CBI503 Introductory Physiology

2016

DIGESTIVE SYSTEM -1
Emma Jakoi. Ph.D.

LEARNING OBJECTIVES
1. Describe the functional anatomy and role of the digestive system.
2. Describe the production of gastric acid in the stomach.
3. Describe the time course of acid secretion in the fed and fasted states
4. Explain the regulation of acid production in the stomach.
5. Explain the pathology of ulcer formation and the target sites of drugs used for treating ulcers.

OVERVIEW
The digestive system provides nutrients, water, and electrolytes to the cells of the body from the
external environment. Food enters the oral cavity and is propelled by muscular contractions
through the gastrointestinal (GI) tract moving towards the anus. At various points along the GI
tract, digestive enzymes, acid, and buffers are added to facilitate the breakdown of complex foods
(such as steak and rice) into simple molecules (such as amino acids, fatty acids, and glucose).
These products are then absorbed into the body and delivered to the liver. The various secretions
of the GI tract (enzymes, mucus, and water) sum to about 7 liters which must be reabsorbed to
prevent dehydration. Unabsorbed nutrients and waste products are eliminated from the body as
feces (100 mL 500mL per day).

ANATOMY
The digestive system includes the GI tract and accessory organs (Fig 1).
The GI tract is a muscular tube about 5 meters in length with variable cross sectional diameter. It
includes the mouth, pharynx, esophagus, stomach, small intestine and large intestine (colon).
Voluntary control occurs at the top and bottom of the tube. Movement through the rest of the
tract is involuntary and unidirectional from mouth to anus.
Salivary glands
Liver

Gall
bladder

Pancreas

Figure 1. Functional regions of the GI tract. X marks the sphincters under voluntary control.

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The outside wall of the GI tract has two layers of smooth muscle which are oriented
perpendicular to each other (Fig 2). Constriction of the innermost layer of muscle changes the
diameter of the tube. Constriction of the outermost layer of muscle shortens the tube.
Epithelium

Submucosa
Muscularis externa
(inner & outer layers)

Figure 2. Layers of the GI tract.

The lumen of the GI tract is lined by a layer of cells (called epithelium) which differs in structure
along the tract. At the two ends, esophagus and anus, there is a wear and tear non-secretory,
non-absorptive epithelium (Fig 3). The stomach has a secretory epithelium and the small
intestines, absorptive epithelium.

Figure 3. Changes in the GI tract epithelium reflect function.

There are four accessory organs (salivary glands, liver, pancreas, and gall bladder) (Fig 1).
Secretions from the salivary gland are added to the oral cavity. Those from the liver are stored
within the gall bladder and then released along with those from the pancreas into the duodenum
(first portion of the small intestine).

INGESTION & FRAGMENTATION

Ingestion and fragmentation (chewing) of food occur within the oral cavity. Chewing reduces
the size of the food particle and increases its surface area to facilitate attack by digestive
enzymes. Chewing and later swallowing are aided by the secretion of saliva from three salivary
glands. Enzymes in saliva initiate the breakdown of complex carbohydrates such as bread and
cereals. The bolus of shredded food is then conveyed to the esophagus by the actions of the
tongue during swallowing. Transit through the esophagus to the stomach is rapid.

GASTRIC ACID SECRETION & DIGESTION

The stomach can hold 2-3 liters of food and fluid. It is divided into four regions, cardiac, fundic,
antrum, and pyloric (Fig 4). The epithelium in all four regions secretes a protective barrier of
mucus, a carbohydrate rich material that coats the surface of the lumen. We will consider the
physiologic actions of the fundic region which produces acid and of the antrum which regulates
the production of acid
Digestion of dietary protein starts in the fundic region of the stomach. Here the epithelium lining
the lumen contains 3 cell types: mucous secreting cells, chief cells, and parietal cells.

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Mucous cells secrete mucus that protects the epithelium from acid.
Chief cells secrete pepsinogen, an inactive enzyme, which is converted to an active enzyme
called pepsin by acid in the lumen of the stomach.
Parietal cells secrete intrinsic factor and hydrochloric acid (HCl). Intrinsic factor is a carrier
required for the absorption of vitamin B12 by the ileum (distal region of the small intestine).
Vitamin B12 is necessary for the formation of red blood cells. In the absence of intrinsic factor,
vitamin B12 absorption is insufficient resulting in pernicious anemia. HCl is a strong acid which
lowers the stomach contents to a pH of 2.0.

