General aspects of build-up and functioning of an organism II

(Histology, Embryology)

Histology of Digestive system

Associated Prof: Irina Modebadze
TSU
 Components of Digestive system
The digestive system consists of the digestive tract and its associated glands
 Functions of digestive system
Function is to obtain from ingested food the molecules necessary for the maintenance,
growth, and energy needs of the body. The inner layer of the entire digestive tract forms
an important protective barrier between the content of the tract’s lumen and the internal
milieu of the body’s connective tissue and vasculature.
Structures within the digestive tract allow the following:
Ingestion, or introduction of food and liquid
into the oral cavity.
Mastication, or chewing, which divides
solid food into digestible pieces.
Motility, muscular movements of materials
through the tract.
Secretion of lubricating and protective
mucus, digestive enzymes, acidic and
alkaline fluids, and bile.
Hormone release for local control of
motility and secretion.
Chemical digestion or enzymatic
degradation of large macromolecules in
food to smaller molecules and their
subunits.
Absorption of the small molecules and
water into the blood and lymph.
Elimination of indigestible, unabsorbed
components of food.
 Wall of digestive tract
All regions of the GI tract have certain structural features in common. The
gastrointestinal (GI) tract 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 or adventitia.
 Mucosa and Submucosa
The mucosa consists of an epithelial lining; an underlying lamina propria of loose
connective tissue rich in blood vessels, lymphatics, lymphocytes, smooth muscle cells,
and often containing small glands; and a thin layer of smooth muscle called the
muscularis mucosae separating mucosa from submucosa and allowing local movements
of the mucosa. The mucosa is also frequently called a mucous membrane.

The submucosa
contains denser
connective tissue with
larger blood and lymph
vessels and the
submucosal (Meissner)
plexus of autonomic
nerves. It may also
contain glands and
significant lymphoid
tissue.
 Muscularis externa and Adventitia or Serosa
The thick muscularis (or muscularis externa) is composed of smooth muscle cells organized
as two or more sublayers. In the internal sublayer (closer to the lumen), the fiber
orientation is generally circular; in the external sublayer it is longitudinal. The connective
tissue between the muscle sublayers contains blood and lymph vessels, as well as the
myenteric (Auerbach) nerve plexus of many autonomic neurons aggregated into small
ganglia and interconnected by pre- and postganglionic nerve fibers. This and the
submucosal plexus together comprise the enteric nervous system of the digestive tract.
Contractions of the muscularis, which mix and propel the luminal contents forward, are
generated and coordinated by the myenteric plexus.
The serosa is a thin layer of loose connective
tissue, rich in blood vessels, lymphatics, and
adipose tissue, with a simple squamous
covering epithelium or mesothelium. In the
abdominal cavity, the serosa is continuous
with mesenteries and the peritoneum, a
serous membrane that lines that cavity. In
places where the digestive tract is not
suspended in a cavity but bound directly to
adjacent structures the serosa is replaced by
a thick adventitia, a connective tissue layer
that merges with the surrounding tissues
and lacks mesothelium.
 The oral cavity
The oral cavity is lined with stratified squamous epithelium, which may be keratinized,
partially keratinized, or nonkeratinized depending on the location. Like the keratinized
surface cells of epidermis, the flattened superficial cells of the oral epithelium undergo
continuous desquamation, or loss at the surface. Unlike those of the epidermis, the
shed cells of the nonkeratinized oral epithelium retain their nuclei.
The stratified keratinized squamous
epithelium are best developed in the
masticatory mucosa on the gingiva
(gum) and hard palate.
Stratified nonkeratinized squamous
epithelium predominates in the lining
mucosa over the soft palate, cheeks, the
floor of the mouth, and the pharynx.
Lining mucosa overlies a thick
submucosa containing many minor
salivary glands, which secrete
continuously to keep the mucosal
surface wet, and diffuse lymphoid
tissue. Throughout the oral cavity, the
epithelium contains transient antigen-
presenting cells and rich sensory
innervation.
 Lips The bulk of the internal tissue of the lip is skeletal muscle.
Lips have three differently covered surfaces:
The internal mucous surface has lining mucosa with a thick, nonkeratinized epithelium
and many minor labial salivary glands.
The red vermilion zone of each lip is
covered by very thin keratinized stratified
squamous epithelium and is transitional
between the oral mucosa and skin. This
region lacks salivary or sweat glands and is
kept moist with saliva from the tongue.
The underlying connective tissue is very
rich in both sensory innervation and
capillaries, which impart the pink color to
this region.
The outer surface has thin skin, consisting
of epidermal and dermal layers, sweat
glands, and many hair follicles with
sebaceous glands.
S – skin, V - vermilion border, O – oral mucosa,
G – salivary gland, M – skeletal muscle
(orbicularis oris). H&E
 Tongue
The tongue is a mass of striated skeletal muscle covered by mucosa, which manipulates
ingested material during mastication and swallowing. The muscle fibers are oriented in all
directions, allowing a high level of mobility. Connective tissue between the small fascicles
of muscle consisting of mucus and serous salivary glands continuous with the lamina
propria, which makes the mucous membrane strongly adherent to the muscular core.
H&E

