Copyright
© The McGraw-Hill Companies.
Chapter
15. Digestive Tract
Digestive Tract: Introduction
The digestive system consists of the digestive
tract—oral cavity, esophagus, stomach, small and large intestines,
rectum, and anus—and its associated glands—salivary glands, liver, and
pancreas (Figure 15–1). Its function is to obtain
from ingested food the molecules necessary for the maintenance, growth,
and energy needs of the body. Macromolecules such as proteins, fats,
complex carbohydrates, and nucleic acids are broken down into small
molecules that are more easily absorbed through the lining of the
digestive tract, mostly in the small intestine. Water, vitamins, and
minerals from ingested food are also absorbed. In addition, the inner
layer of the digestive tract is a protective barrier between the content
of the tract's lumen and the internal milieu of the body.
The first step in digestion occurs in the mouth,
where food is moistened by saliva and ground by the teeth into smaller
pieces; saliva also initiates the breakdown of carbohydrates. Digestion
continues in the stomach and small intestine, where
the food's basic components (eg, amino acids, monosaccharides, free fatty
acids) are absorbed. Water absorption occurs in the large intestine,
causing undigested material to become semisolid.
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General Structure of the
Digestive Tract
The entire gastrointestinal tract has certain common
structural characteristics. It is a hollow tube with a lumen of variable
diameter and a wall made up of four main layers: the mucosa,
submucosa, muscularis, and serosa. The structure of these
layers is summarized below and is illustrated for the small intestine in
Figure 15–2.
The mucosa comprises an epithelial
lining; an underlying lamina propria of loose connective
tissue rich in blood vessels, lymphatics, lymphocytes and smooth muscle
cells, sometimes also containing glands; and a thin layer of smooth
muscle called the muscularis mucosae usually separating mucosa
from submucosa. The mucosa is frequently called a mucous membrane.
The submucosa contains
denser connective tissue with many blood and lymph vessels and the submucosal
plexus of autonomic nerves. It may also contain glands and lymphoid
tissue.
The thick muscularis is
composed of smooth muscle cells that are spirally oriented and divided
into two sublayers. In the internal sublayer (closer to the lumen), the
orientation is generally circular; in the external sublayer, it is mostly
longitudinal. In the connective tissue between the muscle sublayers are
blood and lymph vessels, as well as another autonomic myenteric nerve
plexus. This and the submucosal plexus together comprise the local enteric
nervous system of the digestive tract, containing largely autonomic
neurons functioning independently of the central nervous system (CNS).
The serosa is a thin
layer of loose connective tissue, rich in blood vessels, lymphatics, and
adipose tissue, with a simple squamous covering epithelium (mesothelium).
In the abdominal cavity, the serosa is continuous with the mesenteries
(thin membranes covered by mesothelium on both sides), which support the
intestines, and with the peritoneum, a serous membrane that lines the
cavity. In places where the digestive tract is not suspended in a cavity
but bound to other structures, such as in the esophagus (Figure 15–1),
the serosa is replaced by a thick adventitia, consisting of
connective tissue containing vessels and nerves, lacking mesothelium.
The main functions of the digestive tract's
epithelial lining are to:
§
Provide a selectively permeable barrier between the
contents of the tract and the tissues of the body,
§
Facilitate the transport and digestion of food,
§
Promote the absorption of the products of this digestion,
§
Produce hormones that affect the activity of the digestive
system,
§
Produce mucus for lubrication and protection.
The abundant lymphoid nodules in the lamina propria
and the submucosal layer protect the organism (in association with the
epithelium) from bacterial invasion, as described in Chapter 14. The necessity for this immunologic support is obvious,
because the entire digestive tract—with the exception of the oral cavity,
esophagus, and anal canal—is lined by a simple thin, vulnerable
epithelium. The lamina propria, located just below the epithelium, is a
zone rich in macrophages and lymphocytes, some of which actively produce
antibodies. These antibodies are mainly immunoglobulin A (IgA) and are
secreted into the intestinal lumen bound to a secretory protein produced
by the epithelial cells. This complex protects against viral and
bacterial invasion. IgA is resistant to proteolytic enzymes and can
therefore coexist with the proteases present in the lumen.
The muscularis mucosae allows local movements of the
mucosa independent of other movements of the digestive
tract, increasing contact of the lining with food. The contractions of
the muscularis, generated and coordinated by autonomic nerve plexuses,
propel and mix the food in the digestive tract. These plexuses are
composed mainly of nerve cell aggregates (multipolar visceral neurons)
that form small parasympathetic ganglia. A rich network of pre- and
postganglionic fibers of the autonomic nervous system and some visceral
sensory fibers in these ganglia permit communication between them. The
number of these ganglia along the digestive tract is variable; they are
most numerous in the regions of greatest motility.
MEDICAL APPLICATION
In certain diseases, such as Hirschsprung disease (congenital megacolon) or Chagas
disease (Trypanosoma cruzi infection), the plexuses in the
digestive tract are severely injured and most of their neurons are
destroyed. This results in disturbances of digestive tract motility, with
frequent dilatations in some areas. The abundant innervation from the
autonomic nervous system that the digestive tract receives provides an
anatomic explanation of the widely observed action of emotional stress on
this tract.
