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Discussion post – Adv. Patho
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Question: The gastrointestinal (GI) tract is the body’s entry point for nutrients, including fluids and electrolytes needed to sustain life. Disorders of the GI tract are often grouped into the following categories: alteration of digestive function, absorptive function, immunologic function, and neuroendocrine function.
What are the stimuli to the multiple substances that control gastric acid secretion? What risks result from having strong acidity in the stomach?
What is the pathophysiology of Helicobacter pylori?
Book:
Advanced Physiology and Pathophysiology
Essentials for Clinical Practice
Tkacs, Nancy C., PhD, RN |
Herrmann, Linda L., PhD, RN, AGACNP-BC, GNP-BC, ACHPN, FAANP |
Johnson, Randall L., PhD, RN
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13
GASTROINTESTINAL TRACT
Wilson Crone
THE CLINICAL CONTEXT
T
he gastrointestinal (GI) tract is the body’s
point of entry for nutrients, including fluids
and electrolytes needed to sustain life. The GI
tract is also the route of most medications that
are administered, including prescribed, overthe-counter, and many street drugs. GI functions
are complex, and clinicians must appreciate the
varied components of those functions and implications for nutritional homeostasis, immune function, and quality of life.
GI disorders are common in the United States
and globally. Abdominal pain is estimated to
account for 27 million annual office visits in the
United States. Common conditions, such as gastroesophageal reflux (7 million diagnoses annually), hemorrhoids (4 million diagnoses annually),
constipation, diarrhea, and nausea and vomiting,
are often self-diagnosed and managed (although
this may not be appropriate!).1 Although GI drugs
such as proton pump inhibitors and laxatives are
not prescribed with the frequency of medications for chronic disorders such as diabetes and
hypertension, over-the-counter sales of these and
other GI drugs constitute more than 15% of the
retail market. Sales for heartburn products alone
totaled $3.23 billion in 2018, indicating that many
people experience occasional or frequent heartburn and self-medicate.2
Disorders of the GI tract are often grouped into
the following categories: alteration of digestive
function, absorptive function, immunologic function, and neuroendocrine function. Some disorders are organic, whereas others are functional
disorders. Many acute GI disorders result from
infections with bacteria, viruses, or parasites.
Copyright Springer Publishing Company. All Rights Reserved.
From: Advanced Physiology and Pathophysiology
DOI: 10.1891/9780826177087.0013
These can be self-limiting or can progress to
chronic infections such as Helicobacter pylori
and Clostridioides difficile. Chronic inflammatory bowel diseases such as Crohn disease
and ulcerative colitis cause significant disability
including intestinal failure. Cancer of the colon
and rectum ranks third in prevalence among all
cancer cases in the United States, and pancreatic
cancer deaths rank third among all deaths due to
cancer. This chapter reviews the structure, function, and regulation of the GI tract and the most
common disorders associated with each site.
OVERVIEW OF GASTROINTESTINAL
STRUCTURE AND FUNCTION
The GI tract is surprising in its complexity, functioning as:
• The gateway to oral nutrient, drug, and toxicant
access to the rest of the body
• The most critical site of fluid and electrolyte homeostasis outside the kidneys
• The site of digestion and absorption of nutrients
• The route of excretion of insoluble dietary fiber,
products of liver transformation of endogenous
compounds and xenobiotics, and cholesterol
Beyond these well-known functions, there are
several other important characteristics of the GI tract.
• It is the body’s largest immune organ, with cells and
tissues of both innate and adaptive immunity.
• It is the only organ with a freestanding nervous
system, the enteric nervous system.
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Advanced Physiology and Pathophysiology: Essentials for Clinical Practice
• It has a high concentration and variety of neurotransmitters, modulators, and hormones, greater
than most other organs outside the brain.
• Its mucosal epithelial cells have a high cell turnover
rate, potentially removing cells that have sustained
damage (but also associated with vulnerability to
malignant transformation).
