Federal State Budgetary Educational Institution of Higher Education

«Irkutsk State Medical University»

of the Ministry of Healthcare of the Russian Federation

Department of histology, embryology, cytology

L. S. Vasilieva, O. A. Makarova, A. S. Dadueva

Lecture notes on sections

«Special histology» and «Human embryogenesis»

Study guidance

Irkutsk
ISMU
2017
УДК 611.018(075.8)=111
ББК 28.86я73
V 30

Recommended by the CKMB of the FSBEI HE ISMU MOH Russia as a study

guidance for English speaking students trained upon higher education program –
specialist`s degree program in General medicine
(record № 5 from 15.06.2017)

Аuthors:
L. S. Vasilieva – Dr. of biol. sciences, professor, head of the dep. of histology,
embryology, cytology of the FSBEI HE ISMU MOH Russia
O. A. Makarova – Cand. of biol. sciences, assistant of professor of the dep. of
histology, embryology, cytology of the FSBEI HE ISMU MOH Russia
A. S. Dadueva – senior teacher of the dep. of foreign language with courses of Latin
and Russian for foreigners of the FSBEI HE ISMU MOH Russia

Reviewers :
T. I. Shalina – Dr. of med. sciences, professor, head of the dep. of human anatomy of
the FSBEI HE ISMU MOH Russia
S. O. Korshunova – Cand. of phil. sciences, associate professor of dep. humanitarian
and informational disciplines of the Irkutsk Institute of the RSJU (RLA of the
Ministry of justice)

V 30 Lecture notes on sections «Special histology» and «Human

embryogenesis» : study guidance / L. S. Vasilieva, O. A. Makarova, A. S.
Dadueva ; FSBEI HE ISMU MOH Russia, Department of histology,
embryology, cytology. – Irkutsk : ISMU, 2017. – 112 р.

Study guidance «The text of the lectures on sections «Special histology» and «Human
embryogenesis»» is made for classroom and extracurricular work of foreign students. Study
guidance contains the text of the lectures on sections «Special histology» and «Human
embryogenesis».
It is intended for foreign students of 1–2 courses of the FSBEI HE ISMU MOH Russia.

УДК 611.018(075.8)=111
ББК 28.86я73

© Vasilieva L. S., Makarova O. A.,

Dadueva A. S., 2017
© FSBEI HE ISMU MOH Russia, 2017
2
 THE CONTENTS
INTRODUCTION ......................................................................................................... 4
Lecture 1. Nervous system ............................................................................................ 5
Lecture 2. ANALYZERS. SENSE ORGANS. The ear and balance .......................... 11
Lecture 3.The ORGAN of VISION ............................................................................ 15
Lecture 4. The CARDIOVASCULAR SYSTEM ....................................................... 20
Lecture 5. SKIN (INTEGUMENT) and ITS DERIVATIVES ................................... 25
Lecture 6. ENDOСRINE SYSTEM ............................................................................ 31
Lecture 7. Organs of HEMOPOIESIS and IMMUNOGENESIS ............................... 42
Lecture 8. DIGESTIVE SYSTEM – general characteristics ORAL CAVITY .......... 48
Lecture 9. THE MIDDLE SECTION of the digestive tract ....................................... 61
Lecture 10. LIVER. PANCREAS ............................................................................... 69
Lecture 11. RESPIRATORY SYSTEM...................................................................... 74
Lecture 12. URINARY SYSTEM ............................................................................... 81
Lecture 13. DEVELOPMENT of REPRODUCTIVE SYSTEM. MALE
REPRODUCTIVE SYSTEM ...................................................................................... 88
Lecture 14. Female reproductive system..................................................................... 95
Lecture 15. HUMAN EMBRYOGENESIS .............................................................. 103
Recommended literature............................................................................................ 111

3
 INTRODUCTION
The manual «Lecture notes on sections «Special histology» and «Human
embryogenesis» is made up in accordance with the Federal State Educational
Standard of higher education (FSES HE) and the standard academic program on
discipline «Histology, embryology, cytology». It contains materials of the basic
course units. The manual is aimed at successful studying histology as a compulsory
subject in medical education as well as at the formation of the competencies
necessary for future specialists:
1) ability and readiness to analyze socially significant problems and processes,
to use the methods of humanitarian, scientific, biomedical and clinical sciences in
various professional and social activities;
2) ability and readiness to realize ethical and deontological aspects of medical
activities in dealing with colleagues, medical staff and patients;
3) ability and readiness to conduct the morphological analysis of biopsy,
operative and sectional material and interpret the results;
4) ability and readiness to analyze the laws of functioning of organs and
systems, to use knowledge of Anatomy and Physiology, and the basic methods of
assessing the functional state of the body of adults and teenagers;
5) ability and readiness to study the scientific and medical information,
domestic and foreign experience on research topic;
6) ability and readiness to participate in mastering modern theoretical and
experimental methods of study with the view of creating new advanced means, in the
organization of works on practical use and implementation of study results.

4
 Lecture 1. Nervous system
SPECIAL HISTOLOGY studies the microscopic structure of organs. An organ
is a historically formed system of tissues with a general function. In the organ the
tissues keep their structure and properties, but acquire an organ specificity. The
neurohumoral system unites the organs into the organism.
The NERVOUS SYSTEM is uniform, but it has 2 functional parts: 1 –
somatic, carries out external reactions, 2 – vegetative, carries out internal reactions.
There is the central nervous system (CNS) consisting of the brain and the spinal cord,
and the peripheral nervous system (PNS) consisting of ganglia, nerves and their
endings. The spinal cord and the brain are covered with three meningeal layers of
connective tissue called the dura, arachnoid and pia maters. The dura mater is an
external thick layer made up of dense connective tissue; it is badly regenerated. The
arachnoid has two components: 1 – a sheet of connective tissue in contact with the
dura mater and 2 – a system of loosely arranged trabeculae continuous with the
underlying pia mater. The trabeculae are surrounded by a large sponge-like cavity
called the subarachnoid space with liquor. The pia mater consists of loose connective
tissue with divided cells and it penetrates between a cerebral bends.
The SPINAL CORD. It is developed from the body part of the neural tube and
lies in the vertebral canal, connected with the periphery by 31 pairs of mixed spinal
nerves. The spinal cord is a long white cord divided into two halves by the ventral
median fissure and the dorsal white commissure (from pia mater and gliocytes). The
ventral and dorsal roots go out from the surface of the spinal cord. The spinal cord is
segmented. The segment is a part of the spinal cord with two pairs of roots. There is
dark grey matter in the center (on the slice it is shaped like a butterfly). The grey
matter consists of the neuron bodies forming the functional centers of the spinal cord
called neural nuclei. The neuron processes form a light white matter around the grey
matter. The grey matter forms short and massive anterior horns, thin and long
posterior horns and an intermediate zone between them which has lateral horns in
the interval between the 8th cervical and 2nd lumbar segments. The right and left
halves of the grey matter are connected with the central canal lined with the

5
ependima and containing the liquor by the grey commissure. The grey matter horns
divide the white matter into 3 pairs of funiculi: ventral, lateral and dorsal.
The GREY MATTER contains 3 kinds of multipolar neurons: 1 – root motor
neurons, their axons form ventral roots and go to the skeletal muscles; 2 – internal
associative neurons, carry out communications in their own segment; 3 – bundle
associative neurons, carry out communications between the segments and the brain,
their axons form conduction tracts.
The posterior horns begin with the marginal zone from the neuron processes
and neuroglia. Under the zone there is a spongy substance and a jelly-like layer of
neuroglia with few neurons. In the posterior horns there are sensory nuclei consisting
of the associative neurons, they provide tactile, pain and temperature sensitivity. In
the middle of the horn the proper nucleus lies (their axons form 3 ascending tracts on
the opposite side: ventral spinocerebellar tract, and lateral and ventral spinothalamic
tracts). In the horn basis the thoracic nucleus (dorsal, Clark's column) lies, it consists
of large neurons (their axons form the dorsal spinocerebellar tracts in the lateral
funiculi of their own side).
The intermediate zone contains 2 nuclei: medial and lateral. The axons of the
medial nucleus join the spinothalamic tract of their own side. The lateral, or
sympathetic nucleus, lies in the lateral horn and contains large neurons; its axons
constitute the ventral roots and go to the sympathetic ganglions. Near the lateral
horns the reticular formation lies (consisting of neutron processes).
The anterior horns contain motor nuclei: medial (muscles of the trunk) and
lateral (those of the hands and feet). They consist of the largest root motor neurons
(100 to 140 microns). Their axons form ventral roots and go to the skeletal muscles.
If they are damaged (e. g. in poliomyelitis) paralysis develops.
The spinal grey matter contains a lot of fine bundle neurons, their axons form
the proper tracts of the spinal cord: ventral, lateral and dorsal.
The WHITE MATTER consists of bundles of nerve fibers forming 3 groups of
conduction tracts: 1 – proper, connect segments; 2 – ascending, go to the brain; 3 –
descending, go from the brain. The dorsal funiculi contain 2 ascending tracts formed

6
of the long branches of the axons of the sensory neurons of the spinal ganglia:
Gaulle's thin bundle (in the center) and Burdagh’s sphenoid bundle. They provide the
pain, temperature, tactile and deep muscular sensitivity, and terminate in the medulla
oblongata. The lateral funiculi contain 5 ascending and 4 descending tracts. The
ascending tracts: dorsal and ventral spinocerebellar, spinotectal, lateral and ventral
spinothalamic. The descending tracts: corticospinal (pyramidal) lateral, rubrospinal,
thalamospinal, vestibulospinal. Ventral funiculi contain 4 descending tracts:
tectospinal, corticospinal ventral, reticulospinal and olivospinal. All descending
tracts inhibit the motor neurons of the spinal cord.
The SPINAL GANGLIA lie in the vertebral canal along the way of the dorsal
roots. The ganglion is covered with a capsule made up of dense connective tissue.
The bodies of the pseudo-unipolar sensory neurons lie under the capsule and are
covered with the neuroglial satellites. Their processes pass in the ganglion center and
are covered with the Schwan`s lemmocyte sheath. The dendrites come to the organs
and terminate with the receptors. The axons compose the dorsal roots of the spinal
cord. In the marginal zone of the posterior horns they are divided into 2 branches:
short descending branch goes to the nuclei of the posterior horns, long ascending
branch forms the Gaulle`s and Burdach`s columns of the dorsal funiculi. The ventral
funiculi of the spinal cord do not come into the ganglion, and are united with the
dendrites of the ganglion neurons to form the mixed spinal nerve.
The BRAIN consists of the trunk and the pallium (both the trunk and the
pallium develop from 3 brain bubbles). The trunk consists of the medulla oblongata,
the pons, the mesencephalon, the thalamus and the basal ganglia of the end brain. The
grey matter is placed in the center as nuclei. The pallium is composed of the cerebral
and cerebellar cortex.
The CEREBELLUM. It is the main center of balance and movement
coordination. It has the form of two hemispheres. On their surface the most part of
the grey matter forms the cerebellar cortex with sulci and gyri, the smaller part forms
nuclei in the white matter in the middle of the cerebellum. The dentate nucleus
transfers the information to the cerebral cortex and to the spinal cord; other nuclei

7
transfer the impulse to the spinal cord. The cerebellar cortex has 3 layers. The
external molecular layer is light, has inhibitory neurons and neuron processes of all
layers. The middle ganglionic layer consists of one layer of large efferent neurons –
piriform Purkinje neurons (the size is 35–60 microns). The internal granular layer is
dark; it contains synaptic complexes «Cerebellum glomeruli» and 10 billion fine
neurons. There are 3 groups of them: 1 – exciting cells-grains with a large dense
nucleus and little cytoplasm, 2 – inhibitory Golgi cells of the second type with a short
axon, 3) associative neurons – horizontal and Golgi cells of the first type with a long
axon, connect the cortex sites.
2 kinds of afferent tracts come to the cerebellum: the moss fibers from the
cerebral cortex and the climbing fibers from the spinal cord and the organ of balance.
The climbing fibers pass into the molecular layer, climb along the dendrites of the
Purkinje cells and excite them. The moss fibers come into the granular layer and
branchlike moss. They form exciting synapses with the dendrites of the cells-grains
which branch like a bird's foot. These synapse complexes form «the cerebellum
glomeruli». The axons of the cells-grains go from them into the molecular layer,
divide like T and excite all cortex neurons. The excited inhibitory neurons take part in
processing the information and inhibit the piriform Purkinje neurons. The Purkinje
cells collect the information and transfer it to the cerebellum nuclei.
The inhibitory neurons are of 4 kinds. 3 kinds of them lie in the molecular
layer: 1 – basket neurons which form baskets around the bodies of the Purkinje cells;
2, 3 – fine and large stellate neurons which form inhibitory synapses with their
dendrites. In the granular layer the 4th kind of the inhibitory neurons lies. It is Golgi
cells of the 2nd type, their short axons enter the cerebellum glomeruli and inhibit the
transfer of impulses from the moss fibers onto the cells-grains. Thus, they can inhibit
the excitation of the Purkinje cells. Each Purkinje`s cell forms up to 60 thousand
synapses.
The inhibitory neurons can strengthen or block the exciting impulses, that leads
to the inhibition or counter inhibition of the Purkinje cells. An intense impulse
inhibits the Purkinje cells, blocks their inhibiting influence on the dentate nucleus.

8
The nucleus neurons become excited and inhibit the pyramids of the cerebral cortex
that leads to the counter inhibition of the motor neurons of the spinal cord, and a
movement is made. And on the contrary, a weak impulse disinhibits the Purkinje
cells, and a movement is not made. By the same principle the majority of reflexes
work including the higher nervous activity.
The CEREBRAL CORTEX. The thickness of the cerebral cortex is 3 to 5
mm, it contains 14 to 17 billion neurons, all of them are multipolar, have different
forms, pyramids prevail. They have the top and lateral dendrites, the axon passes
from the basis of the cell. The pyramids can be small – 10 to 12 microns, middle-
sized – 20 to 30 microns, greater – 40 to 80 microns, and huge – 120 microns. New
synapses are formed on the process terminals in the form of thorns and swellings, in
nutritional disorder they die, but they remain near the perikaryon, that is why old men
have long-term memory but no short-term memory.
THE STRUCTURE. The cerebral cortex has cell- and myeloarchitectonics, or
the certain arrangement of fibers and cells forming the cortical areas – the centers of
the higher nervous activity. The cortical neurons lie in 6 layers: 1 – the molecular
layer, external, contains fine neurons and many processes of neurons from all layers
forming the tangential plexus; 2 – the external granular layer composed of fine
inhibitory neurons; 3 – the pyramidal layer, the widest, pyramids are of different size.
The top dendrite goes into the molecular layer, the lateral dendrites branch in their
own layer and form a plexus – external Bajarge’s strip, the axons form radial rays
and make up the cortico-cortical and pyramidal tracts; 4 – the internal granular layer
contains echinate stellate neurons, accepting excitation from the thalamo-cortical
tracts; 5 – the ganglionar layer composed of huge pyramids – Besth’s cells (120
microns). Their axons form the pyramidal tracts, and the lateral dendrites form the
internal Bajarge’s strip in the same layer; 6 – the layer of polymorphic cells, their
axons compose the pyramidal ways.
There are 2 types of cortex zones: 1 – granular type with well developed
granular layers – the sensory zones where the higher analysis of information is

9
performed; 2 – agranular type where pyramidal layers are well developed – these are
motor zones.
The structural and functional unit of the cortex is the MODULE. It is a
column with the diameter of 0,1 to 0,5 mm, consists of neurons of all layers
comprising up to 100 thousand. The cortex has 3 million modules.
The module has 3 parts: the entrance one accepts an impulse, the inserted one
analyzes, the exit one sends it out from the cortex. The 1st part (entrance) is 1
cortico-cortical fiber, excite cell pyramids, and 2 thalamo-cortical ones, excite the
echinate stellate cell in the internal granular layer. These cells transfer excitation to
all pyramidal and inhibitory neurons of the module. The 2nd part is 4 kinds of
inhibiting neurons. Three from them inhibit pyramids: 1st kind – the cells with axon
brush lying in the molecular layer and contacting with the pyramid dendrites, 2nd kind
– the basket cells lying in the external granular layer and contacting with the pyramid
bodies, 3rd kind – the axo-axonal cells lying in the pyramidal layer and contacting
with the pyramid axons. 4th kind is special – the neurons with a double bouquet of
dendrites, they lie in the pyramidal layer and inhibit all the inhibitory neurons, that
leads to the secondary excitation of the pyramids. The 3rd part (efferent) is pyramids;
their axons send the impulse out from the cortex. Inhibition or counter inhibition of
the pyramids adjusts the transfer of impulse from the cortex to organs, the force, the
concentration or diffusion of impulse, its read dressing to other cortical areas, so the
analysis and synthesis of the information is performed.