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Oral Cavity
The oral cavity (Figure 15–1) is lined with
stratified squamous epithelium, keratinized or
nonkeratinized, depending on the region. The keratin layer protects the
oral mucosa from damage during masticatory function and is best developed
on the gingiva (gum) and hard palate. The lamina propria in these regions
has many papillae and rests directly on bony tissue. Nonkeratinized
squamous epithelium covers the soft palate, lips, cheeks, and the floor
of the mouth. Surface cells are shed continuously and replaced by progeny
of stem cells in the basal epithelial layer. The lamina propria has
papillae similar to those in the dermis of the skin and is continuous
with a submucosa containing diffuse small salivary glands. The soft
palate also has a core of skeletal muscle and lymphoid nodules. In the lips,
there is also striated muscle and a transition from the oral
nonkeratinized epithelium to the keratinized epithelium of the skin
(Figure 15–3).
Tongue
The tongue is a mass of striated muscle covered by a
mucous membrane whose structure varies according to
the region. The muscle fibers cross one another in three planes and are
grouped in bundles separated by connective tissue. Because the connective
tissue of the lamina propria penetrates the spaces between the muscular
bundles, the mucous membrane is strongly adherent to the muscle. The
mucous membrane is smooth on the lower surface of the tongue. The
tongue's dorsal surface is irregular, covered anteriorly by a great
number of small eminences called papillae. The posterior third of
the tongue's dorsal surface is separated from the anterior two thirds by
a V-shaped groove, the terminal sulcus. Behind this boundary is
the root of the tongue, whose surface shows the many bulges of the
lingual tonsils and smaller collections of lymphoid nodules (Figure
15–4).
The numerous papillae on the
anterior portion of the tongue are elevations of the mucous membrane that
assume various forms and functions. Four types are recognized (Figure
15–4):
§
Filiform papillae (Figure 15–5) are very numerous, have
an elongated conical shape, and are heavily keratinized, which gives
their surface a gray or whitish appearance. Their epithelium lacks taste
buds (described below) and their role is mechanical in providing a rough
surface that facilitates food movement during chewing.
§
Fungiform papillae (Figure 15–5) are less numerous,
lightly keratinized, and mushroom-shaped with connective tissue cores and
scattered taste buds on their upper surfaces. They are irregularly
interspersed among the filiform papillae.
§
Foliate papillae are poorly developed in adults, but
consist of parallel ridges and furrows on the sides of the tongue, with
taste buds.
§
Vallate (or circumvallate) papillae (Figure 15–5)
are the least numerous and largest lingual papillae, and have over half
the taste buds on the human tongue. With diameters of one to three mm,
seven to twelve circular vallate papillae normally form a V-shaped line
just before the terminal sulcus. Ducts from several serous salivary (von
Ebner) glands empty into the deep groove that surrounds each vallate
papilla. This moatlike arrangement provides a continuous flow of fluid
over the taste buds abundant on the sides of these papillae, which washes
food particles from the vicinity so that the taste buds can receive and
process new gustatory stimuli. These glands also secrete a lipase that
prevents the formation of a hydrophobic film over the taste buds that
would hinder their function.
Taste buds are also present in
other parts of the oral cavity, such as the soft palate, and are
continuously flushed by numerous small salivary glands dispersed
throughout the oral mucosa.
Taste buds are ovoid structures, each containing
50–75 cells, within the stratified epithelium of the tongue and the oral
mucosa (Figure 15–6). About half the cells are elongated gustatory
(taste) cells, which turn over with a 7- to 10-day life span. Other
cells present are slender supportive cells, immature cells, and
basal stem cells which divide and give rise to the other two
types. The base of each bud rests on the basal lamina and is entered by
afferent sensory axons that form synapses on the gustatory cells. At the
apical ends of the gustatory cells microvilli project through an opening
called the taste pore. Molecules (tastants) dissolved in saliva contact
the microvilli through the pore and interact with cell surface taste
receptors (Figure 15–6).
Taste buds detect at least five broad categories of
tastants: metal ions (salty); hydrogen ions from acids (sour); sugars and
related organic compounds (sweet); alkaloids and
certain toxins (bitter); and certain amino acids such as glutamate
(umami; Jap. umami, savory). Salty and sour tastes are produced by
ion channels; the other taste categories are mediated by
G-protein-coupled receptors. Receptor binding produces depolarization of
the gustatory cells, stimulating the sensory nerve fibers which send
information to the brain for processing. Conscious perception of tastes
in food requires olfactory and other sensations in addition to taste bud
activity.
Pharynx
The pharynx, a transitional space between the oral
cavity and the respiratory and digestive systems, forms an area of
communication between the nasal region and the larynx (Figure 15–1). The
pharynx is lined by stratified nonkeratinized squamous
epithelium in the region continuous with the esophagus and by ciliated
pseudostratified columnar epithelium containing goblet cells in the
regions close to the nasal cavity.
The pharynx contains tonsils (described in Chapter
14) and the mucosa also has many small mucous
salivary glands in its lamina propria. The constrictor and longitudinal
muscles of the pharynx are located outside this layer.
Teeth
In the adult human there are normally 32 permanent teeth, arranged in two bilaterally
symmetric arches in the maxillary and mandibular bones (Figure 15–7).
