DIGESTIVE SYSTEM

ORAL CAVITY
 The digestive system—a long, tortuous, hollow tube—comprises the
mouth (or oral cavity), pharynx, and digestive tube or tract (also called
the alimentary canal). Associated with this tract are accessory glands of
digestion: salivary glands, liver, gallbladder, and pancreas, which lie
outside the wall of the tube but are connected to it via ducts. The
digestive system engages in many functions such as propulsion,
secretion, absorption, excretion, immunologic protection, and hormone
production. For convenience, this system can be divided into upper and
lower tracts. The upper digestive tract facilitates ingestion and initial
phases of digestion. It includes the oral cavity and associated structures
(lips, teeth, palate, tongue, cheeks), pharynx, and esophagus. The
lower tract deals mostly with digestion, absorption, and excretion. It
includes the stomach, small and large intestines, and anal canal.
 Ingest
1200 mL water Saliva 1500 mL
800 g food pH 6.8-7.0

Gastric secretions
2000 mL
pH 1.5-3.0

Bile 500 mL
Small intestine pH 7.8 -8 .0
absorbs
8500 mL

Pancreatic secretions
1500 mL
pH 8 .0 -8.4

Intestinal secretions
Large intestine 1500 mL
absorbs pH 7.8 -8.0
400 mL

Excreted
100 mL water
50 g solids
 The oral cavity consists of the mouth and its structures, which include the tongue, teeth
and their supporting structures (periodontium), major and minor salivary glands, and tonsils.
The oral cavity is lined by the oral mucosa that consists of masticatory mucosa, lining mucosa,
and specialized mucosa.

The masticatory mucosa is found on the gingiva (gums) and the hard palate. It has a
keratinized and,in some areas, a parakeratinized stratified squamous epithelium.
Parakeratinized epithelium is similar to keratinized epithelium except that the superficial cells do
not lose their nuclei and their cytoplasm does not stain intensely with eosin. The nuclei of the
parakeratinized cells are pyknotic (highly condensed) and remain until the cell is exfoliated. The
keratinized epithelium of the masticatory mucosa resembles that of the skin but lacks a stratum
lucidum. The underlying lamina propria consists of a thick papillary layer of loose connective
tissue that contains blood vessels and nerves, some of which send bare axon endings into the
epithelium as sensory receptors, and some of which end in Meissner’s corpuscles. Deep to the
lamina propria is a reticular layer of denser connective tissue. As in the skin, the depth and
number of connective tissue papillae contribute to the relative immobility of the masticatory
mucosa, thus protecting it from frictional and shearing stress. At the midline of the hard palate,
in the palatine raphe, the mucosa adheres firmly to the underlying bone. The reticular layer of
the lamina propria blends with the periosteum, and thus, there is no submucosa. The same is
true of the gingiva. Where there is a submucosa underlying the lamina propria on the hard
palate, it contains adipose tissue anteriorly (fatty zone) and mucous glands posteriorly
(glandular zone) that are continuous with those of the soft palate. In the submucosal regions,
thick collagenous bands extend from the mucosa to the bone.
 Lining mucosa is found on the lips, cheeks, alveolar mucosal surface, floor of the mouth, inferior
surfaces of the tongue, and soft palate. At these sites, it covers striated muscle (lips, cheeks, and tongue),
bone (alveolar mucosa), and glands (soft palate, cheeks, inferior surface of the tongue). The lining mucosa
has fewer and shorter papillae so that it can adjust to the movement of its underlying muscles. Generally,
the epithelium of the lining mucosa is nonkeratinized, although in some places, it may be parakeratinized.
The epithelium of the vermilion border of the lip (the reddish portion between the moist inner surface and
the facial skin) is keratinized. The nonkeratinized lining epithelium is thicker than keratinized epithelium. It
consists of only three layers:
• Stratum basale, a single layer of cells resting on the basal lamina
• Stratum spinosum , which is several cells thick
• Stratum superficiale, the most superficial layer of cells, also referred to as the surface layer o f the
mucosa
The cells of the mucosal epithelium are similar to those of the epidermis of the skin and include
keratinocytes, Langerhans’ cells, melanocytes, and Merkels cells.
The lamina propria contains blood vessels, nerves that send bare axon endings into the basal layers of
the epithelium, and encapsulated sensory endings in some papillae. The sharp contrast between the
numerous deep papillae of the alveolar mucosa and the shallow papillae in the rest of the lining mucosa
allows easy identification of the two different regions in a histologic section.
A distinct submucosa underlies the lining mucosa except on the inferior surface of the tongue. This
layer contains large bands of collagen and elastic fibers that bind the mucosa to the underlying muscle; it
also contains the many minor salivary glands of the lips, tongue, and cheeks. Occasionally, sebaceous glands
not associated with a hair follicle are found in the submucosa just lateral to the corner of the mouth and in
the cheeks opposite the molar teeth. They are visible to the eye and are called Fordyce spots. The
submucosa contains the larger blood vessels, nerves, and lymphatic vessels that supply the subepithelial
neurovascular networks in the lamina propria throughout the oral cavity.
Specialized mucosa is associated with the sensation of taste and is restricted to the dorsal surface of
the tongue. It contains papillae and taste buds responsible for generating the chemical sensation of taste.
 Section through the upper lip.

Hair shaft
Oral surface
Mucous glands
Sebaceous glands
Epidermis
Lamina propria
Orbicularis oris muscle

Submucosa

Stratified squamous
epithelium
Mucocutaneous
junction

Early carcinoma of the lip.