Questions for self-control:

1. What functional parts does the nervous system have?
2. What organs does the central nervous system include?
3. What organs does the peripheral nervous system include?
4. What is the grey and white matter of the spinal cord?
5. What components make up the spinal ganglion?
6. Name the layers of the cerebellar cortex.
7. Name the layers of the cerebral cortex.
8. What is a structural and functional unit of the cortex?
10
 Lecture 2. ANALYZERS. SENSE ORGANS. The ear and balance
Analyzers carry out communication with the environment. They can be of 3
types: 1) peripheral receptors, 2) intermediate receptors and 3) central (cortical)
receptors. The peripheral types form 5 organs of sense: primary and secondary. The
primary sense organs (vision and olfactory) have neurosensory cells. The endings of
their dendrites are receptors. The secondary sense organs (taste, hearing and balance)
have sensory-epithelial cells, entwisted with dendrites of sensory neurons. The skin-
muscular (musculo-cutaneous) sense organ has primary and secondary receptors
scattered all over the organism (skin, muscles, joints, etc.).
The organ of HEARING and BALANCE consists of the external, middle and
internal ears. As the organ of hearing it perceives sounds, and as the organ of balance
– awareness of the body position.
The external ear receives sound waves and consists of the ear concha
(auricle, pinna), external auditory (acoustic) meatus, tympanic membrane
(eardrum).The middle and internal ears are located in the temporal bone pyramid.
The middle ear transmits sound waves from the air to fluids; it is filled with
air and consists of the auditory (acoustic) tube, tympanic cavity and auditory ossicles
(three small bones). The auditory tube (also called the Eustachian or
pharyngotympanic tube) connects the tympanic cavity with the nasopharynx in order
to equalize the air pressure in it with the atmospheric one. In the medial wall the
tympanic cavity has two apertures – the oval and round windows, closed with
membranes. The auditory ossicles (malleus or hammer, incus or anvil, stapes or
stirrup) are connected with joints and form the system of levers which connects the
eardrum with the oval window and strengthens the sound wave (in children the
acoustic tube is short and wide, infection can easily get into the middle ear, and otitis
develops).
The internal ear consists of the bony labyrinth with the built-in membranous
labyrinth. The bony labyrinth consists of 3 parts: the vestibule, the cochlea and 3
semicircular canals (ducts). It is filled with perilymph, similar to liquor, and is
connected with the subarachnoid space. Infection can get through it into the skull

11
cavity and cause otitic meningitis. The membranous labyrinth is filled with
endolymph containing much K (150 mM) and little Na (16 mM). In the vestibule it
forms 2 membranous sacs: round (or saccule) and oval (or utricle).Three
semicircular canals with ampoules in their basis are placed perpendicularly to each
other and connect with the utricle.
The organ of balance (VESTIBULAR ORGAN) is presented by the receptors
called maculae and ampullar crests (cristae ampullares) which are placed in the
membranous wall of the utricle and ampoules of the semicircular canals. These
receptors have sensory epithelium made up of the basic and hair cells. The hair cells
are of 2 types: piriform and columnar. They contact with the dendrites of the sensory
neurons of the vestibular ganglia and have 60–80 motionless stereocilia and 1 mobile
kinetociliumat – the cellapex. Ampullar crests (cristae ampullares) are located
across the ampoules of the semicircular canals. They are the receptors of angular
accelerations. The sensory epithelium lies on the periosteum outgrowth and is
covered with a high gelatinous cupula (dome) composed of glycoproteins and GAG.
The hairs of the sensory cells penetrate into the dome. When the head or body rotates,
endolymph is displaced, the dome deviates, the hairs are bent, and the action potential
appears. The maculae lie on the membranous wall of the utricle; they are the
receptors of gravitation, linear accelerations and vibration. The hairs penetrate into
the otolithic membrane with the crystals of Ca carbonate – they are called otoliths
(otoconia).When the body changes its position in relation to gravitation otoliths are
displaced and irritate the hairs.
The organ of hearing (EAR) is located in the cochlea. It is a spiral organ, its
bony labyrinth forms 2,5 turns around the bone axis to which the spiral bone plate is
attached. The spiral ganglion lies in its basis. It contains sensory neurons; their
dendrites contact with the sensory cells, and the axons form the cochlear nerve which
goes into the bone axis of the cochlea. In the middle of the cochlea bone canal the
membranous canal is located, so on the axial section of the cochlea 3 cavities are
visible in each turn. The top cavity is called Scala vestibuli; it begins from the oval
window. The lower cavity is Scala tympani; it begins from the round window. At the

12
top of the cochlea they are connected by an aperture. The middle cavity is the
membranous canal (cochlear duct); from above it is bound by the vestibular
membrane (Reissner’s membrane), below – by the basilar membrane (fibroelastic),
and on the sides – by the spiral ligament which is a thickening periost of the cochlea
bone wall. The spiral ligament is covered with the vascular strip (stria vascularis)
composed of the stratified epithelium with vessels (capillaries of an unusual
intraepithelial plexus); it produces endolymph. The internal angle of the cochlear duct
is filled with limbus (a thickening periost of the spiral bone lamella). The basilar
membrane consists of 20 thousand thin collagenous fibers stretched like a string
between the spiral ligament and the lower lip of the limbus. At the cochlea’s basis the
fibers are short (40 microns) and vibrate under the action of high-pitched sounds. At
the cochlea’s top the fibers are long (500 microns) and vibrate under the action of
bass-pitched sounds. On the basilar membrane the Corti’s organ is located. It
consists of the basic and sensory hair cells, which are immersed in the gelatinous
tectorial membrane. The free end of the tectorial membrane is located above the hair
cells, and the other end is attached to the upper lip of the limbus.
The basic cells are of 5 kinds:
1) outer and innerpillar cells are high and lie spirally in 2 rows, forming a
spiral inner tunnel; along this tunnel the dendrites of the spiral ganglion neurons go to
the hair cells;
2) phalangeal cells are inner (1 layer) and outer (3–5 layers), located near the
pillar cells and have apical processes supporting the hair cells;
3) limiting cells are high, with the nucleus in the apical part; they carry out the
supporting and trophic functions;
4) outer sustaining cells are cubic, light, with microfibers; they remove
metabolic products from the endolymph into the blood;
5) basal sustaining cells are fine, basophilic, and have an ability to divide.
The hair cells are of 2 kinds. The inner hair cells are piriform. They lie on the
inner phalangeal cells and form a spiral row. There are 30–60 hairs. They are
damaged by streptomycin. Vitamin A is necessary for their regeneration. The outer

13
hair cells are columnar and lie on the outer phalangeal cells in 3–5 spiral rows. There
are up to 100 hairs. They are damaged by strong sounds and not restored.
The sound wave in the form of a perilymph wave rises from the oval window
membrane into the scala vestibuli up to the top of the cochlea, goes down the scala
tympani to the round window and is extinguished by its membrane. Under the
pressure of this wave the whole membranous canal makes fluctuation, the hairs of the
sensory cells are displaced in the tectorial membrane, and the action potential occurs,
which is accepted by the spiral ganglion neurons.

Questions for self-control:

1. Which components make up the analyzers?
2. What are the parts of the hearing organ?
3. What is the structure of the balance organ?
4. What are the main cells of the Corti organ.

14
 Lecture 3.The ORGAN of VISION
The organ of vision (EYE) consists of the eyeball and the auxiliary organs
including eye-moving muscles, eyelids and lacrimal apparatus. The muscles direct
the eye at an object and provide fine oscillatory movements of the eyes for the
volumetric image. From within the eyelids are lined with the mucous membrane –
conjunctiva, – which fuses with the eyeball forming an arch. The tear is produced by
the lacrimal glands lying in the conjunctive arch. The glands are alveolar and tubular
with myoepithelial cells. Tears humidify the cornea and are discharged through the
channels into the nasal cavity.
The EYE has 4 types of functional apparatuses.
1. Dioptrical apparatus is a system of lenses consisting of the cornea, the eye
chambers, the crystalline lens and the vitreous body.
2. Accommodative apparatus is a system of the crystalline lens and ciliary
bodies with the suspensory ligament. It changes the crystalline lens curvature for
focusing the nearby and distant objects.
3. Adaptative apparatus is a system of the iris and pigmentary epithelium of
the retina which adapts the eye to the light brightness.
4. Photosensory apparatus is the optical retina which is irritated by the light.
The eye is filled with the vitreous body which contains much hyaluronic acid,
water and transparent protein vitrein. It does not regenerate and flows out in case of
trauma, and the eye dies. In front of the vitreous body the crystalline lens lies. The
suspensory ligament connects the lens with the eye wall. The crystalline lens is an
elastic biconvex lens composed of stratified epithelium; the basal membrane forms a
transparent capsule. The basal cell layer has a nucleus and is able to divide at the
equator. The other layers of lens epithelium have no nucleus. These cells are filled
with transparent protein crystalline and turn to lens prisms or fibers. With age
elasticity of the crystalline lens decreases, crystalline denaturation begins, and
cataract can develop.
The eye wall has 3 sheaths: 1 – external fibrous, 2 – middle vascular, 3 –
internal retina. In the anterior and posterior eye hemisphere they are different.

15
 The fibrous layer contains the posterior sclera and the anterior cornea joining
at the limbus. The sclera consists of dense connective tissue with vessels, cells and
thick wavy collagenous bundles. That is why it is white and opaque. The cornea is
transparent since it has 2 features: 1 – it is made up of smooth collagenous plates in
which fibers lie in parallel, but at the right angle to each other, 2 – it has no vessels
and few cells, only fibrocytes. In the cornea there are 5 layers:
1) the external epithelium, which is stratified non-squamous (moist) epithelium
rich in nerve endings (the corneal reflex), and regenerates well;
2) the anterior limiting Bowman’s membrane, which is 6–9 mcm thick,
supports the form and nutrition of the cornea, has many GAG and no cells;
3) proper substance (stroma), which is composed of collagenous plates;
4) the posterior limiting Descemet’s membrane, which is 5–10 microns thick; it
is the basal membrane of posterior epithelium of the cornea;
5) the inner epithelium, which is simple squamous epithelium.
The middle vascular layer known as uvea contains 3 parts: the ciliary body
and the iris in the anterior hemisphere, and the choroid in the posterior hemisphere.
The choroid has 4 layers: 1 – supra vascular lamina made up of loose
collagenous tissue with melanocytes; 2 – vascular lamina, which contains a plexus of
arteries and veins; 3 – choroido-capillary lamina, with a capillary network; 4 – the
basal complex, or Bruch’s membrane, which is an extracellular complex composed of
the basal membrane of pigmentary epithelium, collagen and elastic fibers.
The ciliary body consists of the ciliary ring and the ciliary crown. The ciliary
crown is formed with processes made up of loose connective tissue and is covered
with two-layer epithelium of pars caeca retinae: the basal layer is pigmentary; the
second layer is non-pigmentary cubic, it produces intraocular liquid and forms thin
fibers of the suspensory ligament. The ciliary ring is a circular smooth muscle with 3
layers: external meridional, middle radial, internal circular. This muscle provides
accommodation, since it changes the crystalline lens curvature. When focusing on a
nearby object the ciliary muscles contract, the suspensory ligament relaxes, the
crystalline lens becomes convex, the focal length decreases. When focusing on a

16
remote object the ciliary muscles relax, the suspensory ligament is stretched, the
crystalline lens becomes flat, the focal length increases. With age the crystalline lens
loses elasticity and the ability to become convex, and the far-sightedness develops.
The iris of the eye extends away from the ciliary body, and lies before the
crystalline lens. It is an opaque disk with an aperture in the center, which is called the
pupil (euglena). The iris has 5 layers: 1 – the anterior simple squamous epithelium; 2
– the external limiting layer of loose connective tissue with melanocytes; 3 – the
vascular layer; 4 – the internal limiting layer (like the external one); 5 – the posterior
pigmented epithelium of retina. The iris is the eye diaphragm, which adapts the eye to
the light brightness, changing the diameter of the pupil by means of 2 smooth
muscles of the neuronal origin. The circular muscle the sphincter muscle of the
pupils lies around the pupil, narrowing it. The muscle has parasympathetic
innervation. Radially there are bundles of the dilator muscle of the pupils. This
muscle expands the pupil and has sympathetic innervation.
The iris separates the anterior and posterior chambers of the eye with
intraocular liquid (aqueous humor) which is first caught in the posterior chamber, and
then through the pupil in the anterior one. On the inner surface of the limbus the
Iridocorneal angle, or the the EYE angle, contains a system of irregular
endothelium-lined canals called the trabecular network or pectinale ligament with
fountain spaces, which continues into a large space of the sclera venous sinus or
Schlemm’s canal. By these ways intraocular liquid flows from the anterior chamber
into the circular vein. When the liquid outflow is damaged its pressure rises, and
glaucoma develops.
The internal layer of the eye wall is the retina. It consists of 2 parts: the thick
optical retina in the posterior hemisphere, and the thin non-optical (or caeca) retina
in the anterior hemisphere. The border between them is called serrated edge. The
non-optical (caeca) retina has 2 layers in the ciliary body and one layer in the iris.
The optical retina is the photosensory apparatus of the eye. It has 10 layers and is
composed of pigmentary epithelium, neurons, their processes and neuroglia:

17
 1 – pigmented single-layered epithelium composed of cubic cells with
processes;
2 – the rods-and-cones layer;
3 – the external limiting membrane (composed of the glial Műller cells);
4 – the outer nuclear layer;
5 – the outer plexiform layer;
6 – the inner nuclear layer;
7 – the inner plexiform layer;
8 – the ganglionic layer;
9 – the layer of nerve fibers;
10 – the internal limiting membrane.
The retina neurons form neural circuits with 3 neurons in each: 1 –
photosensory, 2 – associative, 3 – ganglionic. Dendrites of photosensory neurons are
directed at the pigmented epithelium and form terminations – rods and cones. The
rods’ number is 120 million, they are thin, long, provide black-and-white perception.
The cones’ number is 6–7 million, they are shorter and thicker, provide color
perception. Rods and cones contain 2 segments – external and internal, which are
connected by cilium. The internal segment contains organelles and enzymes, and in
the cones there is an optical filter from the carotenoid granule. The external segment
contains membrane disks which consist of the photosensory pigment: coneopsin in
the cones and rhodopsin in the rods (the complex of opsin and vitamin A).
Rhodopsin is synthesized in darkness and is destroyed in the light, which leads to
depolarization of disk membranes and to appearance of the nervous impulse. In case
of vitamin A deficiency rhodopsin is not synthesized. Coneopsin can be of 3 kinds. In
the 1st type coneopsin decays under the action of the red light, in the 2nd type
coneopsin reacts to the dark blue light, in the 3rd type – to the green light. When
synthesis of one of the coneopsins is disturbed daltonism develops.
The bodies of photosensory neurons lie in the outer nuclear layer; their axons
go to the outer plexiform layer and transfer the impulse onto the dendrites of

18
associative neurons whose bodies lie in the inner nuclear layer. Associative neurons
are of 3 kinds:
1) bipolar – they transfer the impulse in the inner plexiform layer from
photosensory to ganglionic cells,
2) horizontal – they bind photosensory neurons,
3) amacrine – they bind ganglionic neurons. The bodies of ganglionic neurons
form the ganglionic layer, and their axons form the layer of nerve fibers which gather
into the optic nerve. It forms a blind spot called Macula caeca (a disk of the optic
nerve); it has no photoreceptors. Close to it a yellow spot lies. It is called Macula
lutea with a central pit. It is the site of the best vision where the internal layers of
the retina are moved apart, and the retina thickness is reduced up to 3 layers. In the
central pit only cones lie.
Pigmented epithelium of the retina and iris adapt the eye to the light intensity.
In the bright light the pupil is narrowed, in the retina epithelium the melanin moves to
cells’ processes which separate rods and cones. Thus eye sensitivity decreases, and
contrast range rises. In the darkness the pupil dilates, melanin in retina epithelium
moves from processes to the bodies of cells, the access of light to photoreceptors
increases, eye sensitivity rises, and contrast range decreases.

Questions for self-control:

1. What are the functional apparatuses of the eye?
2. What are the tunics of the eye wall?
3. Name the layers of the cornea.
4. Name the layers of the optic part of the retina.

19
 Lecture 4. The CARDIOVASCULAR SYSTEM
The cardiovascular system consists of the heart, blood and lymphatic vessels.
In the organs some portion of blood plasma leaves the vessels for tissues provides
them with nutrition, collects metabolic products and turns into the lymph. The lymph
passes into lymphatic vessels, is cleared in the lymph nodes and returns to the blood.
The vessels develop from the yolk sac mesenchyme at the 2nd–3rd week. Their
formation is influenced by hemodynamic conditions, it est the vessel’s function,
blood pressure and the rate of blood flow. The arteries carry blood from the heart to
organs; the pressure in them is high, and the blood flow is rapid. The microcirculation
vessels (arterioles, capillaries, venules) are responsible for metabolism between the
blood and tissues; the blood flow rate is slowed down, the pressure is low. The veins
carry blood from organs to the heart; the pressure is still low, the blood flow rate is
slow. All vessels are lined with inner endothelium. It is a continuous layer of
squamous cells on the basal membrane.
The ARTERIES are of the large, medium and small size. By structure they
can be elastic, mixed, or muscular. The vessel walls have 3 concentric tunics:
1) the internal tunica intima of 3 layers – endothelium, subendothelial layer of
the loose connective tissue and the internal elastic membrane, 2) the middle tunica
media of smooth myocytes and elastic fibers, 3) the external tunica adventitia of the
loose connective tissue with nerves and vessels, and the external elastic membrane.
Large arteries, the aorta and the pulmonary artery, go away from the heart and have
an elastic structure. The pressure in them is high, so the middle layer has a lot of
elastic elements. The aorta has 40–70 elastic fenestrated membranes connected by
elastic fibers into a single framework. The endothelial cells are large, often
multinuclear. The subendothelial Langhans’s layer contains a lot of basic substance
and non-differentiated cells; there is no internal elastic membrane, but a plexus of
elastic fibers instead. In the adventitia thick collagenous bundles lie along the vessels
for the aorta not to extend.
The cephalic (common carotid) artery is muscular-elastic in structure, with the
equal amount of muscular and elastic elements. The medium and small size arteries

20
are distributive, of the muscular type. Their walls have 3 layers of the typical
structure. The middle layer is muscular; it discharges blood to the periphery
(peripheral heart), contains some spiral continuous layers of smooth myocytes. While
contracting, they narrow the opening of the vessels and reduce their length. Arteries
never collapse, since they have a uniform elastic framework formed by the elastic
fibers of the tunica media. They are attached to the internal and external elastic
membranes.
The VEINS can be small, medium and large; by structure they are muscular
and non-muscular. Non-muscular veins are intraorganic (in the eye retina, bones,
brain, spleen, liver), have no middle muscular layer. Muscular veins have a middle
muscular layer and can be of 3 kinds: those with a weak, average and high level of
muscular elements’ development. The vein with a weak development of muscular
elements is the upper Vena cava, which has a powerful adventitia made of the dense
connective tissue. It cannot be extended since blood flows due to the gravity. The
vein with a strong development of muscles is the lower Vena cava carrying blood
from the lower body organs. Such veins have a lot of longitudinal bundles of smooth
myocytes in the adventitia, which push blood against the gravity. 50 % of such veins
have valves – permanent folds of the tunica intima. But skin veins have no valves and
can form varices.
Work of vessels is adjusted by the neuroendocrine system and endothelium
which produces the factors causing blood coagulation and microvessel contraction. In
old people the walls of vessels lose elasticity because collagenous fibers harden and
expand, and fats and Ca salts are deposited in the adventitia (atherosclerosis
develops).
The MICROCIRCULATORY BLOOD STREAM provides metabolism and
protective reactions. They include vessels less than 100 microns in diameter. They
are arterioles, capillaries and venules. Arterioles are short, d=50–100 microns, and
regulate the blood supply of organs. The wall structure is like that in arteries, but all
sheaths are thin. In the tunica media myocyte bundles are circular. The adventitia has
non-differentiated cells and labrocytes. Capillaries are from 4,5–7 to 20–40 microns