Each quadrant has eight teeth: two incisors, one canine, two premolars,
and three permanent molars. Twenty of the permanent teeth are preceded by
deciduous (baby) teeth which are shed; the others
are permanent molars with no deciduous precursors. Each tooth has a crown
exposed above the gingiva, a constricted neck at the gum, and one
or more roots below the gingiva that hold the teeth in bony
sockets called alveoli, one for each tooth (Figure 15–7).
The crown is covered by the extremely hard enamel and the roots by a bone-like tissue called
cementum. These two coverings meet at the neck of the tooth. The
bulk of a tooth is composed of another calcified material, dentin,
which surrounds a soft connective tissue-filled space known as the pulp
cavity (Figure 15–7). The pulp cavity narrows in the roots as the
root canals, which extend to the tip of each root, where an opening (apical
foramen) permits the entrance and exit of blood vessels, lymphatics,
and nerves of the pulp cavity. The periodontal ligaments are
fibrous connective tissue bundles of collagen fibers inserted into both
the cementum and alveolar bone, fixing the tooth firmly in its bony
socket (alveolus).
Dentin
Dentin is a calcified tissue consisting of 70%
calcium hydroxyapatite, making it harder than bone. The organic matrix
contains type I collagen fibers and
glycosaminoglycans secreted by odontoblasts, tall polarized cells
that line the tooth's internal pulp cavity (Figure 15–8). Mineralization
of the predentin matrix involves matrix vesicles in a process
similar to that in osteoid (Chapter 8). Long, slender apical odontoblast
processes lie within dentinal tubules (Figure 15–9) which
penetrate the full thickness of the dentin, gradually becoming longer as
the dentin becomes thicker. Along their length the processes extend fine
branches into smaller lateral branches of the tubules (Figure 15–8).
Odontoblasts remain active in predentin secretion into adult life,
gradually reducing the size of the pulp cavity.
Teeth are sensitive to stimuli such as cold, heat,
and acidic pH, all of which can be perceived as pain.
Pulp is highly innervated and some unmyelinated nerve fibers extend into
the dental tubules near the pulp cavity (Figure 15–9). The different
stimuli can affect fluid inside dentinal tubules, stimulating these nerve
fibers located near odontoblast processes.
MEDICAL APPLICATION
Unlike bone, dentin does not turn over or
get remodeled, persisting as a mineralized tissue long after loss of the
odontoblasts. It is therefore possible to maintain teeth whose pulp and
odontoblasts have been destroyed by infection (canal
treatment). In adult teeth, destruction of the covering enamel by erosion
from use or dental caries (tooth decay) usually triggers a reaction in
odontoblasts that causes them to resume the synthesis of dentin components.
Enamel
Enamel is the hardest component of the human body,
consisting of nearly 98% hydroxyapatite and the rest organic material
including at least two unique proteins, amelogenin
and enamelin, but no collagen. Other ions, such as fluoride, can
be incorporated or adsorbed by the hydroxyapatite crystals; enamel
containing fluorapatite is more resistant to acidic dissolution caused by
microorganisms, hence the addition of fluoride to toothpaste and water
supplies.
Enamel consists of interlocking rods or columns, enamel rods (prisms), bound
together by other enamel. Each rod extends through the entire thickness
of the enamel layer; the precise arrangement of rods in groups is very
important for enamel's strength and mechanical properties.
In developing teeth enamel
matrix is secreted by a layer of cells called ameloblasts, each of
which produces one enamel prism (Figure 15–10). An ameloblast is a long,
polarized cell with numerous mitochondria, well-developed RER and Golgi
apparatus, and an apical extension, the ameloblast process,
containing numerous secretory granules with proteins for the enamel
matrix. After finishing the synthesis of enamel, ameloblasts form a
protective epithelium that covers the crown until the eruption of the
tooth, a function important in preventing several enamel defects.
Enamel is produced by cells of
ectodermal origin, whereas most of the other structures of teeth derive
from mesodermal and neural crest cells. Together these cells produce a
series of structures around the developing oral cavity, the enamel
organs, each of which forms one tooth (Figure 15–11).
Pulp
Tooth pulp consists of connective tissue resembling
mesenchyme. Its main components are the layer of odontoblasts, many
fibroblasts, thin collagen fibrils, and ground substance (Figure 15–11).
Pulp is a highly innervated and vascularized tissue.
Blood vessels and myelinated nerve fibers enter the apical foramen and
divide into numerous branches. Some nerve fibers lose their myelin
sheaths and extend into the dentinal tubules. Pulp fibers are sensitive
to pain.
Gperiodontium
The periodontium comprises the structures
responsible for maintaining the teeth in the maxillary and mandibular
bones. It consists of the cementum, periodontal
ligament, alveolar bone, and gingiva.
Cementum covers the
dentin of the root and is similar in composition to bone, although
osteons and blood vessels are absent. It is thicker in the apical region
around the root, where there are cementocytes, cells resembling
osteocytes, in lacunae. Unlike osteocytes, however, cementocytes do not
communicate via canaliculi and their nourishment comes from external
tissues. Like bone, cementum is labile and reacts to the stresses to
which it is subjected by resorbing old tissue or producing new tissue.
Continuous production of cementum in the apex compensates for the
physiologic wear of the teeth and maintains close contact between the
roots of the teeth and their sockets.
MEDICAL APPLICATION
In comparison with bone, the cementum has
lower metabolic activity because it is not irrigated
by blood vessels. This feature allows the movement of teeth within
alveolar bone by orthodontic appliances without significant root
resorption.