BV LP
Ep
BV

De

HF
*
SSE *
HS

LMs of parts of the lip. Left, The vermilion border is stratified squamous epithelium (SSE) with a thin layer of surface keratin, below. Underlying
connective tissue—lamina propria (LP)—contains many blood vessels (BV). The highly corrugated interface between epithelium and connective tissue
shows tall papillae (*) penetrating the epithelium to take capillaries close to the surface. Right, The external cutaneous surface, of typical thin skin, consists
of epidermis (Ep) and underlying dermis (De). A hair follicle (HF) and associated hair shaft (HS) are seen. Left: 130×; Right: 85×. H&E.
The tongue is a muscular organ projecting into the oral cavity from its
inferior surface. Lingual muscles (i.e., muscles of the tongue) are both
extrinsic (having one attachment outside of the tongue) and intrinsic
(confined entirely to the tongue, without external attachment). The
striated muscle of the tongue is arranged in bundles that generally run
in three planes, with each arranged at right angles to the other two. This
arrangement of muscle fibers allows enormous flexibility and precision
in the movements of the tongue, which are essential to human speech
as well as to its role in digestion and swallowing. This form of muscle
organization is found only in the tongue, which allows easy identification
of this tissue as lingual muscle. Variable amounts of adipose tissue are
found among the muscle fiber groups. Grossly, the dorsal surface of the
tongue is divided into an anterior two-thirds and a posterior one-third
by a V-shaped depression, the sulcus terminalis. The apex of the V
points posteriorly and is the location of the foramen cecum, the
remnant of the site from which an evagination of the floor of the
embryonic pharynx occurred to form the thyroid gland.
 Dorsum of tongue.
Epiglottis
Palatine tonsil Ep
Lingual tonsil
Root Foramen cecum
Schematic stereogram of
Circumvallate area indicated above.
LP
Foliate Filiform papillae
papillae Lingual tonsil
Body Filiform
Fungiform
SM

Fungiform papilla
Duct of gland
Section of taste bud. LM of the dorsum of the tongue at low
Intrinsic muscle Crypt magnification. Many lingual papillae give the
Mucous glands epithelial surface (Ep) an irregular contour.
Sustentacular cell Circumvallate papilla
Sensory cell Stratified epithelium rests on a lamina propria
Taste buds
Taste pore (LP). Deep in underlying connective tissue are
Serous glands of von Ebner fascicles of skeletal muscle fibers (SM)
sectioned in different planes. 7×. H&E.

Left: LM of the undersurface of

CVP the tongue. The smooth mucosa has a
relatively simple contour. The nonker-
* * atinized stratified squamous epithelium
Ep LP (Ep) consists of many layers of cells and
rests on a lamina propria (LP) of loose
connective tissue. Upward projections of
lamina propria into the epithelium form
connective tissue papillae (*). 120×. H&E.
*
SG
* * Right: LM of the dorsal surface of
the tongue. A deep trench-like furrow
SM (*) surrounds the circumvallate papilla
LP (CVP) on the mucosal surface. Serous
glands of von Ebner (SG) drain into the
base of each furrow via small ducts
(arrows). Deep to the lamina propria
(LP) are bundles of skeletal muscle
fibers (SM). 20×. H&E.
Papillae cover the dorsal surface of the tongue. Numerous mucosal irregularities tongue anterior to the
sulcus terminalis. The lingual papillae and their associated taste buds constitute the specialized mucosa of
the oral cavity. Four types of papillae are described: filiform, fungiform, circumvallate, and foliate.
• Filiform papillae are the smallest and most numerous in humans. They are conical, elongated projections
of connective tissue that are covered with highly keratinized stratified squamous epithelium. This epithelium
does not contain taste buds. The papillae serve only a mechanical role. Filiform papillae are distributed over
the entire anterior dorsal surface of the tongue, with their tips pointing backward. They appear to form rows
that diverge to the left and right from the midline and that parallel the arms of the sulcus terminalis.
• Fungiform papillae, as the name implies, are mushroom-shaped projections located on the dorsal surface
of the tongue. They project above the filiform papillae, among which they are scattered, and are just visible
to the unaided eye as small spots. They tend to be more numerous near the tip of the tongue. Taste buds
are present in the stratified squamous epithelium on the dorsal surface of these papillae.
• Circumvallate papillae are the large, dome-shaped structures that reside in the mucosa just anterior to the
sulcus terminalis. The human tongue has 8 to 12 of these papillae. Each papilla is surrounded by a moat-like
invagination lined with stratified squamous epithelium that contains numerous taste buds. Ducts of lingual
salivary (von Ebner's) glands empty their serous secretion into the base of the moats. This secretion
presumably flushes material from the moat to enable the taste buds to respond rapidly to changing stimuli.
• Foliate papillae consist of parallel low ridges separated by deep mucosal clefts, which are aligned at right
angles to the long axis of the tongue. They occur on the lateral edge of the tongue. In aged individuals, the
foliate papillae may not be recognized; in younger individuals, they are easily found on the posterior lateral
surface of the tongue and contain many taste buds in the epithelium of the facing walls of neighboring
papillae. Small serous glands empty into the clefts. In some animals, such as the rabbit, foliate papillae
constitute the principal site of aggregation of taste buds. The dorsal surface of the base of the tongue
exhibits smooth bulges that reflect the presence of the lingual tonsil in the lamina propria.
 fo lia te p apilla