21
in diameter. They have 2 parts: narrow arterial and wide venous. The rate of blood
flow is 0,5 mm/second, the pressure is low, about 20–40 mm/Hg. Capillary networks
have an organ specificity: the number of capillaries in the skeletal muscle is 2–3
times bigger than in the skin. In newborns the networks are denser. At rest about half
the capillaries work, on exertion the others enter the blood. The capillary wall is thin.
It contains 3 layers of cells: endothelium cells with a basal membrane, pericytes and
adventitial cells. Endothelium cells possess bilateral permeability. Their apical
surfaces have microvilli and few organelles in the cytoplasm; there are transporting
vesicles and myofilaments that contract the cell. Through the fissures or by means of
vesicles blood components pass into the tissue. Pericytes are fine cells with
processes; they lie in the basal membrane splitting; their functions are contraction and
phagocytosis. Their contraction changes the diameter of capillaries and the rate of
blood flow. Adventitial cells are non-differentiated, during regeneration they can turn
into endothelium, smooth myocytes and fibroblasts. By structure capillaries are
divided into 3 types: 1) somatic, or main capillaries found in the skin, muscles, lungs;
d=4,5–7 microns; the endothelium has a continuous basal membrane; they are 30–70
nanometers thick; 2) fenestrae, with fenestrated endothelium; they are thinner refined
parts of the endothelium which facilitate the transport of substances; the basal
membrane is continuous and frequently thickened up to 90–150 nanometers; they are
found in the kidney glomerulus; 3) sinusoidal capillaries, d=20–40 microns, with
perforations in endothelial cells and the basal membrane; they are found in the liver,
haemopoietic and endocrine organs. Histamine and heparin of labrocytes influence
permeability of capillaries. Histamine increases it and causes a microedema, which is
a spasm of smooth myocytes, and Quincke’s edema at allergy. Heparin, on the
contrary, reduces permeability of vessels.
Venules are wider than capillaries and have a similar structure; their
permeability is high. Venules can be postcapillary (d=12–30 microns) and collecting
(30–50 microns), they have no smooth myocytes. Large venules are of the muscular
type (d=100 micron); they pass into veins.

22
 Arteriolovenular anastomosis (AVA) or shunts in organs discharge
superfluous blood into the veins, by passing the capillaries. In closed anastomosis the
blood flows through capillaries and back. By structure shunts can be simple (they
adjust the blood flow by the muscular sheath of arterioles) and complex with special
devices (they block the blood flow with a roller which is formed during contraction
of longitudinal bundles of smooth myocytes in the tunica intima and muscular
layers).
The LYMPHATIC VESSELS carry lymph from organs into the blood system.
Lymphatic capillaries begin in organs blindly; they have no basal membrane and
pericytes; endothelial cells have microvilli on their basal surface. With the other end
lymphatic capillaries run into intraorganal non-muscular lymphatic vessels (like
veins). Extraorganal lymphatic vessels are muscular, with valves and a developed
adventitia. The main lymphatic ducts (thoracic and right) run into large veins of the
neck. The thoracic duct is similar to the lower Vena cava and has 9 half-lunar valves.
The site between the valves is referred to as a lymphangion.
The HEART pumps blood and lymph like a pump. Its walls have 3 tunics:
endocardium, myocardium, and epicardium. The myocardium and epicardium
develop from the myoepicardial plate of the mesoderm visceral layer. The
endocardium develops at the 3rd week from the mesenchyme, like a vessel. It
consists of 4 layers: 1) the endothelium layer made of large cells on the thick basal
membrane; 2) the subendothelial layer, like in the aorta, 3) the musculoelastic layer
of smooth myocytes and elastic fibers; 4) the external connective tissue layer with
fine vessels.
The myocardium contains 3 types of cardiomyocytes: 1) contracting typical; 2)
conductive atypical; 3) secretory endocrine. Endomysium is poorly developed and
has a lot of reticular fibers and a dense capillary network. The myocardium layer does
not regenerate, since it has no non-differentiated muscular cells. At a defected site a
scar is left. Contracting cardiomyocytes are larger in ventricles, rectangular, have a
lot of mitochondrions, myoglobin, well developed myofibrils and a T-system. They
are connected with each other by inserted disks forming the muscular fibers which

23
anastomose and form a three-dimensional network – the Cardiac Syncytium.
Atypical cardiomyocytes have a few myofibrils and little myoglobin; there is no T-
system. They form the conductive system of the heart which consists of sinoatrial and
atrio-ventricular nodes and conduction tracts. Atypical cells are divided into 3 kinds:
− P-cells (pacemakers) are pacings of the rhythm; they generate 60–90
impulses per minute, are small and lie in the sinoatrial node; P-cells influence the
autonomic nervous system: the sympathetic system accelerates the rhythm of
contractions, and the parasympathetic system slows it down;
− transitive cells are larger; they transfer impulses to the cells of the
conduction tracts and lie in the atrioventricular node;
− Purkinje cells are the largest; they form the conduction tracts (the
atrioventricular bundle and Purkinje myofibers).
Secretory cardiomyocytes make the endocrine system of the heart. They lie in
the auricles. They are fine, with processes, have few myofibrils and a well developed
endoplasm reticulum. They secrete atriopeptides into the blood. Atriopeptides have
the following properties: 1) stimulate lipolysis, 2) prevent blood coagulation, 3) the
atrial natriuretic peptide (ANUP) increases removal of Na from the kidneys and
lowers the blood pressure.
The epicardium is the serous tunica made of the irregular dense connective
tissue covered with mesothelium. It contains large vessels, nerves and the adipose
tissue.

Questions for self-control:

1. What organs belong to the cardiovascular system?
2. Name the tunics of the blood vessels wall.
3. What are the types of arteries by the size and structure of the wall?
4. What are the types of veins by the size and structure of the wall?
5. List the microvasculature vessels.
6. Name the heart tunics.
7. What are the types of cardiomyocytes?

24
 Lecture 5. SKIN (INTEGUMENT) and ITS DERIVATIVES
Skin is the largest single organ of the body. It is also known as the integument
or cutaneous layer.
Skin is composed of two layers: epidermis, an epithelial layer of ectodermal
origin, and dermis, a layer of mesodermal connective tissue. With the underlying
tissues skin connects via the hypodermis (subcutaneous fat). Skin thickness is from
0.5 to 5 mm. The functions of the skin: 1) protection against mechanical, physical and
chemical effects, 2) participation in the water-salt metabolism (releases about 500 ml
of water per day), 3) heat transfer, 4) excretory (elimination of substances with
sweat), 5) synthesis of vitamin D, 6) blood depots (contains many blood vessels), 7)
participation in immune responses (contains many lymphocytes being the immune
barrier), 8) tactile, temperature, pain sensitivity (contains receptors).
EPIDERMIS is a keratinized stratified squamous epithelium composed of
epithelial cells called keratinocytes. They are able to form a corneum substance
keratin and accumulate it. So in the epidermis the formation of new cells and turning
them into cornified squames takes place constantly. In accordance with the stages of
keratinization five layers are distinguished in the epidermis: basal (stratum basale),
spinous layer (stratum spinosum), granular layer (stratum granulosum), lucid layer
(stratum lucidum) and cornified layer (stratum corneum).
The basal layer (stratum basale) rests on the basement membrane and consists
of one layer of cylindrical keratinocytes with basophilic cytoplasm.
Spinous layer (stratum spinosum) rests on the basal layer cells and is composed
of 5 to 10 layers of keratinocytes, having a polygonal shape and cytoplasmic
processes in the form of short spines connecting desmosomes. The cells of the basal
and spinous layers contain tonofibrils and are capable of mitosis, so that these two
layers are combined in a germ (Malpighian) layer (stratum germinativum). The
epidermis is renewed within 20 days. In the germ layers the melanocytes, epidermal
macrophages (Langerhans cells) and Merkel cells are found. Melanocytes have neural
origin, long and branching processes and melanin granules in the cytoplasm.
Epidermal macrophages or Langerhans cells have mesenchymal origin. Merkel cells

25
are epithelial receptor discs having ectodermal origin, they contact with the dendrites
of the sensory neurons.
Granular layer (stratum granulosum) is composed of 2 to 4 layers of planar
rhomboid cells, they are incapable of cell division and contain the keratohyalin grains
(keratin precursor) in the cytoplasm.
Lucid layer (stratum lucidum) consists of 3 to 4 layers of flat enucleate cells
filled with eleidin which is formed from keratohyalin and tonofibrils.
Cornified layer (stratum corneum) is the surface layer which is composed of
dead skin cells called cornified squames packed with air bubbles and keratin rich in
sulfur. Its deficiency leads to skin diseases.
There are thick skin (on the fingers, palms and soles) and thin skin (on other
parts of the body). Thin (hairy) skin has the epidermis of 4 layers, the lucid layer is
absent and the cornified layer is thin. Thick skin (hairless) has 5 layers of the
epidermis with a very thick cornified layer.
DERMIS is a layer of connective tissue and consists of two sublayers: the
papillary layer and the reticular one. The papillary dermis consists of a loose
irregular connective tissue that forms dermal papillae, deeply invading the
epidermis, while the epidermis juts out into the papillary layer (between dermal
papillae) in the form of the epidermal ridges. The shape and height of the papillae
determine the strictly individual skin pattern (papillary lines). Papillae perform
receptor and trophic functions. They lead up the blood and lymph capillaries and
nerve fibers to the epidermis, some of which give free nerve terminals, and the other
part forms encapsulated tactile Meissner corpuscles lying in the papillae. Reticular
dermis is a much thicker, strong and elastic layer. It consists of a dense irregular
connective tissue, in which thick bundles of collagen fibers interwoven with a
network of elastic fibers. There are large blood vessels, nerve trunks and ducts of
sweat glands in this layer, and secretory units of the sweat glands and encapsulated
nerve terminals – Fater-Pacini corpuscles (baroreceptors, often called lamellar
pacinian corpuscle) lie on the border with the epidermis.

26
 HYPODERMIS (subcutaneous layer) is formed of adipose tissue lobules with
connective tissue septa, which contain secretory units of the sweat glands, blood
vessels, Fater-Pacini corpuscles.
SKIN GLANDS – sebaceous, sweat, mammary glands.
Sweat glands are simple tubular linear. Secretory unit and a part of the
excretory duct are twisted into a glomerulus, so they are called glomerular glands.
They are found in the reticular layer of the dermis. Excretory duct passes through all
the layers of the skin and opens on the surface of the epidermis as sweat pore.
Secretory unit consists of two layers of cells: 1) the internal layer, which contains
large secretory cells of the pyramidal shape, light and dark, 2) the outside layer,
which contains flattened myoepithelial cells with processes. They can contract and
squeeze the secretion out to the excretory duct. The excretory duct is formed by a
two-layer cubic epithelium with basophilic cytoplasm. Its cells are smaller and darker
than the secretory cells. According to the way of secretion the sweat glands can be
apocrine and merocrine. Apocrine glands have large secretory unit of oxyphilous
cells. The secretion is rich in mucus, proteins and products of their metabolism (uric
acid, urea); it escapes into the hair funnel (crater). The intensity of secretion depends
on the sexual cycle. Merocrine glands have weakly basophilic secretory cells and the
secretion contains more water, less mucus, proteins and urea, the ducts open onto the
surface of the epidermis, the secretion is independent of the sexual cycle.
The sebaceous glands are simple compound alveolar ones with holocrine
secretion. They are located in the thin skin and secrete sebum, release secretion into
the hair funnels. Ducts and terminal units are constructed of multilayered epithelium.
On the basement membrane in the secretory unit the first layer consists of small
basophilic dividing basal cells that ensure the restoration of secretory cells. The
middle layer cells are sebocytes synthesizing and accumulating the secretion. The
center of the secretory unit contains secreting sebocytes destroyed during the
secretion.
Mammary glands (breast) are derivatives of apocrine sweat glands, but
functionally they are closely related to the reproductive system. These glands have

27
compound an alveolar-tubular structure. Glandular stroma is formed by a dense
irregular connective tissue with bundles of smooth muscle cells. The layers of the
connective tissue form septa and divide the gland into 15 to 20 lobes, located in the
peripapillary part. There are interlobar excretory lactiferous ducts and lactiferous
sinuses, blood vessels and nerves in this stroma (in the connective tissue). The
glandular lobes consist of glandular lobules, each of them contains terminal
(secretory) units, intralobular excretory ducts and layers of a loose connective tissue
with lobules of the adipose tissue. Terminal units at a non-lactating gland are
presented with thin tubules that turn into bubbles called the alveoli in a lactating
gland. These tubules and alveoli are composed of double-layer epithelium containing
two kinds of cells – lactocytes (cubic or cylindrical) and myoepithelial cells. During
lactation lactocytes secrete milk by the apocrine type. Milk is a secretion rich in
nutrients, vitamins and calcium. Myoepithelial cells surround lactocytes with their
processes which contract and ensure the removal of the secretion from the alveoli and
small excretory ducts. Intralobular excretory (lactiferous) ducts are lined with two-
layer epithelium of cubic and myoepithelial cells. They merge into interlobular
lactiferous ducts (lined with the same epithelium) which branch out and go into the
advanced lactiferous sinuses, serving as reservoirs for the accumulation of milk. They
are also lined with two-layer epithelium of prismatic and myoepithelial cells. These
sinuses merge in efferent lactiferous ducts lined with two-layer cubic epithelium.
They merge in pore-like openings (deepening of the epidermis into the dermis, in the
number of 8 to 15) on the top of the nipple. They are lined with the stratified
squamous epithelium. The nipple is thickening of the skin, covered with a pigmented
epidermis (5 layers) and dermis (papillary and reticular layers), which forms the
areola and contains radial bundles of smooth muscle cells and sensory nerve
terminals.
The development of the mammary gland in ontogenesis is monitored by
estrogens and the preparation for lactation – by the hormone of yellow body (the
corpus luteum) of ovaries, progesterone. The production (synthesis) of milk is

28
stimulated by the pituitary hormone prolactin (LTG), and its removal – by oxytocin
(stimulating contraction of smooth muscle cells).
CORNIFIED SKIN DERIVATIVES – hair and nails, – are formed from the
keratinized cells of the epidermal cornified squame cells. They have (as the
epidermis) both a cornified part and a germ part (to update the cornified parts).
Hair consists of a scapus (a cornified part, rising above the surface of the skin)
and root (a germ part, deep in the dermis). At the boundary between the scapus and
the root of the hair epidermis forms a recess in the dermis – the hair funnel (crater),
on the fundus of which the ducts of the sebaceous glands open. A hair root is in the
hair sack whose wall is composed of internal and external hair invaginated root
epithelium. Together they make up a hair follicle, which is surrounded by the
invaginated root dermis – a hair sack. The hair sack is formed of the dense
connective tissue composed of three layers: the basal membrane (bordered by the
external root epithelium), the internal circular layer of collagen fibers, and collagen
fibers of the outer layer along the root of the hair. The arrector pili muscle, a small
bundles of smooth muscle cells, extends from the midpoint of the hair sack to the
dermal papillary layer. When their «goose bumps» contract appears, they promote the
release of sweat glangs, reduces blood flow and reduce heat loss. The external root
epithelium is an extension of the germ layer of the epidermis, and ends the hair bulb.
Internal root epithelium begins from the hair bulb and ends in the fundus of the hair
funnel (crater). It contains 3 layers: 1) the cuticle (one layer of dead skin cells –
cornified squames, imbricate located on the cortex of the hair), 2) the granular layer
of Huxley (cells contain grains with trichohyaline), 3) a layer of Henle (half-cornified
cells).
The hair bulb is composed of several layers of actively dividing epithelial cells
and it is a source of growth of hair and internal root epithelium. The bulb has the hair
papilla growing from the hair sack of loose connective tissue with blood vessels
feeding the follicles cells. The bulb cells reproduce many new cells and they move
away the papilla vessels. Then they accumulate a solid keratin and turn in keratinized
cells forming the internal root sheath, cuticle, the cortex and the medulla of hair.

29
Cortex of hair consists of heavily keratinized epithelial cells with granules of
melanin. The medulla is colored lighter and contains larger, vacuolated, and
moderately keratinized cells. Cells of the medulla and internal root epithelium
completely cornify while they move to the surface of the skin so the structure of the
hair root is not the same at various levels. The epithelium of the bulbs has
melanocytes that synthesize the pigment that determines hair color. With age, the
pigment synthesis is reduced and air bubbles are accumulated in cells, the hair
becomes grey.

Questions for self-control:

1. What layers is skin composed of?
2. What skin functions do you know?
3. What skin glands do you know?
4. Explain the hair structure.