The periodontal ligament
is connective tissue 150 to 350 m thick with
collagen fiber bundles connecting the cementum and the alveolar bone of
the tooth socket (Figure 15–12). It permits limited movement of the tooth
within the socket and the fibers are organized to support the pressures
exerted during mastication. This avoids transmission of pressure directly
to the bone which would cause localized bone resorption. Unlike typical
ligaments, it is highly cellular and has a rich supply of blood vessels
and nerves, giving the periodontal ligament supportive, protective,
sensory, and nutritive functions. Collagen of the periodontal ligament
has an unusually high turnover rate (as demonstrated by autoradiography)
and a high content of soluble collagens, with the space between its
fibers filled with glycosaminoglycans (GAGs).
MEDICAL
APPLICATION
The high rate of collagen renewal in the
periodontal ligament allows processes affecting protein or collagen
synthesis, eg, protein or vitamin C deficiency (scurvy),
to cause atrophy of this ligament. As a consequence, teeth become loose
in their sockets; in extreme cases they fall out.
The alveolar bone is in
immediate contact with the periodontal ligament, which serves as its
periosteum. It is primary (immature) bone, with the collagen fibers not
arranged in the typical lamellar pattern of adult bone. Many of the
collagen fiber bundles of the periodontal ligament penetrate this bone
and bind it to the cementum (Figure 15–12). The bone closest to the roots
of the teeth forms the socket. Vessels run through the alveolar bone and
penetrate the periodontal ligament along the root, with some vessels and
nerves entering the pulp at the apical foramen of each root.
The gingiva is a mucous
membrane firmly bound to the periosteum of the maxillary and mandibular
bones (Figure 15–13). It is composed of stratified squamous epithelium
and lamina propria with numerous connective tissue papillae. A
specialized part of this epithelium, named junctional epithelium,
is bound to the tooth enamel by means of a cuticle resembling a thick
basal lamina. The epithelial cells are attached to this cuticle by
numerous hemidesmosomes. Between the enamel and the epithelium is the gingival
sulcus, a groove up to 3 mm deep surrounding the neck (Figure
15–13a).
MEDICAL APPLICATION
The depth of the gingival sulcus, measured
during clinical dental examinations, is an important indicator of
potential periodontal disease.
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Esophagus
The part of the gastrointestinal tract called the esophagus is a muscular tube whose function is to
transport food from the mouth to the stomach. It is lined by
nonkeratinized stratified squamous epithelium with stem cells scattered
throughout the basal layer (Figure 15–14). In general, the esophagus has
the same major layers as the rest of the digestive tract. In the
submucosa are groups of small mucus-secreting glands, the esophageal
glands, secretions of which facilitate the transport of foodstuffs
and protect the mucosa. In the lamina propria of the region near the
stomach are groups of glands, the esophageal cardiac glands, which
also secrete mucus.
Swallowing begins with
controllable motion, but finishes with involuntary peristalsis. In the
proximal third of the esophagus the muscularis is exclusively skeletal
muscle like that of the tongue. The middle third contains a combination
of skeletal and smooth muscle fibers (Figure 15–14) and in the distal
third the muscularis contains only smooth muscle. Also, only the most
distal portion of the esophagus, in the peritoneal cavity, is covered by
serosa. The rest is enclosed by a layer of loose connective tissue, the adventitia,
which blends into the surrounding tissue.
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Stomach
The stomach, like the small intestine, is a mixed
exocrine-endocrine organ that digests food and secretes hormones. It is a
dilated segment of the digestive tract whose main
functions are to continue the digestion of carbohydrates initiated in the
mouth, add an acidic fluid to the ingested food, transform it by muscular
activity into a viscous mass (chyme), and promote the initial
digestion of proteins with the enzyme pepsin. It also
produces a gastric lipase that digests triglycerides . Gross inspection
reveals four regions: cardia, fundus, body, and pylorus
(Figure 15–15). The fundus and body are identical in microscopic
structure so that only three histologically distinct regions are
recognized. The mucosa and submucosa of the empty stomach have
longitudinally directed folds known as rugae, which flatten when
the stomach is filled with food. The wall in all regions of the stomach
is made up of all four major layers (Figure 15–16).
Mucosa
Changing abruptly at the esophago-gastric junction,
the mucosa of the stomach consists of a simple columnar surface
epithelium that invaginates into the lamina propria, forming gastric
pits (Figures 15–17 and 15–18). Emptying into the gastric pits are
branched, tubular glands characteristic of the stomach region (cardiac,
gastric, and pyloric). Stem cells for the entire epithelial lining of the
stomach are located in the upper regions of these glands near the gastric
pits. The vascularized lamina propria that surrounds and supports
these pits and glands contains smooth muscle fibers and lymphoid cells.
Separating the mucosa from the underlying submucosa is a layer of smooth
muscle, the muscularis mucosae (Figure 15–16).