The major function of the gut is to mechanically
and chemically process materials (digestion) for
absorption. In particular, the process of chemical
digestion depends on hydrolysis, or the breaking
down of dietary macromolecules into their components: starches into monosaccharides (sugars), proteins into peptides and amino acids, and lipids into
fatty acids, monoglycerides, and cholesterol. This
breakdown is followed by transport of these components across intestinal epithelial cells (IECs) that
line the lumen. Accessory organs such as salivary
glands, liver and gallbladder, and pancreas supply
digestive fluids such as saliva, bile, and digestive
enzymes, respectively.
To place these processes and functions into context, this chapter provides a proximal to distal survey
of the organs of the GI tract, from the mouth and salivary glands, through the esophagus, stomach, small
intestine, pancreas, and large intestine, highlighting
their contributions to nutritional processing, and also
providing examples of pathological processes that can
arise. Included is an overview of general organizing
principles of digestion.
Many viral or bacterial infectious disorders cause
acute, self-limited GI dysfunction, including vomiting and diarrhea. Chronic GI disorders may present
with pain, diarrhea, or constipation, as well as signs
and symptoms of malabsorption and critical nutrient
deficiencies. Some chronic conditions improve upon
identification and remediation of dietary and lifestyle
triggers, whereas others (e.g., type 3 intestinal failures)
require chronic treatment.
ALIMENTARY CANAL STRUCTURE
AND MOTOR ACTIVITY
The different segments of the alimentary canal have
characteristic contributions to digestion and absorption, including motor activity, secretions, and transit
time (average duration from entry to exit) as listed here
and shown in Figure 13.1.
• Mouth: Chewing begins food breakdown, swallowing moves food to esophagus; 10 seconds to 2
minutes transit time; secretions are saliva, amylase
(begins starch digestion), and lingual lipase (initiates fat digestion)
Mouth
Esophagus
Stomach
Small
intestine
Colon
FIGURE 13.1 Gastrointestinal tract overview.
• Esophagus: Peristalsis quickly moves food to stomach;
transit time is less than 30 seconds; mucus secretion
• Stomach: Grinds and mixes food with secretions,
peristalsis moves food to small intestine; 15 minute
to 3 hour transit time; secretes hydrochloric acid
(HCl), pepsin to initiate protein digestion, lipase to
continue fat digestion, and intrinsic factor to aid in
vitamin B12 absorption
• Small intestine: Segmentation contractions mix
food with digestive enzymes and improve absorption, peristalsis to move food along length; 2-5 hour
transit time; secretions from pancreas (enzymes and
bicarbonate), bile from liver and gallbladder, mucus
secretion
• Large intestine: Segmentation contractions and
peristalsis; 12-24 hour transit time; mucus secretion
Structurally, the alimentary canal is a single tube
from the mouth to the anus, consisting of four layers
with specific functions (Figure 13.2 and Box 13.1).
The muscle layer (muscularis) of the GI tract consists of smooth muscle cells with the mechanisms of
contraction described in Chapter 4, Cell Physiology
and Pathophysiology. Contractions of the circular
smooth muscle layer squeeze the intestinal contents,
whereas contractions of the longitudinal muscle
layer propagate action potentials along the length
Chapter 13 • Gastrointestinal Tract
469
Artery Mesentery
Submucosa
Submucosal plexus
Glands in
submucosa
Vein
Nerve
Gland in mucosa
Duct of gland
outside tract
Lymphatic
tissue
Lumen
Mucosa:
Epithelium
Lamina propria
Muscularis
mucosae
Muscularis:
Circular muscle
Longitudinal muscle
Myenteric plexus
Serosa
FIGURE 13.2 The general structure of GI tract components surrounding the lumen. These layers include
the mucosa, the layer of epithelial cells over connective tissue and a thin muscle layer; submucosa,
containing blood vessels, glands, lymphoid tissues, and a nerve plexus; muscularis, layers of circular
and longitudinal smooth muscle separated by blood and lymph vessels and a nerve plexus; and serosa,
connective tissue and covering epithelial layer.