Figure 4. Functional regions of the stomach.

SECRETION OF GASTRIC ACID BY PARIETAL CELLS
The production of gastric acid by the parietal cells requires the activity of the enzyme, carbonic
anhydrase. In the presence of carbonic anhydrase, CO2 and H2O are converted to HCO3- and H+.
c.a.
CO2 + H2O = H2CO3 = HCO3- + H+
As shown in figure 5, the newly generated proton (H +) is transported into the lumen of the
stomach via the H+- K+ ATPase (called the proton pump). Concurrently, HCO3- exits from the
basal surface (blood side) of the parietal cell via the HCO3- - Cl- antiporter.
The chloride ion (Cl- ) needed to form HCl, enters the parietal cell from the blood via the HCO3- Cl- antiporter and exits at the luminal side by the Cl- channel. Once within the lumen of the
stomach, Cl- combines with H+ to form HCl.
The lumenal K+ that is needed to maintain the activity of the proton pump (H+-K+ ATPase),
enters the parietal cells from the stomach lumen by the H+-K+ ATPase and then recycles back
into the lumen of the stomach by the K+ channel (Fig 5).
The acidic pH in the stomach lumen is needed to convert pepsinogen (inactive pepsin) to pepsin
(active enzyme) and to provide an optimal pH for pepsin action. In addition, gastric acid kills any
bacteria that enter with the food.
Within the lumen of the stomach, muscle contractions mix the food particles with the HCl and the
enzyme pepsin producing a semi-digested liquid called chyme. This starts the digestion of
proteins.

Figure 5. Mechanism of HCl secretion by parietal cells uses a H +-K+ ATPase (proton pump) to
generate concentrated HCl in the stomach lumen.
With entry of food into the lumen of the stomach, acid secretion increases and reaches a peak
output by 90 minutes (Fig 6). Acid production subsequently falls as food leaves the stomach
lumen to enter the small intestine. It takes ~ 4 hours to empty the stomach after a meal because
only a few milliliters of acidic chyme exit to enter the proximal small intestine (duodenum) at any
time.

Figure 6. Secretion of gastric acid during fed and fasting states. Why does the pH initially rise
then fall by 2 hours after a meal?
CEPHALIC PHASE OF ACID SECRETION
The cephalic phase of gastric acid production is a feed forward control mediated by the
parasympathetic nervous system. In the cephalic phase, the smell of food, the thought of food,
chewing and/or swallowing food leads to an increase in the secretion of gastric acid. The cephalic
phase accounts for about 40% of the total acid production.

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Increased parasympathetic nervous activity affects cellular activity in two regions of the
stomach: fundic and antrum.
In the fundic region, parasympathetic stimulation of the parietal cells increases activity of the H +K+ ATPase (proton pump) and thereby increases acid secretion.
In the antrum, parasympathetic stimulation leads to an increase in secretion of the hormone,
gastrin. Gastrin, in turn, stimulates the H+ - K+ ATPase (proton pump) of the parietal cells. Gastrin
also acts on the ECL cells located adjacent to the parietal cells to increase the secretion of
histamine from these cells (Fig 7). Histamine in turn, acts as a paracrine to increase the activity of
the H+ - K+ ATPase in the parietal cells.
*** Note that the final effector for acid production in the cephalic phase is the proton pump
of the parietal cell.

Figure 7. Acetylcholine and gastrin directly stimulate acid production by the parietal cell which
is potentiated by histamine from the ECL cell.
GASTRIC PHASE OF ACID SECRETION
The second phase of acid secretion is called the gastric phase. It is initiated by mechanical
distension of the stomach by food and by the arrival of amino acids, alcohol, and caffeine within
the antrum region of the stomach. These events stimulate the secretion of gastrin, a hormone,
from G cells of the antrum (Fig 8). Gastrin acts in the fundic region to increase the activity of the
parietal cell proton pump as described above. The gastric phase accounts for about 60% of the
gastric acid secretion.