The lower (ventral) surface of the tongue is smooth,

with typical lining mucosa. The dorsal surface is
irregular, having hundreds of small protruding papillae
(made of mucosa) of various types on its anterior two-
thirds and the massed lingual tonsils on the posterior
third, or root of the tongue. The papillary and tonsillar
areas of the lingual surface are separated by a V-shaped
groove called the sulcus terminalis.
 Papillae

Filiform Papillae - are very numerous, have

an elongated conical shape, and are
heavily keratinized, which gives their
surface a gray or whitish appearance. They
provide a rough surface that facilitates
movement of food during chewing.

H&E

Fungiform Papillae - are much less

numerous, lightly keratinized, and
interspersed among the filiform papillae.
They are mushroom-shaped with well-
vascularized and innervated cores of
lamina propria.
 Papillae

Foliate Papillae - consist of several parallel

ridges on each side of the tongue, anterior
to the sulcus terminalis, but are
rudimentary in humans, especially older
individuals.

Vallate (or circumvallate) papillae are the

largest papillae, with diameters of 1 to 3 mm.
Eight to twelve vallate papillae are normally H&E
aligned just in front of the terminal sulcus.
Ducts of several small, serous salivary (von
Ebner) glands (product is lingual lipase) empty
into the deep, moatlike groove surrounding
each vallate papilla. This provides a continuous
flow of fluid over the taste buds that are
abundant on the sides of these papillae,
washing away food particles so that the taste
buds can receive and process new gustatory
stimuli.
 Taste buds
Taste buds are ovoid structures within the stratified epithelium on the tongue’s surface,
which sample the general chemical composition of ingested material. Approximately 250
taste buds are present on the lateral surface of each vallate papilla, with many others
present on fungiform and foliate (but not the keratinized filiform) papillae.
A taste bud has 50 to 100 cells, about
half of which are elongated gustatory
(taste) cells, which turn over with a 7-
to 10-day life span. Other cells
present are slender supportive cells,
and slowly dividing basal stem cells
that give rise to the other cell types.
The base of each bud rests on the
basal lamina and is entered by
afferent sensory axons that form
synapses with the gustatory cells. At
the apical ends of the gustatory cells,
microvilli project toward a 2-μm-wide
Conscious perception of tastes
opening in the structure called the
in food requires olfactory and
taste pore.
other sensations in addition to
Molecules (tastants) dissolved in saliva
taste bud activity.
contact the microvilli through the pore
and interact with cell surface taste
receptors.
 Salivary Glands
Exocrine glands in the mouth produce saliva, which has digestive, lubricating, and
protective functions. With a normal pH of 6.5 to 6.9, saliva also has an important
buffering function and in some species is also important for evaporative cooling.
There are three pairs of large salivary glands: the parotid, submandibular, and
sublingual glands, in addition to the numerous minor mucosal salivary glands
throughout the oral cavity, which secrete about 10% of the total saliva volume.
The stroma - a connective tissue capsule surrounds each major salivary gland and
send the septa to the parenchyma arranged in lobules. The parenchyma of each
major salivary gland consists of secretory units (acini, tubules, mixed tubuloacinar
secretory units) and a branching duct.
 Cells of Salivary Glands
Serous cells are polarized protein-secreting cells, usually pyramidal in shape, with round
nuclei, well-stained RER, and apical secretory. Serous cells form a somewhat spherical
secretory unit called an acinus (L. grape) (or alveoli), with a very small central lumen.
Mucous cells are somewhat more columnar in shape, with more compressed basal nuclei.
Mucous cells contain apical granules with hydrophilic mucins that provide lubricating
properties in saliva but cause poor cell staining in routine preparations. Mucous cells are
most often organized as cylindrical tubules rather than acini.
Myoepithelial cells small,
flattened cells are found inside
the basal lamina surrounding
acini, tubules, and the proximal
ends of the duct system. These
cells exhibit contractile function
and their activity is important
for moving secretory products
into and through the ducts.
Saliva is modified by the cells of the
duct system draining the secretory
units, with much Na+ and Cl−
reabsorbed while certain growth
factors and digestive enzymes are
added.
 Duct system
In the intralobular duct system, secretory acini and tubules empty into short intercalated
ducts, lined by cuboidal epithelial cells, and several of these ducts join to form a striated
duct. The more columnar striated characterized by radial striations - infoldings of the
basal plasma membrane with numerous elongated mitochondria that are aligned parallel
to the infolded membranes.
The striated ducts of each lobule converge and drain into ducts located in the connective
tissue septae separating the lobules, where they become interlobular, or excretory, ducts.
They are initially lined with pseudostratified or stratified cuboidal epithelium. The main
duct of each major salivary gland ultimately empties into the oral cavity and is lined with
nonkeratinized-stratified squamous epithelium.