BOX 13.1
Structure of the Gastrointestinal Tract
From the luminal side to the serosa, the layers of
the alimentary canal are as follows:
1. Mucosa: The mucosal epithelium varies,
depending on its location in the GI tract. In the
mouth and esophagus, the epithelium consists of a
nonkeratinizing stratified squamous epithelium. In
the rest of the tract for the stomach and intestines, the
epithelium consists of simple columnar epithelium.
Loose connective tissue—the lamina propria—
underlies the epithelium. Regional specializations
can be seen along the length of the mucosa.
Examples include gastric pits in the stomach and the
projections of villi in the small intestine. The mucosa
is delineated from the submucosa by a thin muscle
layer, the muscularis mucosae, which is innervated
by the submucosal plexus.
2. Submucosa: Additional dense connective tissue
with an extensive vascular supply distinguishes the
submucosa from the mucosa. A notable feature is
the submucosal glands (Brunner glands) in the
duodenal region that secrete bicarbonate-rich fluid
to neutralize acidic chyme exiting from the stomach.
3. Muscularis (externa): This tissue consists of
internal circular and external longitudinal smooth
muscle layers that perform the primary actions
of peristalsis and segmentation. These two
layers are joined in the stomach by an additional
oblique layer of musculature, contributing to the
churning activities of the stomach. In the colon,
the longitudinal muscles are separated out as
teniae coli that, at the cecum, converge at the
base of the vermiform appendix. The muscle is
innervated by the myenteric plexus. Each gut
region has specific motility patterns of muscle
contraction that contribute to moving the food
bolus through and onto the next region.
4. Adventitia/serosa: This outer layer is either
a collection of loose connective tissue, as an
adventitia that attaches the intestines to the
dorsal wall of the abdomen, or as a squamous
cell–covered serosal layer that allows the
abdominal organs to slide against each other.
This serosal layer is continuous with the visceral
peritoneum that extends from the posterior
abdominal wall in a dorsal mesentery pattern.
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of the tract and also shorten the tract. Three major
types of motor activity characterize GI motility:
1. Peristalsis moves GI tract contents away from the
mouth, toward the anus (called aboral movement),
caused by contractions that progress from one segment to the next segment of the tract.
2. Segmentation contractions mainly occur in the small
intestines. Alternate rings of intestine contract, then
relax, without an appreciable wave sweeping from
one segment to the next. These contractions aid in
mixing the gut contents to optimize the exposure of
dietary macromolecules to digestive enzymes and the
exposure of products of digestion (monomers) to the
absorptive brush border of the mucosa. Periodically
peristalsis will occur, moving intestinal contents in
the aboral direction. A similar type of activity is found
in the colon and promotes exposure of the colon contents to the mucosal surface responsible for fluid reabsorption that reduces fecal volume and fluidity.
3. The migrating motor complex is a wave of contractions that occurs every 1 to 2 hours between meals,
propelling any GI tract contents from the stomach
through the end of the small intestine.
Medulla
Thoracic spinal cord
Sympathetic
neuron
Vagal
sensory
neuron
Parasympathetic
neuron
NEURAL, HUMORAL, AND IMMUNE REGULATION
OF GASTROINTESTINAL FUNCTION
The principal functions of the gut to digest and absorb
ingested food require intermittent changes in motor activity, the nature of which varies depending on the gut segment, and release of secretions (saliva, gastric juice, bile,
pancreatic fluid) that are also segment specific and time
dependent. Mediators synthesized and secreted by neurons, endocrine cells of the gut, and other specialized cell
types contribute to coordinated regulation of GI motor
and secretory function. Optimal digestion and absorption
are achieved by integrated signals during the progress of a
meal as foodstuffs proceed longitudinally along the tract.