When the luminal surface of the
stomach is viewed under low magnification, numerous small circular or
ovoid invaginations of the epithelial lining are observed. These are the
openings of the gastric pits (Figures 15–17 and 15–18). The epithelium
covering the surface and lining the pits is a simple columnar epithelium,
the cells of which produce a protective mucus layer. Glycoproteins
secreted by the epithelial cells are hydrated and mix with lipids and
bicarbonate ions also released from the epithelium to form a thick,
hydrophobic layer of gel with a pH gradient from almost 1 at the luminal
surface to 7 at the epithelial cells. The mucus firmly adherent to the
epithelial surface is very effective in protection, while the superficial
luminal mucus layer is more soluble, partially digested by pepsin and
mixed with the luminal contents. Hydrochloric acid, pepsin, lipases, and
bile in the stomach lumen must all be considered as potential endogenous
aggressors to the epithelial lining. Surface epithelial cells also form
an important line of defense due to their mucus production, their tight
intercellular junctions, and ion transporters to maintain intracellular
pH and bicarbonate production. A third line of defense is the underlying
circulatory bed, which provides bicarbonate ions, nutrients, and oxygen
to the mucosal cells, while removing toxic metabolic products. The rich
vasculature also favors the rapid healing of superficial wounds to the
mucosa.
MEDICAL APPLICATION
Stress and other psychosomatic factors;
ingested substances such as aspirin, nonsteroidal
anti-inflammatory drugs or ethanol; the hyperosmolality of meals; and
some microorganisms (eg, Helicobacter pylori) can disrupt this epithelial
layer and lead to ulceration. The initial ulceration may heal, or
it may be further aggravated by the local aggressive agents, leading to
additional gastric and duodenal ulcers. Processes that enable the gastric
mucosa to rapidly repair superficial damage incurred by several factors
play a very important role in the defense mechanism, as does an adequate
blood flow that supports gastric physiologic activity. Any imbalance
between aggression and protection may lead to pathologic alterations. As
an example, aspirin and ethanol irritate the mucosa partly by reducing
mucosal blood flow. Several anti-inflammatory drugs inhibit the
production of prostaglandins of the E type, which are very important
substances for the alkalinization of the mucus layer and, consequently,
important for protection.
Regional Differences in the Stomach Mucosa
The cardia is a narrow
circular region, only 1.5–3 cm in width, at the transition between the
esophagus and the stomach (Figure 15–15). The pylorus is the
funnel-shaped region opening into the small intestine. The mucosa of
these two stomach regions contains tubular glands, usually branched, with
coiled secretory portions called cardial glands and pyloric
glands (Figure 15–19). The pits leading to these glands are longer in
the pylorus. In both regions the glands secrete abundant mucus, as
well as lysozyme, an enzyme that attacks bacterial walls.
In the fundus and body,
the mucosa's lamina propria is filled with branched, tubular gastricglands,
three to seven of which open into the bottom of each gastric pit. Each
gastric gland has an isthmus, a neck, and a base; the distribution of epithelial
cells in the glands is not uniform (Figures 15–15 and 15–20). The isthmus,
near the gastric pit, contains differentiating mucous cells that migrate
and replace surface mucous cells, a few undifferentiated stem cells, and
a few parietal (oxyntic) cells; the neck of the glands consists of
stem cells, mucous neck cells (different from the isthmus mucous cells),
and parietal cells (Figure 15–20); the base of the glands contains
parietal cells and chief (zymogenic) cells. Various enteroendocrine cells
are dispersed in the neck and the base of the glands.
These cells of the gastric
glands provide key stomach functions. Important properties of each are as
follows:
§
Mucous neck cells are present in clusters or as single
cells between parietal cells in the necks of gastric glands (Figure
15–20a). They are irregular in shape, with the nucleus at the base of the
cell and the secretory granules near the apical surface. Their mucus
secretion is less alkaline and quite different from that of the surface
epithelial mucous cells.
§
Parietal cells are present mainly in the upper half
of gastric glands, with fewer in the base. They are large rounded or
pyramidal cells, each with one central spherical nucleus and cytoplasm
that is intensely eosinophilic due to the high density of mitochondria
(Figures 15–20 and 15-21). A striking feature of the active secreting
cell seen in the electron microscope is a deep, circular invagination of
the apical plasma membrane, forming an intracellular canaliculus
(Figure 15–22). Parietal cells secrete both hydrochloric acid (HCl)
and intrinsic factor, a glycoprotein required for uptake of
vitamin B12 in the small intestine. Carbonic anhydrase
produces H2CO3 which dissociates in the cytoplasm
into H+ and HCO3+ (Figure 15–23). The
active cell also releases K+ and Cl– and the Cl–
ions combine with H+ to form HCl. The abundant mitochondria
provide energy for the ion pumps located mainly in the extensive cell
membrane of the microvilli projecting into the canaliculi. Secretory
activity of parietal cells is stimulated both through cholinergic nerve
endings (parasympathetic stimulation) and by histamine and a polypeptide
called gastrin, both secreted by local enteroendocrine cells.
MEDICAL
APPLICATION
In cases of atrophic
gastritis, both parietal and chief cells are much less numerous, and
the gastric juice has little or no acid or pepsin activity. In humans,
parietal cells are the site of production of intrinsic factor, a
glycoprotein that binds avidly to vitamin B12 . In other species,
however, the intrinsic factor may be produced by the chief cells.
The complex of vitamin B12 with intrinsic
factor is absorbed by pinocytosis into the cells in
the ileum; this explains why a lack of intrinsic factor can lead to
vitamin B12 deficiency. This condition results in a disorder
of the erythrocyte-forming mechanism known as pernicious anemia,
usually caused by atrophic gastritis. In a certain percentage of cases,
pernicious anemia seems to be an autoimmune disease, because antibodies
against parietal cell proteins are often detected in the blood of
patients with the disease.