Parotid glands are branched acinar ID

glands with exclusively serous acini. A
Secrete abundant α-amylase (that
hydrolysis of carbohydrates) and
proline-rich proteins (with A
antimicrobial and other protective ID
properties). Saliva from the parotids is
serous and watery. A
A – Acini, ID – Intralobyular duct.
H&E
 Submandibular glands (a), which produce two-thirds
of all saliva, are branched tubuloacinar glands,
having primarily serous acini, but with many mixed
tubuloacinar secretory units with group of serous
cells called serous demilunes (c). Serous cells of the
submandibular gland secrete other enzymes,
including lysozyme for bacterial wall hydrolysis.

A – Acini, M - Mucus cell, S - Serous demilunes, ID –

Intralobyular duct. a
H&E
Sublingual glands are ID
M S
branched tubuloacinar
glands, but here secretory
tubules of mucous cells
predominate and the
main product of the gland M
is mucus. The few serous M
cells present in demilunes
add amylase and
lysozyme to the secretion.
b c
Those glands produce a seromucous secretion.
Teeth & Associated Structures
In the adult human there are
normally 32 permanent
teeth, arranged in two
bilaterally symmetric arches
in the maxillary and
mandibular bones. Each
quadrant has eight teeth: two
incisors, one canine, two
premolars, and three
permanent molars. Twenty of
the permanent teeth are
preceded by primary teeth
(deciduous or milk teeth) that
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 that fit firmly into bony
sockets in the jaws called dental
alveoli.
 Teeth
The crown is covered by very hard,
acellular 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
neck calcified material, dentin, which
surrounds an internal pulp cavity.
Dental pulp is highly vascular and well-
innervated and consists largely of
loose, mesenchymal connective tissue
with much ground substance, thin
collagen fibers, fibroblasts, and
mesenchymal stem cells. The pulp
periodontal cavity narrows in each root as the root
ligament
canal, which extends to an opening
apical foramen (apical foramen) at the tip of each root
for the blood vessels, lymphatics, and
nerves of the pulp cavity.
 Tooth formation
ectodermal epithelium
Tooth formation begins in the embryo
when ectodermal epithelium lining the
oral cavity grows into the underlying
mesenchyme of the developing jaws.
At a series of sites corresponding to
each future tooth, these epithelial cells
proliferate extensively and become
organized as enamel organs, each shaped like a wine glass
with its stem initially still attached to the oral lining.
Ameloblasts form from the innermost layer of cells in the
enamel organ. Mesenchymal cells of the dental papilla,
inside the concave portion of the enamel organ include
neural crest cells that differentiate as the layer of
odontoblasts with their apical ends in contact with the
apical ends of the ameloblasts.

Ameloblasts

Odontoblasts

H&E
 Dentin and odontoblasts
Dentin is a calcified tissue harder than bone, consisting of 70% hydroxyapatite. The organic
matrix contains type I collagen and proteoglycans secreted from the apical ends of
odontoblasts (O), tall polarized cells derived from the cranial neural crest that line the
tooth’s pulp cavity. Enamel
Long apical odontoblast processes (OP) extend from the
odontoblasts within dentinal tubules that 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. The odontoblast processes are Silver
important for the maintenance of dentin matrix.
Odontoblasts continue predentin production into adult
life, gradually reducing the size of the pulp cavity, and
are stimulated to repair dentin if the tooth is damaged.

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 unmyelinated nerve fibers Mallory trichrome

extend into the dental tubules along with

odontoblast processes near the pulp cavity. Such
stimuli can affect fluid inside the dentinal tubules,
stimulating these nerve fibers and producing tooth
sensitivity.
 Enamel
Enamel is the hardest component of the human
body, consisting of 96% calcium hydroxyapatite
and only 2-3% organic material including very
few proteins and 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 A – enamel; B- dentin;
triangle –branching
the addition of fluoride to toothpaste and water odontoblast fibers
supplies. Growth of the hydroxyapatite crystals
to produce each elongating enamel rod is guided
by a small (20 kDa) protein amelogenin, the
main structural protein of developing enamel.
Enamel consists of uniform, interlocking
columns called enamel rods (or prisms), each
about 5 μm in diameter and surrounded by a Cross section of the
enamel rods
thinner layer of other enamel. Each rod extends
through the entire thickness of the enamel
layer, which averages 2 mm. The precise,
interlocked arrangement of the enamel rods is
crucial for enamel’s hardness and resistance to
great pressures during mastication.
 Enamel
In a developing tooth bud, the
matrix for the enamel rods is
secreted by the ameloblasts from
the enamel organ. An apical
extension from each ameloblast,
the ameloblast (or Tomes) process,
contains numerous secretory
granules with the proteins of the
enamel matrix. The secreted matrix
undergoes very rapid
mineralization. Each enamel rod
represents the product of one
H&E
ameloblast. No cellular processes
occur in enamel, and the layer of A - ameloblasts, B - enamel, C - condensed epithelium
ameloblasts surrounding the of enamel organ, D - capillaries, E - terminal bars, F -
developing crown is completely lost Tomes' processes, G - dentin, H - dentin-enamel
during tooth eruption. junction.

