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Digestive System Physiology
Objectives after studying this chapter, you should be able to . . .
1. Describe the gross and microscopic anatomy and the basic functions of the digestive system.
2. Describe the composition and functions of saliva, and explain how salivation is regulated.
3. Describe the mechanisms of chewing and swallowing.
4. Explain how gastric secretion and stomach motility are regulated.
5. Explain the mechanism of vomiting.
6. Describe the role of the gallbladder and state the role of bile in digestion and describe how its entry
into the small intestine is regulated.
7. Describe how entry of pancreatic juice into the small intestine is regulated and state the role of
pancreatic juice in digestion.
8. List the major functions of the large and small intestine.
9. Describe the regulation of defecation.
List the enzymes involved in chemical digestion; name the foodstuffs on which they act.
10. List the end products of protein, fat, carbohydrate, and nucleic acid digestion.
11. Describe the process of absorption of breakdown products of foodstuffs that occurs in the small
intestine.
12. Describe the main functions of liver.
The digestive system prepares food for use by cells through five basic activities:
1. Ingestion or the taking of food into the body.
2. Peristalsis or the physical movement or pushing of food along the digestive tract.
3. Digestion or the breakdown of food by both mechanical and chemical mechanisms.
4. Absorption or the passage of digested food from the digestive tract into the cardiovascular and
lymphatic systems for distribution to the body’s cells.
5. Defecation or the elimination from the body of those substances that are indigestible and cannot be
absorbed.
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The primary function of the alimentary tract is to break down food and to provide the body with a
continual supply of water, electrolytes and nutrients. In order to achieve these functions, the
gastrointestinal tract (GIT) must perform the following processes: ingestion, movement, digestion,
absorption, secretion and defecation. The adult GIT is a tube running through the body from mouth to anus.
Anatomical features: The organizations of the structures that make up the wall of the gastrointestinal tract
(GIT) from the posterior pharynx to the anus generally are as follow from the outer surface inward (figure
5.1):
Figure 5.1: Histological cross section of the digestive tract.
1. Serosa which continues onto the mesentery, which contains the nerves, lymphatics, and blood vessels
supplying the tract.
2. Longitudinal muscle.
3. Myenteric (Auerbach’s) p1exus which controls mainly the GIT movement.
4. Circular muscle which causes a decrease in the diameter of the lumen of the GI tract when it
contracts.
5. Submucous (Meissner’s) plexus which is important in controlling secretion and blood flow and also
subserves many sensory functions, receiving signals from chemoreceptors in the gut epithelium and from
stretch receptors in the gut wall.
6. Mucosa and submucosa which consists of epithelium and subepithelial connective tissue and are
specialized for secretion and absorption.
The enteric nervous system (ENS): The GIT has an intrinsic nervous system of its own called the enteric
nervous system which controls most GI functions, especially GIT movements and secretion. The enteric
nervous system is composed of two layers of neurons and connecting fibers, the outer layer is called the
myenteric (Auerbach’s) plexus, the inner layer is called the submucous (Meissner’s) plexus.
The degree of activity of this enteric nervous system can strongly be altered by extrinsic (autonomic)
nervous system, i.e. parasympathetic and sympathetic nervous systems. Both systems send signals to GIT
from the brain and spinal cord to modulate the activity of the enteric nervous system.
The parasympathetic nerve fibers: Stimulation of the parasympathetic nerves fibers releases
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acetylcholine and causes in general:
 An increase in the activity of most GIT functions.
 Relaxation of sphincters (except the lower esophageal sphincter, which they stimulate).
The parasympathetic supply to the gut is divided into:
Cranial division: Is mediated almost entirely through the vagus (X cranial nerve). Vagus nerves
innervate esophagus, stomach, pancreas, gallbladder and first half of the large intestine, and little
innervations to the small intestine
Sacral divisions: The sacral divisions originate in S2, 3, 4 sacral segments of the spinal cord, and pass
through the pelvic nerves to the distal half of the large intestine. These fibers function especially in the
defecation reflex. Because the parasympathetic nervous system plays a dominant role in the digestive
process, it is often referred to as the “rest and digest”division.
The sympathetic nerve fibers: The sympathetic nerve endings secrete norepinephrine. In general,
stimulation of the sympathetic nervous system:
 Inhibits activity in the GIT
 Contraction of sphincters, causing effects essentially opposite to those of the parasympathetic
system.
The sympathetic nerve fibers to the GIT originate in the spinal cord between the segments T- 8 and L 2. The preganglionic fibers after leaving the cord pass through the sympathetic chains to outlying ganglia,
such as the celiac, hypogastric, and mesenteric ganglia. Here, the postganglionic neuron bodies are located,
and postganglionic fibers spread from them along with the blood vessels to all parts of the gut, terminating
principally on neurons of the enteric nervous system.
Reflexes of GIT are either occur entirely within the enteric nervous system (short reflex arc), or the
reflex arc is originated from the gut and to the CNS (spinal cord or brain stem) and then back to the gut
(long reflex arc) (figure 5.2). Signals transmitted through these reflexes can cause reflex excitation or
inhibition of intestinal movements or secretion.
In addition to its anatomic complexity, the ENS utilizes many different neurotransmitters, including
acetylcholine, adenosine triphosphate (ATP), nitric oxide, and numerous peptides.
Hirschsprung’s disease is a congenital absence of the myenteric plexus, usually involving a portion
of the distal colon. The pathologic non-ganglionic section of large bowel lacks peristalsis and undergoes
continuous spasm, leading to a functional obstruction. The normally innervated proximal bowel dilates as a
result of the obstruction and can lead to the most feared complication of Hirschsprung’s disease, toxic
megacolon.
Types of GIT smooth muscle contractions: The smooth muscle of GIT is almost exclusively unitary smooth
muscle while that of pharynx, upper one third of the esophagus, and external anal sphincter are striated
muscles. Although the upper esophageal sphincter surrounds the upper part of the esophagus consists of
skeletal muscle, but is not under conscious or voluntary control.
There are two main types of smooth muscle contractions:
[A] Phasic (rhythmical) contractions
[B] Tonic contractions
[A] Phasic (rhythmical) contractions that occur in the esophagus, stomach, and intestine. They include
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peristaltic (figure 5.3 A), migrating Motor Complex (MMC), segmentation and haustration contractions
(figure 5.3 B).
 In peristalsis, contraction of a small section of proximal muscle is followed immediately by
relaxation of the muscle just distal to it. The resulting wavelike motion moves food along the GIT in a
proximal to distal direction. Peristaltic wave could be of two types:
[1] Primary peristaltic wave which is a continuation of the peristaltic wave that begins proximally and
mediated by vagovagal reflexes, long reflex arc.
[2] Secondary peristaltic wave which is generated by the enteric nervous system (short reflex pathway),
initiated from the distension of the viscus by the retained food if the primary peristaltic wave fails to move
all the food that has entered the viscus.
 MMC is a distinct pattern of electromechanical activity observed in gastrointestinal smooth
muscle during the periods between meals, and it is interrupted by feeding. It is thought to serve a
"housekeeping" role and sweep residual undigested material through the digestive tube. The cycle recurs
every 1.5 to 2 hours. These motor complexes trigger peristaltic waves, which facilitate transportation of
indigestible substances such as bone, fiber, and foreign bodies from the stomach, through the small
intestine, past the ileocecal sphincter, and into the colon. An intact enteric nervous system is essential for
propagation of migrating motor complexes along the bowel. The MMC is thought to be partially regulated
by motilin (by a direct action on smooth muscle and by activation of excitatory enteric nerves and it is
released during the interdigestive period). MMC is initiated in the stomach as a response to vagal
stimulation. Control of the MMC is complex. MMC with an antral origin can be induced in humans through
intravenous administration of motilin, erythromycin or ghrelin, whereas administration of serotonin or
somatostatin induces MMC with duodenal origin. The role of the vagus nerve in control of the MMC seems
to be restricted to the stomach, as vagotomy abolishes the motor activity in the stomach, but leaves the
periodic activity in the small bowel intact.
 In segmentation contraction, nonadjacent segments of alimentary tract organs, especially small
intestine, contract and relax, moving food forward then backward, resulting in food mixing and slow food
propulsion. Segmentation contraction is the primary motility pattern of the digestive period in humans, and
is defined as irregular and uncoordinated contraction of the circular muscle layer. This pattern, which
develops in response to intestinal wall distention, is determined by activation of preprogrammed neural
circuits within the myenteric plexus. The combined contractions of the circular and longitudinal smooth
muscle cause the unstimulated portion in large intestine to bulge outward into baglike sacs called
haustration. Therefore, the fecal material in the large intestine is squeezed, moving back and forth along
the colon in a manner similar to that for the segmentation contractions in the small intestine.
Distention-induced contraction of gastrointestinal smooth muscle develops as the result of long
(vago-vagal) and local (enteric nerves) reflexes. The importance of long versus local reflex pathways varies
along the gut. Secondary esophageal peristalsis, intestinal segmentation, and migrating motor complexes
are unaffected by vagotomy, whereas primary peristaltic wave and proximal stomach peristalsis is
decreased but not abolished by vagotomy.
[B] Tonic contractions that occur in the lower esophageal sphincter, pyloric sphincter, ileocecal sphincter,
and internal anal sphincter. Tonic contraction is continuous, occasionally increases or decreases in
intensity.
Electrical slow wave activity in the gastrointestinal tract appears to originate from specialized
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pacemaker cells (interstitial cells of Cajal) located between the longitudinal and circular muscle layers and
within the submucosal and myenteric plexuses. These pacemaker cells input directly onto the smooth
muscle and receive input from enteric nerves.
Figure 5.2: Arrangement of reflexes of the digestive system.
Table 5A: Differences Between the Myenteric and Submucosal Plexuses
Myenteric Plexus
Submucosal Plexus
It is concerned mainly with controlling muscle activity It is mainly concerned with controlling function
along the length of the gut with specific effects:
within the inner wall of each minute segment
(i) Increased “tone" of the gut wall
of the intestine such as:
(ii) Increased intensity of the rhythmical contractions
(i) local intestinal secretion
(iii) Slightly increased rate of the rhythm of
(ii) local absorption
contraction
(iii) local contraction of the submucosal muscle
(iv) Increased velocity of conduction of excitatory
waves along the gut wall, causing more rapid
movement of the gut peristaltic waves
Composed of excitatory as well as inhibitory neurons
Inhibitory neurons are useful for inhibiting some of
the intestinal sphincter muscles such as pyloric
sphincter and the sphincter of the ileocecal valve
Composed mainly of excitatory neurons
Different Types of Neurotransmitters Secreted by Enteric Neurons
1. Acetylcholine
2. Norepinephrine
3. Adenosine triphosphate
4. Serotonin
5. Dopamine
6. Cholecystokinin
7. Substance P
8. Vasoactive intestinal polypeptide
9. Somatostatin
10. Leu-enkephalin
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11. Met-enkephalin
12. Bombesin
The specific functions of many of these are not known well enough to justify discussion here, other than to point out
the following.
Acetylcholine most often excites gastrointestinal activity.
Norepinephrine and epinephrine almost always inhibit gastrointestinal activity.
Figure 5.3: Types of GIT smooth muscle contractions.
Paralytic ileus is a temporary cessation of gut motility that is most commonly caused by abdominal surgery.
Other common causes appendicitis, hypokalemia, and narcotics. Signs and symptoms of paralytic ileus
include nausea and vomiting, abdominal distension, and absent bowel sounds.
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Mastication (chewing): Is the
process by which food taken into
the mouth is chewed by the teeth.
The chewing reflex (figure 5.3A) is
controlled by nuclei in the medulla
and cerebral cortex. Most of the
muscles of chewing are innervated
by the motor branch of the 5th
cranial nerve (trigeminal N).
Voluntary contraction of the
muscles of chewing is in response to
the presence of a bolus of food in
the mouth compresses the bolus
against the linings of the mouth and
push the food to come in contact
with the buccal receptors. The
contact of food with buccal
receptors causes reflex inhibition of
the muscles of mastication, which
allows the lower jaw to drop. The
drop in turn initiates a stretch reflex
of the jaw muscles (the masseter,
medial pterygoid, and temporalis Figure 5.3A: The chewing reflex.
muscles) that leads to rebound
contraction. This automatically raises the jaw to cause closure of the teeth, but again, it also compresses
the bolus against the linings of the mouth and pushes the food to come in contact with the buccal
receptors, which inhibit the jaw muscles once again and allowing the jaw to drop and rebound another
time, and this is repeated again and again.
Chewing is important because:
[1] Chewing breaks down the indigestible cellulose membranes around the nutrient portions of food
before the food can be utilized.
[2] Chewing increases the surface area of food so the rate of digestion of food by the digestive enzymes is
increased.
[3] Chewing grinds the food to a very fine particulate consistency prevents excoriation of the GIT and
increases the ease with which food is swallowed and emptied from the stomach into the small intestine and
thence into all succeeding segments of the gut.
[4] Chewing mixes the food with salivary gland secretions which initiates the process of starch digestion
(by salivary amylase) and to much less extent of lipid digestion (by lingual lipase) and to lubricate and soften
the bolus of food, making it easier to swallow.
[5] Chewing brings food into contact with taste receptors and releases odors that stimulate the olfactory
receptors. The sensations generated by these receptors increase the pleasure of eating and initiate gastric
secretions.
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Salivary glands: The daily normal secretion of
saliva is between 500—1500 ml. Saliva is secreted
from the glands of salivation, the parotids (25%),
submandibular glands (70%), and sublingual
glands (5%). In addition, there are many small
buccal glands.
In comparison to plasma, saliva is:
 Hypotonic.
 Contains higher concentration of K ions
and bicarbonate ions and lower
concentrations of Na and Cl ions.
 Saliva has a pH 6.0 - 7.4.
The structure of each gland is similar to a
bunch of grapes (figure 5.4). The acinus is lined
with acinar cells and secretes initial saliva which is
a plasma-like solution (isotonic) containing
amylase and/or mucin. A branching duct system is
lined with columnar epithelial cell, which modify
the initial saliva by:
 Active absorption of Na+ (3Na+-2K+
Figure 5.4: Secretion of saliva and electrolytes.
ATPase),
 Passive reabsorption of Cl- ions (due to electrical gradient) in exchange to HCO3- ions which are
secreted actively (Cl- - HCO3- secondary active counter-transport).
 Saliva is an important route of iodide excretion; its concentration in saliva is 20–100 times that in
plasma.
 It is saturated with calcium ions; calcium salts are laid down as plaque on the teeth.
Therefore, the composition of saliva varies with the salivary flow rate:
[1] At the lowest flow rates, saliva has the lowest osmolarity (about 100 mOsm/L) and lowest Na+, and Clconcentrations, but has the highest K+ and HCO3- ion concentration.
[2] At the highest flow rates, saliva is most like the initial secretion from the acinus and its composition is
closet to that of plasma.
Saliva consists of two major types of protein secretions:
1. Serous secretion (watery saliva) containing ptyalin (α-amylase which is an enzyme for digesting starches)
and electrolytes.
2. Mucous secretion containing mucin (glycoprotein) for lubricating purposes.
 The parotid glands secrete entirely the serous type.
 The submandibular and sublingual glands secrete both the serous type and mucus.
 The buccal glands secrete only mucus.
Control of salivary secretion: Salivary glands are controlled by salivatory nuclei which are located at the
juncture of the medulla and pons.
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• Mainly
through
parasympathetic fibers through
7th cranial nerve (Facial N) and
9th
cranial
nerve
(Glossopharyngeal
N)