fu n g ifo rm p apilla

i re u n id a 11at<
p a p illa

s e ro u s ^
g la n d s ^ -
 Teeth are a major component of the oral cavity and are essential for the beginning
of the digestive process. Teeth are embedded in and attached to the alveolar
processes of the maxilla and mandible. Children have 10 deciduous (primary, milk)
teeth in each jaw, on each side. During a period of years, usually beginning at about
age 6 and ending at about age 12 or 13, deciduous teeth are gradually replaced by 16
permanent (secondary) teeth in each jaw.
Each tooth consists of a free crown projecting above the gingiva, and one or more
roots embedded in a bony socket (or alveolus) of the jaws. Despite different forms
and functions, all teeth share the same histologic plan. Each root is attached to bone
by densely packed collagen fibers, which form the periodontal membrane. A central
pulp chamber extends into root canals. These communicate via apical foramina, at
root tips, with a periodontal membrane and the tooth exterior. The pulp chamber
contains a core of loose connective tissue—soft, gelatinous dental pulp. Pulp contains
blood vessels, lymphatics, and nerves that enter and leave via apical foramina. Three
mineralized tissues—dentin, enamel, and cementum—make up tooth walls. Dentin
surrounds the pulp cavity and is the bulk of the tooth. Enamel forms a cap over the
outer dentin surface in the area of the crown and may be 2.5 mm thick in some teeth.
On roots, cementum covers dentin.
 Teeth are made up of three specialized tissues:
Enamel, a hard, thin, translucent layer of acellular mineralized tissue that covers
the crown of the tooth. Enamel is the hardest substance in the body; it consists of 96%
to 98% calcium hydroxyapatite. Enamel is an acellular mineralized tissue that covers
the crown of the tooth. Once formed, it cannot be replaced. Enamel is a unique tissue
because, unlike bone, which is formed from connective tissue, it is a mineralized
material derived from epithelium. Enamel is more highly mineralized and harder than
any other mineralized tissue in the body; it consists of 96% to 98% of calcium
hydroxyapatite. Enamel varies in thickness over the crown and may be as thick as 2.5
mm on the cusps (biting and grinding surfaces) of some teeth. The enamel layer ends
at the neck, or cervix, of the tooth at the cementoenamel junction; the root of the
tooth is then covered by cementum, a bone-like material.
Enamel is composed of enamel rods that span the entire thickness of the enamel
layer. The nonstoichiometric carbonated calcium hydroxyapatite enamel crystals that
form the enamel are arranged as rods that measure 4 µm wide and 8 µm high. Each
enamel rod spans the full thickness of the enamel layer from the dentinoenamel
junction to the enamel surface. When examined in cross-section at higher
magnification, the rods reveal a keyhole shape; the ballooned part, or head, is
oriented superiorly, and the tail is directed inferiorly toward the root of the tooth. The
enamel crystals are primarily oriented parallel to the long axis of the rod within the
head, and in the tail, they are oriented more obliquely. The limited spaces between
the rods are also filled with enamel crystals.
 The root is the part of the tooth that fits into the alveolus or jaw socket in the maxilla or
mandible. Cementum is a thin layer of bone-like material that covers roots of teeth beginning at
the cervical portion of the tooth at the cementoenamel junction and continuing to the apex.
Cementum is produced by cementoblasts (large cuboidal cells that resemble the osteoblasts of
the surface of growing bone). Cementoblasts secrete an extracellular matrix called cementoid
that further undergoes mineralization. A layer of cementoblasts is present on the outer surface
of the cementum, adjacent to the periodontal ligament. During cementogenesis, cementoblasts
are incorporated into the cementum and become cementocytes, cells that closely resemble
osteocytes in bone. Like bone, cementum is 65% mineral and contains the highest concentration
of fluoride of any mineralized tissue. The lacunae and canaliculi in the cementum contain the
cementocytes and their processes, respectively. They resemble those structures in bone that
contain osteocytes and osteocyte processes. Unlike bone, cementum is avascular. In addition,
the lacunae are irregularly distributed throughout the cementum and their canaliculi do not
form an interconnecting network. Collagen fibers that project out of the matrix of the
cementum and embed in the bony matrix of the socket wall form the bulk of the periodontal
ligament. These fibers are another example of Sharpey's fibers. In addition, elastic fibers are
also a component of the periodontal ligament. This mode of attachment of the tooth in its
socket allows slight movement of the tooth to occur naturally. It also forms the basis of
orthodontic procedures used to straighten teeth and reduce malocclusion of the biting and
grinding surfaces of the maxillary and mandibular teeth. During corrective tooth movements,
the alveolar bone of the socket is resorbed and resynthesized but the cementum is not.
 Dentin lies deep to the enamel and cementum. It contains less hydroxyapatite than
enamel, about 70%, but more than is found in bone and cementum. Dentin is secreted by
odontoblasts that form an epithelial layer over the inner surface of the dentin, that is, the
surface that is in contact with the pulp. Like ameloblasts, odontoblasts are columnar cells that
contain a well-developed rER, a large Golgi apparatus, and other organelles associated with the
synthesis and secretion of large amounts of protein. The apical surface of the odontoblast is in
contact with the forming dentin; junctional complexes between the odontoblasts at that level
separate the dentinal compartment from the pulp chamber. The layer of odontoblasts retreats
as the dentin is laid down, leaving odontoblast processes embedded in the dentin in narrow
channels called dentinal tubules. Predentin is the newly secreted organic matrix, closest to the
cell body of the odontoblast, which has yet to be mineralized. Although most of the proteins in
the organic matrix are similar to those of bone, predentin contains two unique
proteins:
• Dentin phosphoprotein (DPP), highly acidic phosphorylated protein, which is rich in
aspartic acid and phosphoserine and binds large amounts of calcium. DPP is involved in the
initiation of mineralization and in control of mineral size and shape.
• Dentin sialoprotein (DSP), proteoglycan that is rich in aspartic and glutamic acids, serine,
glycine, and chondroitin 6-sulfate. DSP is also involved in the mineralization process.
Dentin is the first mineralized component of the tooth to be deposited. As the odontoblasts
move centrally, the odontoblastic processes elongate; the longest are surrounded by the
mineralized dentin. In newly formed dentin, the wall of the dentinal tubule is simply the edge of
the mineralized dentin. With time, the dentin immediately surrounding the dentinal tubule
becomes more highly mineralized; this more mineralized sheath of dentin is referred to as the
peritubular dentin. The remainder of the dentin is called the intertubular dentin.
 Supporting tissues of the teeth include the alveolar bone of the alveolar processes of the
maxilla and mandible, periodontal ligaments, and gingiva.
The periodontal ligament is the fibrous connective tissue joining the tooth to its
surrounding bone. This ligament is also called the periodontal membrane, but neither term
describes its structure and function adequately. The periodontal ligament provides for the
following:
• Tooth attachment (fixation)
• Tooth support
• Bone remodeling (during movement of a tooth)
• Proprioception
• Tooth eruption
A histologic section of the periodontal ligament shows that it contains areas of both dense
and loose connective tissue. The dense connective tissue contains collagen fibers and fibroblasts
that are elongated parallel to the long axis of the collagen fibers. The loose connective tissue in
the periodontal ligament contains blood vessels and nerve endings.
The gingiva is a specialized part of the oral mucosa located around the neck of the tooth. It
is firmly attached to the teeth and to underlying alveolar bony tissue. The gingiva is composed
of two parts:
• Gingival mucosa, which is synonymous with the masticatory mucosa described above
• Junctional epithelium, or attachment epithelium, which adheres firmly to the tooth.
The term periodontium refers to all the tissues involved in the attachment of a tooth to the
mandible and maxilla. These include the junctional epithelium, the cementum, the periodontal
ligament, and the alveolar bone.
enamel
lines of Retzius