Primary teeth complete development and begin to erupt about 6 months after birth.
Development of the secondary tooth buds arrests at the “bell stage,” until about 6 years of
age, when these teeth begin to erupt as the primary teeth are shed.
Cementum and Periodontal ligament
Cementum covers the dentin of the root
and is similar in composition to bone,
although haversian systems and blood
vessels are absent. It is thicker in the
apical region of the root, where there are
cementocytes, cells with the appearance
of osteocytes. Like osteocytes, they are
encased in lacunae; cementocytes do not
communicate through canaliculi.

The periodontal ligaments are fibrous

connective tissue bundles of collagen
fibers inserted into both the cementum
and the alveolar bone. This ligament
serves as the periosteum of the alveolar
in tooth sockets and is also continuous
with developing layers of cementum. Its
permits limited movement of the tooth.
Its fibers are organized to support the
pressures exerted during mastication.
H&E
 Periodontium
The periodontium comprises the structures
responsible for maintaining the teeth in the maxillary
and mandibular bones, and includes the cementum,
the periodontal ligament, and the alveolar bone with
the associated gingiva.

Around the peridontium the keratinized

oral mucosa of the gingiva is firmly bound
to the periosteum of the maxillary and
mandibular bones. Between the enamel
and the gingival epithelium is the gingival
sulcus, a groove up to 3 mm deep
surrounding the neck.

A specialized part of this epithelium, the

junctional epithelium, is bound to the
tooth enamel by means of a cuticle, which
resembles a thick basal lamina to which
the epithelial cells are attached by
numerous hemidesmosomes.
 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.
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 the tonsils.

The mucosa of the pharynx

also has many small mucous
salivary glands in its lamina
propria, composed of dense
connective tissue.
The constrictor and
longitudinal muscles of the
pharynx are located outside
this layer.
 Esophagus
The esophagus is a muscular tube, about 25 cm long in adults, which transports swallowed
material from the pharynx to the stomach. The four layers of the GI tract first become well-
established and clearly seen in the esophagus.
The esophageal mucosa has nonkeratinized stratified squamous epithelium, lamina propria
and muscularies mucosa and the submucosa contains small mucus-secreting glands, the
esophageal glands, which lubricate and protect the mucosa.
Near the stomach the mucosa also H&E
contains groups of glands, the
esophageal cardiac glands, which E
secrete additional mucus. In the
upper third of the esophagus, the
muscularis externa consists of
striated skeletal muscle. In the
lower third, smooth muscle makes
up the two layers of the muscularis
externa. In the middle third is a
mixture of the two types of
muscle. Beyond the muscle layers
is a coat of adventitia that blends
in with the connective tissue of the
thoracic cavity
A – mucosa epithelium, B – esophageal gland,
C – submucosa, D – muscularis externa, E – adventitia.
 Stomach
The stomach is a greatly dilated segment of the H&E

digestive tract whose main functions are:

• To continue the digestion of carbohydrates
initiated by the amylase of saliva. A
• To add an acidic fluid to the ingested food and
B
mixing its contents into a viscous mass called
chyme by the churning activity of the
muscularis.
• To continue digestion of triglycerides by a C
secreted lipase.
• To promote the initial digestion of proteins
with the enzyme pepsin.
The junction of the esophagus with the stomach
There is an abrupt change in the epithelial lining
from the stratified squamous epithelium to the
simple columnar epithelium of the stomach. The
surface columnar cells of the stomach secrete
mucus that protects the mucosa from the acidic
environment of the lumen. A – esophageal mucosa epithelium, B – esophageal
gland, C – stomach mucosa epithelium, arrow – junction
of epithelium.
 Regions of Stomach
Four major regions make up the stomach:
the cardia, fundus, body, and pylorus. The
cardia is a narrow zone, 1.5-3 cm wide,
the pylorus is the funnel-shaped region
that opens into the small intestine. Both
these regions consist of glands in lamina
propria and are primarily involved with
mucus production and are similar
histogically. The much larger fundus and
body regions are identical in microscopic Wall of the Stomach, H&E
structure and are the sites of gastric
glands releasing acidic gastric juice.