abundant watery saliva rich in
enzymes.
• And to less extent by
sympathetic nervous signals
originates from the superior
cervical ganglia and then travels
along blood vessels to the
salivary glands  scanty thick
saliva rich in mucus. This is why
the mouth may feel sticky or dry
under conditions of stress.
Under basal conditions,
saliva is almost entirely of the
mucus type and is secreted all
the time except during sleep
Figure 5.4A: Control of salivary secretion.
when the secretion becomes
very little. Unlike the autonomic
nervous system elsewhere in the body, sympathetic and parasympathetic responses in the salivary
glands are not antagonistic.
Salivatory nuclei are excited or inhibited by (figure 5.4A):
[A] Signals from the mouth: Taste (especially the sour taste excitatory, bitter taste inhibitory)
and tactile stimuli (especially smooth objects  excitatory) from the tongue and other areas of the mouth.
[B] Signals from higher centers of CNS: Salivation can also be stimulated or inhibited by impulses
arriving in the salivatory nuclei from higher centers of CNS. For instance, when a person smells or sees
favorite foods, salivation is greater than when disliked food is smelled or seen.
[C] Signals from GIT: Salivation also occurs in response to reflex originating in the stomach and
upper intestine particularly when very irritating foods are swallowed or when a person is nauseated. The
swallowed saliva may help to remove the irritating factor in the GIT by diluting or neutralizing the irritant
substances.
Saliva production is decreased (via inhibition of the parasympathetic nervous system) by sleep,
dehydration, fear, and anticholinergic drugs (such as atropine).
Functions of saliva:
[A] Protection of the mouth by:
 Cooling hot foods,
 By maintaining healthy oral tissues. The mouth is loaded with pathogenic bacteria that can easily destroy
tissues and can also cause dental caries. However, saliva helps prevent the harmful effects of bacteria by:

Continuous washing away the pathogenic bacteria as well as the food particles that provide the bacteria
with metabolic support.
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
Saliva contains many factors that can kill bacteria such as thiocyanate ions, proteolytic enzymes, and
antibodies (IgA).
[B] Digestion of starch by α-amylase (which is ultimately inactivated by the low pH of the stomach), and fat
by lingual lipase.
[C] Lubrication of food and making swallowing easier, and moisten the mouth, facilitating speech. It also
neutralizes any gastric acid that refluxes from stomach into the lower esophagus (heartburn).
Xerostomia is defined as dry mouth resulting from reduced or absent saliva flow. Xerostomia is not a
disease, but it may be a symptom of various medical conditions, a side effect of a radiation to the head
and neck, or a side effect of a wide variety of medications. Xerostomia is a common complaint affecting
approximately 20 percent of the elderly.
Swallowing (deglutition): The voluntary initiation of swallowing takes place in higher brain centers and
starts with oral stage. From here on, the process of swallowing becomes entirely or almost entirely
automatic and controlled by swallowing (or deglutition) center which is located at the medulla and the
pons. The afferent (sensory) fibers to this center are:
 Trigeminal (5th cranial nerves),
 Glossopharyngeal (9th cranial nerves),
The efferent (motor) nerve fibers from the swallowing center are conducted through:
 Trigeminal (5th cranial nerves),
 Glossopharyngeal (9th cranial nerves),
 Vagus (10th cranial nerves),
 Hypoglossal (12th cranial nerves),
 Few of the superior cervical nerves to the pharynx and upper esophagus
Swallowing can be divided into the following stages:
 Oral stage.
 Pharyngeal stage.
 Esophageal stage.
 Relaxation of lower esophageal sphincter.
[A] Oral (voluntary) stage of swallowing: Food is voluntarily squeezed posteriorly in the mouth to
the oropharynx by pressure of the tongue upward and backward against the hard palate. From here on, the
process of swallowing becomes entirely or almost entirely automatic and cannot be stopped.
[B] Pharyngeal (involuntary) stage: When the bolus of food is pushed backward in the mouth, it
stimulates swallowing receptor areas around the opening of the pharynx  afferent impulses pass to
Swallowing center to initiate a series of automatic pharyngeal muscular contractions and to inhibit the
respiratory center of the medulla during swallowing, halting respiration at any point in its cycle to allow
swallowing to proceed. The sequence of events of the pharyngeal stage of the swallowing is as follows:
1. The soft palate is pulled upward to close the posterior nares preventing reflux of food into the nasal
cavities.
2. The palatopharyngeal folds on either side of the pharynx are pulled medial ward to approximate
each other. In this way these folds form sagital slit through which the food must pass into the posterior
pharynx. This slit performs a selective action, allowing food that has been masticated properly to pass with
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ease while impede the passage of large objects.
3. The vocal cords of the larynx are strongly approximated, and the hyoid bone and larynx are pulled
upward and anteriorly by the neck muscles causing epiglottis to swing backward over the superior opening
of the larynx. All these effects (especially the approximation of vocal cords) prevent passage of food into
the trachea.
4. The upward movement of the larynx also stretches the opening of the esophagus. At the same time,
the upper 3 to 4 cm of the esophagus, an area called the upper esophageal sphincter (or
pharyngeoesophageal sphincter or the cricopharyngeal muscle), relaxes, thus allowing food to move easily
and freely from the posterior pharynx into the upper esophagus. This sphincter between swallows, remains
tonically and strongly contracted (by the continual firing of the vagal fibers), thereby prevents air from
going into the esophagus during respiration.
5. At the same time that the larynx is raised and the upper esophageal sphincter is relaxed, the
superior constrictor muscle of the pharynx contracts, giving rise to a rapid peristaltic wave passing
downward over the pharyngeal muscles and into the esophagus, which also propels the food into the
esophagus.
Swallowing becomes a great concern for the elderly since strokes and Alzheimer's disease can
interfere with the autonomic nervous system. As you can gather from the information written above, there
are multiple areas of the central nervous system which, if affected by a stroke, could disrupt the ability to
swallow. This is especially true for strokes of the medulla, as this is a relatively small area that contains
multiple structures that are critical in carrying out the swallowing reflex. In fact, people with medullary
strokes frequently require temporary or permanent feeding tube placement.
[C] Esophageal stage of swallowing: The esophagus functions to conduct food from the pharynx to
the stomach. The movement of food down the esophagus is an active process (primary esophageal
peristalsis integrated at swallowing center) that does not depend on gravity for its normal function. The
upper esophageal sphincter and lower esophageal sphincter are closed in normal resting state. Closure of
the upper esophageal sphincter prevents air from being drawn from the mouth into the esophagus during
inspiration. Closure of the lower esophageal sphincter prevents gastric contents to move back from the
stomach to the esophagus. Because most of the esophagus is contained within the thoracic cavity, the
pressure in the lumen of the resting esophagus is approximately equal to intra-thoracic pressure
(atmospheric or slightly below atmospheric) when the upper esophageal sphincter and lower esophageal
sphincter are closed (normal resting state). During pulmonary inspiration, the intra-esophageal pressure will
be sub-atmospheric. The term secondary esophageal peristalsis describes esophageal peristalsis and lower
esophageal relaxation associated with distension or irritation of the smooth muscle portion of the
esophageal body. The event is limited to the smooth muscle component of the esophagus and is the result
of activation of enteric nerves. Initiation of secondary peristalsis does not involve extrinsic neural reflexes
and, thus, is not accompanied by the oral-pharyngeal phase of swallowing.
[D] Relaxation of lower esophageal sphincter: The lower esophageal sphincter is not anatomically
separate identifiable muscles. The fundus of the stomach and lower esophageal sphincter extending about
2-5 cm above its junction with the stomach both relax during a swallow while the bolus of food is still higher
in the esophagus. This phenomenon is called receptive relaxation. Receptive relaxation is vagally mediated,
Nitric oxide is the neurotransmitter thought to mediate receptive relaxation at the smooth muscle cell
allowing food to pass to the stomach.
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Reflux of the acidic contents of the stomach
up to the esophagus damages the
esophageal mucosa. This is prevented by:
[1] The muscles of the lower esophageal
sphincter normally remains tonically
contracted due to tonic activity of the vagal
fibers innervating the esophagus (in contrast
to the mid- and upper portions of the
esophagus
which
normally
remain
completely relaxed). Vagal efferent nerve
fibers control contraction and relaxation of
the LES. Vagal excitatory fibers synapse on
post-ganglionic, enteric motor neurons that
release acetylcholine within the musculature of the LES. Vagal inhibitory fibers synapse on enteric
inhibitory motor neurons that release nitric oxide (NO). These neurons may also utilize ATP and VIP as
inhibitory transmitters, but NO is the primary inhibitory neurotransmitter. Sympathetic neurons also
provide excitatory input to the LES via excitatory motor neurons.
[2] Another factor that prevents reflux is the oblique entrance of the esophagus to the stomach which acts
like a valve-like mechanism of that portion of the esophagus that lies immediately beneath the diaphragm.
Greatly increased intra-abdominal pressure caves the esophagus inward at this point at the same time that
the abdominal pressure also increases the intragastric pressure, preventing the high pressure in the
stomach from forcing stomach contents into the esophagus.
Esophageal reflux: Reflux of stomach acid to the esophagus causes esophageal pain (heartburn) and may
lead to esophagitis.
An increase in the intraabdominal pressure (by the ingestion of a very large meal, production of
intestinal gas, pregnancy, an abdominal mass such as a tumor, bending at the waist, straining against a
closed glottis as in defecation) will facilitate gastro-esophageal reflux if the LES is not contracted or there is
distortion of the valve-like mechanism.
Esophageal reflux may occur if:
[A] If the intragastric pressure raises high enough to force the lower esophageal sphincter open.
[B] If the lower esophageal sphincter is unable to maintain its normal tone.
[C] If the lower esophageal sphincter is forced through the diaphragm and into the thoracic cavity as in
hiatal hernia, in which the oblique entrance of the esophagus to the stomach is distorted, and consequently
the valve-like mechanism is impaired.
Belching (eructation): Following a heavy meal or the ingestion of large amounts of gas (e.g., from
carbonated beverages), the gas bubble that is usually in the fundus of the stomach is displaced to the
cardia. When lower esophageal sphincter relaxes during the swallowing process, gas enters the esophagus
and is regurgitated.
Dysphagia: Difficulty in swallowing. Persons with dysphagia usually report choking, coughing, or an
abnormal sensation of food sticking in the back of the throat or upper chest when they swallow. If
swallowing is painful, it is referred to as odynophagia. Dysphagia can result from altered nerve function or
from disorders such as:
 Narrowing of the esophagus.
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 Lesions of the central nervous system (CNS), such as a stroke, often involve the cranial nerves that
control swallowing.
 Strictures and cancer of the esophagus and strictures resulting from scarring can reduce the size of the
esophageal lumen and make swallowing difficult.
Achalasia: In which the lower esophageal sphincter fails to relax; food that has been swallowed has
difficulty passing into the stomach, and the esophagus above the lower esophageal sphincter becomes
enlarged. One or several meals may lodge in the esophagus and pass slowly into the stomach. There is
danger of aspiration of esophageal contents into the lungs when the person lies down.
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.
The functions of the stomach:
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
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hours and very closely regulated so that
nutrient absorption is maximized and H+ in
the duodenum has time to be neutralized.
Gastric secretion
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 (figure 5.5):
[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 Figure 5.5: Histological cross section of gastric mucosa.
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 HCl secretion: HCl is secreted into the parietal cell canaliculi by the following steps (figure 5.6):
[1] CO2 diffuses from blood to inside the parietal cells.
[2] Within the parietal cells, carbonic acid is formed from the reaction: CO 2 + 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
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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.
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Figure 5.6: Steps of gastric HCl secretion.
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 (<3.0) on gastrin release. The
hypergastrinemia that develops may actually increase the number of parietal cells as a result of the trophic
effects of the hormone. In addition, two other drugs can also be used for treatment of peptic ulcer and
these are cimetidin and ranitidine. 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.
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
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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 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
Figure 5.7: The components of gastric mucosal barrier.
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 components of gastric mucosal barrier enable the stomach to contain acid without injuring
itself are (figure 5.7):
 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.
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Gastric hormonal secretion: Gastrin, main gastrointestinal hormone, is secreted by antral G cells and has
the following effects:
 It stimulates the parietal cells to secret HCl.
 It stimulates the chief cells to secret pepsinogen.
 It stimulates the enterochromaffin-like cells (ECL cell, or enteroendorine cells) to release histamine.
 It enhances muscle contractions of pyloric pump (minor effect) and has a slight constrictor effect on the
gastroesophageal sphincter.
 It stimulates contraction of intestinal muscle, relaxes ileocecal valve,
and stimulates mass movements.
Other hormones such as histamine, serotonin, and somatostatin release
directly into the interstitial fluid of the mucosa of the stomach and act
as chemical messengers.
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.
Phases of gastric motility and secretion:

