the GI Tract
The GI tract is one of the most complex and important organ systems.
It comprises the alimentary canal, a hollow structure extending
from the mouth to the anus, and associated glandular organs (salivary
glands, pancreas, gallbladder, and liver) that empty their contents into the canal (Figure
13–1). The GI tract, which is 7–9 m in the
adult, includes the mouth, esophagus (23–25 cm), stomach,
small intestine (duodenum, jejunum, ileum; 6–7 m), large
intestine (cecum and colon; 1.0–1.5 m), rectum, and anus.
The GI tract is connected to the salivary glands, the pancreas,
and the gallbladder, the sources of exocrine secretions
that play an essential role in digestion.
Progress of food along the alimentary canal. Food undergoes
mechanical as well as chemical changes to render it suitable for
absorption and assimilation.
(Redrawn, with permission, from Mackenna BR,
Callander R. Illustrated Physiology, 6th ed. Churchill
The wall of the GI tract is composed of four main layers. From
the lumen outward, these include the mucosa, submucosa, muscularis
externa, and serosa (Figure
13–2). The precise structure of some of these layers,
most notably the mucosa, varies from one region of the GI tract
to the next. The mucosa has three components: specialized
epithelial cells that line the lumen; the underlying lamina
propria, a layer of connective tissue that contains small
blood and lymphatic vessels, immune cells and nerve fibers; and
the muscularis mucosa, a thin layer of muscle cells.
The muscularis mucosa is an important boundary in determining whether
cancer of the GI tract is still localized to its site of origin
or is likely to have metastasized (ie, spread to distant regions
of the body). The submucosa is a layer of loose connective
tissue directly beneath the mucosa containing larger blood and lymphatic
vessels and a nerve plexus of the intrinsic or enteric nervous
system, termed the submucosal nerve (Meissner’s) plexus. This
nerve plexus is particularly important for control of secretion
in the GI tract. In some areas, the submucosa also contains glands
and lymphoid tissue. The muscularis externa is composed
of an inner circular and an outer longitudinal layer of smooth muscle
and is responsible for motility of the GI tract. Between these muscle
layers lies the myenteric nerve (Auerbach’s) plexus,
a division of the enteric nervous system that regulates motility.
The serosa is an outer sheath of squamous epithelial
cells and connective tissues, where larger nerves and blood vessels
travel in a bed of connective and adipose tissue.
Schematic structure of a portion of the digestive tract
with various possible components.
(Redrawn, with permission, from Bevelander G. Outline
of Histology, 7th ed. Mosby, 1971.)
the GI Tract
The overall function of the GI tract is to take in nutrients
and process them to a form that can be used by the body and to eliminate
wastes. The major physiological processes that occur in the GI tract
are digestion, secretion, motility, and absorption.
Food is taken into the mouth as large particles containing macromolecules
that are not immediately absorbable into the body. Digestion is
the process that converts nutrients in food to products that can
be absorbed by cells of the mucosa. Digestion includes physical
processes (eg, chewing, GI contractions) that break up the
food, mix it with digestive secretions, and propel it along the
alimentary canal, and chemical processes (eg, digestive
enzymes) that degrade food components (proteins, fats, polysaccharides) to
products that can be absorbed (amino acids, fatty acids, monosaccharides).
Digestive enzymes arise from exocrine glands (salivary gland, pancreas,
gallbladder, and liver) and from cells and glands in the mucosa
or are found on the apical surface of certain epithelial cells.
During the process of digestion, large volumes of fluid are secreted into
the lumen of the GI tract. Secretions arise from exocrine glands
(salivary glands, pancreas, gallbladder) and from epithelial cells
lining the gastrointestinal lumen (or glands that connect to the
lumen). The daily fluid load in the GI tract is approximately 2
L of oral intake and 7 L of secretions (1.5 L saliva, 2.5 L gastric
juice, 0.5 L bile, 1.5 L pancreatic juice, and 1 L intestinal secretions).
From this total of 9 L, approximately 100 mL ends up in stool daily;
the balance is recycled (Figure 13–3).
Approximate flow rates per day and ionic constituents
of fluid passing through different levels of the intestine.
(Redrawn, with permission, from Fine KD, Krejs
GJ, Fordtran JS. Diarrhea. In: Gastrointestinal Disease, 5th
ed. Sleisenger MH, Fordtran JS [editors]. Saunders,
Secretions and luminal contents are moved from mouth to anus
and mixed by a process termed motility, because of
the coordinated contractions of smooth muscle. Smooth muscle cells
have a resting membrane potential (small excess of negative charge)
in their interior as a result of the activity of pumps in the plasma
membrane. When a cell is depolarized, this potential difference
is transiently abolished, generating a signal that (1) triggers
events within that cell, leading to sliding of actin and myosin
filaments, and (2) is propagated to neighboring cells, resulting
in the coordinated response of muscle contraction. Depolarization
of a cell can occur spontaneously or in response to a neural or
hormonal stimulus depending on the specific characteristics of different
cells. GI smooth muscle displays differences in contractile properties
in different regions of the tract. “Slow-wave” oscillating
depolarizations occur in some areas and rapid “spike” depolarizations
in other areas. Each type occurs with a characteristic intrinsic
frequency, but each can also be triggered by specific stimuli such
as stretch, neuronal input, or hormones. Short bursts of spikes cause
phasic motor activity; longer bursts cause tonic muscle contraction.
Tonic contraction occurs at sphincters (“gates” that
allow further movement down the GI tract only during relaxation).
Phasic electrical activity occurs at the intervening regions of
the GI tract (between sphincters).
The products of digestion (amino acids, small peptides, monosaccharides,
fatty acids) are taken into the body by the process of absorption. Absorbed
molecules can pass across (transcellular
route) or between (paracellular route) the epithelial
cells lining the intestine to enter the blood or lymphatic systems.
In general, this transport can occur by either a passive, energy-independent
mechanism that occurs down an electrochemical gradient (of
charge or concentration), or by an active, energy-requiring
process that occurs against an electrochemical gradient. Passive
transport can occur by simple diffusion (random
molecular motion) of uncharged molecules that readily pass the lipid
layer plasma membrane. In this manner, short-chain fatty acids are
absorbed in the small intestine. Charged molecules that cannot cross
the plasma membrane diffuse through specialized channels (transmembrane
proteins) within the apical and basolateral membrane of epithelial
cells. For instance, water is absorbed by diffusion through water
channels or aquaporins in the small intestine. Some molecules that
are absorbed by diffusion bind to transporter proteins in the plasma membrane
that facilitate their transfer into the cell (facilitated diffusion).
For example, fructose is absorbed into epithelial cells of the small
intestine by facilitated diffusion through the apical membrane GLUT-5
Active transport requires metabolic energy. There
are two classes of active transport. In primary active transport, the transport
molecule itself hydrolyzes adenosine triphosphate (ATP). An example
of primary active transport is the Na-K ATPase found in the basolateral
membrane of intestinal epithelial cells, which expels three Na+ ions
from cells in exchange for two K+ ions that are
pumped into the cell. This unequal transport of ions generates a
transmembrane potential (negative inside; ie, transport is electrogenic).
In secondary active transport, the transporter itself
does not hydrolyze ATP, but transport depends on an electrochemical
gradient that has been established by primary active transport.
The Na-K ATPase maintains a low intracellular Na+ concentration
and an inside negative potential in epithelial cells, thereby providing
the electrochemical gradient for secondary active transport of many
absorbed molecules. For example, glucose is absorbed against a concentration
gradient across the apical membrane of epithelial cells in the small
intestine by secondary active transport with Na+ ions
by the SGLT1 transporter. Two Na+ ions are transported
down their electrochemical gradient (generated by the Na-K ATPase),
dragging with them one glucose molecule. For large molecules such
as proteins, transport occurs by pinching off from, and fusion of membrane
vesicles with, the plasma membrane. These processes are termed endocytosis (uptake
into epithelial cells) and exocytosis (export out of
In addition to the major roles of the GI tract that are related
to digestion and absorption, the digestive tract has other functions that
are essential for maintenance of health and homeostasis.
The mucosa of the GI tract is the largest surface of the body that
is exposed to the environment, and the gut, like the skin, must
protect the body from the external environment. Defense involves
protection against ingested toxins, bacteria, and viruses, as well
as the bacteria and toxins that normally exist in the large intestine
(Table 13–2). The magnitude of the problem is illustrated by the
observation that there are more bacterial cells in the human colon
than cells in the entire body. Defense involves two mechanisms.
Immunologic defense—The mucosal
immune system or gut-associated lymphoid tissue (GALT) comprises
Peyer’s patches (aggregates of lymphoid cells in the small
intestine) and diffuse populations of mucosal immune cells (Figure 13–4). The GALT protects
against bacteria, viruses, and toxins and allows tolerance to potentially
immunogenic dietary substances and bacteria.
Nonimmunologic defense—These mechanisms
include secretion of gastric and intestinal fluid, electrolytes
and mucus, and the tight junctions between epithelial cells. The
secretions neutralize and flush away potentially damaging bacteria
and macromolecules, and the tight junctions prevent their ingress
Certain peptides secreted into the intestinal lumen contribute
to defense and healing. Defensins are antimicrobial
peptides that are secreted by epithelial cells in the intestine.
They form holes in bacterial cell walls and prevent them from colonizing
the small intestine. Trefoil peptides are secreted
into the lumen of the GI tract with mucus. Among their many effects,
they appear to promote healing of mucosal lesions.