The mucosa and submucosa of the

empty stomach have large,
longitudinally directed folds called
rugae, which flatten when the stomach
fills with food. The wall in all regions of
the stomach is made up of all four
major layers.
 Stomach Mucosa and Cells of Gastric Gland
Mucosa component are simple columnar epithelium, lamina proria and muscularis
mucosa. Surface epithelium that invaginates deeply into the lamina propria forms gastric
pits (GP), at base of which there are small openings of gastric glands.
The surface mucous cells that line the lumen and gastric pits secrete a thick, adherent, and
highly viscous mucous layer that is rich in bicarbonate ions and protects the mucosa from
both abrasive effects of intraluminal food and the corrosive effects of stomach acid.
Mucous neck cells are present in
the necks of gastric glands. They
are less columnar and have
round nuclei and apical secretory
granules. Their mucus secretion
is less alkaline than that of the
surface epithelial mucous cells.
SEM

Lining epithelium of the Stomach.

GP – gastric pit
 Cells of Gastric Glands
MV – microvilli, M – mitochondria, Parietal (oxyntic) cells produce hydrochloric acid (HCl)
IC – intracellular canaliculus,
TV – tubulovesicular struct. and intrinsic factor, a glycoprotein required for uptake
G – golgi aparatus of vitamin B12 in the small intestine. They present
among the mucous neck cells and throughout deeper
parts of the gland. They are rounded or pyramidal, each
with one central round nucleus. The cytoplasm is
intensely eosinophilic due to the high density of
mitochondria. An active parietal cell has a deep, circular
invagination of the apical plasma membrane to form an
intracellular canaliculus with a large surface are
produced by thousands of microvilli. While the gastric
secretion becomes highly acidic, the mucosa itself
remains at a more neutral pH partly because of the
Secretory bicarbonate released into the lamina propria.
granules
Chief (zymogenic) cells predominate in the lower regions of
the gastric glands and have all the characteristics of active
protein-secreting cells. Ultrastructurally chief cells show
abundant RER (rough endoplasmic reticulum) and numerous
apical secretory granules. The granules contain inactive
enzyme pepsinogens, precursors which are converted in the
RER acid environment of the stomach into active. Chief cells also
produce gastric lipase, to digest lipids.
Stem cells for the epithelium that lines the
glands, pits, and stomach lumen are found in a
narrow segment (isthmus) between each gastric
pit and the gastric glands. The pluripotent stem
cells divide asymmetrically, producing progenitor
cells for all the other epithelial cells.
Enteroendocrine cells are scattered epithelial
cells in the gastric mucosa with endocrine or
paracrine functions. Various enteroendocrine
cells secreting different hormones (serotonin,
gastrin, histamine), usually peptides, and are of
major importance for function of the digestive
tract.

GP – gastric pits, M – muscularis mucosa,

P – parietal cell, Ch – chiff cell. Mucosa of the Stomach Body region, H&E
 Stomach Submucosa, Muscularis externa and Serosa
In all stomach regions the submucosa is composed of dense connective tissue with large
blood and lymph vessels and many lymphoid cells, macrophages, and mast cells. The
muscularis has three poorly defined layers of smooth muscle: an outer longitudinal
layer, a middle circular layer, and an innermost oblique layer. Rhythmic contractions of
the muscularis thoroughly mix ingested food and chyme with mucus, HCl, and digestive
enzymes 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.
Muscularis
externa:

Serosa
Pyloric sphincter
H&E
 Small intestine
The small intestine is the site where the digestive processes are completed and 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:
the duodenum, jejunum, and ileum. These segments have most histologic features in
common and are discussed together.
The lining of the small intestine shows a series of permanent circular or semilunar folds
(plicae circulares), consisting of mucosa and submucosa which are best developed in the
jejunum.
Densely covering the entire mucosa of the small intestine are short (0.5- to 1.5-mm)
mucosal outgrowths called villi that project into the lumen. These finger- or leaflike
projections are covered by a simple columnar epithelium of absorptive cells called
enterocytes, with many interspersed goblet cells. Each villus has a core of loose connective
tissue that extends from the lamina propria and contains fibroblasts, smooth muscle fibers,
lymphocytes and plasma cells, fenestrated capillaries, and a central lymphatic called a
lacteal (through which lipids are transported). Smooth muscle fibers produce rhythmic
movements of the villi that increase the absorption efficiency.
Between the villi are the openings of short tubular glands called intestinal glands or crypts
(or crypts of lieberkühn) and the epithelium of each villus is continuous with that of the
intervening glands.
Fibers of the muscularis mucosae also produce local movements of plicae circulares that
help propel lymph from the lacteals into submucosal and mesenteric lymphatics.
Small intestine
 Small intestine (jejunum) mucosa
H&E

V – villi, C – cript, E – simpl columnar epithelium, G – goblet cell, LP – lamina propria,