Gastrointestinal Innervation
The innervation of the gut has two components: the extrinsic nervous system and enteric (intrinsic) nervous system
(Figure 13.3). Extrinsic input is via the autonomic nervous system, providing sympathetic and parasympathetic
control. Sympathetic innervation reflects the embryological formation of the alimentary canal, with its developmental regions of foregut (associated with celiac arterial
blood supply and sympathetic ganglia), midgut (associated with the superior mesenteric artery and ganglia), and
Spinal sensory
neuron
Sacral spinal
cord
Myenteric
plexus
Vagal nerves
Sympathetic
chain
Parasympathetic
neuron
Extrinsic
nerve
Mesentery
Medulla
Prevertebral
ganglia
Thoracic
spinal
cord
Sacral
spinal
cord
Pelvic nerves
Submucosal
plexus
(a)
Mucosa
(b)
FIGURE 13.3 Overview of GI innervation. (a) Neurons in the two plexuses of the enteric nervous
system have sensory and motor connections with the autonomic nervous system. Parasympathetic
efferent supply comes from the brainstem dorsal motor nucleus of the vagus and sacral
parasympathetic nuclei, vagal afferents project to the brainstem. Sympathetic supply comes from
preganglionic neurons in the thoracic spinal cord that relay via sympathetic ganglia, accompanied
by spinal afferent fibers. (b) Overview of anatomical arrangement of extrinsic GI innervation.
Chapter 13 • Gastrointestinal Tract
hindgut (associated with the inferior mesenteric artery
and ganglia). In contrast, the parasympathetic supply for
most of the alimentary tract consists of the vagus nerve
(cranial nerve [CN] X), which supplies the proximal GI
tract through the ascending colon. The parasympathetic
pelvic autonomic nerves supply the distal colon. Although
most of the parasympathetic nerve supply is afferent (sensory), there is also efferent tone. This circuit facilitates
vagovagal reflexes that stimulate smooth muscle activity
and release of digestive secretions.
Autonomic control of the gut is by parasympathetic
neurons of the vagus nerve and sympathetic neurons
from the spinal cord (Figure 13.4). Cell bodies of vagal
neurons projecting to the GI tract via the vagus nerve (X)
are located in the medullary dorsal motor nucleus of the
vagus nerve (DMV). Sympathetic preganglionic neurons
(spinal sympathetic neurons [SSNs]) projecting to the GI
tract have cell bodies in the thoracic spinal cord relaying
Amygdala
Hypothalamus
VLM
SSNs
NTS
AP
DMV
X
GI tract
FIGURE 13.4 Brainstem control of the GI tract. Vagal
parasympathetic neurons (blue) are located in the DMV, with
efferent fibers carried by the vagus nerve (cranial nerve X—
identified by X in the figure). Gut afferents (sensory fibers
indicated by projections from the GI tract back to the brain)
relay sensations of stretch, pressure, irritation, and pain via
autonomic nerves. Vagal sensory fibers terminate in the NTS.
Neurons of the VLM regulate the activity of SSNs (red), which
also receive spinal sensory inputs. Within the brainstem, the
area postrema (AP—chemoreceptor trigger zone) and NTS
modulate both parasympathetic and sympathetic outflows.
Higher centers, particularly limbic cortex, interact via multiple
pathways (not shown) that project through the amygdala
to the hypothalamus to influence GI activity via autonomic
nerves. These centers (purple) contribute to stress-induced
alterations in GI signaling and disorders.
DMV, dorsal motor nucleus of the vagus nerve; NTS, nucleus
of the tractus solitarius; SSNs, spinal sympathetic neurons;
VLM, ventrolateral medulla.
471
to postganglionic neurons in the sympathetic ganglia
listed earlier. Sensory fibers travel in the vagus nerve to
the nucleus of the tractus solitarius (NTS) in the medulla.
The NTS then can relay impulses to the DMV. Vagal activity can also be modulated by impulses from the area
postrema (chemoreceptor trigger zone, discussed later).
Some GI sensory neurons travel with sympathetic fibers,
providing reflex input to SSNs. Higher centers alter GI
activity during acute and chronic stress states by stimulating the amygdala and subsequently the hypothalamus.