Table 13–2 Mechanisms of Defense of the GI Tract (and Features of Structure and Function Involved). |Favorite Table|Download (.pdf)
Table 13–2 Mechanisms of Defense of the GI Tract (and Features of Structure and Function Involved).
|Forms of Defense||Structural Adaptations||Functional Adaptations||Mechanism of Defense|
|Defense from acid|
|Mucus production||Large numbers of mucus-secreting stomach surface
cells||Mucin gene expression||Prevents direct contact of acid with epithelium|
|Bicarbonate production (alkaline tide)||Duodenal Brunner’s glands||Neutralizes any acid that breaches epithelium|
|Prostaglandin production||Specialized prostaglandin-producing cells in lamina propria||Cyclo-oxygenase 1 and 2 (COX1/2) gene expression||Attenuates acid production|
|Tight junctions||Tight junction formation||Prevents breach of epithelium|
|Bicarbonate from pancreas||Pancreatic duct opening into duodenum||Response of secretin to gastric acid||Neutralizes acid leaving stomach|
|Defense from infection|
|Secretory immune system||Mucosa-associated lymphoid tissue and transcytotic
epithelial cells||Machinery for transcytosis of immunoglobulin||Extends to GI tract lumen the protective umbrella
of blood-borne immunity|
|Rapid epithelial cell turnover||Cell proliferation in glands/crypts; cell release
into lumen||Limits the consequences of enterocyte infection|
|Normal colonic microbiota||Induce expression of specific antimicrobial proteins (angiogenin4,
|Stomach acid||Gastric glands containing parietal cells||Multiple humoral controls on acid secretion (histamine, acetylcholine,
and gastrin)||Kills pathogenic organisms on ingestion|
Systemic and local features of gut immunology.
(Redrawn, with permission, from Kagnoff M. Immunology and
disease of the gastrointestinal tract. In: Gastrointestinal Disease, 6th
ed. Sleisenger MH, Fordtran JS [editors]. Saunders,
of Fluid and Electrolyte Balance
The small intestine receives 8–9 L of fluid with electrolytes
per day and secretes a further 1 L and electrolytes per day. Most
of the fluid is absorbed. Thus, secretion and absorption must be regulated
to maintain balance. Increased secretion or diminished absorption
causes diarrhea, which can be fatal because of fluid and electrolytes
Undigested food products, bacteria, and certain heavy metals (eg,
copper and iron excreted in bile) are excreted in feces.
- 4. What are the major functions
of the GI tract?
- 5. Describe the four major layers of
a cross-section through the GI tract.
- 6. What volumes of fluid are transferred
into and out of the GI tract each day?
- 7. Describe the general mechanism of
electrolyte transport across epithelial cells.
- 8. Describe the defense mechanism of
the GI tract.
Regulation of the GI Tract
The processes of motility, secretion, digestion, and absorption are
under close physiologic regulation by nerves, hormones, and paracrine
substance (Figure 13–5).
Neural, endocrine, and paracrine mechanisms of control
in the GI tract.
There are two components of GI innervation.
Intrinsic innervation by the enteric nervous
system—The enteric nervous system is the third division
of the autonomic nervous system (Figure 13–6).
An enteric neuron has its cell body within the wall of the GI tract
and is thus intrinsic to the gut. The enteric nervous system comprises
a series of ganglionated nerve plexuses that extend from the esophagus
to the rectum, which are organized into two principal components:
1) the myenteric, or Auerbach’s, plexus, which is sandwiched
between the layers of the muscularis externa; and 2) the submucosal
or Meissner’s plexus, which lies in the submucosa. The
enteric nervous system is very extensive, containing as many neurons
as are present in the spinal cord. It contains sensory or afferent
neurons (sometimes called intrinsic primary afferent neurons [IPANs])
that sense the environment (eg, intestinal pH, osmolality, wall
stretch), interneurons (the connectors), and secretomotor or efferent
neurons that control many cell types to stimulate or inhibit motility,
secretion, absorption, and immune function of the GI tract. In this
manner, the enteric nervous system can regulate the GI tract in
a reflex manner without input from the CNS. For this reason, it
is often called the “little brain.” Enteric neurons
use many neurotransmitters, most notably neuropeptides.
The degree to which the CNS regulates the enteric nervous system
varies with region. The characteristic functions of structures derived
from the embryonic foregut (eg, esophageal peristalsis, relaxation
of the lower esophageal sphincter, gastric accommodation and peristalsis,
pyloric sphincter function) are more dependent on CNS control. However, functions
of structures derived from the embryonic midgut and hindgut (eg,
intestinal peristalsis and mucosal secretion) can continue without
input from the CNS.
The clinical importance of the enteric nervous system is seen
in clinical syndromes in which its function is lost, which can occur
at several levels. In esophageal achalasia, for example, as a result
of enteric nervous system defects, the body of the esophagus is
quiet and the lower sphincter is tonically contracted, making ingestion
of food difficult or impossible. Similarly, loss of enteric nervous
system function in syndromes of pseudo-obstruction of the small bowel
or Hirschsprung’s disease in the colon have severe clinical
consequences, including abdominal pain, distension, and a risk of
catastrophic intestinal perforation.
Extrinsic innervation by parasympathetic and sympathetic
nerves—Extrinsic neurons that innervate the GI tract
have cell bodies outside of the gut wall and allow a bidirectional
communication between the brain and the gut (the brain-gut
axis) (Figure 13–7). This
communication can regulate the function of the enteric nervous system
or directly control the activity of other
The enteric nervous system. Left: Enteric nervous
system of the small intestine shows that enteric neurons are organized
in two nerve plexuses, the submucosal plexus and myenteric plexus,
with other plexuses including the deep muscular, periglandular,
and villous plexus.
(Redrawn with permission from Costa M, Furness
JB, Llewellyn-Smith IJ. Histochemistry of the enteric nervous system.
In: Physiology of the Gastrointestinal Tract, 2nd
ed, Johnson LR [editor]. Raven Press, 1987.)
Right: The enteric nervous system includes sensory
neurons, interneurons, and motor neurons. Complete reflex arcs exist
within the enteric nervous system.
The extrinsic innervation of the GI tract by the parasympathetic
and sympathetic nerves. Preganglionic parasympathetic nerves from
the medulla and the sacral spinal cord project fibers in the vagal
and pelvic nerves, respectively, to the wall of the GI tract and
innervate enteric neurons that serve as postganglionic parasympathetic
nerves. Preganglionic sympathetic nerves project fibers from the
thoracolumbar regions of the spinal cord to the prevertebral ganglia,
where they innervate postganglionic sympathetic nerves that project
to the GI tract. Both the parasympathetic and sympathetic preganglionic
nerves release acetylcholine (ACh), which activates nicotinic receptors
on postganglionic nerves. Postganglionic parasympathetic nerves
release acetylcholine and peptides, whereas postganglionic sympathetic nerves
release norepinephrine (NE).
In parasympathetic innervation, the vagus nerve
(cranial nerve X) innervates the esophagus, stomach, gallbladder,
pancreas, and the first part of intestine, cecum, and proximal colon.
The pelvic nerve from the sacral spinal cord innervates the distal
colon and the rectum. Preganglionic cell bodies in the medulla (vagus)
or sacral spinal cord (pelvic nerve) project fibers to some enteric
neurons in the gut wall, which are thus in a sense postganglionic
parasympathetic nerves. The preganglionic nerves use acetylcholine
as a neurotransmitter, which activates nicotinic receptors on
enteric neurons. The postganglionic enteric nerves use acetylcholine (acting
on muscarinic receptors) and neuropeptides as neurotransmitters.
Parasympathetic stimulation can stimulate and inhibit GI functions.
In sympathetic innervation, preganglionic sympathetic nerves
arise from cell bodies in the thoracic spinal cord and project fibers
to prevertebral ganglia (celiac, cranial, and caudal mesenteric
ganglion). They release acetylcholine as a neurotransmitter that
interacts with nicotinic receptors on the postganglionic
nerves. Postganglionic fibers innervate some enteric neurons or
directly innervate effector cells in the GI tract, such as vascular
smooth muscle cells. Norepinephrine is the major postganglionic
neurotransmitter. Sympathetic innervation is often inhibitory to
Regarding extrinsic sensory nerves, parasympathetic
and sympathetic nerves tracts also carry sensory fibers from the gut
to cell bodies that are located in nodose ganglia and the dorsal
root ganglia, respectively. Cell bodies in the nodose and dorsal
root ganglia then project fibers to the brain stem (from nodose
ganglia) or spinal cord (from dorsal route ganglia). Sensory nerve
fibers in the wall of the GI tract detect mucosal pH and osmolality
and can respond to amino acids or glucose, temperature, tension,
and touch. In this manner, the extrinsic sensory nerves sense changes
in the environment of the intestine and trigger central reflexes
that initiate secretomotor changes to maintain normal homeostasis.
Extrinsic sensory nerves also contribute to GI inflammation and
pain. Sensory nerve endings in the wall of the gut detect noxious chemical
and mechanical stimuli, including acid, inflammatory agents, and
distension. These stimuli trigger the release of the neuropeptides,
substance P, and calcitoningene-related peptide, from the endings
of sensory nerves within the gut wall, where they induce extravasation
of plasma proteins and infiltration of granulocytes and arteriolar
vasodilatation to cause neurogenic inflammation. The same stimuli
induce release of neuropeptides from the central projections of
these neurons, where they participate in pain transmission. Additional
research is required to define the mechanisms of neurogenic inflammation
and GI pain.
Hormones are blood-borne messengers released from endocrine cells
or glands into the circulation, which carries them to distant target
cells (Figure 13–5). This mechanism
of endocrine regulation was discovered in the GI tract in 1902,
when Bayliss and Starling discovered the hormone secretin in
the small intestine and showed that it stimulates secretion from the
exocrine pancreas. Since then, a large number of hormones have been
identified in all regions of the GI tract. In this respect, the
GI tract is the largest endocrine organ.