M – muscularis mucosa.
 Cripts
The epithelium of the intestinal glands includes following cells:
Enterocytes, the absorptive cells, are tall
columnar cells, each with an oval nucleus
located basally. The apical end of each
enterocyte displays a densely packed
microvilli covered by glycocalyx called the
striated (or brush) border, through which
nutrients are taken into the cells. Each
microvillus is a cylindrical protrusion of the
apical cytoplasm approximately 1 μm tall
and 0.1 μm in diameter containing actin
filaments and enclosed by the cell
membrane. Each enterocyte has an
average of 3000 microvilli. Microvilli, villi,
and the plicae circulares all greatly increase
the mucosal surface area in contact with
E – enterocite, G – goblet cell, LP - lamina
nutrients in the lumen, which is an
propria, BB - brush border (PAS-Hematoxylin).
important feature in an organ specialized
for nutrient absorption.
Goblet cells are interspersed among the absorptive enterocytes. They secrete glycoprotein
mucins that are then hydrated to form mucus, whose main function is to protect and
lubricate the lining of the intestine.
 H&E
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.
Paneth cell granules release lysozyme,
phospholipase A2, and hydrophobic
peptides called defensins, all of which bind
and break down membranes of
microorganisms and bacterial cell 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 peptide
hormones. Many of these are of the “open”
Arrow – panet cell, Arrow head –
type, in which the constricted apical end of enteroendocrine cell, E – enterocytes, LP –
the cell contacts the intestinal lumen and lamina propria, M – muscularis mucosa.
has chemoreceptors similar to those of
taste buds, sampling levels of certain
nutrients such as sugars to regulate
hormone release basally.
M (microfold) cells are specialized epithelial cells in the mucosa of the ileum overlying
the lymphoid follicles of Peyer patches. These cells are characterized by the presence of
basal membrane invaginations or pockets containing many intraepithelial lymphocytes
and antigen-presenting cells. M cells selectively endocytose antigens and transport
them to the underlying lymphocytes and dendritic cells, which then migrate to lymph
nodes for an appropriate immune response.

TEM

Arrow – germinal center, N– lymphatic

nodule, V – villi, M – muscularis
externa. H&E
 Small intestin Submucosa
The submucosa has larger blood and lymph
vessels and the diffuse, interconnected
neurons of the submucosal (Meissner) nerve
plexus. The proximal part of the duodenum
has in the submucosa large clusters of
branched tubular mucous glands, the
duodenal (or Brunner) glands, with small
excretory ducts opening among the intestinal
crypts. Mucus from these 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 well-developed mucosa-
associated lymphoid tissue (MALT), consisting
of the large lymphoid nodule aggregates
known as Peyer patches underlying the
epithelial M cells.
Arrow – duodenal gland, Arrow head – lymphatic
nodul, Courved arrow – intestinal villi, S –
submucosa, ME – muscularis externa. H&E
 Small intestine (duodenum)

V – intestinal villi, C – cript, SG – duodenal glands in submucosa, LP – lamina propria,

M – muscularis mucosa, L – lymphatic tissue.
Small intestin Muscularis externa and Serosa
The muscularis is well developed in the
small intestine, composed of an internal
circular layer, an external longitudinal
layer, and between them the neurons of
the myenteric (Auerbach) nerve plexus
which produce peristalsis. Neurons of
both the submucosal and myenteric
plexuses are largely autonomic and
collectively make up the large enteric
nervous system. The small intestine is
covered by a thin serosa with
mesothelium continuous with that of
mesenteries.

Artery of
Mesenteries

Serosa
 Large intestine
The large intestine or bowel, which absorbs
water and electrolytes and forms indigestible
material into feces, has the following
regions: the short cecum, with the ileocecal
valve (fold) and the appendix; the ascending,
transverse, descending, and sigmoid colon;
and the rectum, where feces is stored prior
to evacuation. The mucosa lacks villi and
except in the rectum has no major folds. Less
than one-third as long as the small intestine,
the large intestine has a greater diameter (6-
7 cm).