The hypothalamus can modulate DMV activity and activity of the ventrolateral medulla (VLM), a region of sympathoexcitatory pathways.
In contrast, neurons of the intrinsic (enteric) nervous
system can independently control contractile, secretory,
and endocrine functions of the GI tract, although modulated by autonomic system input. Of all the internal
organs, the GI tract is unique in the number and roles of
neurons that mainly function independently of the central nervous system. As noted, the neurons of the enteric
nervous system are found in two layers of the gut wall:
Neurons in the submucosal plexus principally regulate
GI secretions and the microcirculation; neurons in the
myenteric plexus regulate motility by stimulating or
inhibiting circular and longitudinal smooth muscle contraction. This intrinsic behavior can be seen causing peristaltic contraction of the small intestine. The presence
of the semidigested chyme from the stomach within
the lumen triggers an ascending/excitatory pathway
of neurons to stimulate depolarization and subsequent
contraction of the muscle behind the bolus, whereas a
descending/inhibitory pathway causes the muscle in
front of the bolus to hyperpolarize and to relax.
Gastrointestinal Hormones and Mediators
Modulate Gastrointestinal Function
Peptide hormones (e.g., those made by GI endocrine cells)
and paracrine signaling agents synthesized and secreted
within the mucosa interact with membrane G-protein–
coupled receptors and typically trigger rapid responses
from stimulation of second messenger systems. Gut hormones allow signaling from one segment of the GI tract
to distant segments, gallbladder, and pancreas, to coordinate responses in successive phases of meal digestion
and absorption. Unlike classical hormones secreted by
endocrine glands and tissues, gut hormones are secreted
by a variety of enteroendocrine cells interspersed among
the cells of the stomach and IEC layer.
Four major peptide hormones assist in coordinating the digestive activities of the stomach, small intestine, liver (bile), and pancreas. Gastrin is secreted by
G cells of the stomach and stimulates parietal cells to
secrete hydrochloric acid (HCl) and intrinsic factor.
Cholecystokinin (CCK) is secreted by I cells of the small
intestine in response to nutrient sensing and stimulates
gallbladder contraction and pancreatic enzyme secretion,
as well as slowing gastric emptying. Secretin is secreted
by S cells of the small intestine and stimulates pancreatic
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Advanced Physiology and Pathophysiology: Essentials for Clinical Practice
Cellular sources
Enteric neurons
Endocrine cells
Immune cells
Opioid messengers
Met-and leu-enkephalin
Dynorphin
β-Endorphin
Cellular targets
Enteric motor neurons
Enteric secretomotor neurons
Extrinsic primary afferent neurons
Immune cells
Molecular targets
µ-Opioid receptors
κ-Opioid receptors
δ-Opioid receptors
Constipation
Inhibition of enteric nerve activity
• Reduction of enteric nerve excitability
• Pre- and postsynaptic inhibition of excitatory and inhibitory pathways
Inhibition of propulsive motor activity
• Inhibition of distention-induced peristalsis
• Elevation of muscle tone
• Induction of non propulsive motility patterns
Inhibition of ion and fluid secretion
FIGURE 13.5 Endogenous opioids regulate GI function through opioid receptors. Their actions are
inhibitory, thus promoting constipation. Exogenous opioids used for pain management often cause
severe constipation.
GI, gastrointestinal.
Source: From Holzer P. Opioid receptors in the gastrointestinal tract. Regul Pept. 2009;155:11–17.
secretion of water and bicarbonate. There is also glucosedependent insulinotropic peptide (GIP), secreted by K
cells of the duodenum; it inhibits gastric acid secretion
and enhances insulin response to oral glucose.
In addition to hormones, several classes of gut peptides
act in a hormone- or neurotransmitter-type fashion. These
include paracrine peptides secreted by endocrine cells of
the GI tract with an intended local action, such as somatostatin, a peptide that inhibits many GI functions. Other
gut peptides act as hormones on other target tissues,
including glucagon-like peptide 1 (GLP-1), released from
the distal small intestine, which decreases stomach motility in addition to stimulating pancreatic insulin secretion.