30
 Lecture 6. ENDOСRINE SYSTEM
The endocrine system regulates body functions under the control of the
nervous system. It secretes hormones. Each of them changes the function of specific
cells or metabolism. The hormones, peptides and steroids, are produced in small
portions and rapidly destroyed in tissues. Peptides do not penetrate into the cell and
act via membrane receptors. Steroids are liposoluble, they enter into the cell and act
through nuclear receptors. Hormones are produced by endocrine cells or glands.
Endocrine glands are ductless, so the secretion is released directly into the blood or
lymph.
The endocrine system is divided into the central and peripheral parts. The
central part includes hypothalamus, pituitary and pineal gland. They are connected
with the nervous system, receive from it the information about the body needs and
regulate the operation of the peripheral endocrine system. It operates on the internal
organs and includes: 1 – glands having only the endocrine function (adrenal glands,
thyroid, parathyroid glands); 2 – mixed function organs (placenta, pancreas and sex
glands), 3 – diffuse endocrine system of individual cells in various organs. According
to the origin, these cells are divided into two groups. 1 – endocrinocytes of the non-
nervous origin, they secrete the peptide and steroid hormones and depend on the
pituitary; there is a lot of them in the urogenital system. 2 – neuroendocrine APUD-
cells, they are able to absorb and decarboxylate the precursors of amines, they are
developed from neuroblasts and depend only on the nervous system; they secrete
biologically active amines (histamine, serotonin, A, NA) and peptide hormones
(gastrin, bombesin, somatostatin). They include secretory neurons of the
hypothalamus, C-cells of the thyroid gland, adrenal chromaffin cells,
enterochromaffin cells of the gastrointestinal tract, the secretory cardiomyocytes,
labrocytes, and others. The endocrine glands are constructed from the epithelial
trabeculae. According to the structure, they are divided into 3 types: reticular,
trabecular and follicular.
The hypothalamus links the nervous system with the endocrine system. It is
connected with all divisions of the central nervous system and is the top center of the

31
autonomic nervous system. Its anterior parts consist of the parasympathetic centers
and the posterior parts – the sympathetic centre. Some hypothalamus nuclei are
neurosecretory endocrine ones. Their neurons secrete neurohormones and are
sensitive to the blood composition and have no hemato-encephalic barrier.
Neurosecretory nuclei are divided into macro- and parvocellular:
1) Macrocellular nuclei are supraoptic (secrete vasopressin) and
paraventricular (oxytocin). The axons of neurons form the hypothalamic-pituitary
tract and go to the back lobe of the pituitary, where they secrete neurohormones into
the blood. Oxytocin causes the contraction of the smooth muscle of the uterus,
bladder and rectum. Vasopressin increases the blood pressure and the reabsorption of
water in the kidneys (so called antidiuretic hormone), stimulates memorization. In
stress its production increases, so everything is remembered firmly.
2) Parvocellular nuclei are arcuate, dorsomedial and ventromedial, they
produce the releasing factors liberins and statins, and release them into the primary
capillary plexus of the ashen tuber (grey hill). These factors go from the primary
plexus through the portal veins, and then fall into the secondary capillary plexus of
the anterior pituitary. Liberins stimulate and statins inhibit the production of pituitary
hormones.
The pituitary (hypophysis) is the lower appendage of the hypothalamus.
Together they form a single hypothalamic-pituitary system. The pituitary lies in the
hollow sella and has the infundibulum. The infundibulum has an oval shape, d=0,5–1
cm, and is covered with a dense collagen tissue capsule. It consists of 3 lobes –
anterior, intermediate, posterior.
The pituitary gland is developed from 2 germs: epithelial and neural. During
the 4th week an epithelial protrusion grows up from the roof of the mouth. It is
Rathke's pouch. It comes off in a vial. At the 6th week the bottom of funnel of the
third brain ventricle grows against it as a ledge. Two germs contact with each other
and differentiate. The neural germ expands in the posterior lobe of the pituitary gland
– the neurohypophysis. In the epithelium germ the front wall of the vial expands and
forms the anterior pituitary. A thin posterior wall forms a narrow intermediate lobe.

32
The space between them is grown over with the connective tissue. Part of the anterior
lobe goes onto the infundibulum and forms pars tuberalis. Anterior pituitary, Pars
intermedia, Pars tuberalis together form the adenohypophysis.
The adenohypophysis is 70–80 % of the pituitary gland. This is a complicated
reticular gland of adenocyte trabeculae surrounded by blood sinusoids. Adenocytes
secrete tropic peptide hormones that act on the peripheral endocrine organs. There are
chromophilic and chromophobic (or major) adenocytes. There are 50–60 %
chromophobe cells. They include: 1) the precursors of chromophils, 2) chromophils
after removing the secretions, 3) real chromophobes – follicular-stellate not secreting
cells; they phagocytose the dead cells and the colloid remnants. Chromophilic cells
contain the secretion granules and are divided into acidophils (30–40 %) and
basophils (10–20 %).
The acidophilic hormones act directly on the cells of the internal organs.
Acidophils are divided into 2 types. Type 1 – somatotrophs; they have a large size, an
oval form and small red granules. They secrete the growth hormone – a somatotropic
hormone (STH, GH) which stimulates protein synthesis and body growth.
Hypersecretion of the growth hormone causes gigantism in children and acromegaly
at adults. Hyposecretion develops dwarfism (nanism) in children. Type 2 –
lactotrophs; they are smaller and have yellow granules. They secrete prolactin (the
lactotropic hormone, LTG). It stimulates the growth of the mammary glands,
production of milk and progesterone. In males it adapts the organism to hypoxia and
increases hardiness.
Basophils are larger than acidophils but their granules are smaller. Basophils
are divided into 3 types. Type 1 – thyrotrophs with small granules. They secrete TTH
– thyrotropin; it stimulates the thyroid gland to produce thyroid hormones. Type 2 –
gonadotrophs with large granules and light macula near the nucleus. They secrete
two gonadotropins – folliculotropin (FSH) and the luteinizing hormone (LH). Their
synthesis is stimulated with hypothalamic gonadoliberins, but they are released into
the blood one by one, «on the principle of feedback». FSH stimulates the production
of estrogens and inhibins. Accumulated in the blood, they suppress the secretion of

33
FSH. LH stimulates the synthesis of progesterone and testosterone. Being
accumulated in the blood, they inhibit the secretion of LH. A lack of sex hormones
causes the appearance of the castration cells with a large vacuole near the macula.
Type 3 – corticotrophs; they are with the macula too, but there is a light ring
around a dense center in the granules. Corticotrophs synthesize POMLC –
proopiomelanolipocortin, which is split into 4 hormones: 1) adrenocorticotropin
(ACTH), which stimulates the secretion of glucocorticoids by the adrenal glands, 2)
beta-endorphin with the analgetic effect, 3) lipotropin, which stimulates fat
metabolism, 4) melanotropin (MSH), which activates melanocytes.
Corticoliberin of hypothalamus, pituitary ACTH, adrenal GC and adrenaline
are the stress hormones that adapt the organism to any influence. The release of
adrenaline is stimulated by the sympathetic centers of the hypothalamus. Adrenaline
and GC activate the work of the heart, circulation, respiration, and discharge glucose
reserves into the blood; it is quickly broken down by the cells and gives a lot of
energy needed for the adaptation. So, the physiological stress is realized as an
adapting reaction. A severe exposure can cause an abnormal pathologic stress when
the stress hormone is secreted excessively. It leads to the cell destruction in the
stomach, liver, heart, lungs, etc.
The intermediate lobe of the pituitary is made up of a narrow layer of
chromophobe cells, wide layers of connective tissue and a small amount of basophils
of melanotrophs, which also synthesize POMLC, but discharge only melanotropin
and lipotropin into the blood. The remnant is accumulated as a colloid by
chromophobs forming pseudofolliculae.
The neurohypophysis consists of pituicytes. These are fibrous glia astrocytes.
The space between them is filled with their processes and axons of neurosecretory
cells of hypothalamus macrocellular nuclei. In the neurohypophysis they contact with
the wall of the capillaries and secrete oxytocin and vasopressin into the blood. The
contacting axonal terminations accumulate hormones forming basophilic thickening –
Hering’s body.

34
 The adenohypophysis receives blood supply from the superior pituitary artery
and neurohypophysis – from the inferior one. The superior artery enters the ashen
tuber and falls into the primary capillary plexus. Then blood passes into the portal
veins that come in the anterior pituitary and fall into the secondary sinusoidal
capillary plexus. The releasing factors influence the adenocytes that secrete their
hormones into these capillaries. The inferior artery comes in the neurohypophysis
and falls into capillaries. Oxytocin and vasopressin are secreted into these capillaries.
They are collected in the pituitary veins which go into the venous sinuses of the dura
mater.
Peripheral Endocrine Organs
Adrenal (or suprarenal) glands are vital paired organs, covered with the
connective tissue capsule. Under the capsule the cortical substance lies and in the
center there is a medullar substance. Cortex and medulla develop from different
primordia. The cortical substance is 2/3 of the glandular mass and develops from the
celomic epithelium. Medulla develops from neuroblasts (like the sympathetic
ganglion).
In the cortex the adrenocorticocytes are arranged in the form of strands,
compactly. Near the capsule the strands are bent to form arches. This area is called
zona glomerulosa (15 % of cortex). In the center of the cortex the strands run in
parallel with each other and form zona fasciculata (65–80 % of cortex). Near the
medulla the strands are at different angles. They anastomose and form zona
reticularis (10 % of cortex). The strands are densely entwisted by reticular fibers and
blood capillaries. Under the capsule a layer of small undifferentiated cells forms a
subcapsular layer. Due to their multiplication the glomerular portion regenerates.
Between zone glomeruloza and zone fascilata small undifferentiated cells form a
sudanophobic layer, due to which zona fascilata and zona reticularis regenerate.
These cells do not stain with Sudan, as they do not contain fat inclusions. At the
boundary of zona fascilata and zona reticularis acidophilic cells may occur; they are
the remnants of the fetal cortex and form the X-zone. It is believed that these cells
produce male sex hormones androgens, as this area is well developed in women and

35
eunuchs. Androgens regulate metabolism and protein synthesis in skeletal muscle. In
humans a normal X-zone is reduced in childhood.
Adrenocorticocytes synthesize steroid hormones from cholesterol. They
remove the low density lipoproteins from the blood, cleave cholesterol and
accumulate it in the lipid droplets. The structural features of adrenocorticytes are
well-developed EPR and Golgi complex, a lot of mitochondria with densely packed
tubular cristae, lipid droplets and many lysosomes. Adrenocorticocytes contain much
ascorbic acid which is required for the storage of finished hormone. The apical pole
of adrenocorticocyte has microvilli and faces the capillaries.
Adrenocortical cells of the glomerular zone contain a small amount of lipid
droplets in the cytoplasm. They produce mineralocorticoid hormones – aldosterone
and deoxycorticosterone, – which reduce the reabsorption of water and sodium in the
kidneys contributing to high blood pressure. Their secretion does not depend on the
pituitary and is regulated via the renin-angiotensin system.
Zona fasciculata consists of large cells. They are highly vacuolated because
their cytoplasm has many lipid droplets. These cells secrete glucocorticoid hormones
– corticosterone, cortisone and hydrocortisone (cortisol). The most active hormone is
hydrocortisone which is the main hormone in humans. Very little corticosterone is
produced. It has the properties of both mineral- and glucocorticoids. Glucocorticoids
increase the carbohydrate-protein-lipid metabolism. Large doses of glucocorticoids
are released during stress and quickly provide the body with energy material –
glucose, – because they activate the breakdown of fats and proteins and stimulate
hepatic gluconeogenesis (synthesis of glucose from amino acids). In addition, they
have anti-inflammatory and cytotoxic effects on T-lymphocytes. The synthesis and
secretion of glucocorticoids are stimulated by pituitary hormone ACTH and
suppressed at a high level of glucocorticoids in the blood (with a regulatory
feedback).
Zona reticularis consists of smaller cells with fewer lipid droplets. They
produce mainly sex hormones – the main proportion of testosterone-like androgens

36
and a little estrogen and progesterone. The secretion is stimulated by ACTH and
suppressed by a high level of sex hormones and glucocorticoids in the blood.
The adrenal medulla is represented by groups or strands of chromaffin cells
that stain with chromium salts, osmium and silver, so they are often called
osmiophilic, argyrophilic cells. They are large polygonal cells with basophilic
cytoplasm which has fine granules containing catecholamines (epinephrine or
adrenaline and norepinephrine or noradrenaline) and opioid peptides – enkephalins.
Histochemical methods reveal two types of cells: 1) light adrenocytes with
epinephrine granules, 2) dark noradrenocytes with norepinephrine granules. They
have well-developed EPR and Golgi complex. Norepinephrine is a neurotransmitter
of SNS, so adrenal medulla can be viewed as a modified sympathetic ganglion.
Epinephrine (methylated norepinephrine) is a real hormone, it has effects similar to
those of the SNS (narrows all vessels except for the coronary ones, accelerates blood
flow and increases blood pressure, relaxes smooth muscles in the intestine causing
diarrhea). Moreover, it stimulates the breakdown of the liver glycogen to glucose and
increases the glucose level in blood, giving the organism material to get energy. In
addition to chromaffin cells, the adrenal medulla has multipolar sympathetic neurons
(like in ganglia) and supporting neuroglial cells. The secretion by adrenal medulla is
activated by means of adrenoglomerulotrophine of pineal gland and sympathetic
nerves. During stress the secretion of epinephrine increases.
Blood supply of the adrenal glands is abundant, general for the cortex and
medulla, so their hormones enter the blood simultaneously. The capsular artery falls
into fenestrated capillaries, which run through the cortex, enter the medulla and are
transformed into sinusoids, then flow into the venous sinuses, and merge into the
central vein, and from it into the general circulation.
In addition to the adrenal glands, the mesentery has additional accumulations
of cortex – interrenal bodies, and clusters of chromaffin cells – adrenal bodies. The
sympathetic ganglia have many chromaffin cells too.
In newborns the adrenal cortex has 2 parts: 1 – a definitive (final) cortex under
the capsule where there are few lipids; 2 – the inner zone, a wider fetal cortex (80 %

37
of the cortex). Gradually, the definitive cortex grows, and the fetal cortex is reduced,
and by 1 year of life just separate cells are left from it. The differentiation of
chromaffin cells finishes by 3 years of life.
THYROID GLAND. The main thyroid hormones are thyroxine
(tetraiodothyronine, T4) and triiodothyronine (T3). The formed in the thyroid T3 is
called direct T3, it is 10 times more active than thyroxine. In the liver inactive reverse
T3 is formed (from T4 by removing one iodine atom). Thyroxine regulates the body's
basal metabolism. With an excess of the thyroid hormones (or iodine)
hyperthyroidism develops. A person is very excitable, interferes with everything, and
always feels choky and very tired. In hypofunction of thyroid and a lack of thyroxin
cretinism develops in children and myxedema (oedema, reduced metabolism and
body, severe psychosis) in adults.
The thyroid gland is laid as exocrine during the 4th week of embryogenesis
from the pharyngeal epithelium of the intestine at the level of 1–2 pairs of gill
pockets. The derivatives of the 5th pair of gill pockets – ultimobranchial bodies, – and
neuroblasts grow into the thyroid epithelium rudiments. During the 8th–12th week the
ultimobranchial epithelium cells begin to secrete an inactive prohormone, and
follicles are formed.
In adults the thyroid gland is located at the level of the thyroid cartilage of the
larynx, it weighs 20–30 grams. It is covered with a fibrous capsule from which septa
extend and divide the gland into lobules. The lobule consists of follicles and
interfollicular islets. Follicle is a structural and functional unit of the thyroid gland.
Its wall is composed of a single layer of epithelium, whose cells are called thyrocytes.
Thyrocytes are of 2 types: 1 – follicular thyrocytes, there are a lot of them; 2 –
parafollicular thyrocytes (calcitoninocytes, C-cells), they are fewer in number. The
lumen of the follicle is filled with colloid. The apical part of thyrocytes faces inside
the follicle and the colloid, and the basal part of the cells lies on the basement
membrane surrounding the follicle. Each follicle is surrounded with the fenestrated
capillaries. The septa between the follicles carry the vessels, nerves and lymphatics.
Clusters of spare epithelial cells form interfollicular islets which form new follicles.

38
C-cells (singly or in groups) occur in interfollicular islets, too. There are a lot of
labrocytes which produce mainly serotonin and don’t produce histamine.
Follicular thyrocytes produce hormones: thyroxine and triiodothyronine. The
secretory cycle consists of several phases: 1 – uptake of precursors (amino acids and
iodides) from blood, 2 – synthesis of the glycoprotein part of hormone (prohormone),
3 – excretion of prohormone into the cavity of the follicle, 4 – oxidation of iodine
ions and its connection with prohormone, 5 – absorption of iodinated prohormone
and its maturation (into cells), 6 – excretion of the secretion into the blood. The
absorption of amino acids from the blood and iodide is carried out through the
basement membrane and the basal part of the thyrocytes. The synthesis of
prohormone needs thyrosine. The prohormone is glycoprotein, called thyroglobulin
synthesized in EPR of cells. Thyroglobulin is excreted through the apical surface into
the lumen of the follicle. Thyroglobulin accumulates there in the form of a colloid.
The colloid is an antigen; if it penetrates into the connective tissue an autoimmune
reaction develops. To avoid this, thyrocytes are connected with each other by means
of the endplates (the densest junctions). The apical surface of thyrocytes has
microvilli with high activity of thyroperoxidase enzyme which destroys peroxide and
releases atomic oxygen. The iodine ions are transported intact across the cell. On the
thyrocyte apical surface they are oxidized with oxygen to form atomic iodine. In the
follicular cavity the atomic iodine is connected with thyrosine into thyroglobulin
molecule forming iodinated thyroglobulin which is resorbed (absorbed) by
thyrocytes. In this case, the colloid may have the resorptional vacuoles. In the
thyrocyte cytoplasm the iodinated thyroglobulin is broken down into fragments,
mono-, and dithyronines, by means of lysosomes. Then they are connected in tri- and
tetraiodothyronines. As a result, T3 and T4 are formed and secreted into the blood
through the basal part of thyrocytes.
Normal thyrocytes have a cubic shape, and there are a few small resorption
vacuoles in a colloid. When the function of the follicle increases, the cell shape
becomes prismatic, pseudopodia may appear, and the colloid is diluted. It becomes
frothy, has numerous vacuoles, the follicle size decreases. With a decreased function

39
the colloid becomes dense, the number of vacuoles decreases. The colloid
accumulates and stretches the follicle, thyrocytes are flattened. These follicles are
usually located on the periphery of the lobules. Their number becomes greater with
age.
Parafollicular thyrocytes (calcitoninocytes or C-cells) are located in the wall
of the follicle between follicular thyrocytes, but do not reach the follicle cavity with
their apical pole. They are well-identified with the impregnation with silver nitrate
(like nerve cells). The cytoplasm has granules with a secretion. C-cells are APUD-
cells of the diffuse endocrine system which produce somatostatin, calcitonin,
norepinephrine, serotonin. They are characterized with a high activity of monoamine
oxidase – the enzyme oxidizing the biogenic amines (norepinephrine, epinephrine,
serotonin). Calcitonin reduces the level of calcium in the blood because it increases
the excretion of calcium with the urine and promotes the formation of osteoblasts and
the bone calcification processes. Serotonin and norepinephrine regulate thyrocyte
functions. Somatostatin inhibits protein synthesis.
Regulation of secretion. The thyroid gland is a hypophysis-dependent gland.
The pituitary TSH stimulates the iodinated thyroglobulin hydrolysis and the
formation of hormones in thyrocytes. The hormone secretion is stimulated with the
sympathetic nervous system. Norepinephrine and serotonin and brought by the blood
epinephrine, histamine and immunoglobulins. The secretion is inhibited by the
parasympathetic nervous system, hypothalamic somatostatin and cells of the diffuse
endocrine system. Parafollicular cells (calcitoninocytes or C-cells) are APUD-cells
and react only on the nerve impulses and the level of calcium in blood.
In 20 % of newborns the thyroid gland has follicular type of structure. In 60 %
of newborns the thyroid gland has sleeping follicles and desquamated epithelium – a
desquamative type of structure. 18% of newborns have a gland of mixed type. During
the first two weeks of life follicles with colloid appear in the gland of the
desquamated type, and they gradually turns to the gland of the follicular type. By 15–
16 years there are follicles with squamous epithelium, the gland structure becomes
closer to the structure of the adult.