Cephalic phase

Gastric phase

Intestinal phase
 1. The cephalic phase: It occurs even before the food enters the
stomach (figure 5.8A). It results from the sight, smell, thought, tactile
sensation in the mouth, taste of food, or emotional state. Neurogenic
signals causing the cephalic phase of secretion can originate in the
cerebral cortex or in the appetite centers of the amygdala or
hypothalamus and transmitted through the vagi to the stomach (insulin induced hypoglycemia also
stimulates the vagus nerve). Psychic states have marked effects on gastric secretion and motility. Anger and
hostility were associated with hypersecretion of the gastric mucosa and enhance gastric motility while fear
and depression decrease gastric secretion and inhibit gastric motility. Almost 30% of the gastric secretions
released during a meal occur as a result of cephalically induced vagal stimulation (figure 5.8). During this
phase, the non-distended stomach secretes hormone Ghrelin from cells in the stomach. Ghrelin the
"hunger hormone” is a peptide hormone produced by cells in the gastrointestinal tract which functions as a
neuropeptide in the central nervous system. It acts on hypothalamic brain cells both to increase hunger,
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and to increase gastric acid secretion and gastrointestinal motility to prepare the body for food intake.
When the stomach is empty, ghrelin is secreted. When the stomach is stretched, secretion stops. Ghrelin is
also a stimulator of the growth hormone secretagogue receptor in the anterior pituitary, a receptor that
mediates growth hormone release.
2. The gastric phase: 60% of gastric secretions are associated with this phase. It starts once the food enters
the stomach (see figure 5.8 and 5.8A):
[A] The stomach excitatory signals:
 Distension of the antrum by food  through myenteric reflexes, increase in the activity of the
pyloric pump and at the same time inhibits the pyloric sphincter.
 The presence of the protein (small peptides and amino acids or other substance like caffeine) in the
diet (the presence of protein digestion products in the diet is the most important determinant of acid
secretion during the gastric phase)  a reflex stimulation of G cell of mucosa to release gastrin.
Consequently increase in gastric secretion and motility of pyloric pump as shown in figure 5.8. Therefore,
carbohydrates empty fastest, followed by protein. Fats take longest to empty.
 decreasing in gastric [H+] (i.e. high pH)
[B] The gastric inhibitory signals: The most potent inhibitor of HCl secretion and pyloric pump activity is the
drop of pH (increasing in gastric [H+]) of the gastric content below 2-3. This inhibition is mediated by two
mechanisms:
 A low pH directly inhibits G cells and gastrin secretion, consequently inhibits HCl secretion and
pyloric pump activity (figure 5.8). Plasma gastrin levels are related inversely to acid secretory capacity
because of a feedback mechanism by which antral acidification inhibits gastrin release. Thus, plasma gastrin
levels are reduced in persons with duodenal ulcers.
 A low pH stimulates antral D cells to release somatostatin, which inhibit secretion of parietal
cells, ECL cells, and G cells (not shown in figure 5.8), thus turning off the HCl-secreting cells and their most
potent stimulatory pathway.
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Facts about Gastric emptying:
a. The rate of gastric emptying is fastest when the stomach
contents are isotonic. If the stomach contents are hypertonic
Figure 5.8: Cells involved in gastric
or hypotonic, gastric emptying is slowed.
b. Fat inhibits gastric emptying (i.e., increases gastric emptying secretion during cephalic and gastric
phases.
time) by stimulating the release of CCK.
+
c. H in the duodenum inhibits gastric emptying via direct
neural reflexes. H+ receptors in the duodenum relay information to the gastric smooth muscle via
interneurons in the GI plexuses.
d. The initial rate of the gastric emptying varies directly with the volume of the meal ingested.
Another phase of acid secretion is known as the basal state which occurs in the times between
meals (interdigestive phase). The level of acid secretion during these times is regulated by body weight,
individual, number of parietal cells, and time of day. Acid secretion is lowest in the morning before
awakening and highest at night. The stomach secretes only few milliliters of gastric juice per hour during
the interdigestive period (between meals) when little or no digestion is occurring anywhere in the gut which
is almost entirely of non-oxyntic type i.e., it is composed mainly of mucus containing very little pepsin and
almost no acid. However, strong emotional stimuli frequently increase the interdigestive secretion to 50 ml
or more of highly peptic and highly acidic gastric juice per hour in very much the same manner that the
cephalic phase of the gastric secretion excites secretion at the onset of a meal. This increase of secretion
during the presence of emotional stimuli is believed to be one of the factors in the development of peptic
ulcers.
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3. The intestinal phase: Intestinal receptors monitor the composition of chyme and elicit feedback
mechanisms that regulate gastric acid secretion and gastric emptying. Absence of feedback leads to an
increased presence of excitatory mediators of gastric function. 10% of gastric secretion is associated with
the intestinal phase. This is achieved through hormones and nervous reflexes. The rate at which the
stomach empties is regulated by signals from both the stomach and the duodenum. However, the
duodenum provides by far the more potent of the signals, controlling the emptying of chyme into the
duodenum at a rate no greater than the rate at which the chime can be digested and absorbed in the small
intestine. These feedback inhibitory mechanisms work together to slow the rate of emptying when (1) too
much chyme is already in the small
intestine or (2) the chyme is
excessively acidic, contains too
much unprocessed protein or fat, is
hypotonic or hypertonic, or is
irritating.
[A] The intestinal excitatory signals:
1. Nervous Feedback: Slight
stretching the wall of the upper
portion of the small intestine,
particularly in the duodenum by
food.
2. Hormonal Feedback:
The
presence of small amounts of food
(especially
protein
digestion
products) stimulates small amount
Figure 5.9: The role of the intestinal inhibitory signals on
of intestinal gastrin to be released
gastric secretion and pyloric pump.
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from the duodenal mucosa. This can slightly increase the
activity of pyloric pump and gastric juice secretion
(through the same mechanism mentioned before).
[B] The intestinal inhibitory signals:
1. Nervous Feedback:
 Duodenal wall distension or irritation of duodenal
mucosa provokes inhibitory reflex effect from the
duodenum to the stomach. When food enters the
duodenum, multiple nervous reflexes are initiated from
the duodenal wall receptors. These reflexes are mediated
through the enteric nervous system, or through long, and
short nervous reflexes  These signals depress the
gastric juice secretion and at the same time decrease
pyloric pump activity and usually increase pyloric tone to
prevent the flow of chyme from exceeding the ability of
the intestine to handle it.
 Osmolarity of the chyme: Iso-osmotic gastric
contents empty faster than hyper or hypo-osmotic
contents due to feedback inhibition produced by duodenal wall chemoreceptors (hyper more inhibitory
than hypo).
 pH of chyme: Small intestinal chyme of < 3.5-4 stimulates the duodenal wall chemoreceptos and
will activate reflexes that ultimately inhibits pyloric pump through.
 Presence of fats and protein digestion products in the duodenum.
2. Hormonal Feedback: The chyme coming from the stomach is normally hypertonic, acidic, and contains
high concentrations of fat, protein, and carbohydrates.
The intestinal inhibitory signals are:
 Fats entering the duodenum  stimulate inhibitory hormone CCK which inhibits the pyloric pump.
CCK is the most potent inhibitor of pyloric pump.
 Acidic chyme in the duodenum  stimulates inhibitory hormone secretin which inhibits the pyloric
pump.
 Fat, protein, and carbohydrates in the duodenum  stimulate inhibitory hormones Gastric
inhibitory peptide (GIP) that has a general but weak effect of decreasing gastrointestinal motility.
CCK and secretin hormones are collectively called enterogastrones (figure 5.9).
Inflammation of the duodenum may lead to increased acid output, hypocalcemia, and microcytic
anemia. Increased basal and maximal acid outputs may result from excessive stimulation of the parietal cell
(e.g., hypergastrinemia) or reduced inhibitory feedback (i.e., reduced effect of enterogastrone and the
enterogastric reflex). The latter may occur when the proximal small intestine is inflamed.
In summary: In humans, gastric acid secretion by the parietal cell occurs in response to (figure 5.8A):
 Excitatory neural (acetylcholine), hormonal (gastrin), and paracrine (histamine) stimuli.
 Inhibitory feedback regulation of acid output also involves neural (enterogastric reflex), hormonal
(enterogastrone), and paracrine (somatostatin) influences.
Obviously, these feedback signals allow chyme to enter the duodenum only as rapidly as it can be
processed by small intestine. For example, whenever the pH of the chyme in the duodenum falls below 5.5
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– 4.0, the duodenal inhibitory signals are immediately elicited, thus reducing or even blocking further
release of acidic stomach content into the duodenum until the duodenal chyme can be neutralized by
pancreatic and other secretion. Another example, hypo- or hypertonic fluids will elicit the duodenal
inhibitory signals to prevent too rapid flow of non-isotonic fluids into the small intestine, thereby
preventing marked changes in the body fluid osmolality.
This feedback inhibition of the gastric glands plays an important role in protecting the stomach
against excessively acid secretion, which would readily cause peptic ulceration. In addition to this protective
effect, the feedback mechanism is also important in maintaining optimal pH for function of the peptic
enzymes in the digestive process because whenever the pH rises above 2.5 - 3.5 gastrin begins to be
secreted again and more acid is secreted.
NB: Speed of delivery of nutrients from stomach to small intestine is as follow: CHO > protein > fat.
Peptic ulcer (gastric and duodenal ulcers): Basically an ulcer forms when the capacity of the gastric mucosa
to protect itself is overwhelmed by the existing level of gastric juice production. Gastric ulcers are
frequently due to reduced defensive capacity, whereas, duodenal ulcers are frequently the result of
increased exposure of the duodenal mucosa to gastric juice. Factors that may play a role in maintaining
mucosal resistance are adequate blood flow to the gastric mucosa, the production of mucus, cellular
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renewal, chemical factors (i.e. gastrin, prostaglandins, etc). Prostaglandins have been shown to dramatically
increase the resistance of cells to toxic conditions. NSAIDs (nonsteroidal anti-inflammatory drugs) work by
inhibiting prostaglandin synthesis. Chronic use of NSAID is a common cause of gastric ulceration. Recent
studies have shown that the major acquired factor responsible for both gastric and duodenal ulcers is the
bacterium Helicobacter pylori. H. pylori infections have high urease activity and metabolize urea into NH4+
which neutralizes the pH in the immediate area of the bacterial cells. This may be the major cause of H.
pylori cytotoxicity because NH4+ directly damages epithelial cells and weakens the mucosal barrier.
Treatment of ulcers with H2-receptor blockers or omeprazole in combination is very effective and has
essentially replaced surgical and other forms of treatment. However, the ulcer frequently returns when
treatment is discontinued unless the patient is also treated with oral antibiotics.
In addition to its effect by inhibiting prostaglandin synthesis, Aspirin, is nonionized and lipid soluble
in acid solutions, rapidly diffuses across this lipid layer, increasing mucosal permeability and damaging
epithelial cells. Gastric irritation and gastric bleeding caused by gastric irritation occur in a significant
number of persons who take aspirin on a regular basis. Alcohol, which also is lipid soluble, disrupts the
mucosal barrier; when aspirin and alcohol are taken in combination, as they often are, there is increased
risk of gastric irritation. Bile acids also attack the lipid components of the mucosal barrier and afford the
potential for gastric irritation when there is reflux of duodenal contents into the stomach.
The dumping syndrome: Is a condition that can develop after surgery to remove all or part of your stomach
or after surgery to bypass your stomach to help you lose weight. It occurs because food moves from
stomach into small bowel too quickly. Rapid emptying of the stomach can lead to low pH, elevated tonicity
in the duodenum, incomplete digestion of food by the pancreas, liver, and duodenal mucosa and in
incompletely emulsified fats in the duodenum. The increased rate of travel of food coupled with the
reduced rate of digestion can ultimately result in incomplete digestion and absorption, particularly of fat
and protein. The unabsorbed food retains osmotically water, which in conjunction with the increased rate
of intestinal transport, can lead to diarrhea and steatorrhea (fat in the feces). The by-products of the
bacterial metabolism of undigested food in the terminal ileum and colon can cause intestinal cramping, gas,
and bloating. Weakness, dizziness, and sweating, are due in part to hypoglycemia, underly the presentation
of dumping syndrome. Another cause of the symptoms is rapid entry of a hypertonic meal into the
intestine, which promotes the movement of an abundance of water into the gut, producing significant
hypovolemia and hypotension.
Gastric digestion and absorption: Carbohydrate digestion in the stomach depends on the action of salivary
amylase, which remains active until halted by the low pH in the stomach. Protein digestion occurs in the
stomach by about 10% and mediated by HCl and later by gastric pepsin. Fat digestion is minimal in the
stomach due to restriction of gastric lipase activity.
Very little absorption of nutrients takes place in the stomach. The only substances absorbed to any
appreciable extent are highly lipid-soluble substances (e.g., the non-ionized triglycerides of acetic,
propionic, and butyric acids). Aspirin at gastric pH is non-ionized and fat soluble, after absorption, it ionizes
intracellularly, damaging mucosal cells and ultimately producing bleeding. Ethanol is rapidly absorbed in
proportion to its concentration. Water moves in both directions across the mucosa. Water-soluble
substances including Na+, K+, glucose, and amino acids, are very poorly absorbed.
Vomiting (emesis): It is a forceful expulsion of contents of the stomach and upper intestinal tract through
the mouth. Vomiting is a reflex coordinated by the region in the brain stem medulla known as the vomiting
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center. From here, motor impulses that cause the actual vomiting are transmitted from the vomiting center
through parasympathetic vagal and sympathetic nerves to the lower tract and through motor spinal nerves
to the diaphragm and abdominal muscles. Stimuli that elicit vomiting include (figure 5.10):