dentin showing dentinal tubules

interglobular spaces

odontoblasts

gingival sulcus

epithelium of gingiva
cementoenamel junction

epithelial attachment

pulp chamber

granular layer of Tomes

fibers of periodontal

cementum

alveolar bone
with marrow
pulp canal
cementum

foramen
F I G U R E 1 6 . 9 ▲ Diagram showing th e basic organization and
structure o f enam el rods. The enamel rod is a th in structure extending
from the dentinoenam el ju n ctio n to th e surface o f the enamel. Where the
enamel is thickest, at the tip o f the crown, th e rods are longest, measuring
up to 2,000 jim On cross-section, th e rods reveal a keyhole shape. The
upper, ballooned part o f th e rod, called th e head, is oriented superiorly,
and the lower part of the rod, called the tail, is directed inferiorly. Within
the head, most o f the enamel crystals are oriented parallel to the long
axis o f each rod. W ithin the tail, the crystals are oriented more obliquely.
 enamel rods (long axis)
5 months
in utero
secretory-stage
ameloblasts

neonatal
3

distal terminal
web

junctional
complex
hydroxyapatite
crystals

F I G U R E 1 6 . 1 3 ▲ Schematic diagram s o f a p artia lly form ed to o th showing details o f amelogenesis. a . The enamel is drawn to show
th e enamel rods extending from the dentinoenam el ju n ctio n to the surface o f the tooth. A lthough the full thickness o f the enamel is formed, the full
thickness o f the dentin has n o t yet been established.The contour lines w ithin the dentin show the extent to w hich the dentin has developed at a partic­
ular tim e, as labeled in the illustration. Note th a t th e p ulp cavity in the center o f the to o th becomes smaller as the dentin develops. (Based on Schour I,
Massler M. The neonatal line in the enamel and dentin o f the human deciduous teeth and first perm anent molar. J Am Dent Assoc 1936;23:1948.)
b. During amelogenesis, enamel form ation is influenced by the path o f the ameloblasts. The rod produced by the ameloblast forms in the wake o f the
cell. Thus, in mature enamel, the direction o f th e enamel rod is a record o f the path taken earlier by the secretory-stage ameloblast. c. A t the apical pole
o f th e secretory-stage ameloblasts are Tomes'processes, surrounded by the developing enamel. Junctional complexes at the apical pole and distal
term inal w eb are also shown. Note the numerous m atrix-containing secretory vesicles in the cytoplasm o f the processes.
 [oaoTitQgiasre]

iprLe:qentini ipriexaeritiri]
dental pulp

blood
vessels

Odontoblasts

F I G U R E 1 6 . 1 7 A Dental pulp and structure o f d e n tin .This photom icrograph o f a decalcified to o th shows the centrally located dental pulp,
surrounded by dentin on both sides. The dental pulp is a soft tissue core o f the to o th that resembles em bryonic connective tissue, even in the adult. It
contains blood vessels and nerves. Dentin contains th e cytoplasmic processes o f the odontoblasts w ith in dentinal tubules. They extend into the denti-
noenamel junction. The cell bodies o f th e odontoblasts are adjacent to the unmineralized dentin called the predentin. X120. Left inset. Longitudinal
profiles o f the dentinal tubules. X240. Right inset. Cross-sectional profiles o f dentinal tubules. The dark outline o f the dentinal tubules, as seen in both
insets, represents the peritubular dentin, which is the more mineralized part o f the dentin. X240.
 gingival sulcus
margin of gingiva>

free gingiva

free
junctional
gingival
groove epithelium
attached circular
fibers
gingiva
dento-
gingival
fibers
muco- dento-
gingival periosteal
junction fibers
cementum
alveolar
mucosa dentin