Peptide YY, also released from the distal small intestine
and the colon, acts on the brain as a satiety signal.
Peptides that are present in the gut may serve primarily
as neurotransmitters, modulating enteric neuron activity
or directly targeting gut motility and secretion. Vasoactive
intestinal peptide, a vasodilator, also serves as a gut transmitter, causing smooth muscle relaxation and increasing
intestinal secretions. Substance P is an excitatory neurotransmitter in the gut. The gut is also richly endowed
with opioid receptors (primarily the μ type, although δ and
κ opioid receptors are also present), and several opioid
transmitters have been localized to the gut. Stimulation of
gut opioid receptors inhibits gut neurotransmission, motility, and secretion. Thus, morphine and other opioid drugs
used for pain management or taken as drugs of abuse have
the significant side effect of constipation. Therapeutically,
these actions of opioids, such as loperamide (which does
not cross the blood–brain barrier), are the basis of their
use as antidiarrheal agents (Figure 13.5).
Gastrointestinal Amine Neurotransmitters
and Mediators
Acetylcholine is the neurotransmitter of the parasympathetic nervous system that increases gut motility
and secretion. Norepinephrine is the sympathetic neurotransmitter that decreases gut motility and secretion.
The mediators, histamine and serotonin, which function
in inflammation and blood clotting, have these and other
actions in the GI tract. In fact, the GI tract contains 90%
of the serotonin in the body.3 Enterochromaffin-like cells
in the wall of the stomach produce histamine as a mediator that stimulates gastric acid secretion. Similar cells
in the intestinal mucosa produce serotonin as an excitatory mediator promoting intestinal motility through its
actions on the enteric nervous system and gut afferents.
Chapter 13 • Gastrointestinal Tract
This multitude of mediators in GI physiology and
pathophysiology provides the rational basis for pharmacological management of GI disorders. As new mediators are identified, additional therapies are developed,
allowing people who suffer from disabling functional
gut disorders to have improved activity levels and quality of life. Major peptides, transmitters, and other factors influencing GI activity are listed in Table 13.1.
Gastrointestinal Immunology
Ingestion of food and beverages required for nutritional and metabolic support and fluid and electrolyte
473
homeostasis also represents a threat to the organism,
as environmental toxins and pathogens are internalized through this route. Furthermore, the gut microbiota, resident bacterial species that have a commensal
role in human physiology, stimulate immune defenses
that prevent systemic invasion. The gut has a variety
of structural protective mechanisms as well as surveillance by cells of innate and adaptive immunity
to resist infectious diseases. Many of these mechanisms are summarized in Figure 13.6. Immune cells
(B cells, T cells, macrophages, dendritic cells) are
distributed in many gut-associated lymphoid tissues
TABLE 13.1 Gastrointestinal Tract Hormones and Modulators
Hormone,
Neurotransmitter
Secretion Site
Functions
Peptides
Gastrin
Stomach antrum, duodenum
Stimulates acid and histamine secretion; promotes mucosal growth
Cholecystokinin
Duodenum, jejunum, ileum
Stimulates gallbladder contraction, pancreatic enzyme secretion, and
pancreatic bicarbonate secretion; inhibits gastric emptying, satiety
Secretin
Duodenum, jejunum
Stimulates bicarbonate secretion from pancreas and bile, pancreatic growth,
and insulin secretion; inhibits gastrin and gastric acid secretion
GIP
Small intestine
Promotes glucose-stimulated insulin secretion
Motilin
Duodenum
Stimulates motility, including the migrating motor complex
Somatostatin
Pancreas, throughout GI tract
Inhibits gastric acid secretion, insulin and glucagon secretion, and gut motility
and secretion
Ghrelin
Stomach
Stimulates gastric motility and sensation of hunger
GLP-1
Pancreas, ileum
Signals satiety; decreases gastric motility; stimulates insulin secretion
GLP-2
Ileum, colon
Promotes growth of mucosal cells
Peptide YY
Ileum, colon
Inhibits gastric secretion and emptying, and intestinal motility; signals satiety