Tactile (touch) stimulation of the back of the throat, which is one of the most potent stimuli.

Irritation or distension of the stomach and duodenum.

Stimulation of higher cortical centers by memory, feel, anticipation, sensory input (pain, smell,
sight), elevated intracranial pressure (thus, vomiting after a head injury is considered a bad sign; it
suggests swelling or bleeding within the cranial cavity).

Rotation or acceleration of the head producing dizziness, such as in motion sickness.

Body chemistry disturbances and chemical agents, including drugs or noxious substances that
initiate vomiting (that is, emetics) either by acting in the upper parts of the gastrointestinal tract or
by stimulating a specialized chemoreceptor trigger zone (CTZ, or postrema) next to the vomiting
center in the brain. Activation of this zone triggers the vomiting reflex. For example,
chemotherapeutic agents used in treating cancer often cause vomiting by acting on the
chemoreceptor trigger zone.
The importance of vomiting is to remove the ingested toxic substances before they can be
absorbed. Moreover, the nausea that usually accompanies vomiting may have the importance in
conditioning the individual to avoid the future ingestion of food containing the same toxic substances.
Vomiting begins with:
[1] Vomiting is usually preceded by increased salivation, sweating increased heart rate, pallor,
and feeling of nausea, all are characteristic of a general discharge of the sympathetic nervous system in
response to stress. Vomiting is often proceeded by retching (is the reverse movement (peristalsis) of the
stomach and esophagus without vomiting).
[2] Deep inspiration, closure of the glottis, and elevation of the soft palate.
[3] The abdominal and thoracic muscles contract, raising the abdominal pressure which is
transmitted to the contents of the stomach. In addition, the upper portion of small intestine contracts
(retro peristalsis) and tends to force some of the intestinal contents back into the stomach. Thus some bile
may be present in the vomitus.
[4] The lower esophageal sphincter relaxes, and the high abdominal pressure forces the contents
of the stomach into the esophagus.
Excessive vomiting can
lead to large losses of fluid and
salts which normally would be
absorbed in the small intestine.
This can result in severe
dehydration, upset the salt
balance of the body and produce
circulatory problems due to
decrease in plasma volume. The
loss of acid results in a low of
body acidity.
Figure 5.10: Main neurotransmitters involved in vomiting center
regulation. CTZ = chemoreceptor trigger zone
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Small intestine: The small intestine is the major site of digestion and absorption of carbohydrates, proteins,
and fats in the GIT. The small intestine has three parts: the duodenum, the jejunum, and the ileum.
Although the small intestine is approximately 5 m long, it has an absorptive area of over 250 m 2. Its large
surface area is created by numerous folds of the intestinal mucosa (valvulae conniventes or plica circulares),
by densely packed finger-like projections of the mucosa called villi, which line the entire mucosal surface,
and by microvilli, which protrude from the
surface of the intestinal epithelial cells
(enterocytes). The microvilli give the
intestinal mucosa its characteristics brush
border appearance (figure 5.11).
The life span of a typical epithelial cell
varies from two to three days in the
esophagus to six days in the large intestine.
The divisions of epithelial stem cells
continuously renew the lining of the entire
digestive tract. These divisions normally
keep pace with the rates of cell destruction
and loss at epithelial surfaces. This high
rate of cell division explains why radiation
and anticancer drugs that inhibit mitosis
have drastic effects on the digestive tract.
Lost epithelial cells are no longer replaced.
The cumulative damage to the epithelial
lining quickly leads to problems in
absorbing nutrients. In addition, the
exposure of the lamina propria to digestive
enzymes can cause internal bleeding and
other serious problems.
Though peristalsis in the small
intestine is normally very weak, intense
irritation of the intestinal mucosa, as occur
in some sever case of infectious diarrhea,
can cause both very powerful and rapid
peristalsis called the peristaltic rush. This is
initiated mainly by vagovagal nervous
reflexes to the brain stem and back again
to the gut. The powerful peristaltic
contractions sweep the contents of the
intestine into the colon and thereby
relieving the small intestine of either
irritative chyme or excessive distension.
Function of the ileocecal valve: The
principal function of the ileocecal valve is
Figure 5.11: Histological cross section of small intestinal
mucosa.
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to prevent backflow of fecal content from the colon into the small intestine. The wall of the ileum for
several centimeters immediately preceding the ileocecal valve has a thickened muscular coat called
ileocecal sphincter which normally remains mildly constricted.
 Following meal, gastroileal reflex intensifies peristalsis, and the hormone, gastrin, which is liberated
from the stomach mucosa in response to food in the stomach, has a relaxant effect on the ileocecal
sphincter, both of them cause an increase emptying.
 On the other hand, when the cecum is distended, the degree of contraction of the ileocecal sphincter is
intensified while ileal peristalsis is inhibited, which greatly delays emptying of additional chyme from the
ileum. Also, any irritant in the cecum delays emptying. These reflexes from the cecum to the ileocecal
sphincter and ileum are mediated both by way of the enteric nervous system and through vagovagal
reflexes.
Pancreatic secretions: Approximately 1200 to 1500 ml of clear pancreatic juice is produced daily (about pH
8). Pancreatic juice is secreted mainly in response to the presence of chyme in the upper portions of the
small intestine and the characteristics of the pancreatic juice are determined to some extent by the types of
food in the chyme. Pancreatic juice contains enzymes for digesting all three major types of food proteins,
carbohydrates, and fats. It also contains large quantities of bicarbonate ions which play an important role in
neutralizing the acid chyme emptied by the stomach into the duodenum. Pancreatic juice is isotonic and
with the same Na+ and K+ concentrations and much lower Cl- concentration than plasma. The digestive
enzymes of the pancreas are:



The digestive enzymes for proteins (proteolytic enzymes) which are trypsin, chymotrypsin,
carboxypolypeptidase, ribonuclease, and
deoxyribonuclease. By far the most
abundant of these is trypsin (figure 5.13).
The digestive enzyme for carbohydrates
is pancreatic amylase which hydrolyzes
starches, glycogen and most other
carbohydrates except cellulose to form
disaccharides and a few trisaccharides.
The digestive enzyme for fat which is
pancreatic lipase that is capable of
hydrolyzing neutral fat into fatty acids
and monoglycerides, cholesterol esterase
which cause hydrolysis of cholesterol
esters, and phospholipase which splits
fatty acids from phospholipids.
Pancreas protects itself from autodigestion by
proteolytic enzymes by the following ways:
[1] When synthesized in the pancreatic cells, the
proteolytic enzymes are in the inactive forms
(inactive
zymogens),
trypsinogen,
chymotrypsinogen,
and
procarboxypolypeptidase,
which
are
all
enzymatically inactive (figure 5.13).
Figure 5.13: Mechanisms of activation of pancreatic
proteolytic enzymes.
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Mustansiriyah College of Medicine
[2] These become activated only by trypsin.
[3] Trypsin is activated only after it is secreted into the intestinal tract. Trypsinogen is activated by an
enzyme called enteropeptidase (enterokinase) which is secreted by the intestinal mucosa when chyme
comes in contact with the mucosa. Also, trypsinogen can be autocatalytically activated by trypsin that is
already been formed. Chymotrypsinogen is activated by trypsin to form chymotrypsin, and
procarboxypolypeptidase is activated in a similar manner. It is important that the proteolytic enzymes of
the pancreatic juice not become activated until they have been secreted into the intestine which otherwise
would digest the pancreas itself.
[4] The same cells that secrete the proteolytic enzymes into the acini of the pancreas secrete
simultaneously another substance called trypsin inhibitor. This substance is stored in the cytoplasm of the
glandular cells surrounding the enzyme granules and it prevents activation of trypsin both inside the
secretory cells and in the acini and ducts of the pancreas.
However, when the pancreas becomes severely damaged or when a duct becomes blocked, large
quantities of pancreatic secretion become pooled in the damaged areas of the pancreas. Under these
conditions, the effect of trypsin inhibitor is sometimes overwhelmed, in which case the pancreatic
secretions rapidly become activated and digest the pancreas giving rise to the condition called acute
pancreatitis.
The enzymes of the pancreatic juice are secreted entirely by the acini of the pancreatic glands. On
the other hand, two other important components of the pancreatic juice, bicarbonate ions and water, are
secreted in large amounts mainly by the epithelial cells of the ductules leading from the acini (figure 5.14).
The alkaline ions or the pancreatic juice serves to neutralize acid emptied into the duodenum from the
stomach. The secretion of bicarbonate ions by the pancreas is an active process. The mechanism of
bicarbonate secretion is similar to the process of HCI secretion by the stomach, except that the events on
the two sides of the cells are reversed. Because the amount of bicarbonate secreted by the pancreas is
reflexly regulated by the amount of acid entering the duodenum from the stomach, the amount of
bicarbonate secreted by the pancreas is normally about equal to the amount of acid secreted by the
stomach. This also means that the bicarbonate released into the blood by the stomach is normally equal to
the amount of acid released into the blood by the
pancreas. When the alkaline blood leaving the
stomach mixes with the acidified blood from the
pancreas, the overall result is no change in the
acidity of the blood returning to the heart.
However, a loss of large quantities of
bicarbonate ions from the intestinal tract during
periods of prolonged diarrhea leads to a net
accumulation of acid in the blood, just as, loss of
acid from the stomach by vomiting leads to a net
alkalinization of the blood.
Figure 5.14: Mechanism of pancreatic ductule cell
secretion of electrolytes.
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Regulation of pancreatic secretion: Pancreatic secretion is regulated by both nervous and hormonal
mechanisms. However, hormonal regulation is by far the more important. Like gastric secretion,
pancreatic secretion is divided into the following three phases:
[1] Cephalic phase: The thought, sight, smell, or taste of food produces the cephalic phase of
pancreatic secretion via vagal stimulation. It is scanty and rich in enzymes.
[2] Gastric phase: Pancreatic secretion is slightly enhanced during the gastric phase by:
[A] Distention of the antrum and the body of the stomach, which initiates a vagovagal reflex resulting in a
 low volume of pancreatic secretion containing both bicarbonate ions and enzymes.
[B] Food breakdown digestion products (primarily amino acids and peptides) can stimulate pancreatic
secretions because of their ability to cause the G cells of the antrum to release gastrin. Gastrin produces a
 low-volume, high-enzyme pancreatic secretion.
[3] Intestinal phase: The major stimulants for pancreatic secretion are the hormone CCK and
secretin. They are released from endocrine cells in the duodenum and jejunum during the intestinal phase
of pancreatic secretion in response to the entrance of chyme into the small intestine.
CCK, in addition to its effect on the gallbladder, is a potent stimulant of pancreatic enzyme
secretion. Protein and fat are the major stimuli for CCK secretion. CCK induces secretion of enzyme-rich
pancreatic juice (figure 5.15).
Secretin stimulates the HCO3- secretion. Low pH (< 4.5), caused by the presence of gastric acid (HCl)
in the intestine, is a potent stimulus for the release of secretin. Secretin causes secretion of HCO3−-rich
pancreatic juice (figure 5.16).
Secretin is very important for
two reasons:
[A] Neutralization of the acidic
chyme: Secretin is released
from the mucosa of small
intestine when the pH of the
duodenal contents falls below
4.5 and its release increases
very greatly as the pH falls to
3.0. This immediately causes
large quantities of pancreatic
juice containing abundant
amounts
of
sodium
bicarbonate to be secreted. In
this way, the acid contents
emptied into the duodenum
from the stomach become
neutralized, and peptic activity
of the gastric juice is
immediately blocked. Since the
mucosa of the small intestine
cannot withstand the digestive
action of acid gastric juice. This
is a highly important and even Figure 5.15: The control of pancreatic bicarbonate and digestive
enzyme secretions.
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Mustansiriyah College of Medicine
essential protective mechanism against the development of duodenal ulcers.
[B] Provides a proper alkaline medium for the action of pancreatic enzymes.
Because CCK and secretin are potentiators of each other’s action, small concentrations of CCK and
secretin together can produce significant amounts of pancreatic bicarbonate ions and enzymes secretions,
while either one alone would have little or no effect.
Pancreatitis and Pancreatic Cancer: Pancreatitis is an inflammation of the pancreas that occurs quite
commonly. Pancreatitis involves the release of pancreatic enzymes within the pancreas itself, which digest
pancreatic tissue. It can result from alcoholism, the use of certain drugs, pancreatic duct blockage, cystic
fibrosis, viral infection, or pancreatic cancer. Symptoms can range from mild abdominal pain to systemic
shock and coma. Cancer of the pancreas can obstruct the pancreatic and common hepatic ducts, resulting
in jaundice. Pancreatic cancer may not be detected until the tumor has become fairly large, and it can
become so large as to block off the pyloric region of the stomach.
Bile secretion: Bile is a yellow-green, alkaline solution containing bile salts, bile pigments, cholesterol,
triglycerides, phospholipids (lecithin and others), and a variety of electrolytes. Bile is required for the
digestion and absorption of fats and for the excretion of water-insoluble substances such as cholesterol (the
only route), bilirubin, and some drugs. Bile is formed by liver epithelium (hepatocytes) and by epithelial
cells lining the bile ducts (ductal cells). Between 250 - 1200 ml of bile is formed daily which is normally
stored in 30 - 60 ml volume of gallbladder after being concentrated as much as fivefold up to 18 fold by
continual absorption of water, sodium, chloride, and most other small electrolytes through the mucosa of
gallbladder by an active transport of sodium through the gallbladder epithelium. The concentrated bile
constituents are:
 Bile salts (11%).
 Bile pigments (1%).
 Lipids (cholesterol 0.5%, lecithin 3%).
 Water and electrolytes (84%).
The bile electrolyte concentrations are similar to those of plasma except more HCO3- and less Cl- (pH 7.59.0).
[1] The bile salts: The normal rate of bile salt synthesis is 0.2 – 0.4 g/day. The precursor of bile salts is
cholesterol which is converted by liver to cholic acid or chenodeoxycholic acid. These acids then combined
principally with amino acid glycine and to a lesser extent with taurine to form glyco- and tauro- conjugated
bile acids. These bile acids form sodium and potassium salts in the alkaline hepatic bile. Bile salts have the
propensity to form micelles, which are small spherical globules composed of 20 - 40 molecules of bile salt.
Each bile salt molecule is composed of a sterol nucleus which is highly fat soluble (in which lipids are
dissolved), and a polar group that is highly water soluble. This aggregation causes the polar groups to
project outward to cover the surface of micelle (figure 5.16). Since these polar groups are electrically
charged, they allow the entire micelle globule to become dissolved in the water of the digestive fluids.
These bile salts have two important actions in the intestinal tract:
[A] Break the fat globules into minute sizes: Bile salts have a detergent action (or emulsification action)
on the fat particles in the food which decreases the surface tension of the particles and allows the agitation
in the intestinal tract to break the fat globules into minute sizes (figure 5.17).
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Mustansiriyah College of Medicine
[B] Making lipid droplets highly water
soluble: Bile salts help in the absorption of
lipids and other fat-soluble substances from
the intestinal tract by forming minute
complexes with micelles and become highly
water soluble. The lipids are ferried in this
form to the mucosa where they are then
absorbed. Without the presence of bile salts Figure 5.16: Micelle globule.
in the intestinal tract, up to 40% of the lipids
are lost into the stool. Also, when fats are not absorbed adequately, the fat-soluble vitamins A, D, K, and E
are not absorbed satisfactorily.
Approximately 94% of the bile salts are reabsorbed by an active transport process (Na-bile salt
cotransport) through the intestinal mucosa in the distal ileum. They enter the portal blood and pass to the
liver. On reaching the liver the bile salts are reabsorbed almost totally on the first passage through the
venous sinusoids into the hepatic cells and then resecreted into the bile. The small quantities of bile salts
lost into the feces are replaced by new amounts formed continually by the liver cells. The recirculation of
the bile salts is called the enterohepatic circulation. Removal of the terminal ileum can lead to diarrhea and
steathorrea. Bile salts are necessary for adequate digestion and absorption of fat. In the absence of the
terminal ileum there will be an increase in the amounts of bile acids and fatty acids delivered to the colon.
Fats and bile salts in the colon increase the water content of the feces by promoting the influx (secretion) of
water into the lumen of the colon.
[2] The bile pigments (mainly bilirubin and biliverdin) which are
responsible for the golden yellow color of bile and they are formed as a
major end product of Hb degradation. Bilirubin is fat soluble, and
therefore, highly soluble in all cell membranes and is also very toxic.
Therefore, its excretion in the bile is one of the very important functions
of the liver.
The bilirubin released into the plasma is immediately combined
very strongly with the plasma albumin and is transported in this
combination throughout the blood and interstitial fluids. This type of
bilirubin is called “unconjugated bilirubin” or “indirect bilirubin”. This
type of bilirubin cannot be excreted by the kidneys because it is
insoluble in water and is combined with a protein albumin. Because it is
fat soluble, however, it can enter the brain or the subcutaneous adipose
tissues, especially if high serum level exist. In premature infant, lack of
subcutaneous fat exposes them to greater danger of unconjugated
bilirubin entering the nervous system where it deposited in the basal
ganglia leading to a condition called kernicterus. It should be realized,
however, that only unconjugated bilirubin which is not bound to serum
albumin is free to enter the central nervous system and other tissues,
and the risks of hyperbilirubinaemia are therefore influenced by the
bilirubin binding capacity of the serum albumin. Therefore, kernicterus
consequent upon hyperbilirubinaemia will only develop when the serum
Figure 5.17: Arrangement of
micelles over the surface of
lipid droplet.
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albumin is unable to bind further unconjugated bilirubin.
Within hours, the unconjugated bilirubin is absorbed through the hepatic cell membrane. In this
process being released from the plasma albumin but almost instantly is combined with one of two proteins
(called Y and Z proteins) inside the hepatic cells that trap the bilirubin inside the cells.
Conjugated bilirubin is water-soluble and so readily excreted in the urine or bile, and as it is not
soluble in fat, it is not toxic to the nervous system. A small portion of the conjugated bilirubin formed by the
hepatic cells returns to the plasma. This causes a small portion of the bilirubin in the extracelluler fluids
always to be of the conjugated type.
Once in the intestine, about one half of the bilirubin is converted by bacterial action into the
substance urobilinogen which is responsible for the brown color of stool. Some of the urobilinogen is
reabsorbed through the intestinal mucosa into the blood. Most of this is re-excreted by the liver back into
the gut (enterohepatic circulation), but about 5% is excreted by the kidneys into the urine. After exposure
to air in the urine, the urobilinogen becomes oxidized to urobilin, or in the faces it becomes altered and
oxidized to form stercobilin.
Jaundice: It means a yellowish tint to the body tissues, including yellowness of the skin and also the mucous
membrane and the deep tissues. The usual cause of jaundice is large quantities of bilirubin in the
extracellular fluids either conjugated or unconjugated bilirubin.
Jaundice may result from: [1] Excess production of bilirubin caused by excessive RBC destruction as in
haemolytic anaemia. [2] Inability of hepatocytes to conjugate the plasma free bilirubin as in parenchymal
liver diseases. [3] Obstruction of the bile ducts or liver cells preventing the secretion of conjugated bilirubin.
[3] Cholesterol, phospholipids (primarily lecithin), and fatty acids. Cholesterol is almost insoluble in
water, but the bile salts and lecithin in bile combine physically with cholesterol to form ultramicroscopic
micelles that are soluble in water.
Regulation of gallbladder emptying (contraction): Two basic conditions are necessary for the gallbladder to
empty, the sphincter of Oddi must relax to allow bile to flow from the common bile duct into the
duodenum, and the gallbladder itself must contract to provide the force required to move the bile along the
common bile duct. After a meal both these effects take place in the following manner:
[1] the fat and also partially digested protein in the food entering the small intestine cause the release
of the hormone CCK from the mucosa of the upper region of small intestine which in turn is absorbed into
the blood and on passing to the gallbladder, causes contraction of the gallbladder muscle. This provides the
pressure that forces bile toward the duodenum. CCK is the major stimulus for gallbladder contraction and
sphincter of Oddi relaxation.
[2] Vagal stimulation associated with the cephalic phase of gastric secretion or via a vagovagal reflex
during the gastric phase of digestion, causing contraction of the gallbladder.
Control of biliary secretion from the liver cells: The quantity of bile secreted by the liver is highly
dependent on:
[1] The availability of bile salts: The greater the quantity of bile salts in the enterohepatic
circulation, the greater the rate of bile secretion.
[2] Secretin also increases bile secretion. However, this increase in secretion represents mainly
secretion of a bicarbonate rich watery solution by the epithelial cells of the liver ductules and ducts and
not increased secretion of bile acids by the liver parenchymal cells. The bicarbonate in turn passes into the
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small intestine and joins the bicarbonate from the pancreas in neutralizing the acid from the stomach.
Because bile salts are required for proper digestion and absorption of fats, any condition that
disrupts the enterohepatic circulation as in ileal resection or small intestinal diseases leads to a decreased
bile acid pool and malabsorption of fat and fat-soluble vitamins. The clinical manifestations of such
conditions are steatorrhoea and nutrition deficiency. An increase in fecal losses of bile salts results in
watery diarrhea, since bile salts inhibit water and Na+ absorption in the colon.
Bile, and not the gallbladder, is essential to digestion. After removal of the gallbladder, bile empties
slowly but continuously into the intestine, allowing digestion of fats sufficient to maintain good health and
nutrition. Only high-fat meals need to be avoided.
Gallstones: Cholesterol, secreted by the liver, may precipitate in the gallbladder to produce
gallstones. Cholesterol is not soluble in water and is ordinarily kept in solution by bile salts. Gallstones can
form when there is excess cholesterol in the bile due to a high-cholesterol diet or when cholesterol is overly
concentrated in the gallbladder. Occasionally, a gallstone passes out of the gallbladder and enters the cystic
duct, blocking the release of bile. Such a condition interferes with normal digestion, and the gallstone often
must be removed surgically. If the gallstone moves far enough down the duct, it can also block the
pancreatic duct, resulting in pancreatitis.
Regulatory hormones in the GIT:
 Gastrin: It is released from G cells of the antral mucosa. The functions of gastrin are:
1. ↑ Gastric H+ secretion,
2. Stimulates growth of gastric mucosa.
3. Increases antral muscle mobility and promotes
stomach contractions.
4. Strengthens antral contractions against the pylorus,
and relaxes the pyloric sphincter, which increases the
rate of gastric emptying.
5. Plays a role in the relaxation of the ileocecal valve.
6. Induces pancreatic secretions and gallbladder
emptying.
7. May impact lower esophageal sphincter (LES) tone,
causing it to contract, although pentagastrin, rather
than endogenous gastrin, may be the cause.
8. Gastrin contributes to the gastrocolic reflex.
Its release is stimulated by:
A. The antral distension.
B. The presence of protein digesting products in
the antrum (the most potent are phenylalanine
and tryptophan), coffee, and alcohol.
C. Vagal stimulation via GRP (bombesin).
Its release is inhibited by:
A. High H+ concentration in the stomach (pH < 3).
B. Somatostatin.