GI hormones have several characteristics in common. They are
secreted from endocrine cells that are scattered throughout the
mucosa of the stomach and intestine rather than being concentrated
in specialized glands. This diffuse distribution made purification
a truly Herculean task: Many hundreds of kilograms of intestine
were required to isolate a few milligrams of pure hormone. GI hormones
are invariably peptides, and many of these peptides are present
not only in endocrine cells but also in nerves of the enteric system
and CNS (Table 13–3). Thus, they
have dual functions as hormones and neurotransmitters. After feeding,
there are elevated levels of many GI hormones in the circulation.
When administered to reproduce postprandial plasma concentrations,
these hormones have multiple biological effects, ranging from the
stimulation of gastric acid secretion to the suppression of appetite.
The physiologic role of some GI hormones has been clearly established
by demonstration that antagonists of hormone receptors block certain
physiologic processes. However, in many cases, such antagonists
are not available, and the physiologic relevance of hormones that
cannot be antagonized remains to be determined.
Table 13–3 Secretory Products of the GI Tract. |Favorite Table|Download (.pdf)
Table 13–3 Secretory Products of the GI Tract.
|Products||Physiologic Actions||Site of Release||Stimulus for Release||Disease Association|
|Gastrin||Stimulates acid secretion and growth of gastric
oxyntic gland mucosa||Gastric antrum (and duodenum)||Peptides, amino acids, distension, vagal stimulation||Zollinger-Ellison syndrome, peptic ulcer disease|
|CCK||Stimulates gallbladder contraction, pancreatic enzyme and
bicarbonate secretion, and growth of exocrine pancreas||Duodenum and jejunum||Peptides, amino acids, long-chain fatty acids, (acid)|
|Secretin||Stimulates pancreatic bicarbonate secretion, biliary bicarbonate secretion,
growth of exocrine pancreas, pepsin secretion; inhibits gastric
acid secretion, trophic effects of gastrin||Duodenum||Acid (fat)|
|GIP||Stimulates insulin release; (inhibits gastric acid secretion)||Duodenum and jejunum||Glucose, amino acids, fatty acids|
|Motilin||Stimulates gastric and duodenal motility||Duodenum and jejunum||Unknown||Irritable bowel syndrome; diabetic gastroparesis|
|Pancreatic polypeptide||Inhibits pancreatic bicarbonate and enzyme secretion||Pancreatic islets of Langerhans||Protein (fat and glucose)|
|Enteroglucagon||Elevates blood glucose?||Ileum||Glucose and fat|
|Somatostatin||Inhibits release of most other peptide hormones||GI tract mucosa, pancreatic islets of Langerhans||Acid stimulates, vagus inhibits release||Gallstones|
|Prostaglandins||Promote blood flow, increase mucus and bicarbonate secretion from
gastric mucosa||Multiple||Various||NSAID-induced gastritis and ulcer disease|
|Histamine||Stimulates gastric acid secretion||Oxyntic gland mucosa||Gastrin and unknown others|
|VIP||Relaxes sphincters and gut circular muscle;
stimulates intestinal and pancreatic secretion||Mucosa and smooth muscle of GI tract||Enteric nervous system||Secretory diarrhea|
|Bombesin||Stimulates gastrin release||Gastric mucosa||Enteric nervous system|
|Enkephalins||Stimulate smooth muscle contraction; inhibit intestinal secretion||Mucosa and smooth muscle of GI tract||Enteric nervous system|
|Intrinsic factor||Binds vitamin B12 to facilitate its absorption||Parietal cells of the stomach||Constitutive secretion||Autoimmune destruction resulting in pernicious
|Mucin||Lubrication and protection||Goblet cells along entire intestinal mucosa and surface cells
in stomach||GI tract irritation||Viscid mucus in cystic fibrosis. Attenuation in some cases
of peptic ulcer|
|Acid||Prevents infection; initiates digestion||Parietal cells of the stomach||Gastrin, histamine, acetylcholine, NSAIDs (indirectly)||Acid-peptic disease|
Many substances that are used for intercellular signaling are rapidly
removed from the extracellular fluid by uptake into nearby cells
or by enzymatic degradation. Such substances have a short half-life
in the extracellular fluid and are consequently only capable of
regulating neighboring cells. Paracrine substances are released
from nonneuronal sensory cells and neurons and regulate the function
of neighboring cells rather than influencing distant organs by passage
through the circulation (Figure 13–5 and Table 13–3). Examples include histamine and somatostatin,
which are released from cells in the stomach to control acid secretion,
and serotonin (5-hydroxytryptamine [5-HT]),
which is released in the small intestine to control activity of
the vagus nerve.
- 9. What are the three general mechanisms
of control observed in the GI tract?
- 10. What are the two components of the
enteric nervous system?
- 11. What are the three general types
of enteric neuron?
- 12. Describe the parasympathetic and
sympathetic innervation of the GI tract.
- 13. What is the relationship between
the enteric and central nervous systems?
of GI Smooth Muscle
The two principal muscle layers that control motility of the
GI tract are the inner circular layer and the outer longitudinal
layer of the muscularis externa. They vary in thickness in different
regions of the GI tract. For example, the muscles are thickened
in the gastric antrum, where strong contractions break up food before
it can enter the small intestine, and muscle layers are thickened
to form sphincters. Most of the GI muscle is smooth muscle, except
the pharynx, parts of the esophagus, and the external anal sphincter,
which are made up of striated (skeletal) muscle. GI
smooth muscle is similar to smooth muscle in other organs: Fusiform
cells are packed together in bundles by connective tissue sheaths. Gap
junctions between cells allow signals to readily pass from
cell to cell so that the contraction of bundles occurs synchronously. Interstitial
cells of Cajal form an extensive network of stellate cells
in the muscle layers of the stomach and intestine that are intimately
associated with smooth muscle cells and enteric neurons (Figure 13–8). They may have two functions.
First, they transmit information from enteric neurons to the smooth
muscle cells. Second, they are the pacemaker cells, which
have the capacity to generate the basic electrical rhythm or slow
waves that are a consistent feature of GI smooth muscle. Animals
lacking interstitial cells of Cajal show markedly abnormal GI motility,
including defective gastric emptying and intestinal stasis or ileus.
Defects in interstitial cells of Cajal may be associated with motility
disturbances in patients, and this is an area of active investigation.
Diagrammatic view of interstitial cells of Cajal (ICC)
in the intestine, showing their interaction with enteric nerves
and smooth muscle cells.
of GI Smooth Muscle
GI smooth muscle cells have a resting membrane potential of –40
to –80 mV as a result of the relative conductances of K+, Na+,
and Cl– ions. An electrogenic Na+-K+ ATPase
contributes significantly to the resting membrane potential. Less
is known about the electrophysiological properties of interstitial
cells of Cajal, in part because of difficulties in isolating these cells
for study. The resting membrane potential of smooth muscle cells
varies characteristically with time and is called a slow wave or
basic electrical rhythm. Slow waves occur at 3–5/min
in the stomach and at 12–20/min in the intestine.
Interstitial cells of Cajal set the frequency of the slow waves,
and slow waves are transmitted between cells through gap junctions. Nerves
and hormones modulate the amplitude of slow waves. Depending on
the amplitude of the slow waves and the excitability of the smooth
muscle, slow waves can give rise to action potentials. If the slow-wave
depolarization reaches a threshold, a train of action potentials
will fire. Action potentials depolarize the membrane of the smooth
muscle cells and induce an influx of Ca2+ ions
into the cytoplasm through voltage-sensitive Ca2+ channels
in the plasma membrane and from intracellular stores, causing contraction.
What causes an action potential to occur? The presence of neurotransmitters
or hormones that are released close to the smooth muscle cells alters
the resting membrane potentials of the cells, which makes the oscillations
in membrane potential (the slow waves) more or less likely to reach threshold
and initiate an action potential. However, not all slow waves induce
action potentials and resultant contractions. The explanation is
that inhibitory motor neurons of the GI tract are highly active
and thus prevent generation of action potentials and contractions.
Action potentials and contractions can only occur when these inhibitory
motor neurons are switched off by input from interneurons. Thus,
the tonic inhibition serves to contrail the inherent excitability
of the pacemaker cells.
Properties of GI Smooth Muscle
Several characteristic patterns of contraction can be observed in
GI smooth muscle. Tonic contractions are best represented by
sphincters that act as one-way valves to prevent retrograde movement
of material from distal to more proximal regions and thus to facilitate
flow in an aboral direction. The proximal parts of the stomach and
the gallbladder also exhibit tonic contractions. Peristaltic
contractions are moving waves of contraction that propel
digesta along the GI tract. Peristalsis involves neurally mediated
contraction of smooth muscle on the oral side of a bolus of digesta
and a neurally mediated relaxation of muscle on the anal side of
the digesta. Peristalsis occurs in the pharynx, esophagus, gastric
antrum, and small and large intestine. Segmental contractions produce
narrow contracted segments between relaxed segments. These movements
allow mixing of the luminal contents with GI tract secretions and
increase exposure to mucosal surfaces where absorption occurs. Segmentation
occurs in the stomach and intestine. Pathologic patterns of
motility include spasms, which are very strong
and often painful contractions that occur continuously in a dysregulated
manner, and ileus, where there is a markedly decreased
or absent contractile activity. Ileus often results from irritation
of the peritoneum involved in surgery, peritonitis, and pancreatitis.
Further research is required to understand the mechanisms of these
abnormal contractions, which may lead to improved therapies.