40
 PARATHYROID GLANDS are 4–6 small ovoid glands. They are located in
the larger capsule of the thyroid gland. They are essential for life. Their removal is
accompanied with a decreased level of calcium in blood and increased K and P,
which leads to the increased excitability of the neuromuscular system, convulsions
and death. A parathyroid hormone is parathyrin. It stimulates the formation and
activity of osteoclasts in the bone tissue. Then it leads to the increased bone
resorption and a rise of calcium in the blood. Parathyrin is an antagonist of calcitonin.
Histologically, the glands are compact, composed of epithelial trabeculae, thin
layers of connective tissue and a lot of capillaries. Sometimes, when the secretion
removal is delayed, pseudofollicles are formed. Most of the cells are the principal
(chief) parathyrocytes, they are small polygonal cells, with a light nucleus. According
to the cytoplasm density, the cells are divided into light and dark. The light cells are
inactive, while the dark cells – synthesize hormones actively and have well-developed
EPR and Golgi complex. In 4–7 years of age large acidophilic cells appear which do
not contain granules. They are considered to be senescent cells. The secretion of the
parathyroid hormone does not depend on the pituitary gland and is regulated by Ca
level in the blood. When the Ca level is increased, the parathyrin secretion is reduced.
In newborns these glands have a reticular structure, and then they turn into compact
glands.

Questions for self-control:

1. What organs refer to the central part of the endocrine system?
2. What organs refer to the peripheral parts of the endocrine system?
3. What hypothalamus nucleus do you know? Name its hormones.
4. Name the adenohypophysis hormones.
5. What zones does the adrenal cortex consist of?
6. What steroid hormones do you know?
7. Name the hormones of the thyroid and parathyroid glands.

41
 Lecture 7. Organs of HEMOPOIESIS and IMMUNOGENESIS
The organs of hematopoiesis and immunogenesis have a reticular stroma of the
connective tissue, or reticular epithelium, and perform three functions: 1) formation
of blood cells, 2) blood or lymph depot, 3) protection (as the result of phagocytosis
and the formation of immune cells). There are central and peripheral organs. Central
organs are red bone marrow and thymus; they contain stem cells and continuously
form blood cells. The peripheral organs are spleen, lymph nodes and lymphoid
formations of the mucous membranes. They do not contain stem cells but they form
mature lymphocytes and plasmocytes when an antigen appears in the body.
BONE MARROW (BM) contains stem cells, forms all blood cells and is
responsible for humoral immunity which generates B-naive lymphocytes. BM is
placed in the cavity of a spongy bone substance. It appears during the 2nd month of
development. First it is involved in the bone formation, and by the 36th week
hematopoiesis begins.
BM is the organ where the formation and maturation of blood cells occurs,
namely, erythropoiesis, granulopoiesis, monocytopoiesis, and thrombocytopoiesis.
The hematopoietic cells are placed in the reticular stroma composed of two kinds of
cells: reticular fibroblast-like cells and A-cells. Between them there are many
macrophages, mast cells, lipocytes, osteoclasts and osteoblasts. These cells make up
the microenvironment for hematopoietic cells and secrete hematopoietins which
determine the direction of stem cells differentiation. A-cells control the output of
mature cells into the blood. They recognize immature cells by means of their
antigenic proteins of cytolemma and do not release them into the blood.
Hematopoiesis occurs in the epiphysis. In diaphysis at the age of 4 the reticular cells
turn into the lipocytes and the red bone marrow becomes yellow. Hematopoiesis is
blocked, but the cells can appear when hematopoiesis is enhanced, for example, after
a blood loss or poisoning. In children there are a lot of lymphocytes as the formation
of immunity takes place.
THYMUS (thymus gland, T) is responsible for the cellular immunity. It
performs 2 functions: 1) hematopoietic – it forms T-helpers and T-suppressors; 2)
endocrine – thymic stromal cells secrete thymic hormones. When the thymus is

42
removed, the immune system is suppressed, an infection spreads rapidly, but a
transplanted tissue does not die off. The thymus develops from the ectoderm of the
pharyngeal section of the gut at the 4–5th week. At the 7th week it is populated by
lymphocytes.
The thymus is covered with the connective tissue capsule and consists of lobes
separated by the septa of interlobular connective tissue. Each lobe has a dark cortex
and a light medulla. The stroma is composed of the squamous reticular epithelium. Its
basal layer lies under the lobular capsule and the surface layers, in the center of the
lobe. The epithelial cells with large processes are called oxyphils. The stromal
epithelium secretes hormones: thymosins into the blood and thymopoietin into the
thymic tissue. They activate the reproduction of lymphocytes and functions of mature
lymphocytes. T-lymphocytes are called thymocytes. They lie between the stromal
epithelial cells.
In the cortex thymocytes lie densely. The subcapsular layer consists of T-
progenitor cells coming from the bone marrow and T-lymphoblasts. In the deep layer
the mature lymphocytes (T-helpers CD4 and T-suppressors CD8), lie. The
thymocytes train while maturing. They form receptors for recognizing protein
antigens. Between the thymocytes and the blood there is hemato-thymus barrier
which contains the capillary endothelium – the pericapillary space with macrophages
and epithelial stroma. Trained T-lymphocytes pass into the bloodstream without
going into the medulla, and migrate to the lymph nodes and spleen. Per day 15 % of
lymphocytes leave the thymus. During training 70–90 % of thymocytes can form
receptors for antigen proteins in the person’s body. If such cells enter the blood, they
destroy normal cells. It leads to an autoimmune disease (systemic erythematosus,
lymphosarcoma, lymphocytic leukemia). For protection the thymus stroma has
epithelial cell-nannies which recognize wrong thymocytes and destroy them by
apoptosis. Then macrophages phagocytize the remnants.
The medulla of the thymus has no barrier to blood. It has 2000 times less
lymphocytes than the cortex. Here they do not reproduce. They come into the thymus
from the blood to examine their receptors by stromal cells. Lymphocytes with
modified receptors are destroyed by macrophages. Old stromal cells form cell

43
aggregates called layered Hassall's corpuscles releasing many cytokines. In the center
of Hassall's corpuscles the epithelial cells are keratinized and die. Gradually, their
number grows.
The thymus is already well-developed in childhood. After the puberty age the
process of involution (reverse development) begins. It is expressed in a decrease in
the number of lymphocytes and proliferation of the adipose tissue. Stress causes a
temporary accidental involution of the thymus, since adrenal glucocorticoids destroy
thymocytes.
PERIPHERAL ORGANS OF IMMUNOGENESIS create immune barriers
to stop the invasion and spread of infection. The outer barrier is formed by a single
immune system of mucosa. The internal barriers are formed by lymph nodes and
spleen. A single mucosal immune system includes the tonsils and lymphoid follicles
of the mucosa of the digestive tube, air passages and urinary tracts. Follicles may be
single (solitary) or in the form of aggregates (Peyer's patches). They are formed by
lymphocytes through a flow of lymph in a loose connective tissue. They have no
blood vessels. A follicle has a light center called the reactive (reproduction) center. It
is a sensitive area where B-naive lymphocytes multiply. The center is surrounded
with a dark basophilic mantle zone of mature lymphocytes and plasmocytes. Between
follicles parafollicular T-dependent areas are placed. T-suppressors multiply there.
Plasmocytes of follicles produce IgA which connects with the secretory component
of epithelial cells. This complex is transferred to the mucosal surface, where IgA
binds antigens. Children have poorly developed follicles which are formed by the age
of 2.
LYMPH NODES develop from mesenchyme during the 3rd month; they begin
myelopoiesis. From the 4th month B-lymphocytes move into the nodes, form dark
cortex and bright medulla. Then T-lymphocytes move into the nodes, myelopoiesis
decreases, lymphopoiesis increases. A lymph node is bean-shaped, d=0,5–1 cm,
located along the lymph vessels, covered with the connective tissue capsule, the
trabeculae depart from it. There is a network of reticulum between lymph nodes.
Lymphoid cells and macrophages are placed in the network hinges.

44
 The node cortex contains 2 zones: cortical B-dependent and paracortical T-
dependent. The cortical area consists of lymph follicles, d=0,5–1 mm. The stroma
consists of A-reticular dendritic cells. They phagocytose AG and transmit it to Th. T-
helpers stimulate transformation of B-naive lymphocytes into B-naive lymphoblasts,
large cells with a bright nucleus. B-lymphoblasts multiply and form a light germinal
follicular center. There T-memory lymphocytes and plasmocytes are formed from B-
lymphoblasts. Plasmocytes have a dense nucleus and a basophilic cytoplasm, they
form a basophilic mantle zone around the germinal (reactive) center. Reactive centers
appear and disappear, in case of infection they increase. Follicles are separated from
the capsule by the edge sinuses and from other follicles and trabeculae by the
intermediate cortical sinuses. The paracortical area is diffuse; it forms a continuous
layer between the follicles and medullary cords. This area has a stroma of
interdigitated reticular cells with short finger-like processes, they secrete cytokines
that stimulate the proliferation of T-suppressors and the formation of T-killers and T-
memory.
The node medulla consists of medulla cords, sinuses and trabeculae. The
mature lymphocytes and plasmocytes are deposited in the cords, from the cords they
come out into the lymph. Lymph node sinuses are spaces lined by the bank reticular
cells without a basement membrane. Inside the sinuses are filled with a network of
the reticular tissue which slows down the flow of lymph, delays lymphocytes,
plasmocytes, macrophages and antigens. Lymph is brought by 3–4 lymph vessels
belonging to the convex side of the node. First it enters the edge sinuses, and then the
intermediate cortical sinuses. B- and T-lymphocytes migrate from lymph into the
node cortex, settling their B- or T-dependent areas. Macrophages of the node cortex
eliminate antigens and foreign particles. Lymph is purified by 99 % and moves into
the medullar sinuses separating medullar cords; mature lymphocytes and plasmocytes
migrate into it, and antibodies are secreted there as well. Purified and enriched lymph
first enters the final sinus, then the efferent vessel that goes out of the node gate on
the concave side.

45
 Infants have large lymph nodes, but their protective function is weak. The
follicles are formed by 2 years, especially rapidly – from 4 to 8 years. This process
finishes by 12.
SPLEEN performs five functions: 1) hematopoietic, 2) immune protection, 3)
blood depot, 4) hemolytic, 5) absorbing iron from erythrocytes. At the 5th week of
development the mesenchyme of the dorsal mesentery forms the spleen germ from
the reticular tissue. Then at the 12th week macrophages and B-lymphocytes appear in
the germ; they group and form follicles of the white pulp. By the 6th month the red
pulp is formed between them. By the 5th month all blood cells have been formed in
the spleen. After birth only lymphopoiesis takes place.
The spleen is covered with the mesothelium and has a connective tissue
capsule and trabeculae with smooth muscle cells. It is a support-contractile apparatus
through which the deposited blood is expelled into the general circulation. Between
the trabeculae the stroma from the reticular tissue is placed. The stroma with
lymphoid cells and erythrocytes forms the white and red pulp.
The white pulp makes up 20 % of the spleen. It consists of lymphatic follicles
and sheaths. Lymphatic sheaths are formed in the adventitia of pulp arteries. Follicles
or spleen bodies are formed around the central arteries located eccentrically in the
follicle. The follicle has 4 zones: 1) periarterial T-zone where T-lymphocytes
proliferate and the stroma consists of interdigital reticular cells; 2) reactive center –
B-zone where B-lymphocytes proliferate and the stroma consists of dendritic reticular
cells; 3) the mantle zone which lies around the reactive center and collects mature T-
and B-lymphocytes and plasmocytes, the stroma consists of fibroblast-like reticular
cells; 4) marginal zone which surrounds the follicle; it is wide, lymphocytes there lie
rarely; it is surrounded with marginal venous sinus; through their wall mature
lymphocytes migrate into the blood.
The red pulp consists of the pulp cords located between the trabeculae and
venous sinuses. Pulp cords and sinuses can deposit blood. In the red pulp cords
plasmocytes mature and old erythrocytes are destroyed. Macrophages phagocytose
their fragments, carry Hb-proteins to the liver and give them for the synthesis of bile
acids, and iron – to the red bone marrow for the Hb synthesis in new erythrocytes. If

46
the reticulum secretes hemolysins excessively, normal erythrocytes die,
splenomegaly and hemolytic jaundice develop. They are treated by the removal of the
spleen.
Circulation. The splenic artery enters through the gates, divides into segmental
and trabecular arteries. They enter the pulp and branch into the pulp arteries going to
the central artery. Follicles are formed around them with their own network of
capillaries which turn into the venous sinuses in the marginal zone of the follicle.
Leaving the follicle, the central artery divides into 4–5 penicillar arterioles that
continue as arterial capillaries surrounded with a cartridge case from the reticular
tissue. Their endothelium can reduce and slow down the blood stream in the white
pulp, increasing the migration of lymphocytes from the blood. From the barrel
capillary the blood goes into the red pulp in two ways: quickly closed and slowly
open. In the closed circulation the blood goes directly into the venous sinuses. In the
open circulation the blood enter the pulp cords, filtered through the stroma, and only
then it enters the venous sinuses. They have smooth muscle sphincters that regulate
the blood flow and enter the trabecular veins. The trabecular veins are of the non-
muscular type. They do not collapse because they are firmly fused with the trabecular
tissue which facilitates the flow of blood into the spleen vein going out of the gate.
The capsule is formed by 14 years, trabeculae – by 20 years. At the age of 18–
20 years involution of the white pulp begins.

Questions for self-control:

1. What are the functions of the reticular stroma of haemopoietic organs?
2. What are the central and peripheral organs of haemopoiesis and
immunogenesis?
3. What cells are formed in the red bone marrow?
4. What cells are formed in the thymus?
5. Name the T- and B-dependent zones in the peripheral haemopoietic organs.
6. What spleen functions do you know?
7. What zones has the spleen follicle?