CCK: It is released from I cells of the mucosa of
Figure 5.17A: Sites of GI hormone release.
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duodenum and jejunum. The functions of gastrin are:
1. Stimulates contraction of gallbladder and relaxation of sphincter of Oddi.
2. ↑ Pancreatic enzyme and HCO3– secretion.
3. ↑ Growth of exocrine pancreas/gallbladder.
4. Inhibits gastric emptying
5. It stimulates gallbladder contraction, and intestinal motility, while inhibits gastric emptying.
Its release is stimulated by:
A. The presence of fat digesting products in the small intestine (triglycerides do not stimulate the
release of CCK because they cannot cross intestinal cell membranes).
B. The presence of protein digesting products in the small intestine.
 Secretin: It is released from S cells of the mucosa of the duodenum and jejunum.
1. Inhibits gastric emptying.
2. ↑ Pancreatic HCO3–, secretion,
3. ↑ Biliary HCO3– secretion,
4. ↓ Gastric H+ secretion
Its release is stimulated by the H+ in the lumen of the duodenum.

Motilin: It stimulates migrating motor complex.
 Glucagon-Like Peptide I: Glucagon-like peptide 1 belongs to a family of hormones called the
incretins, so-called because they enhance the secretion of insulin. Cells found in the lining of the small
intestine (called L-cells) are the major source of glucagon-like peptide 1. Food is the main stimulus of
glucagon-like peptide 1 release, with increased hormone levels detectable after 10 minutes of starting to
eat and remaining raised in the blood circulation for several hours after that. The hormone somatostatin
holds back the production of glucagon-like peptide 1.
1. Glucagon-like peptide 1 increases the feeling of fullness during and between meals by acting on appetite
centers in the brain and by slowing the emptying of the stomach.
2. It slows gastric emptying.
3. Enhances the secretion of insulin
 Glucose-dependent insulinotropic peptide (GIP) also called Gastric inhibitory polypeptide (GIP): It
is released from duodenum and jejunum. The stimulus for secretion is the fatty acids and amino acids and
the presence of oral glucose load. Thus, oral glucose is more effective than intravenous glucose in causing
insulin release and, therefore, glucose utilization. GIP is the only GI hormone that is released in response to
the three main food groups, i.e. fat, protein, and carbohydrate.
1. ↑ Insulin secretion
2. ↓ Gastric H+ secretion
3. Inhibits the gastric and GI motility
 Somatostatin: is secreted by cells throughout the GI tract in response to H+ in the lumen. Its
secretion is inhibited by vagal stimulation. Somatostatin is also released by beta-adrenergic agents. This
observation might explain the inhibition of gastric secretion by anger or excitement. The release of
somatostatin is inhibited by acetylcholine. That makes sense because vagal activity begins even before the
food has been ingested. At that stage, gastric secretion needs to be initiated without a braking influence.
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1. Inhibits the release of all GI hormones.
2. Inhibits gastric H+ secretion.
 Histamine: is secreted by mast cells of the gastric mucosa. It increases gastric H+ secretion directly
and by potentiating the effects of gastrin and vagal stimulation.
 Neurocrines: Are synthesized in neurons of the GI tract, moved by axonal transport down the axon,
and released by action potentials in the nerves. Neurocrines then diffuse across the synaptic cleft to a
target cell. The GI neurocrines are vasoactive intestinal peptide (VIP), GRP (bombesin), and enkephalins.
A. VIP: contains 28 amino acids and is homologous to secretin. It is released from neurons in the mucosa
and smooth muscle of the GI tract.
1. Produces relaxation of GI smooth muscle, including the lower esophageal sphincter.
2. Stimulates pancreatic HCO3– secretion and inhibits gastric H+ secretion. In these actions, it resembles
secretin.
 B. GRP (bombesin): is released from vagus nerves that innervate the G cells. It stimulates gastrin
release from G cells.
 C. Enkephalins (met-enkephalin and leu-enkephalin) are secreted from nerves in the mucosa and
smooth muscle of the GI tract.
1. Stimulate contraction of GI smooth muscle, particularly the lower esophageal, pyloric, and ileocecal
sphincters.
2. Inhibit intestinal secretion of fluid and electrolytes. This action forms the basis for the usefulness of
opiates in the treatment of diarrhea.
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Digestion & Absorption:
Digestion of carbohydrates: Only three major sources of carbohydrates exist in the normal human diet.
These are sucrose (disaccharide) also known as cane sugar or table sugar, lactose (disaccharide) in milk, and
starches (polysaccharides) present in almost all non animal foods especially in the grains. Other
carbohydrates ingested to a slight extent are glycogen, alcohol, lactic acid, pyruvic acid, pectins, dextrins,
and others.
Digestion of carbohydrates in mouth: Because the food remains only for short time in the mouth,
only 3 -5% of all starches that have been eaten will have become hydrolyzed (digested). Enzyme α-amylase
(ptyalin) hydrolyzes starches into the disaccharide maltose and other small polymers of glucose. Starches
(polysaccharide)  Maltose (disaccharide) + Glucose
Digestion of carbohydrates in the stomach: In the stomach the action of salivary ptyalin can
continue for as long as an hour after the food has entered the stomach until the contents of the fundus are
mixed with the stomach secretions. Then the activity of the salivary amylase is blocked by the acid of the
gastric secretions. By this time about 30 - 40% of the starches will have been hydrolyzed mainly to maltose.
Pancreatic digestion of carbohydrates in the small intestine: Pancreatic secretion contains large
quantities of amylase that continue splitting starches into maltose and other small polymers of glucose. By
now, the starches are almost totally converted into maltose and other very small glucose polymers before
they have passed beyond the jejunum.
The small intestine surface digestion and hydrolysis of disaccharides and small glucose
polymers: The brush border of epithelial cells lining the small intestine contain enzymes lactase, sucrase,
and maltase, which are capable of splitting the disaccharides lactose, sucrose, and maltose respectively,
into their constituent monosaccharides when the disaccharides come in contact with this border. The
digested products, the monosaccharides, are then immediately absorbed into the portal blood.
 Lactose (disaccharide)  Galactose + Glucose.
 Sucrose (disaccharide)  Fructose + Glucose.
 Maltose (disaccharide)  Glucose + Glucose.
Absorption of carbohydrates: All carbohydrates are absorbed in the form of monosaccharides, only a small
fraction of a percent being absorbed as disaccharides and almost none as larger carbohydrate compounds.
[1] Glucose and galactose are transported from the small intestinal lumen into the cells by Na+-glucose or
Na+-galactose secondary active cotransport in the luminal brush border of the membrane. When the
intracellular glucose and galactose concentration increased to a higher level than normal, they will diffuse
by facilitated diffusion through the basolateral membrane of the epithelial cell into the extracellular fluid
and then to the blood. The Na+-K+ pump in the basolateral membrane keeps the intracellular Na +
concentration low, thus maintaining the Na+ gradient across the luminal membrane.
[2] Fructose is transported to small intestinal enterocyte by facilitated diffusion. Within the enterocytes, it
is mainly converted into glucose inside the epithelial cell before entering the portal blood.

Deficiency of one or more of these disaccharidase leads to diarrhoea, bloating, and flatulence
after ingestion of sugar. The diarrhea is due to the increased number of osmotically active
oligosaccharides molecules that remain in the intestinal lumen causing the volume of the intestinal
contents to increase. The bloating and flatulence are due to the production of gas (CO 2 and H2) from
disaccharide residues which are metabolized by intestinal flora in the lower small intestine and
colon. Lactose intolerance is the most common cause of carbohydrate malabsorption. It results
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Mustansiriyah College of Medicine
from the inability of the small intestinal cells to produce lactase. In infants, the diarrhea-produced
dehydration can be life threatening. This disorder is primarily hereditary, affecting 5-15% of
Europians and 80-90% of Asians and Africans.
Digestion of fat: By far the most common fats of the diet are the neutral fats (triglycerides). In the usual
diet there are also small quantities of phospholipids, cholesterol, and cholesterol ester. Although the serous
glands of the tongue secrete lingual lipase, very little, if any, lipid digestion occurs in the mouth or stomach.
Essentially all fat digestion occurs in the small intestine as follows:
[1] Emulsification of fat by bile acids: The first step in fat digestion is to break the fat globules into
small sizes so that the water soluble digestive enzymes can act on the globule surfaces. This process is
called emulsification of the fat and it is achieved under the influence of bile salts and aided by lecithin in the
bile. Both decrease the interfacial tension of the fat globules which result in breaking up these globules into
many minute particles when they are agitated. This results in an increase in surface area of fat globules as
much as 1000 fold.
[2] Digestion of fats by pancreatic lipases: It is by far the most important enzymes (lipases,
cholesterol estrase, and phospholipase A2) for the digestion of fat. However, the epithelial cells of the small
intestine also contain a minute quantity of lipase known as enteric lipase. Both of these act alike to cause
hydrolysis of fat.
Most of the triglycerides of the diet are spilt into free fatty acids and monoglycerides. However,
small portions are not digested at all or remain in the diglyceride state.
[3] Transportation of fats to the brush border of the epithelial cells: During triglyceride digestion,
as rapidly as the monoglycerides and free fatty acids are formed they become dissolved in the fatty portion
of the micelles. The bile salt micelles act as a transport medium to carry the monoglycerides and the free
fatty acids to the brush border of the epithelial cells, which would otherwise be relatively insoluble to the
brush border of the epithelial cells. There, the monoglycerides and free fatty acids are absorbed. On
delivery of these substances to the brush border, the bile salts are again released back into the chyme to be
used again and again for this ferrying process. However, few of the monoglycerides are further digested
into glycerol and fatty acids by an epithelial cell, lipase.

Both the cholesterol esters and phospholipids are hydrolyzed by lipases (cholesterol esterase and
phospholipase A2) in the pancreatic secretion that free the fatty acids. The bile salt micelles play identical
role in ferrying free cholesterol and phospholipids as that with monoglycerides and free fatty acids. Indeed,
this role of the bile salt micelles is absolutely essential to absorption of cholesterol and no cholesterol
absorption can take place without bile salts.

Some of the triglycerides can be digested and absorbed even in the absence of bile salts. This is
because short- and medium chain triglycerides are more water soluble and they diffuse through water
layer adjacent to the brush border of the enterocytes and are absorbed intact. Once inside the cell, they are
hydrolyzed by esterase. MCTs are not utilized for re-synthesis of triglycerides and therefore are not
packaged into chylomicrons.
Absorption of fats (figure 5.18): As micelles come in contact with the brush border microvilli, both the
monoglycerides and the fatty acids immediately diffuse through the epithelial membrane, because they are
equally as soluble in this membranes as in the micelles. As these fat products leave the micelles and are
absorbed across the epithelial cell membranes, the micelles can pick up more monoglycerides and free fatty
acids, which have been produced from digestion of other triglyceride molecules in the fat emulsion. Bile
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Mustansiriyah College of Medicine
salts continuously repeat
their
fat-solubilizing
function down the length
of the small intestine
until all fat is absorbed.
Then the bile salts
themselves
are
reabsorbed
in
the
terminal ileum by a Na+dependent
active
transport process.
Although
Figure 5.18: Absorption of fats.
triglycerides,
like
monoglycerides and fatty acids, are highly soluble in the lipid membrane of the epithelial cell, however,
only small quantities of these are normally absorbed because the bile acid micelles will not dissolve either
triglycerides or diglycerides and therefore will not ferry them to the epithelial membrane.
After entering the epithelial cell, the fatty acids and monoglycerides, are taken up by the smooth
endoplasmic reticulum, and here they are recombined to form new triglycerides. Once formed, the
triglycerides aggregate within the endoplasmic reticulum into globules along with absorbed and the newly
synthesized cholesterol and phospholipids. The phospholipids arrange themselves in these globules with
the fatty portions of phospholipids toward the center and the polar portions located on the surface. This
provides an electrically charged surface that makes these globules miscible (water soluble) with the fluids of
the cell. In addition, small amounts of β-lipoprotein, also synthesized by the endoplasmic reticulum, coat
part of the surface of each globule.
In this form the globule diffuse to the side of the epithelial cell and is excreted by the process of
cellular exocytosis into the space between the cells, from these it passes into the lymph in the central
lacteal of the villus. These globules are then called chylomicrons. Chylomicrons propelled along with the
lymph upward through the thoracic duct to be emptied into the great veins of the neck. Small quantities of
short chain fatty acid are absorbed directly into the portal blood rather than being converted into
triglyceride and absorbed into the lymphatics. This is because these short chain fatty acids are more water
soluble and are not reconverted into triglycerides by the endoplasmic reticulum. This allows direct diffusion
of these fatty acids from the epithelial cells into the capillary blood of the villus.
Lipid malabsorption is much more common than carbohydrate or protein malabsorption. It is usually results
from one of the following two conditions: [1] the pancreas does not secrete sufficient quantities of lipase
(as in pancreatitis). [2] The liver does not secrete sufficient quantities of bile (as in liver parenchymal
diseases).
Digestion of proteins: The dietary proteins are derived almost entirely from meats and vegetables. These
proteins in turn are formed of long chain of amino acids bound together by peptide linkages.
Digestion of proteins in the stomach: For pepsin to cause any digestive action on protein, the
stomach juices must be acidic (pH 2 – 3). Pepsin digestion represents 10—30% of the total protein
digestion. This splitting of proteins is a process of hydrolysis occurring at the peptide linkages between the
amino acids.
Digestion of proteins by pancreatic secretions: Most protein digestion occurs principally in the
small intestine under the influence of the proteolytic enzymes of the pancreatic secretion. When the partial
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breakdown proteins leave the stomach, they are attacked by the pancreatic enzymes. Trypsin and
chymotrypsin can split protein molecules into small polypeptides, carboxypolypeptidase then leaves
individual amino acids from the carboxyl ends of the polypeptides.
Digestion of peptides by epithelial peptidases of small intestine: The brush border of the small
intestine contains several different enzymes for hydrolyzing the final peptides linkages of the remaining
dipeptides and other small polypeptides as they come in contact with the epithelium of the villi. The
enzymes responsible are aminopolypeptidase and several dipeptidase. When the food has been properly
masticated and is not eaten in too large a quantity at any one time, about 98% of all the proteins finally
become either amino acids or dipeptides that can be absorbed into the blood.
Absorption of amino acids:
[1] Most proteins are absorbed in the form of amino acids, dipeptides and even tripeptides by Na+amino acid cotransport system in the brush border of the epithelial cell. Once inside the enterocytes,
intracellular peptidases digest some of the polypeptides to
amino acid. The amino acids are then transported from cell
to blood by facilitated diffusion.
[2] Larger molecules, especially in newborn infant, are
engulfed by the plasma membrane of the epithelial cell
(endocytosis), move through the cytoplasm, and are
released on the opposite side of the cell by the reverse
process (exocytosis). The capacity to absorb intact proteins
is greater in a newborn infant and antibodies secreted in
the mother’s milk may be absorbed by the infant in this
manner, providing a short term passive immunity until the
child begins to produce its own’ antibodies. Essentially no
free amino acids can be found in the intestine during
digestion because they are absorbed as rapidly as they are
formed.
Inadequate absorption of proteins due to lack of
trypsin is a common consequence of pancreatic diseases.
Absorption of Na+, Cl- and K+ ions: Electrolytes and H2O
may cross intestinal epithelial cells by either cellular or
paracellular (between cells) routes. Tight junctions attach
the epithelial cells to one another at the luminal
membrane. The permeability of the tight junctions varies
with the type of epithelium. A “tight” (impermeable)
epithelium is the colon. “Leaky” (permeable) epithelia are
the small intestine and gallbladder. The major ions that are
Figure 5.19: Absorption of NaCl, K, HCO3-,
absorbed in the small intestine and proximal colon are Na+,
and water from small intestine and
K+, and Cl-, (figure 5.19): This this achieved primarily by the
+ +
proximal colon.
Na -K -ATPase pumps located at the basolateral membrane
of the enterocytes. This pump creates low intracellular concentration of Na +. This will leads to:
[1] Na+ enters the enterocyte in three ways:
 By passive diffusion down its electrochemical gradient.
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