- 14. What are the positive and negative
regulators of smooth muscle cell action potentials?
- 15. What are the functions of interstitial
cells of Cajal?
- 16. What are the general types of contractions
observed in the GI tract after feeding?
The oropharynx provides entry to the GI tract during swallowing
and to the respiratory tract during breathing. It includes the vocal
cords, which separate the two tracts and provide the structural
basis for speech. Much of the oropharynx is lined with a respiratory-type
ciliated pseudocolumnar epithelium.
The esophagus is a hollow tube (25–30 cm long, 2–3
cm wide). The wall of the esophagus consists of an epithelial cell layer,
an inner layer of circular muscle, a myenteric nerve plexus, and
an outer layer of longitudinal muscle. The first third of esophagus
is composed of striated muscle, the middle third is mixed striated
and smooth muscle, and the lower third is purely smooth muscle.
The esophagus is delimited by an upper esophageal sphincter (a
distinct thickening of striated circular muscle) and a lower
esophageal sphincter (a tonically contracted 3–4
cm ring of smooth muscle). The two sphincters generate small luminal
zones of high pressure, whereas the rest of the esophageal lumen
is at a pressure equal to the surrounding body cavities. Between swallows,
the two sphincters are closed, preventing entry of air and gastric
acid into the esophagus. Regulation of the lower esophageal sphincter
is especially important because it controls the passage of digesta
into the stomach and prevents the reflux of gastric contents into
the esophagus, where they can damage the mucosa. Between swallows,
the lower esophageal sphincter is contracted, in large part by vagal
cholinergic mechanisms. During swallowing, vagal inhibitory fibers
allow the lower esophageal sphincter to relax, possibly because
of release of inhibitory neurotransmitters from enteric nerves,
including nitric oxide and vasoactive intestinal peptide (VIP).
Swallowing begins as a voluntary process that rapidly becomes an
involuntary reflex mechanism. During the voluntary oral phase, the
tongue pushes a bolus of food to the back of the mouth and into
the oropharynx. From there on, the process is involuntary. In the pharyngeal
phase, the food bolus stimulates touch receptors in the pharynx.
Sensory signals pass by the glossopharyngeal, vagal, and trigeminal
nerves to the swallowing center in the medulla and pons. Motor impulses
pass through cranial nerves to control an involuntary process that directs
food into the esophagus and away from the airway. Breathing is interrupted
and the soft palate is elevated, closing the pharyngeal opening
of the nasopharynx and preventing food from entering the internal
openings of the nostrils. The tongue is pressed against the hard
palate, closing the oral opening of the pharynx. The glottis is
pulled under the epiglottis, which blocks the laryngeal opening.
Cartilages around the larynx are pulled together, further restricting
food from entering the respiratory tract. When all openings to the
pharynx are closed, a wave of muscular contraction pushes the bolus
of food toward the opening of the esophagus. As the food reaches
the esophagus, the upper esophageal sphincter relaxes to accept
the material and then closes after the bolus has moved through.
The esophageal phase of swallowing begins when the
bolus passes through the upper esophageal sphincter. Vagal stretch
receptors in the wall of the esophagus detect distension by the
bolus and induce a vagovagal reflex, during which vagal
motor nerves induce a wave of contraction that spreads along the
esophagus at 3–5 cm/s. This is termed primary
peristalsis (Figure 13–9).
As the wave of
primary peristalsis reaches the lower esophageal sphincter, the
sphincter relaxes to allow the bolus to enter the stomach. Distension
of the esophagus by the bolus can initiate another wave of contraction
called secondary peristalsis. Often repetitive waves
of secondary peristalsis are required to clear the esophagus of
food. Various hormones and neurotransmitters, foods, and drugs can
affect the tone of the lower esophageal sphincter pressure.
Primary peristalsis of the esophagus. The tracings show
pressures in the indicated regions of the esophagus at rest and
at various times after swallowing. UES, upper esophageal sphincter;
LES, lower esophageal sphincter.
(Redrawn from data in Conklin JL, Christensen
J. Motor functions of the pharynx and esophagus. In: Physiology
of the Gastrointestinal Tract, 3rd ed., Johnson LR [editor].
New York, LIppincott-Raven, 1994.)
The importance of oropharyngeal motility and its control is seen
in patients who have had strokes or are demented. Inability to swallow
properly often makes them unable to manage their own oral secretions,
resulting in aspiration of oral contents into the lungs with development
of pneumonia. This is a common cause of death in individuals with
these kinds of CNS disorders. Disordered lower esophageal sphincter
tone is a major cause of esophageal reflux, presenting as heartburn.
- 17. What is the histologic difference
between the proximal one third and the distal two thirds of the
- 18. What are the functions of the upper
and lower esophageal sphincters, and how are they regulated?
- 19. Describe the three phases of the
The stomach is a complex glandular organ that is guarded by two
sphincters: the lower esophageal sphincter and the pyloric sphincter (Figure 13–10). The mucosa is composed
of simple glands, consisting of a pit, neck, and a base, that markedly
increase the surface area and are lined with specialized epithelial cells.
The stomach can be divided into several regions on the basis of
structure and function. The cardia is a small region just
distal to the lower esophageal sphincter that does not secrete acid.
The corpus, or body, is the major part
of the stomach. Gastric glands in the corpus contain parietal
cells, which secrete hydrochloric acid and intrinsic
factor, and chief cells, which secrete pepsinogen. The
corpus is a reservoir that is a major site of gastric digestion.
The pyloric antrum is the distal region of the stomach
that secretes the hormone gastrin from G cells. It
is highly muscular, grinds food, and regulates gastric emptying.
All regions of the stomach secrete mucus and bicarbonate.
Anatomy and histology of the stomach.
(Redrawn, with permission, from Boron WF, Boulpaep
EL [editors]. Medical Physiology.
A number of products are secreted from the stomach. Of these,
hydrochloric acid is perhaps the most important from a pathophysiologic
standpoint. Secretion of acid by the parietal cells of the gastric
glands occurs in a basal diurnal pattern but can be stimulated by
such diverse factors as the thought of food, distension of the stomach,
and protein ingestion.
Mechanisms of HCL Secretion
The mechanisms by which parietal cells secrete HCl into the stomach
have been intensively studied because of the importance of acid
secretion to digestion and in disease states. Parietal cells are
pyramidal in shape. Their membranes express a H+-K+ ATPase,
a primary active transporter that is responsible for the secretion
of HCl. Parietal cells undergo a remarkable change in appearance
when stimulated to secrete HCl (Figure 13–11).
In the unstimulated state, a tubulovesicular network that contains
the H+-K+ ATPase characterizes
the cells. On activation, the tubulovesicular membranes fuse with the
plasma membrane to form a canalicular membrane with microvilli.
The result is an increase in the area of the apical membrane by
50–100 fold and insertion of more H+-K+ ATPase
pumps into the plasma membrane. This rearrangement promotes HCl
Acid secretion by parietal cells. Top: Upon stimulation,
tubulovesicular network in the parietal cell fuses to form an extensive
canalicular membrane with microvilli, which increases the surface
area. Bottom: The mechanisms of HCl secretion by parietal
cells, stimulated by histamine, acetylcholine, and gastrin, are
demonstrated. For abbreviations, see legend for Figure
The H+-K+ ATPase is a heterodimer
of an α-subunit (the catalytically active unit)
and a β-subunit (involved in determining the intracellular
location). The H+-K+ ATPase
pumps H+ ions from the cell across the apical
membrane in exchange for K+ ions (Figure
13–11). This is an example of primary active transport
that is driven by ATP, which pumps H+ ions against
an enormous concentration gradient (1 million:1). Tight junctions
between cells prevent the reentry of H+ ions into
the mucosa. The K+ ions that have entered the
cells then recycle to the lumen or enter interstitial fluid by K+ channels. To
maintain electroneutrality, Cl– ions are secreted
passively across the apical membrane into the lumen through Cl– channels,
forming HCl. The secreted H+ ions are provided
by H2O and CO2, which form H2CO3.
Carbonic anhydrase generates H+ ions for secretion
and HCO3– ions, which enter the interstitial
fluid by exchange for Cl– ions. Cl– ions
enter against their electrochemical gradient, driven by efflux of
HCO3– down an electrochemical gradient.
The secretion of HCO3– into the blood
forms the “alkaline tide,” which
can lead to alkalosis when H+ ion secretion is
excessive. Water movement maintains the osmotic balance in all regions.
An understanding of the mechanisms of HCl secretion by parietal
cells permitted the development of proton pump inhibitors (PPIs),
a class of drugs that inhibit the H+-K+ ATPase.