§
Chief (zymogenic) cells predominate in the lower region
of the tubular glands (Figure 15–24) and have all the characteristics of
protein-synthesizing and -exporting cells. The cytoplasmic granules
contain the inactive enzyme pepsinogen. This precursor is rapidly
converted into the highly active proteolytic enzyme pepsin after
being released into the acid environment of the stomach. Pepsins are
aspartate endoproteinases of relatively broad specificity, active at pH
<5. In humans chief cells also produce the enzyme lipase and the hormone
leptin.
§
Enteroendocrine cells are an epithelial cell type in
the mucosa throughout the digestive tract, but are difficult to detect by
routine H&E staining. Different enteroendocrine cells secrete a
variety of hormones, almost all short polypeptides (Table 15–1). They can
be distinguished by TEM but are most easily identified by
immunohistochemistry. In the fundus enterochromaffin cells (EC cells)
are found on the basal lamina of gastric glands (Figure 15–24) and
secrete principally serotonin (5-hydroxytryptamine). In the
pylorus and lower body of the stomach other enteroendocrine cells are
located in contact with the glandular lumens, including Gcells
which produce the polypeptide gastrin. Gastrin stimulates the
secretion of acid by parietal cells and has a trophic effect on gastric
mucosa.
§
Stem cells are few in number and found in the
neck region of the glands. They are low columnar cells with basal nuclei
and divide asymmetrically (Figure 3–20). Some of the daughter cells move upward
to replace the pit and surface mucous cells, which have a turnover time
of 4–7 days. Other daughter cells migrate more deeply into the glands and
differentiate into mucous neck cells and parietal, chief, and
enteroendocrine cells. These cells are replaced much more slowly than are
surface mucous cells.
Table 15–1. Principal
enteroendocrine cells in the gastrointestinal tract.
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|
Cell Type and Location
|
Hormone Produced
|
Major Action
|
X/A-like—stomach
|
Ghrelin
|
Increase
sense of hunger
|
G—pylorus
|
Gastrin
|
Stimulation
of gastric acid secretion
|
S—small
intestine
|
Secretin
|
Pancreatic
and biliary bicarbonate and water secretion
|
K—small
intestine
|
Gastric
inhibitory polypeptide
|
Inhibition
of gastric acid secretion
|
L—small
intestine
|
Glucagon-like
peptide 1 (GLP-1)
|
Decrease
sense of hunger
|
I—small
intestine
|
Cholecystokinin
(CCK)
|
Pancreatic
enzyme secretion, gallbladder contraction
|
D—pylorus,
duodenum
|
Somatostatin
|
Local
inhibition of other endocrine cells
|
Mo—small
intestine
|
Motilin
|
Increased
gut motility
|
EC—digestive
tract
|
Serotonin,
substance P
|
Increased
gut motility
|
D1—digestive
tract
|
Vasoactive
intestinal polypeptide (VIP)
|
Ion and
water gut motility secretion, increased
|
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MEDICAL APPLICATION
Tumors called carcinoids,
which arise from the EC cells, are responsible for the clinical symptoms
caused by overproduction of serotonin. Serotonin increases gut motility,
but high levels of this hormone/neurotransmitter have been related to
mucosal vasoconstriction and damage.
Other Layers of the Stomach
The submucosa is composed
of connective tissue containing blood and lymph vessels; it is
infiltrated by lymphoid cells, macrophages, and mast cells. The muscularis
is composed of smooth muscle fibers oriented in three main directions.
The external layer is longitudinal, the middle layer is circular, and the
internal layer is oblique. Rhythmic contractions of the muscularis serve
to mix ingested food and chyme with the secretions from the gastric
mucosa. At the pylorus, the middle layer is greatly thickened to form the
pyloric sphincter. The stomach is covered by a thin serosa.
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Small Intestine
The small intestine is the site of terminal food
digestion, nutrient absorption, and endocrine secretion. The processes of
digestion are completed in the small intestine, where
the nutrients (products of digestion) are absorbed by cells of the
epithelial lining. The small intestine is relatively long—approximately 5
m—and consists of three segments: duodenum, jejunum, and ileum.
These segments have many characteristics in common and will be discussed
together.
Mucous Membrane
Viewed with the naked eye, the lining of the small
intestine shows a series of permanent circular or semilunar folds (plicae circulares), consisting of mucosa and
submucosa (Figures 15–25 and 15–26), which are best developed in the
jejunum. Intestinal villi are 0.5- to 1.5-mm-long mucosal
outgrowths (epithelium plus lamina propria) and project into the lumen
(Figure 15–25). In the duodenum they are leaf-shaped, but gradually
assume fingerlike shapes moving toward the ileum. Villi are covered by a
simple columnar epithelium of absorptive cells and goblet cells.
Between the villi are small
openings of short tubular glands called intestinal crypts or crypts
of Lieberkühn (Figure 15–27). The epithelium of each villus is
continuous with that of the intervening glands, which contain
differentiating absorptive and goblet cells, Paneth cells,
enteroendocrine cells, and stem cells that give rise to all these cell
types.
Enterocytes, the
absorptive cells, are tall columnar cells, each with an oval nucleus in
the basal half of the cell (Figure 15–28). At the apex of each cell is a
homogeneous layer called the striated (or brush) border.