By Na+- Cl- co-transport system (major mechanism).
By a Na+-glucose, Na+-amino acid, Na+-(di- or tri-) peptide or Na+- water-soluble vitamins (except B12
and folic acid) co-transport system (Na+ enhances glucose absorption in the Glucose-saline
solutions).
 By Na+-H+ counter-transport
[2] Cl- enters the enterocyte through:
 Passive diffusion down its electrochemical gradient established by the active transport of Na +.
 Na+-Cl- co-transport (major mechanism).
 Cl--HCO3- counter-transport.
Once inside the enterocyte, Na+ is transported across the basolateral membrane by a Na+-K+- ATPase
active transport system and Cl- follows.
In the small intestine, Na+–glucose cotransport, Na+–amino acid cotransport, and Na+–H+
exchange mechanisms are most important.
In the colon, passive diffusion via Na+ channels is most important. The Na+ channels and Na+-K+ATPase of the colon are similar to those in the renal distal tubule and
are stimulated by aldosterone (figure 5.19A). When a person becomes
dehydrated, large amounts of aldosterone almost always are secreted
by the cortices of the adrenal glands. Within 1 to 3 hours this
aldosterone causes increased activation of the enzyme and transport
mechanisms for all aspects of sodium absorption by the intestinal
epithelium. And the increased sodium absorption in turn causes
secondary increases in absorption of chloride ions, water, and some
other substances. This effect of aldosterone is especially important in
the colon because it allows virtually no loss of sodium chloride in the
feces and also little water loss. Thus, the function of aldosterone in the
intestinal tract is the same as that achieved by aldosterone in the renal
tubules, which also serves to conserve sodium chloride and water in the Figure 5.19A: Colonic
body when a person becomes dehydrated. However, in doing so, it reabsorption of Na and
causes significant amounts of K+ to be lost from the body.
secretion of K ions.
[3] Absorption and secretion of potassium ions: The daily
dietary K+ intake of approximately 100 mmol is excreted predominantly by the distal tubules of the kidney.
About 10% of the ingested K+ is excreted via the intestine. K is reabsorbed across the intestinal mucosa
through Simple diffusion. In the small intestine, about 85% of ingested K moves to interstitial space by
simple diffusion mainly via paracellular route (i.e. through leaky tight junctions of the mucosa of the small
intestine).
As water is absorbed from the lumen, rising potassium levels in chyme create a concentration gradient
for its absorption. Anything that interferes with water absorption (resulting in diarrhea) not only reduces
potassium absorption but also “pulls” K+ from the interstitial space into the intestinal lumen.
In large intestine, K+ is actively secreted in the colon by a mechanism similar to that for K+ secretion in
the renal distal tubule. As in the renal distal tubule, K+ secretion in the colon is stimulated by aldosterone.
Because of the “tight” nature of the tight junctions that connect cells in the colon, a relatively large
potential difference exists between the luminal (negative) and basal (positive) surfaces of the absorptive
cells. This electrical difference favors the net secretion of K+ into the lumen through paracellular route.
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■ In diarrhea, K+ secretion by the colon is increased because of a flow rate–dependent mechanism similar to
that in the renal distal tubule. In diarrhea, there is less opportunity for [K+] in colon to rise up to significant
level to act as chemical gradient force against the active and passive secretion of K. Therefore, excessive
loss of K+ in diarrheal fluid causes hypokalemia.
Absorption of water: Water is transported across the small intestinal membrane entirely by the process of
osmotic diffusion which obeys the usual laws of osmosis, or through paracellular route between the
enterocytes. Most of the water in the gastrointestinal tract is absorbed in the jejunum, while the duodenum
serving primarily as the site of osmotic equilibration of chyme. Most of the remaining water and
electrolytes are absorbed in the proximal half of the colon, giving this portion the name absorbing colon
whereas the distal colon functions principally for storage and is therefore called the storage colon. In
contrast to the small intestine, the colon has a limited capacity to absorb water (approximately 3 to 6 L per
day). This is because the highly impermeable nature of the tight junctions connecting the colonic epithelial
cells.
Absorption and secretion of bicarbonate ions in the intestine: Absorption of bicarbonate from the small
intestine occurs primarily in the jejunum. Often large quantities of bicarbonate ions reabsorbed from the
upper small intestine in form of carbon dioxide which is readily absorbed into the blood and subsequently
expired through the lungs. This is important because large amounts of bicarbonate ions have been secreted
into the duodenum in both pancreatic secretion and bile.
However, the mucosa of the large intestine actively secretes bicarbonate ions while it
simultaneously actively absorbs equal amounts of chloride ions in an exchange transport process (Cl-HCO3- counter-transport). The bicarbonate helps neutralizing the acidic end products of bacterial action in
the colon.
Intestinal Ca2+ absorption (figure 5.20): Ca2+ is reabsorbed in the duodenum and upper jejunum. About 30–
80% of dietary Ca2+ typically is absorbed (figure 5.20) and is exactly controlled in relation to the need of the
body for Ca2+.
[A] About one third of the net Ca2+ uptake occurs passively via the paracellular route across the tight
junctions.
[B] About two third of the net Ca2+ uptake
occurs actively through regulated Ca2+
transport pathways in the enterocytes and is
stimulated by vitamin D as follows:
■ Ca2+ enters the enterocytes due to
electrochemical gradient via the Ca2+
channels.
■ to prevent an increase in intracellular free
Ca2+ concentration, Ca2+ binds to the protein
calbindin within the cytoplasm, the synthesis
of which is totally dependent on vitamin D.
■ Extrusion of Ca2+ from the cells occurs by
primary active transport (Ca2+-ATPase) and
secondary active transport (3Na+/Ca2+
exchange), against a large electrochemical
Figure 5.20: Regulation of intestinal Ca2+ absorption.
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gradient.
Vitamin D increases synthesis of calbindin
and both apical and basolateral
transporters. It is inhibited by phosphates
and oxalates because these anions form
insoluble salts with Ca2+ in the intestine.
Fe++ ions are also actively
absorbed from the small intestine which is
regulated according to the body need. K,
Mg, phosphate, and other ions can also
actively absorb through the mucosa.
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 B12intrinsic factor complex. Binding requires
calcium and is optimal at pH 6.6.
Absorption is an active transport process.
Figure 5.21: Intestinal NaCl and water secretion.
Intestinal secretions:
[A] Fluid secretion: Both the small intestine and the large intestine secrete fluid from the crypt cells.
Secretion is necessary for lubrication, as evidenced by the high incidence of obstruction of the gut when
secretion is impaired in diseases such as cystic fibrosis. The mechanism of intestinal fluid secretion is
clinically important because it is activated by a number of bacterial enterotoxins that cause secretory
diarrhea. The key step in the mechanism of fluid secretion from the crypt enterocytes is opening of
the Cl− channels in the luminal cell membrane. There are two types of Cl− channels present (figure
5.21)
1. cAMP-activated Cl− channels, for which the enteric nervous system (ENS) neurotransmitter VIP is an
important stimulator. Na+ secretion follows passively via the paracellular pathway, and water secretion
occurs by osmosis.
2. Ca2+-activated Cl- channels, for which acetylcholine from ENS neurons and serotonin from the
enterochromaffin are both stimulators.
Figure 5.21A summarizes the intestinal absorption and secretion.
Enterotoxic Escherichia coli (traveler’s diarrhea due to E coli) and Vibrio cholera (cholera due to V
cholera) both produce enterotoxins. The toxin from V. cholerae (cholera toxin) causes an irreversible
increase in cAMP levels (not cGMP levels) in the enterocytes located in the crypts of Lieberkühn of the small
intestine. This increase in cAMP causes an irreversible opening of chloride channels on the luminal
membrane. Movement of chloride ions into the gut lumen causes a secondary movement of sodium ions to
maintain electrical neutrality. Water follows the osmotic gradient created by sodium and chloride, causing a
tremendous increase in fluid loss into the gut lumen. Severe diarrhea follows.
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Loss of gastric juice results in
hypokalemic, metabolic alkalosis. Excessive loss
of fluid from the gastrointestinal tract can lead
to dehydration and, depending upon the origin
of the fluid loss, electrolyte and acid-base
disturbances. The hydrogen ion and potassium
ion concentration of gastric juice exceeds that
of the plasma. As a result, excess fluid loss leads
to metabolic alkalosis accompanied by
hypokalemia. Because the pancreas, liver,
ileum, and colon secrete bicarbonate, excessive
loss leads to metabolic acidosis. In addition, the
colon secretes potassium. Thus, the acidosis is
accompanied by hypokalemia.
The small intestinal glands normally
secrete 1 to 2 L of intestinal juice daily.
Normally, intestinal juice is slightly alkaline
(7.4–7.8), and isotonic with blood plasma.
Intestinal juice is largely water but also contains
some mucus, which is secreted both by the
duodenal glands and by goblet cells of the
mucosa. The major stimulus for intestinal juice
production comes from hypertonic or acidic
Figure 5.21A: Summary of intestinal absorption and
chyme, distension or irritation of the intestinal
secretion.
mucosa.
Whenever a segment of large intestine becomes intensely irritated or infected, the mucosa then
secretes large amounts of water and electrolytes in addition to the normal viscid solution of alkaline mucus.
This acts to dilute the irritating factors and to cause rapid movement of the feces toward the anus. The
usual result is diarrhoea with loss of large quantities of water and electrolytes but also earlier recovery from
the disease than would otherwise occur.
[B] Mucus:
Mucus in small and large intestine contains bicarbonate ions to protect the mucosa of small
intestine from acidic chyme and the mucosa of large intestine from the acidic end products of bacterial
action in the colon.
Small intestinal mucus is secreted by Brunner’s glands, which are located within the duodenum, and
by Goblet cells, which are located along the length of intestinal epithelium. The mucus is secreted also in
response to:
 Parasympathetic vagal stimulation, and to,
 Decrease pH of the duodenum to 4 or less
 GIT hormones especially secretin.
Brunner’s glands are inhibited by sympathetic stimulation which may lead to peptic ulceration.