Classical and Peptide Neurotransmitters
Acetylcholine
Parasympathetic and enteric
neurons
Stimulates motility and secretions; relaxes sphincters
Norepinephrine
Sympathetic neurons
Decreases motility and secretions; constricts sphincters; stimulates
vasoconstriction of GI vasculature
Dopamine
Sympathetic neurons
Has mixed effects of stimulation and inhibition of motility
Serotonin
Enteric neurons
Stimulates sensory neurons to increase motility and secretions; involved in
nausea and emesis
Enkephalin
Enteric neurons
Inhibits motility
Substance P
Enteric neurons
Increases motility and neurogenic inflammation
Vasoactive intestinal
peptide
Enteric neurons
Inhibits motility; stimulates fluid and electrolyte secretion from epithelium
and bile duct cells
Nonpeptide Modulators
Histamine
Stomach, small intestine
Stimulates gastric acid secretion and inflammatory responses
Nitric oxide
Enteric neurons
Generally inhibitory
GIP, glucose-dependent insulinotropic peptide; GLP, glucagon-like peptide.
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Advanced Physiology and Pathophysiology: Essentials for Clinical Practice
Microbiota
Antigen
uptake
via GAP
Secreted
antimicrobial
peptides
Goblet cells
Mucus
(a) Small Intestine
Crypt
Peyer patches
Microbiota
Enterocyte
T cell
Outer mucus
Monocyte
Inner mucus
Colonocytes
Goblet cells
Bacteria
Paneth cell
B cell
Tuft cell
Myofibroblast
Enteroendocrine
cell
Macrophage
M cell
Seceretory lgA
IEL
Antigen
DC
Plasma cell
Crypt
(b) Colon
FIGURE 13.6 Bacteria are found in both (a) the small intestine and (b) colon. These gut microbiota
are usually nonpathogenic and contribute to normal gut function. To protect against overgrowth
of normal microbiota as well as ingested pathogens, the gut epithelial layer and submucosa have
extensive immune surveillance and effector functions, including antimicrobial-secreting Paneth
cells, plasma cells that secrete IgA, colonic goblet cells that secrete mucin and protective proteins,
M cells that take up antigens and interact with immune cell clusters in the submucosa, gutassociated lymphoid tissues such as Peyer patches, and freely moving DCs, macrophages, and
T and B lymphocytes.
DC, dendritic cell; IEL, intraepithelial lymphocyte; IgA, immunoglobulin A.
Source: From Allaire JM, et al. The intestinal epithelium: central coordinator of mucosal immunity.
Trends Immunol. 2018;39:677–696.
Chapter 13 • Gastrointestinal Tract
(GALT)—clusters of lymph cells called Peyer patches
in the lamina propria beneath the epithelial cell layer.
Peyer patches are found throughout the small intestine
and are particularly numerous in the ileum. In the epithelial layer itself, cells contributing to immunity include
intraepithelial lymphocytes, Paneth cells, and M cells.
IECs lining the small and large intestine are linked
by tight junctions that resist the movement of bacteria
between cells. IECs also express Toll-like receptors,
enabling them to recognize pathogens. Goblet cells
secrete mucus that presents an additional barrier to
bacterial movement. In the small intestine, Paneth cells
in the base of the crypts secrete antimicrobial peptides
that directly attack pathogenic bacteria. Several of the
other cell types also secrete a variety of antimicrobial
substances. B cells secrete immunoglobulin A (IgA),
which moves across the epithelial barrier to neutralize
pathogens within the gut lumen. M cells are specialized
to take up antigens from the lumen and transfer them to
antigen-presenting cells such as dendritic cells within
the mucosal layer. M cells are found above the Peyer
patches, forming a route of communication between the
lumen and the immune defense system. Different types
of lymphocytes are found in the mucosal region and
interspersed between IECs. Absorptive enterocytes at
the tips of the villi can, if infected, undergo breakdown
and move into the gut lumen for excretion in the feces,
removing pathogens from the body. Macrophages
beneath the epithelial layer can phagocytose pathogens
and initiate an inflammatory response to mobilize other
phagocytes to clear invading organisms.4
Thought Questions
1. What are the overall functions of the GI tract, and
how does the general gut structure contribute to
these functions?
