secretin, Gastric inhibitory polypeptide (GIP), Glucagon and,
Somatostatin.
GIP (also known as the glucose-dependent insulinotropic peptide) released from duodenal and jejunal
mucosa in response to the presence of chyme especially by hyperosmolarity of glucose in the duodenum and
inhibits gastric gastrin release and stimulate the release of insulin from pancreas, and inhibit the GI motility
and secretion of acid.

The amount of insulin secreted is greater when glucose is administered orally than intravenously. It is the
only gastrointestinal hormone released by all three major foodstuffs (fats, proteins, and carbohydrates).
PGE2, secretin and somatostatin may be physiologic regulators. Somatostatin inhibits secretion of gastrin
and histamine, and appears to have a direct inhibitory effect on the parietal cell.
The functions of HCl:

[1] It participates in the breakdown of protein: The high acidity of the chyme alters the protein molecules, thereby changing
protein structure so as to break up connective tissue and cells in the ingested food.

[2] It hinders the growth of pathogenic bacteria: HCl kills most of the bacteria that enter along with food. This process is
not 100% effective, and some bacteria survive to take up residence and multiply in the intestinal tract.

[3] It activates pepsinogens and provides an optimal pH for the action of pepsin: Several different types of pepsinogens are
secreted by the peptic cells of the gastric glands and all perform the same function. When the pepsinogens are secreted,
they have no digestive activity.

However, as soon as they come in contact with HCl and especially when they come in contact with previously formed
pepsin plus the HCl, they are immediately activated to form active pepsin which is an active proteolytic enzyme in a highly
acid medium.
Gastric mucus secretion: The surface of the stomach mucosa between glands has a continuous layer of mucous cells that
secrete large quantities of a viscid and alkaline mucus that coats the mucosa with a mucous gel layer (the gastric mucosal
barrier) often more than 1 mm thick, thus providing a major shell of protection for the stomach wall against acidity as well
as contributing to lubrication of food transport.

Even the slightest irritation of the mucosa directly stimulates the mucous cells to secrete copious quantities of this thick,
viscid mucus. This in turn forms a gastric barrier that prevents digestion of the gastric wall and also greatly reduces the
absorption of most substances by the gastric mucosa. If this barrier is damaged by toxic substances, such as occurs with
excessive use of aspirin, and other nonsteroidal anti-inflammatory drugs, or alcohol, the secreted acid does leak down an
electrochemical gradient into the mucosa, causing stomach mucosal damage
The luminal membranes of the gastric mucosal cells are impermeable to H+ so that HCI cannot penetrate into the cells.
The cells are joined by tight junctions that prevent HCI from penetrating between them.
A mucus coating over the gastric mucosa serves as a physical barrier to acid penetration.
The HCO3 - rich mucus also serves as a chemical barrier that neutralizes acid in the vicinity of the mucosa.
Even when luminal pH is 2, the mucus pH is 7.
Mild injury to the mucosal barrier results in increased
mucus secretion and surface desquamation followed
by regeneration. A more serious injury breaks
mucosal barrier and exposes the mucosal surface,
forming an ulcer, and produces bleeding. Breaks of
mucosal barrier and exposure of the mucosal surface
to damage occurs due to highly concentrated HCl,
10% ethanol, salicylic acid, or acetylsalicylic acid
(aspirin).

The damaged mucosa liberates histamine, which in

turn increases acid secretion and produces increased
capillary permeability and vasodilatation. The latter
two effects lead to edema. In addition, the exposure of
mucosal capillaries to the digestive process leads to
bleeding. Erosive gastritis can occur as a result of
chronic use of non-steroidal anti-inflammatory drugs
(NSAIDs).

The mechanism by which NSAIDS cause gastritis

involves the inhibition of prostaglandin synthesis in
the stomach. Prostaglandins normally maintain the
physicochemical barrier on the gastroduodenal
mucosal surface by stimulating the secretion of
mucus and bicarbonate. Loss of the protective mucus
and bicarbonate barrier renders the gastric mucosa
susceptible to damage by the acidic environment.
The H+ -K + -ATPase pump can be inhibited by the drug
omeprazole, which is now used for the treatment of
duodenal and gastric ulcers (peptic ulcers). Inhibition of
pump activity leads to a prolonged increase in gastric pH
and the removal of the inhibitory effect of low pH ( less
than 3) on gastrin release.

In addition, two other drugs can also be used for

treatment of peptic ulcer and these are cimetidin and
ranitidine (Histamine blockers) . They accomplish this by
two mechanisms:

(1) Histamine released by ECL cells in the stomach is

blocked from binding on parietal cell H2 receptors,
which stimulate acid secretion;

(2) therefore, other substances that promote acid

secretion (such as gastrin and acetylcholine) have a
reduced effect on parietal cells when the H2 receptors
are blocked.
Thank You
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