47
 Lecture 8. DIGESTIVE SYSTEM – general characteristics.
ORAL CAVITY
DIGESTIVE SYSTEM.
Man receives energy and building material in the form of biopolymers, which
cannot penetrate into the cells. In addition, dietary proteins are antigens for the
organism. Thus, to be able to use biopolymers you must make them available for
cells. Biopolymers need to be split into monomers and deprived of antigenic
properties and toxicity.
These functions are performed by the digestive system. It consists of the
digestive tract and digestive glands. The splitting of polymers into monomers is
performed gradually as they move through the digestive tract. There are 3 kinds of
digestion: 1) cavernous digestion – in the cavity of the digestive tract, 2) the parietal
and membrane digestion – in the striated border of the microvilli, 3) intracellular
digestion – in the cytoplasm of the columnar border epithelial cells.
The digestive tract consists of 3 sections: anterior, middle and posterior.
The anterior section consists of the oral cavity with teeth, tongue and salivary
glands, gullet and esophagus. The oral cavity takes food and crushes it with teeth.
The saliva moistens it and digests simple carbohydrates. The tongue determines the
taste. The oral mucosa partially absorbs.
The middle section consists of the stomach, small and large intestines, liver and
pancreas. Its function is the chemical digestion, the absorption of products of
digestion and bowel movement.
The posterior section consists of the caudal (final) rectum. It eliminates the
undigested residue.
Antigenic food neutralization is carried out along the entire length of the
digestive tract. Two groups of antigens penetrate into the digestive tract with food:
food proteins and microbes. Dietary proteins lose their antigenic properties after they
are broken down by enzymes to form amino acids. It is a non-specific antigenic
enzymatic barrier. It is most developed in the oral cavity, stomach and intestine.
Specific mucosal immune barrier inactivates microbes; it is present along the entire
48
length of the digestive tract and consists of tonsils in the gullet and the solitary
lymphoid follicles or Peyer's patches in the walls of the gullet (esophagus), stomach
and intestines.
Despite different functions, the structure of the digestive tract has common
features. The wall of the tract consists of 4 tunics: mucosa, submucosa, muscle and
the outer tunica (serosa or adventitia).
The mucosa consists of 3 plates: epithelial lining, an underlying lamina propria
of loose connective tissue and muscular mucosa of a smooth muscle layer. In
different organs of the digestive tract the mucosa has different characteristics and
topography. In the anterior region it is smooth, in the stomach it forms gastric pits,
and in the intestine it forms intestinal villi and crypts, fixed submucosa. Mucosa and
submucosa form folds. The villi, crypts and folds increase the overall absorption
surface of the intestine up to 40-50 m, and the epithelial microvilli increase it even by
a factor of 30–40.
Epithelium has three functions: barrier, absorptive and secretory. The function
determines the type of epithelium in various parts of the tract. The epithelium of the
anterior and posterior parts is subjected to mechanical, chemical, thermal effects,
thus, it has to be strong and recover quickly. These qualities belong to the ectodermal
epithelium of the skin type which is called keratinizing stratified squamous
epithelium. In the middle part of the tract the function of the epithelium is secretion
and absorption. Thus, this time the epithelium is thin, simple, prismatic, of the
entodermal intestinal origine, but it has its peculiarities. In the stomach it is glandular,
in the intestine – with microvilli and goblet cells. The glandular epithelium forms all
glands in the middle section. Some of the epithelial cells of the middle section are
APUD-endocrine cells.
Lamina propria consists of a loose connective tissue with blood vessels,
nerves, lymphoid follicles. In the stomach it contains 3,5 million simple tubular
glands that produce gastric juice. Lamina propria performs three functions: 1)
connects and supports the epithelium and glands, 2) delivers vessels close to the
epithelium and facilitates the transportation of absorbed substances in the blood and

49
lymph, 3) protects against antigens with lymphocytes and plasmocytes that produce
the secretory IgA which enters the cavity of the tract via the epithelium and
neutralizing antigens.
Muscular mucosa consists of 1–3 layers of smooth muscle cells in the two-
layered plate (circular inner layer, longitudinal outer layer). Its function is local
movement of mucosa. It is not fond in the oral cavity and gullet.
Submucosa provides mobility for mucosa. It consists of a loose connective
tissue with vascular plexuses and submucosal Meissner plexus of sympathetic nerves
and parasympathetic ganglia. In the esophagus and duodenum the submucosa
contains glands. On the back and lateral surface of the tongue the submucosa is
absent not found.
The 3rd layer is muscularis externa. It is a smooth muscle in the middle
section and a striated muscles in the anterior and posterior sections. The muscular
layer contains 3 layers in the stomach and 2 sublayers in other sections: inner circular
and outer longitudinal. The circular muscle sublayer forms a compressed spiral, and
the longitudinal muscular sublayer forms a very gentle sloping spiral. Between the
sublayers of muscles the vascular and Auerbach`s intermuscular nerve plexuses lie.
The muscular layer is capable of peristalsis that provides the movement of food
through the digestive tract. Peristalsis is a downward wave of muscle contraction,
regulated by the autonomic nerve system. Meissner`s and Auerbach`s nerve plexuses
contain intramural parasympathetic ganglia, they relay the nerve impulse from the
branches of the vagus nerve to the ganglion neurons that stimulate the smooth
muscles to contract, increase the tone and peristalsis. Through Meissner`s and
Auerbach`s plexuses the axons of sympathetic ganglia neurons (sympathetic nerves)
reach the myocytes without interruption. They weaken the tone, inhibit peristalsis.
Stress often leads to diarrhea.
The outer layer is adventitia or serosa. It consists of a relatively dense
connective tissue with blood vessels, nerves and plexus. The adventitia covers part
of the esophagus and rectum. It merges with the surrounding tissues and fixes the
organ. The serous membrane (serosa) covers the middle section of the digestive

50
tract. It is formed of the visceral peritoneum fused with the wall of the middle
section, so the connective tissue in the serous membrane is covered with the
mesothelium. It is a celomic single-layered flat epithelium. Mesothelium is smooth
and always moist because it is washed with the abdominal peritoneal fluid. It reduces
the friction of organs during peristalsis. When the mesothelium is damaged the
intestinal adhesions can form.
DEVELOPMENT. The digestive system develops from all germ layers. The
primary colon is formed during the 3rd week of development with the entoderm,
mesoderm and visceral layer. During the 4th week it folds into a blindly closed tube.
On the ends of the cranial and caudal tube the invaginations of the ectoderm form the
oral and anal bays, which grow up to the closed ends of the colon, forming a roto-
pharyngeal and cloacal membrane of 2 sheets – the ectoderm and endoderm. On the
4th week these membranes break, and the intestinal tube opens at the both ends.
ORAL CAVITY. The oral cavity with teeth, a tongue and salivary glands
develops from the ectoderm.
The TONGUE is a movable organ composed of skeletal muscles. The muscle
fibers run in 3 reciprocal perpendicular directions. The minor salivary glands, blood
vessels, nerves and adipose tissue are placed between them. The mucosa consists of
stratified squamous epithelium (partly keratinized) and lamina propria. The lower
surface of the tongue is smooth, with a movable mucosa, it has a submucosa. On the
dorsal and lateral surfaces the submucosa is absent. Thus the mucosa is immovable
and forms 4 types of papillae. The basis of the papilla forms the outgrowth of the
connective tissue – the primary papilla, which cuts into the epithelium forming the
small secondary papillae.
The secondary papillae of the 1st type (filiform papillae) are most numerous
and located on the dorsal surface of the tongue covered with the heavily keratinized
epithelium without taste buds. Their function is mechanical protection and touch
sensitivity. In diseases the epithelial keratinization increases forming a white plaque.
The secondary papillae of the 2nd type (fungiform papillae) are located on the tip and
sides of the tongue, covered with non-keratinized epithelium. They have 4–6 taste

51
buds at the top. The secondary papillae of the 3rd type (vallate or circumvallate
papillae) are the largest papillae on the dorsal surface of the tongue in front of the
root. They do not rise above the tongue surface and are surrounded with the epithelial
rollers. The epithelium of the lateral surfaces of the papilla and rolls has a lot of taste
buds. The secondary papillae of the 4th type (foliate papillae) are located on the lateral
surface of the tongue and contain many taste buds. They are well developed in
children, while in adults they are reduced.
The root of the tongue has no papillae, but the surface is uneven. In the
thickness of tubercles a mass of lymph follicles forms a lingual tonsil.
The salivary glands open between the tongue papillae into grooves. The mixed
protein-mucous glands are at the tip of the tongue, the protein glands are in the
tongue body, the mucous glands are near the tongue root.
In newborns the tongue is strong and large, with vallate and foliate papillae. At
2 months of life the filiform and fungiform papillae are formed. Keratinization of
filiform papillae occurs by 1 year. In early childhood the mucosa is delicate, dry, and
contains many blood vessels. The epithelium is thin and consists of 2–3 cell layers,
thus it is vulnerable and permeable to infections. The salivary glands are poorly
developed till 4 months of life, and then they develop and start salivating. The tongue
is completely formed at 5–10 years of age.
The tongue is the organ of taste; it has receptors – taste buds or bulbs. In
humans there are about 2000 taste buds. They are specialized: at the tip of the tongue
taste buds react to sweet; at the root – to bitter; on the lateral surfaces – to sour and
salty. Taste buds lie on the basement membrane of the epithelium. It opens into the
oral cavity as a taste pore under which there is a taste pit. The taste bud contains 3
types of cells: taste, supportive and basal. The taste (gustatory) sensory cells are
narrow and high cells with a light oval nucleus and microvilli on the apical surface.
Microvilli are bonded by glycoproteins into bundles. Chemical compounds are
adsorbed on the microvilli and depolarize the cytolemma of taste cells. Thus a nerve
impulse arises. It is taken by the dendrites of sensory neurons entwisting the basal
part of the taste cells. Between the taste cells the supportive cells lie. They are tall,

52
with a dark nucleus. The basal cells lie at the base of buds. They are small, poorly
differentiated, and renew the taste buds within 10 days.
The salivary glands are complex branched alveolar and alveolar-tubular
glands; they open into the oral cavity. There are three pairs of them: the parotid,
submandibular, sublingual glands. They perform 4 functions:
1) the exocrine function, which is the production of saliva. Saliva is a protein-
mucous secretion rich in enzymes, which act in a neutral environment (pH=6,5–6,9)
and break down polysaccharides, nucleotides, and some proteins;
2) the endocrine function. Saliva contains biologically active substances and
hormones: an insulin-like hormone, a sialogastrin hormone (it inhibits gastric acid
secretion), growth factors for epithelia and nerves, the antianemic factor and others;
3) the excretory function. The uric acid, iron (Fe), creatine, iodine are excreted
with saliva;
4) the bactericidal function. Saliva contains lysozyme which destroys
microbes.
STRUCTURE. The salivary glands develop from the stratified epithelium, and
all their departments retain a multilayer structure. The glands are covered with a
dense connective tissue capsule. Under the capsule the parenchyma lies. It consists of
secretory units on a branching duct system arranged in lobules, separated with the
septa of the connective tissue. The duct system consists of interlobular and
intralobular ducts. The secretory units contain two layers of cells. The inner layer
contains glandular cells (glandulocytes) secreting by the merocrine type of secretion.
The outer layer contains myoepithelial cells; they lie inside the basement membrane
and have long contractive processes, which surround the secretory unit and move the
secretion into the excretory duct.
Glandular cells are of two types: serous and mucous. The serous cells
(serocytes) are protein-secreting and well-staining cells; they are of the pyramidal
form; they have apical secretory granules and secrete enzymes and other proteins of
saliva. The serous cells form a spherical (alveolar) secretory unit called an acinus,
with a very small central lumen. The mucous cells (mucocytes) are of the columnar

53
form; they have cytoplasm with hydrophilic mucins that provide the saliva with
lubricating properties. They are large and poorly staining cells. The mucous cells
form a cylindrical secretory unit called mucous tubule. They may be formed by the
cells of intercalated excretory ducts converted in mucocytes. Mixed units are formed
by the mucous tubular part and lower protein part. At the bottom of the tube the
protein units take the form of a protein crescent.
Duct systems. Glandulocytes discharge the secretion into the intercellular-
accurate secretory capillaries formed by invagination of cytolemma of adjacent cells.
Then the secretion moves into the lumen of the secretory unit. Using the
myoepithelial cells the secretory units discharge the secretion into the short
intercalated ducts lined with cuboidal and myoepithelial cells. The intercalated ducts
merge into the striated ducts. Their diameter is more than that of the protein acinus;
the epithelium is prismatic, with myoepithelial cells. The prismatic striated duct cells
are oxyphil and have a basal striation that is formed with deep folds of the basal
cytolemma and accumulation of mitochondria between them. The basal striation
provides the transport of substances through the basal part of the cell. Striated duct
epithelium produces the insulin-like hormone, and transfers water from the secretion
to the blood. Then the saliva enters the actual intralobular ducts lined with the
double-layer cube epithelium and having no myoepithelial cells. They merge into
interlobular ducts that empty into the common excretory duct composed of the
stratified epithelium.
The secretion of saliva is regulated by ANS: the parasympathetic system
stimulates, sympathetic one inhibits the salivation.
Large salivary glands are formed from the oral epithelium at the 6–8th week of
embryonic development. The secretory units are formed by the 4th month. The
parotid gland is alveolar, protein. It has a thick capsule; accumulations of fat cells
are found in the interlobular septa. It has many intercalated and striated ducts. Up to 2
years of life, the secretion is mucous, and then it becomes protein. The
submandibular gland is alveolar and alveolar-tubular. Lobulation is ill-defined. The
secretion is protein and mucous. The gland consists of 80 % of serous units and 20 %

54
of mixed units. At 5 months of age all secretory units are fully formed. The
sublingual gland is alveolar-tubular, has a thin capsule, but the intralobular
connective tissue and the interlobular septum are powerful. Mucous secretion
predominates. The gland consists of 80–90 % of mucous units and about 10 % of
mixed units. There are a few striated and intercalated ducts.
PHARYNX. It consists of 3 parts: nasopharynx carrying only air, oropharynx
and hypopharynx carrying both food and air. The nasopharynx is lined with the
pseudostratified ciliated epithelium. The oropharynx and hypopharynx are lined with
the stratified non-keratinizing epithelium. The muscular mucosa is absent. The
mucosa and submucosa have many elastic fibers. The submucosa has mucous glands.
The muscular layer consists of 2 layers of skeletal muscle: inner longitudinal and
outer circular. This organ is mostly associated with swallowing. The outside pharynx
is covered with the adventitia.
TONSIL. The mucosa forms folds and crypts on the border of the pharynx and
oral cavity. The crypt is a tubular epithelial ingrowth into the connective tissue. The
accumulation of lymphoid follicles in mucous crypts forms tonsils. There are 2
palatal, 2 tubal, 1 lingual, 1 pharyngeal and 1 laryngeal tonsils. They constitute
Pirogov`s lymphoepithelial peripharyngeal ring. Tonsils have the same structure, but
the number of crypts is different, the largest tonsils are palatine, they have 10–20
crypts. The epithelium of the tonsil crypts is stratified, squamous, non-keratinizing,
with a lot of lymphoid follicles under it. Lymphocytes move from the follicles onto
the epithelium surface destroying the epithelium. Thus physiological wounds are
formed. Such wounds contain a lot of lymphocytes, macrophages and granulocytes
coming from blood. Food particles get into the crypts where leukocytes destroy
bacteria and lymphocytes receive information about the antigens that penetrate into
the body. In the reactive centers of follicles and parafollicular zones the reproduction
of lymphocytes begins. Mature T- and B-lymphocytes accumulate in the mantle zone
of follicles and then go out into the blood or crypts. The follicles have no reticular
stroma and the microenvironment consists of macrophages. Like the pharynx, the
tonsil area has no muscular mucosa. The submucosa forms a dense capsule of the

55
tonsil and enters the mucous folds, forming the septum. In newborns tonsils are not
developed, they appear by 2 years of life, and the laryngeal tonsil – by 6 months of
life. The pharyngeal tonsil is often enlarged and forms adenoids.
TEETH. In humans two sets of teeth change each other. 20 temporary milk
teeth (primary teeth) erupt from 6 months to 2 years of age. 32 permanent teeth erupt
from 6 to 12 years, and the third molars teeth – at 17–25 years of age. The tooth has a
crown, a neck and a root. The crown rises over the gingiva. One or more roots are
attached to the bony socket of the jaw called dental alveolus. It is made of periodontal
ligaments. The tooth has a wall and a cavity. The tooth wall consists of 3 types of
hard tissues – enamel, dentin and cementum. The tooth cavity is filled with a soft
tissue called the pulp and opens at the apex of the root hole. Through it blood vessels
and nerves enter the pulp.
TOOTH DEVELOPMENT. The tooth develops from oral epithelium and
mesenchyme. At the 7th week of embryonic development the germs of milk teeth are
laid, at the 4–5th month the germs of permanent teeth are formed. The development of
teeth has three stages:
Stage 1 – the tooth germ laying. The epithelium settles along the edges of the
mouth, it separates the cheeks from the jaw rollers. The vestibule of the oral cavity is
formed. The epithelial cord (dental plate) goes inward from the bottom of the
vestibule. The tooth germs (enamel buds) are formed on the dental plate according to
the number of teeth. The enamel buds of multi-rooted teeth are formed directly from
the bottom of the vestibule. The mesenchyme grows into the enamel bud, forming the
tooth papillae. The enamel germ (enamel organ) covers the tooth papilla like a
thimble. It is connected with the oral cavity with the epithelial cord called the neck of
the enamel organ which is resolved –later. The mesenchyme around the enamel organ
is compact and forms a tooth sac.
Stage 2 – the tooth germ differentiation occurs as a result of embryonic
induction; it begins in the crown. The first differentiation inductor is the contact of
the dental papilla with the enamel organ in which the epithelial cells form 4 layers:
inner, intermediate, pulp of stellate cells and outer squamous epithelium. The inner

56
epithelium becomes prismatic and at the 4th month it induces the differentiation of the
outer cells of the dental papilla into large pear-shaped cells (odontoblasts).
Stage 3 – histogenesis of dental tissues. Odontoblasts begin to produce
predentin from pre-collagen fibers and ground substance. From the 5th month of
embryonic development the predentin is mineralized and transformed into the dentin.
Dentin induces the differentiation of the internal enamel organ cells. Dentin violates
the nutrition of these cells, so they change their structure and differentiate into
ameloblasts (adamantoblasts). At the same time the cells become highly prismatic;
the inversion of the intracellular organelles and the nucleus is performed there: the
nucleus, mitochondria, endoplasm reticulum move to the apical part, and Golgi
complex moves to the basal part of the cell. Thus, the nutrition of these cells will be
carried out by the enamel organ pulp. Ameloblasts produce pre-enamel above the
dentin; it is mineralized and transformed into enamel. Each ameloblast creates one
protein microfiber which will be the organic basis for one enamel prism. As the
prism elongates, the height of the cell is reduced. By the time of tooth eruption the
ameloblasts will have exfoliated, so the enamel does not regenerate. The cells of the
intermediate layer of the enamel organ are the source of renewal of ameloblasts. The
enamel organ pulp secretes the cuticle on the enamel surface. The outer cells form the
vagina for erupting teeth; after that they are reduced. By the 4th month of age, before
the eruption of the tooth in the inner layer of the dental follicle, the cementoblasts
differentiate. They destroy the enamel of the tooth root, set themselves above the
dentin and start building the cement. The outside of the tooth sac changes itself into
periodont.
TOOTH STRUCTURE. A dental pulp fills the tooth cavity. It consists of a
loose collagen tissue, and contains odontoblasts, a lot of macrophages, lymphocytes,
blood vessels, and nerve endings. The pulp performs 4 functions: trophic, protective,
sensitive and regenerative (regeneration of the dentin). The pulp contains 3 layers:
outer, intermediate and central. The outer layer consists of odontoblasts. They are
large cells with long processes. These processes are called Toms’ fibers; they lie in
the dentinal tubules and pass through the dentin, reaching the enamel. The

57
odontoblasts perform the following functions: 1) regeneration of dentin, synthesis of
dentin of the organic origine, 2) trophism of dentin and enamel along Toms` fibers, 3)
sensitive function: the processes of odontoblasts respond to chemicals and
temperature; irritation is transmitted to the odontoblast bodies, and then to the pulp
nerves. The intermediate layer is composed of undifferentiated pulp cells that renew
the odontoblasts. The central layer contains fibroblasts, macrophages, lymphocytes,
blood vessels and nerves. The crown pulp has all the three layers, and the root pulp
has no intermediate layer.
The DENTIN makes up the bulk of hard dental tissues. In structure it is similar
to the bone. It contains 70–72 % of non-organic and 28–30 % of organic substances
(collagen fibers and the ground substance). The non-organic substances are mostly
calcium phosphates, less of fluorides and carbonates. According to the direction of
the collagen fibers and degree of dentin mineralization the dentin in different parts of
the tooth is different.
There are 6 types of dentin:
1) predentin lies on the border of the dentin and pulp; it is not mineralized;
2) parapulpar dentin lies over the predentin; its collagen fibers run parallel to
the surface and are called Eibner’s fibers;
3) mantle dentin is outer; it contains bundles of collagen fibers directed radially
to the tooth surface; they are called Korf’s fibers;
4) interglobular dentin is non-mineralized and lies near the enamel and cement,
between the globules of hydroxyapatite crystals. In the non-fixed thin section of the
tooth it is destroyed, so it has the form of black spots called interglobular spaces.
They are large in the crown. In the root they are small and numerous, so they form
Toms` granular layer;
5) peritubular dentin is strongly mineralized; it forms the wall of dentinal
tubules radially penetrating into the dentin. They contain the ground substance and
processes of odontoblasts. They bring calcium salts to the enamel and are called
Toms` fibers.