Drugs such as omeprazole, a benzimidazole, are inactive at neutral
pH levels but, when acidified (in the stomach), bind to sulfhydryl
groups of cysteine residues on the external surface of the H+-K+ ATPase,
irreversibly inhibiting activity and blocking hypersecretion of
gastric acid. Other experimental drugs, termed acid pump antagonists, competitively
interfere with K+ ion binding to block acid secretion. These
drugs are widely used to inhibit the hypersecretion of gastric acid,
which causes ulcer disease.
and Inhibitors of HCL Secretion
The three main stimulants of H+ ion secretion
are acetylcholine, gastrin, and histamine, all of which stimulate
HCl secretion and induce characteristic shape changes of the stimulated parietal
cell. Acetylcholine is released from vagal postganglionic
or enteric neurons during feeding. It binds to muscarinic M3-type
muscarinic receptors on parietal cells to stimulate H+ ion
secretion. Gastrin is a peptide hormone of 17 or 34
amino acids that is secreted from G cells in the gastric antrum
during feeding. Gastrin binds to cholecystokinin (CCK) type B receptors
on parietal cells, which also stimulates H+ ion
Both acetylcholine and gastrin receptors activate the same signal
transduction pathways: activation of phospholipase Cβ, leading
to generation of inositol trisphosphate that mobilizes Ca2+ from
intracellular stores, and diacylglycerol, which activates protein
kinase C. Because both acetylcholine and gastrin act through similar
intracellular pathways, the combined effects of gastrin and acetylcholine
Histamine is a paracrine substance secreted by enterochromaffin-like
(ECL) and mast cells in the corpus mucosa during feeding. Histamine
binds to H2 receptors on parietal cells to activate adenylyl
cyclase and increase cAMP. The cAMP activates protein kinase A to
stimulate H+ ion secretion. The combination of
histamine and acetylcholine or gastrin can increase the rate of
acid production by up to 10-fold over basal levels, a much greater
effect than simple addition of the effects of the agonists would
predict. This effect is known as potentiation. Potentiation
requires that two different signal molecules bind to receptors that
act through different intracellular mechanisms. Increased intracellular
Ca2+ and cAMP activate K+ channels
on the apical membrane of parietal cells, thereby promoting K+ ion
efflux from the cell. This hyperpolarizes the cell (more negative
inside) to promote Cl– ion secretion across the
apical membrane. Ca2+ and cAMP also increase insertion
of Cl– channels and H+-K+ ATPase
into the apical membrane. The combined effects are to stimulate
Gastrin also regulates growth of the gastric epithelium. Excess
gastrin produced by certain tumors causes hyperproliferation of
gastric glands and parietal cells and excess secretion of gastric
acid. The excess acid in the small intestine can lead to ulceration
of the mucosa, steatorrhea as a result of inactivation of pancreatic
lipases, and diarrhea. This condition is termed Zollinger-Ellison
syndrome. Excessive administration of proton pump inhibitors
can result in prolonged high luminal pH, which stimulates hypersecretion
of gastric acid and increased mucosal growth. Termination of drug
treatment then results in an acid production rebound because of
the increased content of parietal cells and G cells.
In addition to the direct mechanisms by which acetylcholine, gastrin,
and histamine stimulate HCl secretion from parietal cells, acetylcholine
and gastrin also indirectly stimulate secretion by acting on enterochromaffin-like
cells to promote the release of histamine, which in turn stimulates
parietal cells. The importance of histamine to H+ ion
secretion is illustrated by studies with histamine H2receptor
antagonists, such as cimetidine. These drugs not only inhibit
histamine-stimulated H+ ion secretion but also
block the effects of acetylcholine and gastrin, thus confirming
the indirect pathway. They are effective as they prevent the potentiation
and are widely used to treat the hypersecretion of gastric acid.
Somatostatin, a peptide of 14 or 28 amino acids,
is an important inhibitor of gastric acid secretion. Somatostatin directly
inhibits proton secretion by activating receptors on parietal cells,
which couple to produce inhibition of cAMP. Somatostatin also inhibits
gastrin and histamine secretion, which indirectly inhibits proton
secretion. Somatostatin is secreted by D cells in the
gastric antrum and corpus. D cells in the gastric antrum have direct
content with the stomach lumen (open endocrine cells), allowing
them to sense the luminal contents. Protons in the antrum stimulate
somatostatin secretion, which acts as a paracrine agent to inhibit
gastrin secretion from neighboring G cells and to thereby indirectly reduce
gastric acid secretion. This is an example of negative-feedback
regulation. D cells in the corpus do not have contact with
the lumen (closed cells) and thus cannot sense luminal protons.
Instead, multiple neurohumoral factors (eg, noradrenalin, CCK, VIP)
increase release of corpus somatostatin, which in turn inhibits
acid production indirectly by decreasing histamine release from
ECL cells and directly by inhibiting parietal cells. Vagal ACh and
the TH1 cytokineinterferon-γ inhibit
somatostatin release and promote acid secretion.
Regulation of Gastric Acid Secretion
Secretion of gastric acid between meals is low. Three phases
of acid secretion occur during feeding (Figure 13–12). The cephalic
phase (~30% of response) of secretion is initiated
by the sight, smell, taste, and swallowing of food. These stimuli
activate the dorsal motor nucleus of the vagal nerve in the medulla
and result in vagal discharge and parasympathetic motor nerves.
Stimulation has several consequences. In the corpus, postganglionic
nerves release acetylcholine, which directly activates parietal
cells by M3 receptors. Acetylcholine also induces histamine release from
enterochromaffin cells, which indirectly stimulates H+ ion
secretion by parietal cells. In the antrum, vagal stimulation induces
release of the peptide, gastrin-releasing peptide, from
postganglionic fibers, which stimulates gastrin release and thus
indirectly stimulates secretion of H+ ion secretion. Acetylcholine
also inhibits somatostatin release from D cells in the corpus and
pylorus to stimulate secretion of H+ ions.
Regulation of gastric acid secretion by nerves and hormones.
During the cephalic phase of digestion, vagal cholinergic nerves
directly stimulate parietal cells and induce release of histamine
from ECL cells, which also stimulate parietal cells. Vagal fibers
also release gastrin-releasing peptide (GRP) in the antrum to induce
gastrin secretion, which is carried in the bloodstream to induce
release of histamine and stimulate parietal cells. During the gastric
phase of digestion, food in the stomach triggers vagovagal reflexes
and also stimulates gastrin secretion. Acidification of the gastric antrum
stimulates the release of somatostatin, which inhibits gastrin release
and thus acid secretion; vagal ACh inhibits somatostatin release.
(ACh, acetylcholine; G, gastrin; S, somatostatin; M3-R, muscarinic
3 receptor; H2-R, histamine 2 receptor; CCKB-R, cholecystokinin
B receptor; ECL, enterochromaffin-like; GRP-R, GRP receptor; GRP,
The gastric phase (~70% of response) of
secretion is induced by stimuli within the stomach. Vagal sensory
nerves detect gastric distension with food and trigger a vagovagal
reflex during which vagal motor nerves release acetylcholine in
the stomach to promote acid secretion. Partially digested proteins
and amino acids stimulate gastrin release from G cells in the pylorus.
G cells are open-type endocrine cells that have a brush border,
allowing them to directly sense the contents of the stomach. Gastrin
then stimulates acid secretion. Acidification of the pylorus stimulates
somatostatin release, which inhibits acid secretion by a negative-feedback
loop as described.
During the intestinal phase, the products of protein
digestion, on entering the small intestine, can stimulate gastrin release
from G cells in the duodenum. Many substances, most notably fat
and acid, stimulate the secretion of hormones from the small intestine
that inhibit gastric acid secretion. Examples include secretin and
Helicobacter pylori infection is responsible
for almost all gastric and duodenal ulcers that are not caused by
medications (eg, aspirin-like drugs). H pylori lives
in the mucous layer of the stomach where the enzyme urease is active,
converting urea to CO2 and ammonia. Ammonia buffers luminal acid
and protects the organism. H pylori also secretes
proteins that modulate immune responses and directly alter mucosal cell
signaling pathways. More than half of the world population is infected
with H pylori. In most cases, the infection is mild
and not detectable. In some people, however, the infection leads
to symptomatic inflammation, ulceration, and increased risk of gastric
Chief cells in the glands of the gastric corpus
secrete pepsinogen, an inactive precursor (zymogen)
of the active protease, pepsin. Acetylcholine is the main stimulant
of pepsinogen secretion, although other factors (eg, gastrin) also
stimulate secretion. Once released into the lumen of the stomach,
gastric acid and preexisting pepsin convert pepsinogen to pepsin. Pepsin
has a pH optimum of 3.0 and is thus active in the stomach. It is
an endopeptidase that begins the degradation of dietary proteins
to peptides. However, pepsin accounts for only 10% of the
total protein digestion.
Mucins are high-molecular-weight glycoproteins secreted by
mucous cells of gastric glands in the corpus and antrum. The peptide
backbone of mucins is densely populated with carbohydrate side chains
enriched with sulfate groups. Mucins combine with phospholipids,
bicarbonate, and water to form the mucus gel layer that adheres
to the surface of epithelial cells of the stomach. This layer forms
physical protection for epithelial cells from damage by contractile
grinding of food as well as noxious substances such as acid, pepsin,
and bile acids. Acetylcholine and mucosal irritation stimulate secretion
Epithelial cells of the corpus and antrum secrete HCO3– ions.
Although the secretion of HCO3– is minor
compared with H+ ion secretion, HCO3– plays
a major role in epithelial defense. HCO3– ions
are trapped in the mucous gel to form an “unstirred layer” in
proximity to the epithelium, where the pH is 7.0 compared with 1.0
to 3.0 in the lumen. Acetylcholine and intraluminal acid stimulate
Intrinsic factor is a glycoprotein secreted by parietal
cells that is required for vitamin B12 absorption. Vitamin
B12 (cobalamin) is not made in mammalian cells, and the
only source is the diet: meat, fish, dairy products, but not vegetables
or fruit. In the stomach, acid and pepsin release B12 from dietary
carrier proteins. The acid environment permits binding of B12 to haptocorrin (R
factor), a glycoprotein produced by salivary glands and gastric
glands. The B12-haptocorrin complex enters the duodenum,
where pancreatic proteases digest the haptocorrin. Free intrinsic
factor also enters the duodenum. Intrinsic factor combines with
B12 in the less acidic environment of the small intestine,
forming a degradation-resistant complex for transport to the ileum.