peridontal ligaments
F I G U R E 1 6 . 2 1 ▲ Schematic d iag ram o f g ingiva. This sche­
m atic diagram o f gingiva corresponds to the rectangular area o f the
orientation diagram.The gingival epithelium is attached to the enamel o f
the tooth. Here, the junction between epithelium and connective tissue
is smooth. Elsewhere, the gingival epithelium is deeply indented by
connective tissue papillae, and the junction between the tw o is irregular.
The black lines represent collagen fibers from the cem entum o f th e tooth
and from the crest o f the alveolar bone that extend toward the gingival
epithelium. Note the shallow papillae in the lining mucosa (alveolar
mucosa) that contrast sharply w ith those o f the gingiva.
 Odontogenesis
The first sign of odontogenesis (tooth development) occurs between the sixth and seventh weeks of gestation, when the
ectodermally derived oral epithelium proliferates. The result of this mitotic activity is the formation of a horseshoe-shaped
band of epithelial cells, the dental lamina, surrounded by neural crest–derived ectomesenchyme of the mandibular and
maxillary arches. The dental lamina is separated from the ectomesenchyme by a well-defined basal lamina.
Bud Stage
Shortly after the appearance of the dental lamina, mitotic activity increases on the inferior aspect of this epithelial band of
each arch. This activity is responsible for the formation of 10 discrete epithelial structures, known as buds, initiating the bud
stage of tooth development. These buds presage the 10 deciduous teeth of
both the maxillary and the mandibular arches. At the inferior tip of each bud, ectomesenchymal cells congregate to form
the presumptive dental papilla. Further development, although similar for each bud, is asynchronous, corresponding to the
order of emergence of the various teeth of the child.
Cap Stage
As cells of the bud proliferate, this structure not only increases in size but also alters its shape to form a three-layered
configuration, known as the cap, initiating the cap stage of tooth development. Two of the three layers—the convex simple
squamous outer enamel epithelium (OEE) and the concave simple squamous inner enamel epithelium (IEE)—are
continuous with each other at a rim-like region, the cervical loop. They enclose a third layer, the stellate reticulum (SR),
whose cells have numerous processes that are in contact with one another. These epithelially derived layers, constituting
the “plump” enamel organ, are separated from the surrounding ectomesenchyme by a basal lamina. The concavity of the
cap is occupied by a congregation of ectomesenchymal cells, the dental papilla. The dental papilla becomes vascularized
and innervated during the cap stage of tooth development. The dental papilla and the enamel organ, together, are known
as the tooth germ. One can imagine the enamel organ to resemble an insulated cup in which the handle is the dental
lamina that is connected to the oral epithelium; the outer surface of the cup is the OEE; the inner surface is the IEE; and the
rim of the cup, where the inner and outer surface meet, is the cervical loop. The insulation located between the inner and
outer surfaces is the SR, and the cup is filled with the dental papilla. Ectomesenchymal cells surrounding the tooth germ
form a vascularized membranous capsule, the dental sac (dental follicle), which gives rise to the cementum, PDL, and
alveolus. Cells of the IEE differentiate into preameloblasts, which mature into ameloblasts to form enamel.
 Bell Stage and Appositional Stage
Proliferation of the cells of the tooth germ increases its size, and the accumulation of fluid
within the enamel organ increases its plump appearance. In addition, its concavity deepens, and
another layer of cells develops between the IEE and SR of the enamel organ. This new layer of
cells is the stratum intermedium, and its appearance characterizes the bell stage of tooth
development. In response to the histodifferentiation of the inner enamel epithelial cells, the
most peripheral cells of the dental papilla (those in contact with the basal lamina) also
differentiate to become preodontoblasts that will mature into dentin-producing columnar cells,
known as odontoblasts. Shortly after the odontoblasts begin to elaborate dentin matrix (a
noncalcified material) into the basal lamina, the ameloblasts also begin to manufacture enamel
matrix (also a noncalcified material). The dentin and enamel matrices adjoin each other, and the
junction between them is the dentinoenamel junction (DEJ). The tooth germ is now said to be
in the appositional stage of odontogenesis. This cytoplasmic extension, known as the
odontoblastic process, is surrounded by dentin. The space occupied by the odontoblastic
process is the dentinal tubule. As the ameloblasts secrete enamel matrix, their apical region
becomes constricted by the matrix, forming Tomes process. The ameloblasts then move away
from the newly elaborated enamel, and the constricted region expands to its previous size. The
cyclic nature of the Tomes process formation continues until enamel formation ceases. As
dentin matrix becomes calcified to form dentin, the process of calcification spreads into the
enamel matrix, which also calcifies and becomes known as enamel.
 Root Formation
When all of the enamel and coronal dentin (dentin ofthe crown) have been
manufactured, the tooth germ enters the next stage of odontogenesis, known as root
formation. The outer and inner enamel epithelia of the cervical loop elongate, forming
a two-layered (OEE and IEE) sleeve-like structure known as the Hertwig epithelial root
sheath (HERS), which encompasses ectomesenchymal cells located deep to the
developing crown, forming an elongation of the dental papilla. The absence of the
stratum intermedium prevents the cells of the IEE from differentiating into
ameloblasts; thus, enamel is not formed on the developing root surface. However, the
most peripheral cells of the root dental papilla differentiate into preodontoblasts,
which release nuclear factor Ic, a transcription factor that triggers the initiation of
dentin formation and the differentiation of these cells into odontoblasts, cells that
continue to elaborate root dentin. As the HERS elongates, more and more of the root
continues to be manufactured, and the region of HERS closer to the cervical loop
begins to disintegrate, forming perforations in this sleeve-like structure.
Ectomesenchymal cells from the dental sac migrate through the openings in the HERS,
approximate the newly formed dentin, and differentiate into cementoblasts. These
newly differentiated cells manufacture cementum matrix, which subsequently calcifies
and is referred to as cementum.
 stratum intermedium inner enamel epithelium
of enamel stellate outer enamel enamel
oral epithelium / inner enamel epithelium reticulum / dentin