2. What is the significance of having multiple levels
of regulation of gut function, from neural and
endocrine to paracrine regulation?
3. Why is it so important to have extensive representation of immune cells within the gut wall?
PROPERTIES AND DISORDERS
OF DIGESTIVE TRACT ORGANS
MOUTH
Ingestion and mechanical processing of food occur in
the mouth, with mastication driven by teeth and jaw
muscles. Secretion of saliva assists with lubrication
of the food for improved mixing by mastication. Some
475
chemical digestion also occurs here, particularly in the
form of salivary amylase, which triggers initial carbohydrate breakdown.
Swallowing is an initially voluntary process in the
mouth that shifts to involuntary pharyngeal and esophageal phases. Involuntary propulsion, mediated by
branches of the vagus nerve as controlled by a swallowing center in the medulla, sets up a peristaltic wave
that moves the food down the esophagus to the stomach. The upper esophageal sphincter (UES) opens to
allow the bolus of food to pass from the pharynx to the
esophagus, while the epiglottis closes across the trachea to protect the airway.
SALIVARY GLANDS
There are three major pairs of salivary glands: sublingual, submandibular, and parotid. Their relative contributions of mucus and watery secretions vary, depending
on the histology of the different organs. Their connection
to the mouth can affect the pathophysiology associated
with them, as the shorter parotid (Stensen) duct is not as
prone to sialolithiasis (salivary stones) as the long, winding path of the submandibular (Wharton) duct.
Saliva contains water and mucus to help moisten
food, the digestive enzyme α-amylase (ptyalin) to begin
carbohydrate digestion, antimicrobial agents such as
lysozyme that help to break down bacterial cell walls,
and electrolytes such as calcium and fluoride (to help
maintain enamel) or bicarbonate (to help buffer regurgitated stomach contents). Both parasympathetic and
sympathetic neurons stimulate salivary secretion,
although parasympathetic activity predominates.
The loss of salivary gland function, as occurs with
aging, radiation exposure, or with immunological conditions such as Sjögren syndrome, can result in an increase
in dental caries, from the lack of enamel maintenance;
increased regurgitatory damage, from the loss of
buffering; or dysphagia, from the loss of moistening.
ESOPHAGUS
The esophagus acts as a conduit from the pharynx to
the proximal stomach. This collapsible muscular pipe
is usually kept mildly sealed by means of an upper and
a lower esophageal sphincter (LES). There are three
relative compression points in the esophagus: (a) the
esophageal–pharyngeal junction, (b) the point where
the left mainstem bronchus and aortic arch cross over
it, and (c) the gastroesophageal junction that occurs
through the esophageal hiatus of the diaphragm. Each
of these points can be damaged by ingestion of caustic
substances, leading to narrowing. Esophageal motility
consists of peristalsis of the bolus of swallowed food,
whereas the LES stays in a state of contraction until the
food bolus reaches it, when relaxation allows movement into the stomach.
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Advanced Physiology and Pathophysiology: Essentials for Clinical Practice
Disorders of the Esophagus
Decreased
pressure
Esophageal Obstruction
Esophageal obstruction is typically caused by
mechanical stenosis, most commonly from inflammation, such as by chronic gastroesophageal reflux.
In contrast, achalasia is a condition of esophageal
obstruction due to the loss of inhibitory neuron function in the myenteric ganglia. The loss of inhibition
leads to increased LES tone and the inability of peristalsis to move a food bolus into the stomach. Achalasia
manifests with progressive dysphagia and a classic
radiographic “bird’s beak” presentation of esophageal
dila