In the large intestine the rate of secretion of mucus is regulated principally by:
Direct tactile stimulation of the mucus cells on the surface of the mucosa and by,
Local nervous reflexes to the mucous cells in the crypts of Lieberkuhn.
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
Parasympathetic innervation to the distal two thirds of large intestine also causes marked increase
in secretion of mucus. This occurs along with an increase in motility. Therefore, during extreme
parasympathetic stimulation, often caused by emotional disturbances, so much mucus may be secreted
into the large intestine that the person has a bowel movement of ropy mucus often as every 30 min; the
mucus contains little or no fecal material.
Mucus in the large intestine protects the wall against excoriation, but in addition, it provides the
adherent medium for holding fecal matter together. Furthermore, it protects the intestinal wall from the
great amount of bacterial activity that takes place inside the feces, plus the alkalinity of the secretion (pH of
8.0 caused by large amounts of sodium bicarbonate) also provides a barrier to keep acids formed deep in
the feces from attacking the intestinal wall.
The large intestine: The contractile activity of the large intestine serves two functions: [1] It enhances the
efficiency of water and electrolyte absorption. [2] It promotes the excretion of fecal material remaining in
the colon.
Movement of the colon: There are three types of movements in the colon and these are:
[1] Mixing movements (segmentation, and haustration).
[2] Peristalsis.
[3] Mass movements: A mass movement is a modified type of peristalsis characterized by the following
sequence of events:
1. A constrictive ring occurs at a distended or irritated point in the colon, usually in the transverse colon,
2. Then rapidly thereafter, the 20 or more centimeters of colon distal to the constriction contract almost as
a unit, forcing the fecal material in this segment en masse down the colon. During this process, the
haustration disappear completely.
3. After the contraction is completed, then relaxation occurs before another mass movement takes place,
this time perhaps farther along the colon.
When the mass movements have forced the feces into the rectum, the desire for defecation is felt.
When the mass movements have forced the feces into the rectum, the desire for defecation is felt. The
appearance of mass movements is facilitated by:
 Gastrocolic and duodenocolic reflexes as a result of distension of stomach and duodenum
respectively. These reflexes are transmitted mainly through extrinsic nerves and only weakly
through myenteric plexus. This explains the appearance of mass movement and urge to defecate
after meals. They are greatly suppressed when the extrinsic autonomic nerves to the colon have
been removed.
 Irritation of the colon can also initiate intense mass movement.
 Intense stimulation of the parasympathetic nervous system.
 Overdistension of a segment of the colon.
Defecation reflexes: The average transit time from caecum to pelvic colon is about 12 hours but passage
from the pelvic colon to the anus may take days. When a mass movement forces feces into the rectum, the
desire (urge) for defecation is normally initiated, including reflex contraction of the rectum and relaxation
of the anal sphincters. However, defecation is prevented by tonic constriction of 1. The internal anal
sphincter which is a circular mass of smooth muscle that lies immediately inside the anus and supplied by
sympathetic nerve fiber which is excitatory and by parasympathetic fibers which is inhibitory. 2. The
external anal sphincter which is composed of striated voluntary muscle that surrounds the internal
sphincter and also extends distal to it. The external sphincter is controlled by nerve fibers in the pudendal
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nerve, which is part of the somatic nervous
system and therefore is under voluntary
conscious control.
When the feces enter the rectum,
distension of the rectal wall stimulates
stretch receptors and initiates defecation
reflex through parasympathetic nerve
fibers and involves three processes (figure
5.22):
1. The sensory fibers pass through the
pelvic nerves to the sacral
segments of the spinal cord.
2. The spinal cord returns signals by
way of the parasympathetic fibers
in the pelvic nerves to the enteric
nervous system and produces an
effective and strong peristaltic
wave in the sigmoid and rectum
forcing feces toward anus.
3. At the same time, parasympathetic
fibers relax the internal anal
sphincter to allow the passage of
feces.
4. Both the internal and external anal
sphincters must relax for feces to
be eliminated. However, the
reflexes just mentioned open the
internal sphincter but close the
external sphincter. The actual
release of feces requires a
conscious effort to open the
external sphincter. If circumstances Figure 5.22: Defecation reflex.
are unfavorable for defecation,
voluntary tightening of the external anal sphincter can prevent defecation despite the defecation
reflex. If defecation is delayed, the distended rectal wall gradually relaxes, and the urge to defecate
subsides until the next mass movement propels more feces into the rectum, once again distending
the rectum and triggering the defecation reflex. If circumstances are favorable for defecation,
voluntary relaxation of external anal sphincter can override the contraction directed by somatic
motor neuron and consequently defecation occurs.
When defecation does occur, it is usually assisted by voluntary straining movements, such as taking
a deep breath, closure of the glottis, and contraction of the abdominal muscles (straining) to force the fecal
contents of the colon downward, at the same time causing the pelvic floor to extend downward to pull
outward on the anus to evacuate the feces. If the external sphincter is kept contracted, the defecation will
not occur, and the defecation reflexes die out after a few minutes, and they remain quiescent for several
hours or until additional amounts of feces enter the rectum.
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Distention of the stomach by food initiates contraction of the rectum and frequently a desire to
defecate. This response is called the gastrocolic reflex, which is mediated by parasympathetic fibers,
although there is some evidence that it is due to an action of CCK and gastrin on the colon and is not
neurally mediated. Because of the response, defecation after meals is the rule in children. In adults, habit
and cultural factors play a large role in determining when defecation occurs.
Emotional factors strongly influence large intestinal motility via the extrinsic autonomic nervous
system. Irritable bowel syndrome may occur during periods of stress and may result in constipation
(increased segmentation contraction) or diarrhea (decreased segmentation contractions).
Bacterial action in the colon: Numerous bacteria especially colon bacilli, are present in the absorbing colon.
The substances formed as a result of bacterial activity are vitamin K, vitamin B 12, thiamin, riboflavin, and
various gases that contribute to flatus in the colon especially carbon dioxide, hydrogen gas, N2, NH4+ and
methane. One of the actions of colonic bacteria is to convert NH3 to NH 4+. Thus, a total colectomy would
increase blood ammonia levels, which would be exacerbated in a person with liver cirrhosis. Gas within the
colon is primarily derived from Fermentation of undigested oligosaccharides by bacteria. Vitamin K is
especially important, for the amount of this vitamin in the ingested food is normally insufficient to maintain
adequate blood coagulation. The colonic gas, or flatus, is produced in large intestine. The gas is produced
chiefly through the breakdown of undigested carbohydrates that reach the colon. The amount of gas varies
markedly from one person to another and is influenced by diet; for example, ingestion of large amounts of
beans, which contain indigestible carbohydrates in their hulls, will increase gas formation by intestinal
bacteria. All gases except N2 diffuse readily through the intestinal mucosa. Diffusion of gas from the blood
to the intestinal lumen is responsible for the N2 present in intestinal gas and is influenced by the
atmospheric pressure.
The feces normally are composed of dead bacteria (bacteria such as Escherichia coli make up
about a third of faecal weight), fat (derived from fat formed by bacteria and fat in the sloughed epithelial
cell), inorganic matter, protein, undigested roughage of the food and dried constituents of digestive juices
such as bile pigment and sloughed epithelial cells. The brown color of feces is caused by stercobilin and
urobilin, which are derivatives of bilirubin. The odor is caused by the products of bacterial action which vary
from one person to another depending on each person’s colonic bacterial flora and on the type of food
eaten.
The liver: The total blood flow through the liver is about 1450 ml/min. It has double blood supply from
hepatic artery (20%) and portal vein (80%). The portal vein drains the digestive tract, the spleen, pancreas
and gallbladder. The liver lobule is constructed around a central vein that empties into the hepatic veins
and thence into the vena cave (figure 5.23). The venous sinusoids are lined by two types of cells [1] typical
endothelial cells and [2] large Kupffer cells which are tissue macrophages capable of phagocytizing bacteria
and other foreign matter in the blood. These cells can remove 99% of bacteria in the portal venous blood
before they can pass all the way through the liver sinusoids. The endothelial lining of the venous sinusoids
has extremely large pores, therefore, the plasma substances and even the proteins can move freely from
the blood through the endothelium to the space below it and become in direct contact with hepatic cells.
Because of the pores in the endothelium of the hepatic sinusoids, the plasma proteins can pass to the
interstitial spaces. Therefore the lymph draining from the liver usually has a protein concentration of about
6 gm/dl, which is only slightly less than the protein concentration of plasma. Also, the extreme permeability
of the liver sinusoids allows large quantities of lymph to form. Therefore, about one half of all the lymph
formed in the body under resting conditions arises in the liver.
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Pressure and resistance in
hepatic vessels: The pressure in
the hepatic vein leading from
the liver into the vena cava is
about 0 mm Hg, whereas the
pressure in the portal vein
leading into the liver is about 9
mm Hg. This means that the
resistance to blood flow
through the liver sinusoids is
normally low. However, in
some pathological conditions
such as liver cirrhosis, the
hepatic vascular resistance may
increase markedly because
many
vascular
channels
Figure 5.23: The basic histological structure of a liver lobule.
through the liver are severely
restricted by fibrotic constriction of the sinusoids or even complete blockage or destruction. An increase in
pressure in the veins draining the liver dams blood in the liver sinusoids and thereby causes the entire liver
to swell markedly and congested. The most, common cause of hepatic congestion is cardiac failure. When
the hepatic venous pressure rises only 3-7 mm Hg above normal, excessive amounts of fluid begin to
transudate into the lymph and also to leak through the outer surface of the liver capsule directly into the
abdominal cavity. This fluid is almost pure plasma, containing 80 - 90% as much protein as normal plasma
which may be so large that lead to ascitis (free fluid in the abdominal cavity) especially when the hepatic
venous pressure is between 10-15 mm Hg.
Functions of the liver
[1] Carbohydrate metabolism
 Storage of glycogen: The liver is especially important for maintaining a normal blood glucose
concentration. For instance, storage of glycogen allows the liver to remove excess glucose from the blood,
store it, and then return it to the blood when the blood glucose concentration begins to fall too low. This is
called the glucose buffer function of the liver. Circulating adrenaline and glucagon mobilize this liver
glycogen and convert it to blood glucose. Only liver has the glucose-6-phosphatase necessary for this
breakdown.
 Conversion of monosaccharides galactose and fructose to glucose.
 Gluconeogenesis. When the glucose concentration begins to fall below normal, large amounts of amino
acids are converted into glucose, thereby contributing still another means for maintaining relatively normal
blood glucose.
 Formation of many important chemical compounds from the intermediate products of carbohydrate
metabolism.
[2] Fat metabolism
 Bile salts produced by the liver are essential for the digestion and absorption of fat.
 The fat-soluble vitamins are stored in the liver such as vitamins A and D. In addition, water-soluble
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vitamins such as B12 are also stored in the liver.
 The depot fat is mobilized when required and is converted to the ketone bodies (acetoacetic acid, βhydroxybutyric acid and acetone) by the liver. These ketone bodies are metabolized by other tissues with
production of heat and energy. Ketosis, which is an excess of ketone bodies in the blood, does not occur in
liver failure.
 The liver is the site for the synthesis of large quantities of cholesterol and phospholipids.
 The liver is the site for conversion of large quantities of carbohydrates and proteins to fat.
[3] Protein metabolism
 The liver is the main organ for deamination of surplus amino acids with the production of ammonia. In
liver failure, the amino acids in the blood are increased and they appear in the urine.
 The liver is the only organ that can convert ammonia to urea. . Ammonia is a toxic gas which is difficult
to be excreted out while urea is less toxic and easier excreted. In the absence of this function of the liver to
form urea, the plasma ammonia concentration rises rapidly and results in hepatic coma and death.
 Among the most important functions of the liver is its ability to synthesize certain amino acids and also
to synthesize other important chemical compounds from amino acids. For instance the non-essential amino
acids can all be synthesized in the liver.
[4] Blood
 The liver plays an important role in the formation and destruction of RBC.
 The liver is a site of formation of RBC in fetal life.
 It stores the factors principal for the normal maturation of RBC such as iron and B 12.
 It removes from the blood the bilirubin formed when the RBC are broken down and excretes this
bilirubin down the bile duct into the duodenum, as a bile pigments.
 The liver manufactures the plasma proteins with the exception of some of the globulin fraction (which is
the antibodies formed mainly by plasma cells in the lymph tissue of the body). The plasma albumin exceeds
the plasma globulin and the normal albumin/globulin ratio is 1.7/1. In liver failure the plasma protein
pattern is altered and the globulin fraction may exceed the albumin fraction.
 The blood clotting factors such as prothrombin and fibrinogen, etc.., are made in the liver. In liver
diseases, blood clotting may be impaired leading to bleeding from the skin and mucous membranes.
[5] Vitamin Mineral Storage:
Vitamin A, Vitamin D, Vitamin E, Vitamin K, vitamin B12, and Iron.
[6] Poisons: Many normal physiological substances as well as drugs are modified by the liver in some way
before being excreted by the kidneys. This is called detoxication. Some substances, such as the short-acting
barbiturates, are completely destroyed by the liver. Other, substances are conjugated with glucuronic acid,
glycine, sulphate or acetate.
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