primordium of pulp dental papilla dental papilla dental pulp bone

oral epithelium enamel

dentin
odontoblastic layer gingiva
dental pulp
periodontal ligament
bone

vessels and nerves

 ameloblasts
enamel
dentinoenamel
junction

odontoblasts
 LM of an enamel organ at the bell stage of
Am odontogenesis. Outside, one layer of ameloblasts (Am)
En is closely apposed to newly formed, darker enamel (En).
Deeper in the organ, odontoblasts (Od), which are
differentiated from mesenchymal cells, are at the outer
margin of the dental papilla (DP). They form one row of
cells, next to newly formed dentin (De). At this stage of
tooth development, the papilla is a mass of primitive
mesenchymal cells, which later become dental pulp.
90×. H&E.

De
Od
DP

LM of part of an enamel organ with details of

the dentinoenamel junction. Tall columnar
ameloblasts (Am) form one row on the outer aspect
of the enamel organ. They have basally located nuclei Od
and thin apical projections called Tomes processes
(TP) that extend toward a thin layer of lightly stained
preenamel (PE), which is the organic matrix of newly
formed enamel. A thicker layer of fully mineralized De
enamel (En), more darkly stained, borders the
preenamel. On the opposite side, a layer of PE PD
differentiating odontoblasts (Od) is apposed to a thin, En
lightly stained layer of predentin (PD). Thin apical Am
processes of odontoblasts project across predentin
into dentin (De), which appears darker and radially
striate. A thin, clear artifactual space (arrows) marks
the dentinoenamel junction. 250×. H&E.

TP
 a m e lo b la s ts
en am el
o u te r e n am el
ep ith e liu m stratu m d entin
in term ed iu m
o d o n to b la s ts

s tellate o uter
dental
re tic u lu m • / en am el
sac
ep ith e liu m
 SALIVARY GLANDS
The major salivary glands, as noted above, consist of the paired parotid,
submandibular, and sublingual glands. The parotid and the
submandibular glands are actually located outside the oral cavity; their
secretions reach the cavity by ducts. The parotid gland is located
subcutaneously, below and in front of the ear in the space between the
ramus of the mandible and the styloid process of the temporal bone.
The submandibular gland is located under the floor of the mouth, in the
submandibular triangle of the neck. The sublingual gland is located in
the floor of the mouth anterior to the submandibular gland.
The minor salivary glands are located in the submucosa of different
parts of the oral cavity. They include the lingual, labial, buccal, molar,
and palatine glands.
Each salivary gland arises from the developing oral cavity epithelium.
Initially, the gland takes the form of a solid cord of cells that enters the
mesenchyme.
Secretory acini are organized into lobules. The major salivary glands are surrounded by a
capsule of moderately dense connective tissue from which septa divide the secretory portions
of the gland into lobes and lobules. The septa contain the larger blood vessels and excretory
ducts. The connective tissue associated with the groups of secretory acini blends imperceptibly
into the surrounding loose connective tissue. The minor salivary glands do not have a capsule.
Numerous lymphocytes and plasma cells populate the connective tissue surrounding the acini in
both the major and minor salivary glands. Their significance in the secretion of salivary
antibodies is described below.
Acini are of three types: serous, mucous, or mixed.
The basic secretory unit of salivary glands, the salivon, consists of the acinus, intercalated duct,
and excretory duct. The acinus is a blind sac composed of secretory cells. The acini of salivary
glands contain serous cells (protein-secreting), mucous cells (mucin-secreting), or both. The
relative frequencies of the three types of acini are a prime characteristic by which the major
salivary glands are distinguished.
Thus, three types of acini are described:
• Serous acini, which contain only serous cells and are generally spherical
• Mucous acini, which contain only mucous cells and are usually more tubular
• Mixed acini, which contain both serous and mucous cells. In routine H&E preparations,
mucous acini have a cap of serous cells that are thought to secrete into the highly convoluted
intercellular space between the mucous cells. Because of their appearance in histologic sections,
such caps are called serous demilunes.
Serous cells have a pyramidal shape, with a relatively wide basal surface facing the basal lamina and a small
apical surface facing the lumen of the acinus. They contain large amounts of rER, free ribosomes, a
prominent Golgi apparatus, and numerous spherical secretory granules. As in most protein-secreting cells
that store their secretions in zymogen granules, the granules are located in the apical cytoplasm. Most other
organelles are located in the basal or perinuclear cytoplasm. In H&E sections, the basal cytoplasm of the
serous cell stains with hematoxylin because of the rER and the free ribosomes, whereas the apical region
stains with eosin, in large part because of the secretory granules.
As in other mucus-secreting epithelia, the mucous cells of the mucous salivary acini undergo cyclic activity.
During part of the cycle, mucus is synthesized and stored within the cell as mucinogen granules. When the
product is discharged after hormonal or neural stimulation, the cell begins to resynthesize mucus. After
discharge of most or all of the mucinogen granules, the cell is difficult to distinguish from an inactive serous
cell. However, most mucous cells contain large numbers of mucinogen granules in their apical cytoplasm,
and because the mucinogen is lost in H&E-stained paraffin sections, the apical portion of the cell usually
appears empty. In TEM preparation, the rER, mitochondria, and other components are seen chiefly in the
basal portion of the cell; this part of the cell also contains the nucleus, which is typically flattened against the
base of the cell.
Myoepithelial cells are contractile cells with numerous processes. They lie between the basal plasma
membrane of the epithelial cells and the basal lamina of the epithelium. Myoepithelial cells also underlie the
cells of the proximal portion of the duct system. In both locations, the myoepithelial cells are instrumental in
moving secretory products toward the excretory duct. Myoepithelial cells are sometimes difficult to identify
in H&E sections. The nucleus of the cell is often seen as a small round profile near the basement membrane.
The contractile filaments stain with eosin and are sometimes recognized as a thin eosinophilic band adjacent
to the basement membrane.
 Salivary Ducts
The lumen of the salivary acinus is continuous with that of a duct system that may
have as many as three sequential segments:
• Intercalated duct, which leads from the acinus
• Striated duct, so-called because of the presence of “striations,” the infoldings of the
basal plasma membrane of the columnar cells that form the duct
• Excretory ducts, which are the larger ducts that empty into the oral cavity
The degree of development of the intercalated ducts and striated ducts varies,
depending on the nature of the acinar secretion. Serous glands have well-developed
intercalated ducts and striated ducts that modify the serous secretion by both
absorption of specific components from the secretion and secretion of additional
components to form the final product. Mucous glands, in which the secretion is not
modified, have very poorly developed intercalated ducts that may not be recognizable
in H&E sections. Moreover, they do not display striated ducts.
Intercalated ducts are located between a secretory acinus and a larger duct.
Intercalated ducts are lined by low cuboidal epithelial cells that usually lack any
distinctive feature to suggest a function other than that of a conduit. However, the
cells of intercalated ducts possess carbonic anhydrase activity. In serous-secreting
glands and mixed glands, they have been shown to
• secrete HCO3- into the acinar product.
• absorb Cl- from the acinar product.
Striated ducts are lined by a simple cuboidal epithelium that gradually becomes columnar as it approaches
the excretory duct. The infoldings of the basal plasma membrane are seen in histologic sections as
“striations.” Longitudinally oriented, elongated mitochondria are enclosed in the infoldings. Basal infoldings
associated with elongated mitochondria are a morphologic specialization associated with
reabsorption of fluid and electrolytes. The striated duct cells also have numerous basolateral folds that are
interdigitated with those of adjacent cells. The nucleus typically occupies a central (rather than basal)
location in the cell. Striated ducts are the sites of:
• reabsorption of Na+ from the primary secretion.
• secretion of K+ and HCO3- into the secretion.
More Na+ is resorbed than K+ is secreted, so the secretion becomes hypotonic. When secretion is very
rapid, more Na+ and less K+ appear in the final saliva because the reabsorption and secondary secretion
systems cannot keep up with the rate of primary secretion. Thus, the saliva may become isotonic to
hypertonic.
The diameter of striated ducts often exceeds that of the secretory acinus. Striated ducts are located in the
parenchyma of the glands (they are intralobular ducts) but may be surrounded by small amounts of
connective tissue in which
blood vessels and nerves can be seen running in parallel with the duct.