INHIBITION OF GASTRIC ACID SECRETION

Tight regulation of acid production is needed because excess acid can be caustic and acid is
needed only during feeding. The negative regulation of acid production is mediated by gastric
luminal pH. During feeding, proteins in the chyme act to buffer the pH to usually above 3.0
(Fig 6). However, in the empty stomach, the pH can fall below pH 3. At this low pH, the protons
directly inhibit gastrin secretion by the G cells and stimulate neighboring D cells of the antrum
region of the stomach to secrete somatostatin. Somatostatin acts as a paracrine to inhibit gastrin
secretion from the G cells (Fig 8).

H+ Receptor

Figure 8. Negative feedback by protons (H+) inhibits gastrin secretion.

Acid also initiates a negative feedback mediated by the hormone secretin. Secretin is secreted
by the first part of the small intestine (called the duodenum) in response to the arrival of acidic
chyme. Secretin acts as a hormone to inhibit gastrin secretion from the G cells of the
stomach (Fig.8).

LOSS OF MUCUS BARRIER & GASTRIC ULCERS

The mucous cells that line the stomach lumen secrete mucus, a carbohydrate rich
substance that protects the cells from erosion by acid. Disruption of this mucus barrier
can lead to lesions in the epithelium called ulcers. This is a painful condition that can
lead to severe bleeding if the muscle layers of the stomach wall are also involved.
There are two common causes of ulcers, the excess use of non-steroidal antiinflammatory drugs (NSAIDs) which inhibit the production of mucus by the epithelial
cells and an infection by Helicobacter pylori. Therapy targets include the following:
1. simple buffering of luminal pH
2. inhibition of the parietal cell histamine receptor
3. inhibition of the parietal cell proton pump
The most effective of these treatments is the inhibition of the proton pump but the fastest
effect is simple buffering with either bicarbonate or food. Infection by Helicobacter
pylori is the most common cause of gastric ulcers. This infection is treated with
antibiotics in addition to the proton pump inhibitor.

GENERAL CONCEPTS
1. The digestive system provides nutrients, water and solutes to the cells of the body from the
external environment.
2. the digestive system is comprised of accessory glands and the gastrointestinal tract (GI tube)
that coordinate four basic processes: fragmentation, secretion, digestion, and absorption.

3. The four regions of the GI tract are specialized in structure and function and include:
esophagus and anus (passive conduits), stomach (secretory) and intestines (absorptive).
4. The stomach produces acid from CO2 and water. This reaction occurs in the parietal cells and is
catalyzed by carbonic anhydrase. The acid secretion of the stomach starts the digestion of protein
and provides a barrier against the entry of bacteria.
5. In the fed state, gastric acid secretion and pH of the stomach lumen increase in the first 90
minutes after ingestion of food. In the fasting state, gastric acid secretion and pH of the stomach
lumen decrease returning to basal levels by 4 hours after food ingestion.
6. Secretion of gastric acid is regulated in a positive manner by the parasympathetic nervous
system, by the hormone gastrin and by the paracrine histamine. The final effector for each of
these factors is the proton pump located in the parietal cell.
7. Secretion of gastric acid is regulated in a negative manner by the hormone secretin and by the
paracrine, somatostatin. Secretion of these factors increases in response to low luminal pH. The
target for these negative factors is the G cell of the antrum which secretes gastrin.
8. The stomach has a protective mucus barrier to prevent cellular damage by acid. Disruption of
this barrier leads to erosion of the epithelium lining the stomach lumen (gastric ulcers).

QUESTIONS
Case: A 23- year old male develops severe vomiting for 48 hours.
1. Will this change his acid-base status? If so, then how?
2. Will this alter his minute ventilation?
3. Gastrin is secreted in response to an increase in:
A. amino acids and alcohol within the lumen of the stomach
B. protons (H+) concentration within the lumen of the stomach
C. histamine stimulation of the antral G cells
D. A and B
E. A and C
4. Which of the following best describes human gastric acid secretion in the first 30 minutes after
eating a normal meal?
A. Acid secretion rate and luminal pH both decrease.
B. Acid secretion rate and luminal pH both increase.
C. Acid secretion rate decreases and luminal pH increases.
D. Acid secretion rate increases and luminal pH decreases.

ANSWERS
1. Yes. Loss of H+ in the vomit will lead to metabolic alkalosis.
2. Yes. Minute ventilation will decrease to retain CO2.
3. A
4. B