Cross section. H&E

 Large intestine Mucosa H&E

The mucosa is penetrated throughout its length

by tubular intestinal glands. These and the
intestinal lumen are lined by goblet and
absorptive cells, with a small number of
enteroendocrine cells. The columnar absorptive
cells or colonocytes have irregular microvilli
and dilated intercellular spaces indicating
active fluid absorption. Goblet cells producing
lubricating mucus become more numerous
along the length of the colon and in the
rectum. Epithelial stem cells are located in the
bottom third of each gland. The lamina propria
is rich in lymphoid cells and in lymphoid
nodules that frequently extend into the
submucosa. The richness in MALT is related to
the large bacterial population of the large
intestine. The appendix has little or no
absorptive function but is a significant
component of MALT.
IG – intestinal gland, E – surface epithelium,
G – goblet cell, LP – lamina propria, M –
muscularis mucosa, S – submucosa.
 Large intestine Muscularis externa
The muscularis of the colon has longitudinal and
circular layers but differs from that of the small Appendices
intestine, with fibers of the outer layer gathered epiploicae
in three separate longitudinal bands called Tenia coli
teniae coli (L., ribbons of the colon).
Intraperitoneal portions of the colon are covered
by serosa, which is characterized by small,
pendulous protuberances of adipose tissue.
The distal end of the GI tract is the anal
canal, 3-4 cm long. At the rectoanal
junction the simple columnar mucosal
lining of the rectum is replaced by stratified
squamous epithelium (SE). The mucosa and
submucosa of the anal canal form several
longitudinal folds, the anal columns, in
which the lamina propria and submucosa
include sinuses of the rectal venous plexus.
Near the anus the circular layer of the
rectum’s muscularis forms the internal anal
sphincter. Defecation involves the action of
voluntary muscle comprising the external
anal sphincter. Rectoanal junction H&E
 Appendix
The appendix is an evagination of the
cecum; it is characterized by a
relatively small, narrow, and irregular
lumen that is caused by the presence
of abundant lymphoid follicles in its
wall.
Although its general structure is
similar to that of the large intestine, it
contains fewer and shorter intestinal
glands and has no teniae coli.
 Pancreas
The pancreas is a mixed exocrine-endocrine gland that produces both digestive enzymes
and hormones. It is an elongated retroperitoneal organ, with a large head near the
duodenum and more narrow body and tail regions that extend to the left. The pancreas
has a thin capsule of connective tissue, from which septa extend to cover the larger
vessels and ducts and to separate the parenchyma into lobules. The secretory acini are
surrounded by a basal lamina that is supported only by a delicate sheath of reticular
fibers with a rich capillary network. Endocrine function of the pancreas involves
primarily smaller cells similar to enteroendocrine cells located in variously sized clusters
called the pancreatic islets (islets of Langerhans).
H&E
 Exocrine Pancreas
The digestive enzymes are produced by cells of serous acini in the larger exocrine portion
of the pancreas. This somewhat resembles the parotid gland histologically, although the
pancreas lacks striated ducts and the parotid glands lack islets of endocrine tissue. Each
pancreatic acinus consists of several serous cells surrounding a very small lumen, without
myoepithelial cells. The acinar cells are polarized, with round basal nuclei, and numerous
zymogen granules apically, typical of proteinsecreting cells.
Each acinus is drained by a short intercalated duct of
Stroma Reticular fibers
simple squamous epithelium. The initial cells of these
small ducts extend into the lumen of the acinus as
small pale-staining centroacinar cells that are unique
to the pancreas. Cells of the intercalated ducts secrete
a large volume of fluid, rich in bicarbonate ions, which
alkalinizes and transports hydrolytic enzymes
produced in the acini. The
intercalated ducts merge
with intralobular ducts and
larger interlobular ducts,
which have increasingly
columnar epithelia
beforejoining the main
pancreatic duct that runs
the length of the gland.
 Pancreatic enzymes
The exocrine pancreas secretes approximately 1.5 L of alkaline pancreatic juice per day
and delivers it directly into the duodenum. These digestive enzymes include several
proteases, α-amylase, lipases, and nucleases (DNAase and RNAase). The proteases are
secreted as inactive zymogens (trypsinogen, chymotrypsinogen, proelastase,
kallikreinogen, and procarboxipeptidases).
Trypsinogen is cleaved and activated by enteropeptidases in the duodenum, generating
trypsin that activates the other proteases in a cascade.
Pancreatic tissue is protected against autodigestion by the following:
• Restricting protease activation to the duodenum,
• Trypsin inhibitor, which is copackaged in the secretory granules with trypsinogen,
• The low pH in the acini and duct system due to HCO3− secreted by the centroacinar
and intercalated duct cells, which helps keep all the enzymes inactive.
Exocrine secretion in the pancreas is regulated mainly through two polypeptide
hormones produced by enteroendocrine cells of the small intestine:
Cholecystokinin (CCK) stimulates enzyme secretion by the acinar cells.
Secretin promotes water and HCO3− secretion by the duct cells.
Autonomic (parasympathetic) nerve fibers also stimulate secretion from both acinar and
duct cells.
 Endocrine Pancreas
The islets of Langerhans are multihormonal endocrine microorgans; they appear as rounded
clusters of cells embedded within the exocrine pancreatic tissue
The most islets are 100–200µm in diameter and contain several hundred cells, small
groups of endocrine cells are also found interspersed among the pancreatic exocrine
cells.
There may be more than 1 million islets in the human pancreas, with a slight tendency
for islets to be more abundant in the tail of the pancreas.
Using immunocytochemical methods, four
types of cells—A, B, D, and F—have been
recognized in the islets.
The relative quantities of the four cell
types found in islets are not uniform; they
vary considerably with the islet's location
in the pancreas.
A - glucagon-producing cells (20%); and B -
insulin-producing cells (70%).
A fine capsule of reticular fibers surrounds
each islet, separating it from the adjacent
pancreatic tissue.
Each islet consists of lightly stained polygonal
or rounded cells, arranged in cords separated
by a network of blood capillaries.
 Liver
The liver is the largest internal organ, in adults averaging about 1.5 kg or 2% of the body
weight. Located in the right upper quadrant of the abdomen just below the diaphragm,
the liver has major left and right lobes with two smaller inferior lobes, most of which are
covered by a thin capsule and mesothelium of the visceral peritoneum. The capsule
thickens at the hilum (or porta hepatis) on the inferior side, where the dual blood supply
from the hepatic portal vein and hepatic artery enters the organ and where the hepatic
vein, lymphatics, and common hepatic (bile) duct exit.
About 75% of the blood entering the liver is nutrientrich (but O 2-poor) blood from the
portal vein arising from the stomach, intestines, and spleen; the other 25% comes from the
hepatic artery and supplies the organ’s O2.
 Liver Functions
The main digestive function of the liver is production of bile, a complex substance required
for the emulsification, hydrolysis, and uptake of fats in the duodenum.
The liver is also the major interface between the digestive system and the blood, as the
organ in which nutrients absorbed in the small intestine are processed before distribution
throughout the body.
Other functions:
• Synthesis and endocrine secretion into the blood of the
major plasma proteins, including albumins, fibrinogen,
apolipoproteins, transferrin, and many others
• Conversion of amino acids into glucose
(gluconeogenesis)
• Breakdown (detoxification) and conjugation of ingested
toxins, including many drugs
• Amino acid deamination, producing urea removed from Liver tissue (pig and human)
blood in kidneys
• Storage of glucose in glycogen granules and triglycerides
in small lipid droplets.
• Storage of vitamin A (in hepatic stellate cells) and
other fat-soluble vitamins
• Removal of effete erythrocytes (by specialized
macrophages, or Kupffer cells
• Storage of iron in complexes with the protein ferritin
 Liver Lobules
The liver parenchyma is organized as thousands of small (~0.7 × 2 mm) hepatic lobules
in which hepatocytes form hundreds of irregular plates arranged radially around a
small central vein. The hepatocyte plates are supported by a delicate stroma of
reticulin fibers. Peripherally each lobule has three to six portal areas with more
fibrous connective tissue, each of which contains three interlobular structures that
comprise the portal triad:
• A venule branch of the portal vein, with blood rich in nutrients but low in O 2,
• An arteriole branch of the hepatic artery that supplies O 2,
• One or two small bile ductules of cuboidal epithelium, branches of the bile
conducting system.
Between all of the
anastomosing plates of
hepatocytes of a hepatic
lobule are important
vascular sinusoids that
emerge from the
peripheral branches of the
portal vein and hepatic
artery and converge on the
lobule’s central vein.