Excretory ducts constitute the principal ducts of each of the major glands. They ultim ately connect to the
oral cavity. The epithelium of small excretory ducts is simple cuboidal. It gradually changes to
pseudostratified columnar or stratified cuboidal. As the diameter of the duct increases, stratified columnar
epithelium is often seen, and as the ducts approach the oral epithelium, stratified squamous epithelium may
be present. The parotid duct (Stensen’s duct) and the submandibular duct (Wharton’s duct) travel in the
connective tissue of the face and neck, respectively, for some distance from the gland before penetrating the
oral mucosa.
 salivon parotid submandibular sublingual
F IG U R E 1 6 . 2 2 ▲ Diagram comparing the components of the
salivon in the three major salivary glands. The four major parts o f the
salivon— the acinus, intercalated duct, striated duct, and excretory duct—
are color-coded. The three columns on the right o f the salivon compare the
length o f the different ducts in the three salivary glands. The red-colored
cells o f the acinus represent serous-secreting cells, and the yellow-colored
cells represent mucus-secreting cells. The ratio o f serous-secreting cells to
mucus-secreting cells is depicted in the acini o f the various glands.
 Major Salivary Glands
The paired serous parotid glands are the largest of the major salivary glands. The
parotid duct travels from the gland, which is located below and in front of the ear, to
enter the oral cavity opposite the second upper molar tooth. The secretory units in the
parotid are serous and surround numerous, long, narrow intercalated ducts. Striated
ducts are large and conspicuous.

The large, paired, mixed submandibular glands are located under either side of the
floor of the mouth, close to the mandible. A duct from each of the two glands runs
forward and medially to a papilla located on the floor of the mouth just lateral to the
frenulum of the tongue. Some mucous acini capped by serous demilunes are generally
found among the predominant serous acini. Intercalated ducts are less extensive than
in the parotid gland.