When viewed with the electron microscope, the striated border is seen to
be a layer of densely packed microvilli (Figures 15–25e and
15–28c). As discussed in Chapter 4, each microvillus is a cylindrical
protrusion of the apical cytoplasm approximately 1 m tall and 0.1 m in diameter
containing actin filaments and enclosed by the cell membrane. Each
absorptive cell is estimated to have an average of 3000 microvilli and 1
mm2 of mucosa contains about 200 million of these structures.
Microvilli greatly increase the area of contact between the intestinal
surface and the nutrients, a function also of the plicae and villi, which
is an important feature in an organ specialized for absorption. It is
estimated that plicae increase the intestinal surface three-fold, the
villi increase it 10-fold, and the microvilli increase it 20-fold.
Together, these processes are responsible for a 600-fold increase in the
intestinal surface, resulting in a total absorptive area of 200 m2!
Enterocytes absorb the nutrient
molecules produced by digestion. Disaccharidases and peptidases secreted
by these cells and bound to the microvilli hydrolyze the disaccharides
and dipeptides into monosaccharides and amino acids that are easily
absorbed through active transport. Digestion of fats results from the
action of pancreatic lipase and bile. In humans, most of the lipid
absorption takes place in the duodenum and upper jejunum and Figure 15–29
illustrates basic aspects of lipid absorption.
MEDICAL
APPLICATION
Deficiencies of disaccharidases have been
described in human diseases characterized by
digestive disturbances. Some of the enzymatic deficiencies seem to be of
genetic origin.
The absorption of nutrients is also
greatly hindered in disorders marked by atrophy of the intestinal mucosa
caused by infections or nutritional deficiencies, producing
the malabsorption syndrome.
Goblet cells are
interspersed between the absorptive cells (Figures 15–25 and 15–28). They
are less abundant in the duodenum and more numerous in the ileum. These
cells produce glycoprotein mucins that are hydrated and cross-linked to
form mucus, whose main function is to protect and lubricate the lining of
the intestine.
Paneth cells, located in
the basal portion of the intestinal crypts below the stem cells, are
exocrine cells with large, eosinophilic secretory granules in their
apical cytoplasm (Figures 15–27 and 15–30). Paneth cell granules undergo
exocytosis to release lysozyme, phospholipase A2, and hydrophobic
peptides called defensins, all of which bind and breakdown membranes of
microorganisms and bacterial walls. Paneth cells have an important role
in innate immunity and in regulating the microenvironment of the
intestinal crypts.
Enteroendocrine cells are
present in varying numbers throughout the length of the small intestine,
secreting various peptides (Table 15–1) and representing part of the
widely distributed diffuse neuroendocrine system (Chapter 20).
Upon stimulation these cells release their secretory granules by
exocytosis and the hormones may then exert paracrine (local) or endocrine
(blood-borne) effects. Polypeptide-secreting cells of the digestive tract
fall into two classes: a "closed" type, in which the cellular
apex is covered by neighboring epithelial cells (Figures 15–24 and 15–28)
and an "open" type, in which the apex of the cell has
microvilli and contacts the lumen (Figure 15–31). Peptides produced have
both endocrine and paracrine effects, which include the control of
peristalsis, regulation of secretions necessary for food digestion, and
the sense of being satiated after eating.
MEDICAL
APPLICATION
The hormone secretin, produced by
enteroendocrine cells of the small intestine, was the
very first hormone to be discovered. Two brothers-in-law, William Bayliss
and Ernest Starling, working at University College London in 1900
observed that the factor caused the pancreas to secrete its alkaline
digestive fluid and they named it "secretin." They decided
further to call secretin a "hormone," from the Greek verb
hormaein, "to excite or set in motion." Since that time
hormones purified from tissue or made synthetically have had an enormous
impact in treating innumerable medical disorders.
M (microfold) cells
are specialized epithelial cells in the ileum overlying the lymphoid
follicles of Peyer patches. As discussed in Chapter 14, these cells are
characterized by the presence of basal membrane invaginations or pockets
containing many intraepithelial lymphocytes and antigen-presenting cells
(Figure 14–16). M cells selectively endocytose antigens and transport
them to the underlying macrophages and lymphocytes, which then migrate to
lymph nodes where immune responses to foreign antigens are initiated. M
cells thus serve as sampling stations where material in the lumen of the
gut is transferred to immune cells of the MALT in the lamina propria. The
basement membrane under the M cells is porous, facilitating transit of
cells between the lamina propria and the pockets of M cells (Figure
15–32).
Lamina Propria through Serosa
The lamina propria of the small intestine is
composed of loose connective tissue with blood and
lymph vessels, nerve fibers, and smooth muscle cells. The lamina propria
penetrates the core of each intestinal villus, bringing with it
microvasculature, lymphatics, and nerves (Figures 15–25 and 15–33).
Smooth muscle fibers inside the villi are responsible for their rhythmic
movements, which are important for efficient absorption. The muscularis
mucosae also produces local movements of the villi and plicae circulares.