58
 6) transparent (or sclerotic) dentin appears with age near the enamel. The
dentinal tubules are sclerosed, mineralized, and the dentine becomes transparent due
to the homogeneous mineralization.
Individual Toms’ fibers can penetrate into the enamel, forming the enamel
spindles. The dentin and enamel have the scalloped border that increases the strength
of the enamel-dentine connection.
In the terms of development the dentin can be primary, secondary and tertiary.
The primary dentin is built during the tooth development. The secondary dentin is
built throughout life and has a less correct course of collagen fibers. The tertiary
dentin is formed in damaged areas, so it is called the reparative or substitutive dentin.
It is uneven and poorly mineralized, the tubules are irregular. In pulp inflammation
the dentin can form globular denticles.
The ENAMEL is the hardest tooth tissue; covers the crown; it is not restored.
It is composed of 95–97 % of inorganic substance, 90 % of the crystals of
hydroxyapatite (calcium phosphate), 7–10 % of calcium carbonate and fluoride, Mg
phosphate and other salts. The organic basis is keratin-like, fibrous, Ca-binding
proteins and the ground substance. The structural unit of the enamel is the enamel
prism, d=3–5 mm, 5-sided, S-shaped, oriented perpendicularly to the dentin. The
enamel prism passes through the enamel and consists of a fine network of thin protein
fibers and the elongated crystals of hydroxyapatite deposited in it. Due to the S-
shaped prisms some sides of the prism are located along, and others across the
surface of the section. They refract light differently, and there is visible wide light
and dark Shreger`s bands on the enamel. Furthermore, due to the periodicity of
growth and mineralization of the enamel thin lines of Retzius are visible there. The
enamel is covered with the cuticle; it is a strong microfibrillar film of 0,2 microns
thick. During mastication it is erased and replaced by the pellicle composed of
proteins of microorganisms and saliva.
The CEMENT covers the tooth root; it is similar to the bone, but has no blood
vessels. The cement contains 30 % of organic (collagen fibers and the ground
substance), and 70 % of non-organic substances (Ca salts). The neck of the tooth is

59
covered with the primary acellular cement and the tooth root – with the secondary
cellular cement with cementocytes similar to osteocytes. These processes deliver the
nutrition from the periodont vessels to the dentin tubules of the tooth root.
PERIODONTAL TISSUES (PERIODONTEUM) include the alveolar bone,
the periodontal ligament and the gingiva. They provide dental nutrition, protection
and partial regeneration. The alveolar bone is spongy, covered with gingiva. The
periodontal ligament is formed of a dense connective tissue. Its collagen fibers
always grow into the cement with one end; the other end grows into the alveolar bone
fixing the tooth in the alveolus firmly. Around the neck of the tooth the periodontal
ligament forms a circular fiber bundle combining the teeth into a single unit. A loose
collagen tissue with vessels and nerves lies between the fiber bundles. Gingiva is
keratinized oral mucosa. Its lamina propria made of a dense irregular connective
tissue is firmly bound to the periosteum of the maxillary and mandibular bones.
Between the gingival epithelium and the tooth neck the gingival sulcus (a groove
surrounding the neck) is formed. At the bottom of the sulcus the basement membrane
of the gingival epithelium is tightly fused with the enamel (the junctional epithelium).
If this connection is broken, an inflammation develops; the groove turns into an
infected gingival pocket, which breaks the connection between the tooth and dental
periodontal tissues. Thus, periodontitis develops; the tooth becomes loose and can fall
out.

Questions for self-control:

1. What sections of digestive tract do you know?
2. What types of digestion do you know?
3. What tunics does the wall of the digestive tract consist of?
4. What embryonic germs of the oral cavity organs do you know?
5. What salivary glands do you know? Describe their classification.
6. What is the structure of the taste organ?
7. What stages of tooth development do you know?
8. Describe the tooth structure.

60
 Lecture 9. THE MIDDLE SECTION of the digestive tract
ESOPHAGUS transports the swallowed material from the pharynx to the
stomach. The epithelium develops from the foregut endoderm. Initially, it is single-
layered prismatic, at 4th week it becomes double-row, then multi-row ciliated. It
expands greatly by the 6th month of development and closes the lumen of the
esophagus. Later it is destroyed, and in its place the stratified epithelium of the
pharynx grows. But parts of the ciliated epithelium may remain in the orifices of their
own glands and in places of natural narrowing of the esophagus (from the cricoid
cartilage to the 5th tracheal ring and the entrance to the stomach).
Structure. The wall of the esophagus consists of 4 tunics: the mucosa, the
submucosa, the muscular and the outer tunics – adventitia at the upper and middle
parts of the esophagus, serosa in the low part. The mucous membrane consists of the
stratified squamous non-keratinized epithelium and lamina propria with papillae. At
the point of natural narrowing of the esophagus the lamina propria has cardiac glands.
The muscularis mucosa contains a single layer of longitudinal bundles of smooth
muscle cells. The submucosa and the mucosa form 8–10 longitudinal folds and
contain the terminal units of proper esophageal glands. The muscularis externa has 2
layers: inner circular and outer longitudinal. The muscle tissue is exclusively skeletal
in the upper part of the esophagus, skeletal and smooth in the middle part, and
smooth in the lower part.
Esophageal glands are of 2 types: proper esophageal and cardiac. The proper
esophageal glands are complex branched alveolar-tubular glands that produce mucus
and lie in the submucosa. The small excretory ducts are lined with the monolayer
cubic epithelium, the large ducts – with the double-layer and multi-layer epithelium.
The cardiac glands lie in the lamina propria in the points of natural narrowing of the
esophagus, they contain a lot of endocrine cells, open at the tips of the connective
tissue papillae. Pathology often develops there.
STOMACH performs 7 functions: 1) food reservoir, 2) chemical reduction of
food, 3) mixing, 4) partial absorption, 5) evacuation of food into the intestine, 6)
endocrine (many APUD-cells), 7) anti-anemic (the anti-anemic factor of Kastle is

61
produced; it binds vit. B12 and contributes to its absorption in the small intestine).
Four major parts make up the stomach: the cardiac part, the fundus, the body, and the
pylorus.
The mucous membrane has more than 3,5 million gastric pits and glandular
fields, and forms folds together with the submucosa. The epithelium is simple
columnar glandular. It combines 2 functions: covering and secretory. It creates a
mucous-bicarbonate barrier that produces mucus. The mucus contains bicarbonates
neutralizing chlorides and the sialomucus protecting against thermal and chemical
burns. This barrier is destroyed by alcohol, bile, aspirin, which results in hemorrhage,
edema and erosion. The epithelium absorbs water, salt, alcohol, drugs, vitamins, and
excretes urea and uric acid into the gastric lumen. The lamina propria consists of 3,5
million simple tubular glands, vessels, lymphocytes and sometimes lymphoid
follicles. Muscularis mucosa is 3 layers of smooth muscle cells: the inner and outer
layers are circular, the middle layer is longitudinal.
Submucosa contains blood vessels and Meissner`s nerve plexuses. The
muscularis externa consists of 3 layers of smooth muscle: internal oblique, middle
circular and outer longitudinal. Between the middle and outer layers of muscle
Auerbach`s vascular and nerve plexuses lie. In the pyloric region the circular layer
forms sphincter and the mucous – circular folds. The serosa consists of the densified
connective tissue and mesothelium.
The stomach glands are simple tubular glands. The tubular glandular unit has a
body and a fundus. A short terminal duct, which called «the neck», opens into the
gastric pits. The glands secrete acidic gastric juice, pepsin, its enzymes work in acidic
medium. There are three types of glands: 1) fundic (in the body and fundus of the
stomach), 2) cardiac (in the region where the esophagus enters the stomach), 3)
pyloric (at the junction of the stomach and the intestine).
The fundic glands are most numerous, straight or slightly branched, have a
narrow lumen and the working area of 4 m2. The fundic glands contain 5 types of
cells:

62
 1) chief (zimogenic) cells: they lie in the body and at the bottom of the
glandular unit, have a conical form, a round nucleus, basophilic cytoplasm, developed
granular endoplasmatic reticulum, mitochondria, Golgi’s complex, secretory granules
in the apical part, microvilli on the surface. The secretion contains gastric lipase and
inactive proenzyme pepsinogen. In the gastric cavity, pepsinogens are converted into
active pepsins in the acid environment of the stomach. The pepsins are
endoproteinases which initiate hydrolysis of ingested proteins in the stomach;
2) parietal cells lie laterally in the body and neck of the gland; they are large,
have a rounded form, oxyphilic, have a lot of mitochondria. The endoplasmatic
reticulum forms microtubules merging into an outputting tubule. From there the
secretion enters the intercellular canaliculus, and then the lumen of the gland. The
secretion contains the Kastle’s anti-anemic factor (the intrinsic factor) and the
protein related to chlorides which split on the epithelial surface, forming hydrochloric
acid (HCl). HCl activates pepsinogen and has bactericidal properties;
3) additional mucous cells lie in the body; they are weakly basophilic and
secrete mucus;
4) neck cells lie in the neck; they are small. There are mucous cells and poorly
differentiated cells; they renew all cells of the glands and surface epithelium.
5) enteroendocrine cells regulate the contraction of the stomach and gall
bladder, vasodilatation, HC1 production, secretion of gastric and pancreatic juices
and pancreatic hormones. There are 8 types of endocrine cells: 1) EC cells
(enterochromaffin) – serotonin and melatonin, 2) ECL-cells (enterohromaffin-like) –
histamine, 3) A-cell – glucagon, 4) G-cells – endogenous morphine enkephalin and
gastrin, 5 ) P-cells – bombesin, 6) D-cells – somatostatin, 7) D1-cells – vasointestinal
peptide VIP, 8) X-cells – unknown function (there are more of them in the cardiac
glands).
Cardiac glands are branched glands; there are few chief and parietal cells, but a
lot of endocrine and mucous additional cells; the secretion is mucous, weak acid.

63
 Pyloric glands are highly branched glands, shorter and wider than the fundic
glands; chief and parietal cells are absent. The secretion is mucous, slightly alkaline;
it breaks down dipeptides into amino acids.
DEVELOPMENT. A child has few glands, HCl is absent till two years, there is
little pepsin, the main enzyme is chymosin curdling and digesting the milk proteins.
In old men this enzyme is not present. In children the pyloric sphincter is well
developed, the cardiac sphincter is underdeveloped, that contributes to easy
regurgitation. The increase of the overall acidity and the final formation of the
stomach occur by 10–12 years of age.
The SMALL INTESTINE. The length is about 6 m. The small intestine
consists of 3 parts: the duodenum (30 cm), the jejunum and the ileum. In the
duodenum the digestive processes are completed, in all three parts of the small
intestine the nutrients (products of digestion) are absorbed by the epithelial cells.
These functions determine two organ specificities of the small intestine structure: 1 –
the presence of duodenal digestive glands in the duodenal submucosa, 2 – special
structures of the mucosa maximizing the absorbing surface. There are 3 types of the
special structures: 1) the border epithelium structure which contains the border cells
having the brush border composed of 1,5–3 thousand microvilli on the apical surface;
2) the intestinal villi and crypts which are permanent structures formed by all three
layers of the mucosa and fixed by the submucosa; 3) circular folds which are formed
of mucosa and submucosa; they do not straighten out when the intestine is filled. The
development of folds and villi is associated with the absorption intensity. In the
duodenum absorption is performed in parallel with the splitting of substances; it is
less intense, and its villi are short and wide. In the jejunum the villi are long and thin.
They are most numerous here, because absorption is the main function of the
jejunum. The iliac villi are also thin and long, but less numerous, as most of nutrients
are already absorbed.
The intestinal villus is a fingerlike protrusion of the mucous membrane covered
with a single layer of prismatic border epithelium. There are 3 types of cells in the
epithelium: border, goblet and endocrine. The goblet cells are among the border cells,

64
most of them are in the ileum. They secrete mucus that moistens the mucosa and
contributes to the movement of food particles. The endocrine cells of the intestinal
villus are few in number, only 0,5 %. One kind of them is argentaffin Kulchytsky
cells; they are EC-cells like in the stomach. The border cells make up most of the
intestinal villus epithelium, their function is absorption and membrane digestion. It is
performed using special organelles – microvilli. A microvillus is a cylindrical
protrusion of the apical cytoplasm of the cell. In the center of the microvillus a
microtubule passes. Around it there are actin microfilaments, microtubules, and many
enzymes involved in the breakdown and transport of absorbed substances. The
microvilli are covered with a thick layer of glycocalyx, some of its glycoproteins are
hydrolytic enzymes, and they perform membrane digestion. They break down food
particles into simple compounds which the cell is able to absorb through the
membrane. Simple compounds move into the microtubule of the microvilli, then to
EPR, and then output from the cells through the basement membrane of the
epithelium into the connective tissue of the lamina propria, where they are absorbed
into the blood vessels of the intestinal villi. Lamina propria forms the basis of the
villus and has organic specificities: 1) a lot of blood capillaries under the basement
membrane of the epithelium, 2) the connective tissue contains a lot of lymphocytes
and plasma cells creating an antigen intestinal barrier, 3) in the center of the villus
one large lymph capillary (milky duct) runs, 4) the milk duct is surrounded with
longitudinal smooth muscle bundles, due to which the villus contracts, making 4–6
contractions per minute.
Histophysiology of absorption. A villus operates as a pump. With a
contraction of a villus the arterial sphincters stop the flow of blood into a villus. The
blood pressure in the villus capillaries falls, so the nutrients move from the tissue
fluid into the capillaries and are immediately carried away by the venous bloodstream
or lymph. During relaxation of the villi the blood flow is restored, and the capillaries
are filled with blood. The blood pressure in the capillaries increases, so the absorption
of substances in the capillaries stops till the next contraction of the intestinal villus.
Amino acids and glucose enter the bloodstream, and emulsified fats – the lymph.