The sublingual glands, the smallest of the paired major salivary glands, are located in
the floor of the mouth anterior to the submandibular glands. Their multiple small
sublingual ducts empty into the submandibular duct as well as directly onto the floor
of the mouth. Some of the predominant mucous acini exhibit serous demilunes, but
purely serous acini are rarely present. Intercalated ducts and striated ducts are short,
difficult to locate, or sometimes absent. The mucous secretory units may be more
tubular than purely acinar.
 Parotid duct
Branches of
facial nerve

Parotid gland

Tongue
Masseter muscle

Submandibular duct
Submandibular gland
Lingual nerve
SA
Sublingual gland External carotid artery

BV

Parotid gland: Submandibular gland: mostly Sublingual gland: almost

totally serous serous, partially mucous completely mucous
CT
ID
Secretory acinus Striated and excretory ducts

LM of a lobule of a sublingual gland. All three major

salivary glands are organized into lobules similar to this, with tightly
packed parenchyma surrounded by loose connective tissue stroma
(CT). Grape-like clusters of secretory acini (SA) and a few
intralobular ducts (arrows) are in the lobule; larger interlobular
ducts (ID) and blood vessels (BV) are in the stroma. 60×. H&E.
Secretion of saliva. During salivary secretion, blood flow to secretory
acini is increased via parasympathetic stimulation, and ultrafiltrate from plasma
Na+ (mostly serous fluid) enters the acini. Filtrate from the cells enters the lumen of
K+
Cl– HCO 3–
the acinar cells, mixing with secreted mucus and α-amylase, creating the
“Primary Secretion” primary secretion. This secretion is modified as it passes through the ducts into
Modification of the mouth. Lingual lipase (secreted from von Ebner glands of the tongue) is
ionic content
Saliva added to the saliva in the mouth.
 LM of a parotid gland. Closely packed clusters of
purely serous acini (SA) and a branching interlobular duct
(ID) are visible. Pseudostratified epithelium lines the duct,
Ad which is between parts of two lobules, is surrounded by
dense irregular connective tissue (CT), and accompanies
SA a venule (Ve). Adipocytes (Ad) occur mainly in the parotid,
not often seen in the two other major salivary glands.
175×. H&E.

Ve
ID
LM of a parotid at higher magnification. Loose
Ad connective tissue (CT) of the stroma surrounds many
secretory acini (SA) and two striated ducts (SD). Serous
CT cells in each acinus have round basal nuclei and are
SA arranged around a small central lumen. Simple columnar
epithelium lines the larger lumina of striated ducts, so
named because of striations in the basal cytoplasm of
the lining cells. 340×. H&E.

SA SA

CT

SD

Parotiditis and mumps.

 LM of part of a submandibular gland. Mucous acini (MA) are
made of pyramidal, pale-staining mucous cells with flattened basal
nuclei. These cells surround small central lumina. Darker-staining serous
demilunes (SD) cap some acini. A few myoepithelial cells (My) are
associated with acini and share a basement membrane with the mucous
SD MA cells. 275×. H&E.

LM of a striated duct at high magnification. Lightly eosinophilic

MA columnar cells with basal striations (arrows) line a central lumen (*).
My 1020×. H&E.
SD

LM of part of a sublingual gland showing details of intra-

lobular ducts. An intercalated duct (InD) lined by simple squamous
epithelium drains (arrows) two secretory acini (SA). The intercalated
duct empties into a larger striated duct lined by tall columnar cells with
basal striations. Surrounding stroma is loose, delicate connective tissue
(CT). 800×. H&E.

SA CT

InD
Striated duct

*
SA
Most saliva is produced by the salivary glands. A smaller amount is derived from the
gingival sulcus, tonsillar crypts, and general transudation from the epithelial lining of
the oral cavity. One of the unique features of saliva is the large and variable volume
produced. The volume (per weight of gland tissue) of saliva exceeds that of other
digestive secretions by as much as 40 times. The large volume of saliva produced is
undoubtedly related to its many functions, only some of which are concerned with
digestion. The salivary glands produce about 1,200 mL of saliva a day.
Saliva has numerous functions relating to metabolic and nonmetabolic activities,
including:
• Moistening the oral mucosa
• Moistening dry foods to aid swallowing
• Providing a medium for dissolved and suspended food materials that chemically
stimulate taste buds
• Buffering the contents of the oral cavity because of its high concentration of
bicarbonate ions
• Digesting carbohydrates with the digestive enzyme α-amylase, which breaks one to
four glycosidic bonds and continues to act in the esophagus and stomach
• Controlling the bacterial flora of the oral cavity by the use of lysozyme (muramidase),
an enzyme that lyses the muramic acid in certain bacteria (e.g., staphylococci)
Calcium and phosphate in the saliva are essential for the mineralization of newly erupted teeth
and for repair of precarious lesions of the enamel in erupted teeth. In addition, saliva serves
several other roles in protecting the teeth. Proteins in saliva cover the teeth with a protective
coat called the acquired pellicle.

As noted, saliva contains antibodies, salivary immunoglobulin A (IgA). IgA is synthesized by

plasma cells in the connective tissue surrounding the secretory acini of the salivary glands, and
both dimeric and monomeric forms are released
into the connective tissue matrix. A polymeric immunoglobulin receptor (plgR) protein is
synthesized by the salivary gland cells and inserted into the basal plasma membrane, where it
serves as a receptor for dimeric IgA. When the dimeric IgA binds to the receptor, the plgR-and
lgA complex is internalized by receptor-mediated endocytosis and carried through the acinar
cell to the apical plasma membrane. Here, plgR is proteolytically cleaved and the extracellular
part of the receptor that is bound to lgA is released into the lumen as secretory IgA (slgA). This
process of synthesis and secretion of IgA is essentially identical to that which occurs in the more
distal parts of the gastrointestinal tract, where slgA is transported across the absorptive
columnar epithelium of the small intestine and colon.

Saliva contains chiefly water, proteins and glycoproteins (enzymes and antibodies), and
electrolytes. It has a high potassium concentration that is approximately seven times that of
blood; a sodium concentration approximately onetenth that of blood; a bicarbonate
concentration approximately three times that of blood; and significant amounts of calcium,
phosphorus, chloride, thiocyanate, and urea. Lysozyme and α-amylase are the principal enzymes
present.