The proximal part of the
duodenum has, primarily in its submucosa but extending into the mucosa,
large clusters of branched tubular mucous glands, the duodenal (or
Brunner) glands, with small excretory ducts opening among
the intestinal crypts (Figure 15–34). The product of the glands is
distinctly alkaline (pH 8.1–9.3), which neutralizes chyme entering the
duodenum from the pylorus, protecting the mucous membrane and bringing
the intestinal contents to the optimum pH for pancreatic enzyme action.
In the ileum both the lamina propria and submucosa contain the lymphoid
nodule aggregates known as Peyer patches, an important component
of the MALT.
The muscularis is well developed
in the small intestine, composed of an internal circular layer and an
external longitudinal layer, and is covered by a thin serosa with
mesothelium (Figures 15–25, 15–26 and 15–35).
Vessels & Nerves
The blood vessels that nourish the intestine and
remove absorbed products of digestion penetrate the
muscularis and form a large plexus in the submucosa (Figure 15–34). From
the submucosa, branches extend through the muscularis mucosae and lamina
propria and into the villi. Each villus receives, according to its size,
one or more branches that form a capillary network just below its
epithelium. At the tips of the villi, one or more venules arise from
these capillaries and run in the opposite direction, reaching the veins
of the submucosal plexus. The lymph vessels of the intestine begin as
closed tubes in the cores of villi. These capillaries (lacteals),
despite being larger than the blood capillaries, are often difficult to
observe because their walls are so close together that they appear to be
collapsed. Lacteals run to the region of lamina propria above the
muscularis mucosae, where they form a plexus. From there they are
directed to the submucosa, where they surround lymphoid nodules. Lacteals
anastomose repeatedly and leave the intestine along with the blood
vessels. They are especially important for lipid absorption; chylomicrons
of lipoprotein are preferentially taken up by lacteals rather than blood
capillaries.
Another process important for intestinal function is
the rhythmic movement of the villi. This movement is the result of the contraction of smooth muscle fibers running
vertically from the muscularis mucosae to the tip of the villi (Figure
15–33). These contractions occur at the rate of several strokes per
minute and have a pumping action on the villi that propel the lymph to
the mesenteric lymphatics.
The innervation of the intestines is formed by
intrinsic and extrinsic components comprising the enteric nervous system.
The intrinsic component comprises many small and diffuse groups of
neurons that form the myenteric (Auerbach) nerve
plexus (Figures 15–33 and 15–35) between the outer longitudinal and
inner circular layers of the muscularis and the smaller submucosal
(Meissner) plexus in the submucosa. The enteric nervous system
contains some sensory neurons that receive information from nerve endings
near the epithelial layer and in the muscularis regarding the intestinal
content (chemoreceptors) and the degree of intestinal wall expansion
(mechanoreceptors). Other nerve cells are effectors innervating the
muscle layers and hormone-secreting cells. The intrinsic innervation
formed by these plexuses is responsible for the intestinal contractions
that occur even in the absence of the extrinsic innervation that
modulates the activity.
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Large Intestine
The large intestine or bowel
consists of a mucosal membrane with no folds except in its distal
(rectal) portion and no villi (Figure 15–36). The mucosa is penetrated
throughout its area by tubular intestinal glands lined by goblet and
absorptive cells, with a small number of enteroendocrine cells (Figures
15–37 and 15–38). The absorptive cells or colonocytes are columnar
and have short, irregular microvilli (Figure 15–38d). Stem cells for the
epithelium of the large bowel are located in the bottom third of each
gland. The large intestine is well suited to its main functions:
absorption of water, formation of the fecal mass from undigestible
material, and production of mucus that lubricates the intestinal surface.
The lamina propria is rich in
lymphoid cells and in lymphoid nodules that frequently extend into the
submucosa (Figure 15–37). The richness in MALT is related to the large
bacterial population of the large intestine. The muscularis comprises
longitudinal and circular strands, but differs from that of the small
intestine, with fibers of the outer layer gathered in three longitudinal
bands called taeniae coli (Figure 15–37). Intraperitoneal portions
of the colon are covered by serosa, which is characterized by small,
pendulous protuberances of adipose tissue.
Near the beginning of the large intestine, the appendix is an evagination of the cecum. It is
characterized by a relatively small and irregular lumen, shorter and less
dense tubular glands, and no taeniae coli. Although it has no function in
digestion, the appendix is a significant component of the MALT, with abundant
lymphoid follicles in its wall (Figure 15–39).
MEDICAL
APPLICATION
Because the appendix is a closed sac and
its contents are relatively static, it can easily become a site of
inflammation (appendicitis). With the small
lumen and relatively thin wall of the appendix, inflammation and the
growth of lymphoid follicles in the wall can produce swelling that can
lead to bursting of the appendix. Severe appendicitis is a medical
emergency since a burst appendix will produce infection of the peritoneal
cavity.
In the anal region, the mucous
membrane forms a series of longitudinal folds, the anal columns
(Figure 15–36). About two cm above the anal opening, at the recto-anal
junction, the lining of the mucosa is replaced by stratified squamous
epithelium (Figure 15–40). In this region, the lamina propria contains a
plexus of large veins that, when excessively dilated and varicose, can
produce hemorrhoids.
MEDICAL APPLICATION
Approximately 90–95%
of malignant tumors of the digestive system are derived from gastric or
intestinal epithelial cells, usually in the large intestine. Malignant
tumors of the colon are derived almost exclusively from its glandular
epithelium (adenocarcinomas) and are the second most common cause
of cancer deaths in the United States.
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