Specific receptors on epithelial cells lining the ileum bind the
vitamin B12–intrinsic factor complex, which is
taken into cells by endocytosis. The absorbed complex dissociates
within the epithelial cells, and then vitamin B12 binds
to transcobalamin II, a protein required for exocytosis and transport
to the liver. Destruction of parietal cells by autoimmune mechanisms results
in vitamin B12 deficiency and pernicious anemia, resulting
from impaired synthesis of purines and thymine for which vitamin
B12 is required. The only reliable therapy is regular intramuscular
injections of vitamin B12.
of Gastric Motility
In terms of motility, the proximal and distal regions of the stomach
are distinct. The gastric corpus is a reservoir for gastric digestion.
During each swallow, stretch of the esophagus induces a vagovagal
reflex that causes the gastric corpus to relax in preparation to
receive the food, a phenomenon known as receptive relaxation.
When food enters the stomach, it relaxes further to accommodate
a meal of 1.5 L without any increase in pressure, a phenomenon called accommodation, which
involves vagovagal and local enteric reflexes. Thus, the stomach
is a reservoir for ingested food. The antrum of the stomach is highly
muscular, and here contractions serve to break food to smaller pieces
and thereby facilitate digestion. The pyloric sphincter controls
the rate at which the antral contractions propel partially digested
food, or chyme, into the duodenum. During fasting,
the antrum is relatively quiescent, with occasional forceful contractions
that occur every 75–90 min. These intense contractions,
of 5- to 10-min duration, are part of a general wave of contractions
that sweep the entire length of the GI tract during fasting: the migrating
myoelectric complex. Feeding disrupts the migrating myoelectric complex,
and now the antrum contracts frequently at a rate of about three
contractions per minute. These slow waves of peristaltic contraction
originate from spontaneously active interstitial cells of Cajal
in the pacemaker zone in the middle of the body of the stomach,
and they sweep toward the antrum. When the membrane potential of
muscle cells depolarizes to reach threshold, action potentials fire.
Contractions occur during the plateau phase of the action potential.
Gastrin and acetylcholine stimulate contraction by increasing the
magnitude and duration of the action potentials.
Immediately after a meal, the stomach may contain up to 1 L of
material, which empties slowly into the small intestine. Regulation
of gastric emptying occurs by alterations in motility of the proximal
and distal stomach, pylorus, and duodenum. Gastric emptying is brought
about by an increase in tone (intraluminal pressure) in the proximal
stomach, increase in strength of antral contractions, opening of
the pylorus, and inhibition of duodenal segmental contractions.
The rate of gastric emptying depends on the chemical and physical
composition of chyme that enters the duodenum through the stimulation
of both neural and hormonal pathways. Solids and liquids empty at
different rates: Liquids empty rapidly, and solids empty only after
a lag phase. Acid, fat, and hyperosmolar solutions entering the
duodenum slow gastric emptying through stimulation of neuronal and
hormonal mechanisms. Sensory neurons in the duodenum, both vagal
and spinal, respond to nutrients, H+ ions, and
hyperosmolar content of chyme. Vagal motor nerves decrease antral contractions,
contract the pylorus, and decrease proximal gastric motility. This
results in intestinal feedback inhibition (slowing) of
gastric emptying. The main vagal mediator that stimulates
contraction is acetylcholine. VIP and nitric oxide are neuronal
mediators that inhibit contraction. Many hormones that are released
by endocrine cells in the small intestine have been implicated in
the feedback inhibition of gastric emptying. Secretin, the
release of which is stimulated by acid, inhibits antral contractions
and stimulates contraction of the pyloric sphincter to slow emptying. Cholecystokinin, the release
of which is stimulated by fat, acts on receptors on vagal sensory
nerves to produce a vagovagal reflex that decreases gastric emptying.
The importance of nervous system control over gastric motility
is reflected in the high incidence of the dumping syndrome (nausea,
bloating, flushing, and explosive diarrhea) that occurs as a consequence
of stomach dysmotility in some patients who have undergone surgical
procedures such as partial gastrectomy or nonselective vagotomy.
- 20. Describe the cell types found
in the mucosa of the gastric corpus and antrum, and indicate the
products of each cell type.
- 21. What are the roles of the proximal
and distal stomach?
- 22. Describe the ionic basis of secretion
of HCl from the gastric parietal cells.
- 23. Name a neurotransmitter, hormone,
and paracrine agent that stimulates acid secretion from parietal
- 24. Name a peptide that inhibits acid
secretion from the parietal cells.
- 25. Describe the mechanisms of the cephalic,
gastric, and intestinal phases of gastric acid secretion.
- 26. Name two types of drugs with distinct
mechanisms of action that can be used to treat hypersecretion of
- 27. What is the role of the parietal
cell in absorption of vitamin B12?
- 28. Describe two processes by which
the gastric mucosa is protected from acid in the lumen.
- 29. What are the patterns of motility
in the corpus and the antrum?
- 30. How does the composition of the
digesta in the lumen of the small intestine affect the rate of gastric
The gallbladder is a muscular sac with a resting volume of about
50 mL that lies on the inferior surface of the liver. It is connected
to the hepatic biliary system by the cystic duct, which leads to
the common bile duct whose opening into the proximal duodenum is
controlled by the sphincter of Oddi. The common bile duct and the
pancreatic duct usually join just proximal to this sphincter.
Bile, which is produced by the liver, flows down the hepatic duct
and into the gallbladder through the cystic duct. It is stored there
until stimulation of gallbladder contraction expels the contents
of the gallbladder back through the cystic duct into the common
bile duct and through the sphincter of Oddi into the duodenum. Stimuli
for gallbladder contraction and sphincter of Oddi relaxation necessary
for proper bile flow include both hormones and neural inputs. Fat
in the intestine stimulates secretion of the hormone CCK from I
cells. CCK causes contraction of the gallbladder and relaxation
of the sphincter of Oddi. Depending on how long it remains in the gallbladder,
bile becomes concentrated. Bile composition is further modified
by mucin production under the control of prostaglandins and by saturation
of bile cholesterol controlled in part by estrogens. The most prominent
disorders of the gallbladder involve gallstone formation (see later
Three regions can be distinguished along the approximately 6–7
m length of the small intestine. The pyloric sphincter marks the
beginning of the duodenum, which is largely retroperitoneal
and fixed in its location and is 20–25 cm in length. Because of
this sphincter, stomach contents normally enter the duodenum in
small spurts containing tiny suspended particles. In the duodenum,
gastric contents are mixed with the secretions of the common bile
duct and pancreatic duct. Beyond the duodenum, the small intestine
is mobile and suspended in the peritoneal cavity by a mesentery.
The proximal two fifths is the jejunum. The distal
three fifths is the ileum, which ends at the ileocecal valve
at the start of the large intestine.
The most striking gross structural features of the small intestine
are the numerous villi (projections of the mucosa approximately
1 mm in height) (Figure 13–13).
Each villus contains a single terminal branch of the arterial, venous,
and lymphatic trees. Villi increase the absorptive capacity 5-fold and
allow efficient transfer to the circulatory system of substances
absorbed from the gut lumen by enterocytes (surface epithelial
cells). By electron microscopy, each enterocyte contains 3000–5000 microvilli, plasma
membrane evaginations on the apical side of the cell that further
increase the absorptive surface area by 200-fold. Many digestive
enzymes expressed by intestinal epithelial cells are located at
the tips of these microvilli. As a group, these densely packed microvilli make
up a “brush border” facing the intestinal lumen.
Anatomy and histology of the small and large intestine.
(Redrawn, with permission, from Boron WF, Boulpaep
EL [editors]. Medical Physiology. Saunders,
Invaginations of the intestinal epithelium that surround villi
are called crypts of Lieberkühn. These structures are the location
of epithelial intestinal stem cells and their proliferative daughters
that together constantly produce new differentiated epithelial cells
that form the epithelial lining of the intestine. Each crypt contains
tetrapotential stem cells at or near the crypt base that produces
the four mature epithelial cell types: absorptive enterocytes, mucus-secreting
goblet cells; hormone-secreting enteroendocrine cells, and antimicrobial
peptides and growth factor–secreting Paneth cells. Enterocytes,
goblet, and enteroendocrine cells migrate out of crypts and onto
adjacent villi. These cells then die by apoptosis at the tips of
villi and are extruded into the lumen of the intestine; the average
life span is about 4–6 days. On the other hand, Paneth
cells are much longer lived (~60 days) and they migrate to the crypt
base where they are in close contact with epithelial stem cells.
Absorption in the Small Intestine
The small intestine is the main site of digestion and the principal
site for nutrient absorption. Thus, it is appropriate to review
all steps of digestion in the GI tract and then to consider the
mechanisms by which these nutrients are absorbed.
Carbohydrates, which are mainly present in the diet as polysaccharides
and disaccharides, must be digested to monosaccharides for absorption.
Intestinal microbes contain a large repertoire of glycoside hydrolases
that aid in the breakdown of complex plant polysaccharides. Alpha-amylases
in salivary and pancreatic secretions cleave interior α-1,4
glucose linkages in large polymers of starch to form fragments (disaccharides,
trisaccharides, and oligosaccharides). Oligosaccharidases and disaccharidases
in the brush border of enterocytes digest small fragments to the
monosaccharides, glucose, galactose, and fructose. Glucose and galactose,
along with two Na+ ions, are absorbed across the
apical membrane of enterocytes by the same transporter, SGLT1. Passive
uptake of water also occurs, maintaining osmolality on both sides
of the cell membrane. The extrusion of Na+ out
of the basolateral membrane by the Na+-K+ ATPase
provides an electrochemical Na+ gradient that
drives the absorption of glucose and galactose against their concentration
gradients. Fructose is absorbed into the cell by facilitated diffusion
through the apical membrane by a different transporter, GLUT-5.