The venous and arterial blood mixes in these irregular hepatic sinusoids.
 Liver Lobules
The surface of each hepatocyte is in contact with the wall of the sinusoids, and with the
surfaces of other hepatocytes. Where two hepatocytes tach each other, they delimit a
tubular space between them known as the bile canaliculus.
 Liver Cells
Hepatocytes are cells with diverse functions. Abundant rough ER is focused on synthesis
of plasma proteins and causes cytoplasmic basophilia. Abundant smooth ER, distributed
more evenly throughout the cytoplasm, contains the enzyme systems for the
biotransformation or detoxification of substances in blood, which are then usually
excreted with bile. Glycogen granules and small lipid droplets in hepatocytes, and very
small electron-dense ferritin complexes (hemosiderin) primarily in the Kupffer cells,
respectively mediate temporary storage of glucose, triglycerides, and iron.

Numerous specialized stellate

macrophages, usually called Kupffer
cells, are found within the sinusoid
lining. These cells recognize and
phagocytose aged erythrocytes,
freeing heme and iron for reuse or
storage in ferritin complexes. Kupffer
cells are also antigen-presenting cells
and remove any bacteria or debris
present in the portal blood.
In the perisinusoidal space are
hepatic stellate cells (or Ito cells) with
small lipid droplets that store vitamin
A and other fat-soluble vitamins. Hepatocytes (H), Kupffer cells (K), Bile duct (B),
Portal vein (P). Rat injected with particulate india
ink. X200. H&E
 Gallbladder
The bile produced by the hepatocytes flows through
the bile canaliculi, bile ductules, and bile ducts.
These structures gradually merge, forming a
converging network that ultimately forms the
common hepatic duct that joins the cystic duct from
the gallbladder and continues to the duodenum as
the common bile duct.
The gallbladder is a hollow, pear-shaped organ
attached to the lower surface of the liver, capable of
storing 30-50 mL of bile that is concentrated during
storage.
The wall of the gallbladder consists of a mucosa
composed of simple columnar epithelium and lamina
propria, a thin muscularis with bundles of muscle
fibers oriented in several directions, and an external
adventitia or serosa.
The lining epithelial cells of the gallbladder have
prominent mitochondria, microvilli, and large LP – lamina propria, M – muscularis externa, A –
intercellular spaces, all indicative of cells actively adventitia, Arrow - simple columnar epithelium.
Gal bladder H&E
transporting water, in this case for concentrating bile.
To move stored bile into the duodenum, contraction of the gallbladder muscularis is
induced by cholecystokinin (CCK) released from enteroendocrine cells of the small intestine