All three hexoses leave the cell by facilitated diffusion through
a common transporter, GLUT-2, located in the basolateral membrane.
Lactose intolerance is the most common problem of
carbohydrate digestion. It results mainly from the reduction of
lactase activity in adults. Lactase is expressed normally at high levels
in the jejunum of neonatal and infant humans. In many parts of the
world, lactase levels are gradually reduced after weaning. However,
lactase levels do not decrease significantly in populations where
milk products are an important part of the adult diet. Lactase activity
is rate limiting for lactose digestion in most adults throughout
other regions of the world. If lactase is deficient, nondigested
lactose is not absorbed. The nonabsorbed lactose retains water in
the lumen to maintain the osmolality of chyme equivalent to that
of plasma. This retention of fluid causes abdominal pain (cramps),
nausea, and diarrhea. Bacterial fermentation of lactose in the distal
small intestine and colon further exacerbates these symptoms.
Mutations of the gene encoding SGLT1 impair glucose and
galactose absorption in some patients. Affected individuals develop
diarrhea when they consume sugars that are normally absorbed by
SGLT1, because of defects in absorption of Na+, monosaccharides,
and water. In contrast, fructose, which is absorbed by GLUT-5, does
not cause diarrhea.
Proteins entering the intestine derive from the diet and also from
cells shed from the mucosa. Protein digestion begins in the stomach
by the action of pepsin, but most protein digestion occurs in the
lumen of duodenum and jejunum by the action of pancreatic proteases
(trypsin, chymotrypsin, carboxypeptidases), yielding
small oligopeptides and free amino acids. Peptidases on the surfaces
of intestinal epithelial cells are required for the digestion of
larger oligopeptides to yield smaller peptides and additional amino
acids. Dipeptides and tripeptides are absorbed into enterocytes
by secondary active cotransport with H+ ions by
the oligopeptide cotransporter, PepT1. The H+ ions
in the lumen are provided by a Na+-K+ transporter
in the apical membrane. Amino acid uptake from the lumen occurs through
several different transporters. Each transporter is specific for
various side chain groups: acidic, basic, neutral, and imino. Uptake
of most amino acids into enterocytes is coupled to cotransport with
Na+ ions that is driven by the Na+-K+ ATPase
in the basolateral membrane. Absorbed dipeptides and tripeptides
are hydrolyzed to amino acids within the enterocytes by independent
cytosolic peptidases. Amino acids exit the cell through the basolateral
membrane by cation-independent amino acid transporters. Infants
can absorb proteins by endocytosis, providing a mechanism for transfer
of immunoglobulins, and thus passive immunity, from mother to child.
Triglycerides constitute about 90% of dietary lipid;
cholesterol, phospholipids, sphingolipids, fatty acids, and fat-soluble vitamins
make up the balance. Dietary lipids are first emulsified by mechanical
digestion (chewing, antral contractions, segmentation), which produces
fine droplets that are suspended in aqueous fluid. Digestion of
lipids begins in the stomach by the combined action of swallowed lingual
lipase from salivary glands, and gastric lipase secreted
by gastric gland chief cells in the fundus. These lipases convert
triglycerides to fatty acids and diglycerides. Most lipid digestion
occurs in the duodenum and jejunum. Lipids in the lumen form micelles
as a result of the emulsifying properties of bile salts, phospholipids,
and mixing contractions of the stomach and intestine. The most important
enzyme in lipid digestion is pancreatic lipase. Lipase
is secreted as an active enzyme, but full activity requires an alkaline
pH and binding to a cofactor called colipase. Procolipase
is also secreted in pancreatic juice and is converted to colipase
by trypsin in the intestinal lumen. Lipase is only active at the
oil-water interface of the triglyceride droplets. Colipase promotes
binding of lipase to the surface of micelles and thereby facilitates
digestion. Lipase cleaves the fatty acid ester linkages at the 1
and 3 positions of the glycerol backbone of triglycerides to yield
free fatty acids and a 2-monoglyceride.
The major barrier to lipid absorption is an unstirred layer on the
surface of the enterocytes that is not readily mixed with the bulk
fluid in the intestinal lumen because of the highly convoluted surface
of the epithelium. The short- and medium-chain fatty acids that
are water soluble and the long-chain fatty acids, monoglycerides,
lysophospholipids, and cholesterol in the micelles diffuse through
the unstirred layer to the surface of the enterocytes. Proton secretion
creates an acidic microenvironment at the surface of enterocytes
and promotes the protonation of fatty acids. Protonated fatty acids,
monoglycerides, lysophospholipids, and cholesterol leave the micelles.
Being uncharged (protonated) and thus lipid soluble, they readily
diffuse into the cell. Fatty acids of <10 carbon atoms in length
can pass through cells and enter the blood directly. Uptake of long-chain
fatty acids (and some phospholipids) appears to be mediated by a
specialized fatty acid transporter protein (microvillous membrane fatty
acid–binding protein). Within the enterocyte, long-chain
fatty acids bind to fatty acid–binding proteins that transport
the newly absorbed long-chain fatty acids to the smooth endoplasmic
reticulum for reassembly into triglycerides with absorbed 2-monoglycerides.
The triglycerides, cholesterol esters, and phospholipids are combined
with specific proteins in the Golgi apparatus of enterocytes and assembled
into chylomicrons, which are exported from the basolateral
membrane of the cell. They enter the lymphatic system through the
large intraendothelial channels and subsequently are delivered to
the bloodstream. During a relatively brief circulation, they are
partially lipolyzed by cell-surface lipases and acquire more protein
components. The liver is the main destination for chylomicron remnants.
Note that chylomicrons serve as the primary transporters of fat-soluble
vitamins in the circulation.
The small intestine is the major site of water absorption. Water moves
into and out of the lumen of the intestine to keep its contents
iso-osmotic with plasma. Water transport in either direction is
thus passive, being secondary and proportional to the movement of
ions (especially Na+ and Cl– ions)
and nutrients. In the small intestine, water absorption is greatest
in mature epithelial cells at villous tips. Water secretion is greatest
in immature cells at villous crypts. Most passage of water (and
ions) occurs by transcellular transport through aquaporins, a family of
water channels. There is also some paracellular transport of water
and ions. Epithelial cells lining the GI tract are interconnected
by tight junctions. Junctions are somewhat leaky, allowing some
water and small ions to move between the lumen and the mucosa via
paracellular transport. The resistance of tight junctions is an
important determinant of the relative degree that transcellular
transport occurs, and this resistance varies throughout the intestines.
Tight junctions are most leaky in the duodenum and jejunum, becoming
progressively less leaky (tighter) in the ileum and colon. Larger
ions and organic solutes are more restricted in their movement across
The jejunum is the main site of absorption of Na+ ions.
Na+ absorption is mainly transcellular, either
by cotransport with nutrients (sugars, amino acids)
or by Na+-K+ exchange. There
is also parallel Na+ and Cl– absorption by
a paracellular route. HCO3– ions are
secreted in the proximal duodenum, but in the jejunum HCO3– and
Cl– ions are absorbed in large amounts. In the
ileum, HCO3– is secreted and Cl– is absorbed.
K+ ion absorption from the lumen of the small intestine
occurs mainly by passive paracellular transport. The Na+-coupled
glucose transporter (SGLT1) in the apical membrane of the small
intestine takes up two Na+ ions with each glucose
molecule. This property is central to the development of effective
therapeutic oral rehydration solutions that contain glucose, Na+,
Cl–, and HCO3– to enhance
water and electrolyte uptake during severe diarrhea (eg, cholera).
The absorption of electrolytes and water is regulated by hormones
and neurotransmitters. For example, angiotensin II and aldosterone,
which are generated and released during dehydration, promote absorption
of NaCl in the intestine.
the Small Intestine
The cells of the crypts of Lieberkühn are important
sites of electrolyte and water secretion. The Na+-K+ ATPase
in the basolateral membrane of epithelial cells provides the electrochemical gradients
for secondary active transport and diffusion of other ions. An Na-K-2Cl– transporter
in the basolateral membrane mediates the uptake of Na+,
Cl–, and K+ ions into the cell
(Figure 13–14). This is an example
of secondary active transport: with the entry of Na+ ions,
an electrochemical gradient drives the uptake of K+ and
Cl– ions against electrochemical gradients. Excess
K+ ions leave the cell by basolateral K+ channels
that can be regulated by Ca2+ and cAMP. Cl– ions
diffuse across the apical membrane of the enterocytes and into the
intestinal lumen through a Cl– channel that is
regulated by cAMP. This electrogenic secretion of Cl– ions
provides a small negative charge to the lumen relative to the interstitial
fluid, which drives the secretion of Na+ ions
by a paracellular route. Water follows by transcellular and paracellular
routes to maintain iso-osmolality with plasma. The net result is
thus the secretion of NaCl and water.
Mechanisms of fluid and electrolyte secretion by epithelial
cells of the intestinal crypts. Top: Ionic basis of
secretion of Cl– and Na+ ions. Bottom: Regulation
of fluid and electrolyte secretion by submucosal neurons and mast cells
of the lamina propria. Activated mast cells release histamine, which
either directly acts on epithelial cells or acts on submucosal neurons
to stimulate release of acetylcholine, which then acts on epithelial
Fluid and electrolyte secretion flushes bacterial products and toxins
away from the surface of the epithelium and thus plays a role in
mucosal defense. Numerous substances, termed secretagogues, stimulate
fluid and electrolyte secretion in both health and diseases (Figure 13–14). Neurotransmitter
secretagogues from the submucosal plexus include VIP and
acetylcholine. Paracrine secretagogues include bradykinin,
serotonin, histamine, and prostaglandins. Some products from immune
cells indirectly stimulate secretion by acting on submucosal neurons to
induce release of acetylcholine or VIP, which then act on enterocytes
to stimulate secretion. Luminal secretagogues include
bacterial toxins. A toxin from cholera modifies G proteins
and thereby permanently activates adenylyl cyclase and increases
intracellular levels of cAMP. Strong activation of the apical Cl– channels
of crypt cells results in massive secretion of Cl– ions
and, in consequence, of water and Na+ ions. Patients with
cholera may excrete 20 L of diarrhea per day, leading to rapid dehydration and death.
An inexpensive and effective treatment is oral rehydration with
glucose-containing solutions. The glucose drives the sodium-glucose
cotransporter to transport both molecules into enterocytes, and
with them chloride and water, thereby offsetting the fluid efflux
mediated by the bacterial toxin. Because these cotransporters are lacking
in the colon, its maximum absorptive capacity (5 L/d) is
considerably less than that of the small intestine (12 L/d).
One type of Cl– ion channel in the apical membrane
is encoded by the gene for cystic fibrosis and is termed the cystic
fibrosis conductance regulator, or CFTR. The
CFTR is expressed in many epithelial cells throughout the body.
Mutations in the channel result in improper folding and premature
degradation of the channel protein. The secretion of Cl– ions
and, in consequence, of Na+ ions and water is
diminished. In the airway, this results in production of thick secretions
that impair ventilation.
the Small Intestine
Activity of Small Intestinal Muscle
In the human duodenum, slow waves occur at a frequency of 11–13/min.
The slow-wave frequency declines to the ileum. The slow waves may
or may not be associated with action potentials. In the intestine,
slow waves alone do not cause contractions. However, when action
potentials fire, they give rise to strong but highly localized contractions,
the magnitude of which depends on the frequency of the action potentials.
The slow waves are entirely intrinsic: They are generated within the
intestine and probably depend on the unstable membrane potentials
of the interstitial cells of Cajal. The frequency with which action
potentials fire depends on the excitability of the muscle cells,
which is influenced by circulating hormones, extrinsic nerves, and
the enteric nervous system.
Activity of Small Intestinal Muscle
During periods of fasting, the intestine is quiescent. However, every
90–120 min, there are bursts of action potentials in the muscle
that induce waves of contraction lasting about 5 min. These migrating
myoelectric complexes take 90 min to traverse the small intestine.
By the time the migrating myoelectric complex reaches the ileum,
another begins in the stomach. These waves of contraction clear
the small intestine of its contents, acting as a “housekeeper” to
keep the lumen relatively clean, thereby minimizing bacterial overgrowth
(Figure 13–15). The migrating myoelectric complex
is associated with cycling levels of motilin, a 22-amino acid
peptide hormone secreted by endocrine cells in the duodenum. Motilin
may act on the enteric nervous system to regulate the migrating
myoelectric complex. Its release appears to be under neural control,
although luminal contents can also stimulate motilin release. The
effect of motilin is to stimulate contraction of gastric and intestinal
smooth muscle during the interdigestive period between meals.
Mechanical activity of the small intestine during fasting
and after feeding. The recordings are of intraluminal pressures measured
at indicated regions of the intestine from a conscious dog. The
migrating myoelectric complexes in the fasting state are disrupted by
feeding, which induces segmentation and peristaltic contractions.
(Redrawn, with permission, from Boron WF, Boulpaep
EL [editors]. Medical Physiology.
During feeding, the migrating myoelectric complexes cease, probably
because of the action of the vagus and gut hormones such as gastrin
and cholecystokinin (Figure 13–15).
The migrating myoelectric complexes are replaced by phasic
contractions that are brief (a few seconds at each site)
and restricted to short lengths of intestine (a few centimeters).
Phasic contractions serve both to mix and propel food through the small
intestine. Rhythmic segmented contractions provide
the major local mixing activity in the small intestine. In this
process, a short segment contracts while adjacent segments are relaxed.
Then, the contracted segment relaxes while previously relaxed adjacent
segments contract. As these contractions alternate, chyme is forced
in both directions, mixed with cell secretions, and brought into
contact with cells lining the lumen. Short waves of peristalsis propel
chyme distally, mixing chyme in successive segments and propelling
it through the intestine.
Localized chemical or mechanical stimulation of the small intestine
results in a contraction on the oral side of the stimulus and relaxation
on the anal side. These responses are controlled by the enteric
nervous system. Sensory neurons that respond to chemicals (eg, acids)
or mechanical stimuli (stroking the mucosa or stretch of the muscle
with a bolus of digesta) activate excitatory ascending interneurons,
which then innervate excitatory motor neurons (Figure
13–16). These neurons release excitatory neurotransmitters,
acetylcholine, and the neuropeptide substance P, which activates
receptors on circular muscle cells to trigger contraction. The sensory
neurons also excite descending interneurons that innervate inhibitory
motor neurons. They, in turn, release inhibitory neurotransmitters,
VIP, and nitric oxide, which relax circular muscle.
The peristaltic reflex of the small intestine. Enteric
sensory nerves detect chemical or mechanical stimulation of the
mucosa or stretch of the muscle layer. Signals are transmitted in
an oral or anal direction by interneurons. Excitatory motor nerves
release acetylcholine (ACh) and substance P (SP), which cause muscle
contraction on the oral side of the stimulus. Inhibitory motor nerves
release vasoactive intestinal peptide (VIP) and nitric oxide (NO),
which cause muscle relaxation on the anal side of the stimulus.
Opiate drugs such as morphine, which are highly
effective for relief of chronic pain (eg, cancer pain), have the
detrimental side effect of inhibiting motility of the small intestine.
Opioids act on enteric nerves to inhibit secretion of excitatory neurotransmitters
to thereby inhibit peristalsis. The inhibition of motility slows
down intestinal transit, allowing for a more complete absorption,
so the volume entering the colon is diminished and constipation
- 31. Describe the hormonal reflex
by which fat in the intestine stimulates the secretion of bile.
- 32. Describe the mechanism by which
glucose is absorbed across the apical and basolateral membranes
of an enterocyte.
- 33. What is the mechanism of absorption
of tripeptides across an intestinal epithelial cell?
- 34. What is the role of bile in lipid
absorption in the intestine?
- 35. List three general mechanisms of
absorption of Na+ ions in the small intestine.
- 36. Describe the mechanism of fluid
and electrolyte secretion in the crypts of Lieberkühn.
- 37. Name two neurotransmitters that
- 38. How do certain bacterial toxins
stimulate fluid and electrolyte secretion in the crypts of Lieberkühn?
- 39. Describe the pattern of intestinal
motility during fasting and after feeding.
- 40. Name one hormone that maintains
the fasting pattern of motility and one that induces the fed pattern
of motility in the small intestine.
- 41. Name the neurotransmiters that mediate
the ascending and descending limbs of the peristaltic reflex.
The adult colon is 1.0–1.5 m in length. Its various
segments (cecum, ascending, transverse, descending, sigmoid colon, and
rectum) are involved in absorption of water and electrolytes, secretion
of mucus, and formation, propulsion, and storage of unabsorbed material
(feces). The colon is also the home of the majority of the intestinal
The surface of the colon consists of a columnar epithelium with
no villi and few folds except in the distal rectum (Figure 13–13).
The epithelial cells include absorptive cells and contain microvilli
on their surface as well as mucus-secreting goblet cells. Colonic
crypts contain goblet cells, endocrine cells, absorptive cells,
and epithelial stem cells.
Absorption of the Colon
Digestion in the colon occurs as a consequence of the action
of the colonic microbiota. Short-chain fatty acids released by microbial
action on dietary fiber are an important source of energy for the
colon. More importantly, these short-chain fatty acids promote survival
of healthy colonic epithelium while inducing apoptosis (programmed
cell death) in epithelial cells that are progressing toward malignant
Absorption of fluid and electrolytes has been well studied and
is a major function of the colon. Up to 5 L of water can be absorbed
per day across the colonic epithelium. Furthermore, the colonic
epithelium can also take up sodium against a considerable concentration
gradient. Aldosterone, a hormone involved in fluid and electrolyte
homeostasis, increases colonic sodium conductance in response to
volume depletion, thus playing an important role in maintaining
fluid and electrolyte balance.
The major secretory product of the colon is mucin, a complex glycoprotein
conjugate that serves to lubricate and prevent the opposing sides
of the intestinal tube from sticking together (thus collapsing the
tube). In addition, mucin performs a protective function as antimicrobial
peptides and immunoglobulins bind to mucin molecules, thus forming
a barrier to intestinal microbes and pathogens.
Unlike the stomach and small intestine, the colon is rarely inactive,
although its activity is less easily characterized than that of the
stomach, which has the pattern known as receptive relaxation, or
than that of the small intestine, which displays the pattern known
as the migrating motor complex and segmental to-and-fro action.
Some patterns are discernible, however, such as the gastrocolic
reflex (colonic mass peristalsis after a meal). Disorders of colonic
motility are common complications of autonomic neuropathy in patients
with diabetes mellitus and can cause severe GI complaints. Continence
of stool requires contraction of the puborectalis muscle and the
anal sphincter. Defecation involves relaxation of the puborectalis
by the sacral parasympathetic nerves, resulting in straightening
of the anorectal angle. Rectal distension results in reflex sympathetic-mediated
internal and external sphincter relaxation.
- 42. How does colonic motility differ
from that in the small intestine?
- 43. What is the major secretory product
of the colon?
- 44. What volume of water is the colon
capable of absorbing per day?