65
 The intestinal crypt is a tubular recessed epithelium in the connective tissue of
the lamina propria. In fact, it is a simple tubular gland of mixed secretions; they open
into the gaps between the intestinal villi. Their exocrine function is the participation
in the wall digestion, and the endocrine function is humoral regulation of digestion.
The crypt contains 5 kinds of cells: 1) columnar border cells, 2) cylinder cells without
brush border, 3) goblet cells, 4) cells with exocrine acidophilic granules (Paneth’s
cells), 5) endocrine cells. The goblet and border columnar cells are the same as in the
intestinal villi, but the border cells have a thinner brush border. The cylindrical cells
without a brush border are undifferentiated cells that lie at the bottom of the crypts
and renew all intestinal epithelium every 5–6 days. The exocrine cells with
acidophilic granules (Paneth’s cells) lie at the bottom of the crypts. In the apical part
they have eosinophilic granules containing lysozyme and dipeptidase. There are 7
kinds of endocrine cells in the crypts: a lot of ECs (secrete serotonin, motilin and
substance P – they stimulate peristalsis), A-cells (they are few, secrete
enteroglykagon, increase mucus production), S-cells (they produce secretin, inhibit
peristalsis, increase the secretion of pancreatic juice), I-cells (secrete cholecystokinin
and pancreozymin, increase secretion of pancreatic juice, insulin and mucus), G-cells
(secrete gastrin which increases secretion of pepsin and mucus), D- and D1-cells
(produce somatostatin and VIP, regulate motility, inhibit the secretion of pancreatic
juice).
In the small intestine the antigenic barrier of lymphoid follicles is enhanced in
the lamina propria, thus, follicles can penetrate into the muscular mucosa and
submucosa. Solitary follicles are present through the entire length of the small
intestine, and in the ileum they are grouped into Peyer's patches, 1 cm thick and 12
cm long.
Submucosa, muscularis externa and serosa have a typical structure.
The duodenal submucosa contains duodenal glands – complex branched
tubular glands, open into the intestinal crypts or between the intestinal villi. The
duodenal glands produce intestinal juice containing dipeptidase, amylase and
mucoids. Mucoids neutralize HC1 and create an alkaline environment which activates

66
the enzymes of pancreatic digestive juices. The excretory ducts of the glands have
EC, G, D, D1 and S endocrine cells.
In the intestinal wall in the caudal direction both the number of goblet cells and
lymphoid follicles, as well as the length of villi, increases, but the number of villi and
Meissner’s and Auerbach’s nerve plexuses decreases.
The LARGE INTESTINE. The large intestine (or colon) has the following
regions: the short cecum, with the ileocecal valve and appendix, the colon (ascending,
transverse, descending and sigmoid), and the rectum.
The colon performs 5 functions: 1) absorption of water from the chyme, 2)
formation of feces (produces a lot of mucus, which sticks together undigested
particles), 3) digestion of cellulose with the help of intestinal bacteria, 4) synthesis of
vitamins B and K by bacteria 5) elimination of phosphates, Ca and Mg salts, heavy
metals. The mucosa has no intestinal villi, but there are a lot of semilunar folds and
crypts. The epithelium is cylindrical and single-layer; the brush border is thin and has
many goblet cells, less Paneth’s cells, which disappear in old men. The number of
crypts is greater, they are wide and deep. The lamina propria consists of many
solitary lymphoid follicles distributed in the submucosa. In addition to the lymphoid
tissue the submucosa has many fat cells. The muscularis externa has a well-
developed circular layer, but the outer longitudinal layer has muscle fibers gathered
in three separate longitudinal bands called the teniae coli. In the serosa there are
sometimes the accumulations of the adipose tissue in the form of finger-like
outgrowths.
THE APPENDIX is a rudiment (vestige) of the cecum, its length is from 2 to
25 cm, and the thickness is 0,5 cm. In humans, it performs the protective function.
There are a lot of lymphoid follicles in the wall of the appendix, so it is often called
the intestinal tonsil and referred to the peripheral immune system. When an infection
penetrates into the appendix, the reproductive centers appear in the lymphoid
follicles; lymphocytes can pass into the appendix lumen through the epithelium. Over
the years, the lumen may undergo obliteration getting overgrown with the connective
tissue. The specificity of the structure: 1) fewer goblet cells in the epithelium, 2) the

67
muscular mucosa is poorly developed, partly absent, 3) the lamina propria contains a
lot of lymphoid follicles, 4) the muscular coat (muscularis externa) has a solid
longitudinal layer, 5) the serous membrane forms its own mesentery of the appendix.
Development of the intestine. The epithelium develops from the endoderm. At
the 5th week the epithelial cells are differentiated and the serosa is laid. At the 7–8th
weeks the lamina propria, the submucosa and the muscularis externa are formed from
the mesenchyme. The iliac part of the intestine grows faster than the abdominal
cavity. It folds into a spiral. At the 7–10th weeks the twisted intestinal loop moves
into the extraembryonic celom of the abdominal stalk, forming the physiological
hernia. By the 10th week the abdominal cavity increases and the intestinal loop is
pulled back, so the hernia disappears. Intestinal villi and crypts are laid during the 8–
10th weeks throughout the intestinal tube, but by the time of birth the intestinal villi
disappear from the large intestine. By 4 months the muscular mucosa, the duodenal
glands and the circular folds are laid.

Questions for self-control:

1. What tunics does the wall of the esophagus consist of?
2. What are the functions of the stomach?
3. What cells compose the fundic glands of the stomach?
4. What endocrine cells of the stomach do you know?
5. Name the mucosa structures maximizing the absorption surface.
6. Describe the histophysiology of absorption.
7. What are the structural features of the large intestine and appendix?

68
 Lecture 10. LIVER. PANCREAS
LIVER. Liver is the largest gland which weighs 1.5–2 kg. The liver performs 7
functions:
1) hematopoiesis during embryogenesis, 2) synthesis of plasma proteins (a-, b-
globulins, albumin, fibrinogen, prothrombin, complement proteins, etc.), 3) blood
depot, 4) depot of glycogen (glucose depot) 5) depot of fat-soluble vitamins A, D, E,
6) synthesis of bile which participates in fat hydrolysis and increases peristalsis, 7)
protective function – by phagocytosis and detoxication of toxic substances (converts
toxic ammonia into nontoxic urea). Phagocytosis is performed by the liver
macrophages – Kupffer cells.
Liver is a mixed gland: its exocrine function is secretion of bile into the
digestive tract; the humoral function is secretion of glucose, proteins and vitamins
into blood. The liver recovers well (20% within 10 days).
Liver develops from the endoderm of the front wall of the primary gut at the 3rd
week. Hepatic cells constitute a hepatic field which bulges in the form of the hepatic
bay.
Structure. The liver is covered with a dense connective tissue capsule, which is
fused with the serous membrane. On the lower surface of the liver the capsule grows
inward, forming the gate. The layers of the connective tissue (called the septae) pass
inward from the capsule; they divide the liver into hepatic lobules. Parenchyma from
epithelial cells (hepatocytes) is located in the lobules. 60 % of all cells are
hepatocytes, they have a polygonal shape, the diameter of 20–25 microns, can divide
in the course of amitosis, are binuclear up to 20 %, their number increases during
pregnancy, lactation, fasting. In the cytoplasm they contain a lot of RNA and
glycogen; there may be pigments and lipids. These cells have microvilli on the
surface.
Hepatic lobule is a structural and functional part of the liver. It has the form of
a 6-sided truncated cone, the diameter is 1,5 mm, and the height is 2 mm. In the
interlobular septae the interlobular artery, the vein and the bile duct pass. They form
the hepatic triads, a lymphatic vessel often passes with them. In humans the

69
interlobular septae are thin, but in cirrhosis they grow abnormally, occlude the
vessels, the nutrition of hepatocytes gets disturbed, necrosis develops.
In the lobules hepatocytes form anastomosing radial plates. Each plate consists
of two hepatocyte cords lying tightly and connected with desmosomes and in the
form of the lock. From outside the plates are entwisted by the reticular fibers. Three
types of cells lie on them: reticulo-endothelial, Kupffer cells and pit-cells («natural
killers», or large granular lymphocytes). They line the sinusoidal capillaries which
have no basement membrane. They also extend between the plates and merge into the
central vein. Between sinusoids and hepatocytes Disse spaces are located. They are
filled with the basic substance. The microvilli of hepatocytes and Kupffer cell
processes penetrate in these spaces, where there are small lipocytes. These cells
deposit fat-soluble vitamins and synthesize the reticular fibers. Inside the plate the
cellular cytolemma of adjacent hepatocyte cords invaginate into the cytoplasm and
form the wall of bile capillaries. Their lumen is separated from the intercellular gaps
by the tight junction.
Each hepatocyte in the liver plate has two poles – biliary pole facing the bile
capillaries, and vascular pole facing the sinusoids with blood. Through the vascular
pole the hepatocyte performs the humoral function and through the biliary pole – the
exocrine function (secretes bile). Blood and bile do not mix, as they are separated
with hepatocytes and endothelium. In hepatitis the blood-biliary barrier is destroyed,
so bile enters the bloodstream and jaundice develops.
Circulation. Two large vessels enter the liver through the gate: arteria hepatica,
carrying oxygen, and vena porta, carrying blood from the stomach, intestine and
spleen. Venous blood is rich in nutrients and the products of Hb disintegration. In the
liver both of the vessels branch into the interlobar, segmental, and then interlobular
arteries and the vein of the hepatic triad. They are of the muscular type. They branch
into the surround-lobular arterioles and venules, and then – into the arterial and
venous capillaries, which enter the lobule and merge into wide intralobular sinusoidal
capillaries, 20–40 mm in diameter. There arterial blood mixes with venous blood and
flows slowly. From the blood the hepatocytes absorb oxygen and the substances

70
brought by the portal vein. Into the blood the hepatocytes discharge urea, glucose
and proteins. Kupffer cells can be separated from the endothelium, become stellar
and form processes. They phagocytose particles from the flowing blood, thus clearing
it. Then the sinusoids converge into the central vein of the lobule. The central veins
converge into the sublobular (collective) veins, singly lying in the interlobular septa.
All veins of the efferent vein system are of the non-muscular type. Collective veins
converge into larger veins, which eventually form 3–4 hepatic veins that empty into
the inferior vena cava.
Bile ducts. Hepatocytes secrete bile into bile canaliculi (capillaries). They
begin blindly in the centre of the lobule, then go to the periphery and fall into short
cholangioles (Hering’s canals), lined with a layer of oval epithelial cells. The
cholangioles fall into perilobular bile ducts, and then – into interlobular bile
ductules, lined with cuboidal epithelium. Interlobular ductules are structural elements
of the hepatic triad. They empty into the segmental, then – into interlobar ducts lined
with columnar epithelium with the cell brash border. The interlobar ducts converge
into the right and left hepatic ducts, which merge in the common hepatic duct. It
comes out of the liver gate and enters the cystic duct, which transfers the bile into the
gall bladder with the volume of 40–70 ml. The bladder mucosa forms many
anastomosing folds. From the bladder the common bile duct comes out, it opens into
the duodenum. Extrahepatic ducts have the diameter of about 3–5 mm. Their wall
consists of three layers: mucosa, muscular, adventitia. The mucosa has a high
prismatic epithelium with goblet cells. The lamina propria consists of many elastic
fibers and mucous glands. The muscular layer forms sphincters at the ends of the
cystic and common bile ducts.
Different categories of hepatocyte functions have led to three ways of
considering the lobule of the liver. They differ in the direction of blood flow and bile
in the lobule. The classic hepatic lobule is hexagonal with the central vein in the
center of the lobule and hepatic triads on the periphery. The portal lobule is triangle
with the triad in the center and three central veins on the periphery. The hepatic

71
acinus is rhomboid with two central veins on the distant corners and two triads on the
near corner.
In newborns the liver is large; it has additional veins and arteries. The number
of binucleate hepatocytes is only 5 %. In Disse`s spaces hematopoietic cells lie. The
liver is completely formed by 10 years of age.
PANCREAS. This is a mixed gland which consists of the exocrine part and
endocrine islets. It has a head, a body and a tail. The pancreas is covered with a dense
connective tissue capsule and serosa. From the capsule septa extend to cover larger
vessels and ducts and to divide the parenchyma into lobules. It develops from the
primary colon endoderm.
The exocrine part is 97 % of the pancreas, it is a complicated diverged
alveolar-tubular gland formed with a single layer of epithelium, and it produces
pancreatic juice digesting everything. Glandular units are called acini. Acinus is
composed of one layer of acinar cells – serocytes; they are polarized and cone-
shaped. The basophilic basal pole of these cells, called the homogeneous zone,
contains a nucleus, GrEPR and basal striation. The apical acidophilic zymogen zone
contains zymogen granules. Zymogen is a precursor of enzymes activated in the
lumen of the duodenum. First the secretion enters the intracellular secretory
capillaries formed by the cytolemma invagination of adjacent serocytes. Then the
secretion passes into the acinus lumen, and then – into the short intercalated duct
lined with simple squamous epithelium. From there the secretion passes into the
interacinous intralobular ducts, then into the interlobular ducts, and then into the
main pancreatic duct. Large ducts have mucosa with prismatic epithelium and crypts
that produce mucus. The main pancreatic duct has the sphincter and the mucosa
forms valves for the contents of the intestine not to flow into the pancreas.
The gland acini are divided into simple and complex. The simple acinus is
formed only by serocytes. The complex acinus is formed by extending of intercalated
duct cells into the lumen of the acinus. As a result, the wall of the acinus becomes
double-layered: the external layer of acinar cells (serocytes), the internal layer of
small centroacinar cells (of the intercalated duct).

72
 The endocrine part of the pancreas is presented by Langerhans islets. The
endocrine islet is composed of bands of weakly stained endocrine cells, densely
braided by fenestrated capillaries. They are separated from acini by thin layers of
connective tissue. The islets contain 5 types of cells: 1) A-cells, comprising 20 %, are
large oxyphil cells lying on the periphery of the islet and secreting glucagon which
releases glucose into the blood from the depot (cadmium and cobalt increase the
number of A-cells); 2) B-cells, making up 70 %, are small cubic basophilic cells;
they lie in the center of the islet and produce insulin which provides utilization of
glucose by the cells (in insulin deficiency the level of glucose in blood increases,
glucose does not go into the cells and is excreted with the urine, tissues starve,
diabetes develops); 3) D-cells (dendritic) comprising 5 % produce somatostatin and
lipokain substance to inhibit the secretion of pancreatic juice and activate fat
oxidation in the liver; 4) D1-cells (argyrophilic) (1–3 %) produce vasointestinal
peptide (VIP); 5) PP-cells lie in the head glands (1–2 %), they produce pancreatic
polypeptide enhancing secretion of the pancreas.
The work of the gland is regulated by the blood sugar level and nervous
system: sympathetic system inhibits the secretion, parasympathetic – increases.
In newborns foci of hematopoiesis are found in the connective tissue, and acini
contain insulo-acinar cells with a mixed function. They contain 2 types of granules:
with zymogen and with hormones. The islets begin to work at the 4th month of the
embryonic development. By 10 years of age the pancreas is formed completely.

Questions for self-control:

1. What liver functions do you know?
2. Name the structural and functional part of the liver.
3. Describe the liver circulation.
4. What parts of the pancreas do you know?
5. What is the endocrine part of the pancreas?
6. What is the exocrine part of the pancreas?

73
 Lecture 11. RESPIRATORY SYSTEM
The respiratory system performs the respiratory function and a number of
functions not related to breathing. The respiratory function is gas exchange between
the organism and the environment: O2 is absorbed and CO2 is eliminated.
Non-respiratory functions:
1. The endocrine function: secretion of biogenic amines by APUD-cells of
bronchial epithelium.
2. Inactivation of biogenic amines by enzymes contained in endocrine cells
(children have few of them).
3. Participation in water-salt exchange: converting of the inactive angiotensin-1
into the active angiotensin-2, this constricts blood vessels and keeps Na in the
organism.
4. Production of the blood-coagulation factor thromboplastin and its antagonist
heparin.
5. Absorption of fat-soluble substances from the air.
6. Participation in the immune defense – the bronchial mucosa has lymphoid
follicles and a lot of plasma cells secreting IgA onto the epithelium surface.
The respiratory system consists of 2 parts: the conducting part, or airways, and
the respiratory one. In the airways the air is dried or humidified, purified from
particulate matter, the inhaled air is warmed or cooled. The conducting part consists
of nasal cavities, nasopharynx, larynx, trachea and bronchi. The respiratory part
consists of pulmonary acini where the gas exchange of the blood and the air is
performed.
Development. Respiratory organs develop from the endoderm of the anterior
primary colon. At the 3rd week the larynx, trachea and two lung sacks are laid. From
the 6th month alveoli are formed at the ends of the bronchioles. With the first breath
during the first 2–3 days of life, most of the alveoli open due to the surfactant
covering the alveoli from inside. Up to 1 year of life, there are areas with not opened
alveoli. The production of surfactant is stimulated by prolactin received with the
mother's milk. Since at artificial suckling there is little surfactant, pneumonia
develops easily. Up to 2 years the lungs contain few alveoli and elastic fibers, but a
lot of connective tissue, and the lungs are full-blood. All these specific features

74
contribute to stagnation, blocking the alveoli (atelectasis), infection and pneumonia.
The alveoli are formed by 7–8 years of age, all lung structures – by 14.
The airways have a wall composed of 4 tunics: mucous (mucosa), submucous
(submucosa), fibro-cartilaginous and adventitia. The mucosa is composed of
epithelium, lamina propria and muscular mucosa. Pseudostratified ciliated epithelium
contains ciliary, goblet and endocrine cells. Lamina propria consists of a loose
collagen tissue rich in elastic fibers and vessels; there are lymphoid follicles there.
Muscular mucosa is formed of circular smooth muscle bundles. Submucosa contains
a loose collagen tissue with serous-mucous glands. Fibro-cartilaginous tunic consists
of a dense connective tissue and the hyaline cartilage; the elastic cartilage occurs as
well. The dense connective tissue merges with the perichondrium. Adventitia consists
of a loose collagen tissue with blood vessels and nerves.
ORGANIC DIFFERENCES OF THE AIRWAYS
The nasal cavity has a vestibule, a respiratory region and an olfactory region.
The vestibule is in the cartilage part of the nose, which is based on the hyaline
cartilage, from inside the vestibular cavity is covered with skin, hairs, and sebaceous
glands. Hair entraps coarse dust particles. The respiratory region is covered with
mucosa. The epithelium is ciliated pseudostratified columnar, it is called the
respiratory epithelium. The lamina propria consists of lymphoid follicles and serous-
mucous glands. The cilia of ciliated cells remove dust particles from the air; they
work only in moist environment. Goblet cells secrete mucus, which together with the
secretion of serous – mucous glands, stick the particles together and produce moist
environment for cilia. The lamina propria has a lot of vessels under the epithelium
which provide warming or cooling of the air. In the area of the inferior turbinate
(conchae) the venous plexus is located. In children, the vessels of the plexus become
overfilled with blood easily, which causes the blockage of the nasal passages,
wheezing and difficult suckling. The number of glands in a child is small. The
surface of the mucous membrane is relatively dry, easily damaged and easily
infected.
The olfactory region – is the upper nasal concha, the upper third of the middle
concha and the nasal septum. This area is covered with the special olfactory
epithelium of the neural origin. It makes up the OLFACTORY ORGAN. The

75
olfactory epithelium lying on the basement membrane is also stratified, but higher
than the ciliated epithelium, and has no goblet cells. Its thickness is 60–90 microns.
Below the epithelium, there are special Bowman olfactory glands in the connective
tissue. They produce the serous and mucous secretion dissolving odorous substances.
The olfactory epithelium consists of three types of cells: olfactory, supporting and
basal ones. The olfactory cells are special bipolar neurons. They have a short dendrite
and a long axon. Their nuclei occupy the middle row in the olfactory epithelium. The
dendrite ends with the extension – an olfactory bulb. 10–12 thin processes
(antennules), having the structure of cilia and arranged parallel to the surface
epithelium, go away from a bulb. The cytolemma of the antennules has receptors that
bind the particles of odorous substances dissolved in the mucus, forming a nerve
impulse. It is transmitted to the olfactory brain centers by the axons of the olfactory
cells. The supporting (sustaining) cells are high-prismatic with microvilli, the
cytoplasm contains the yellow pigment lipochrom. Their nuclei occupy the top row of
the epithelium. These cells separate the olfactory cells from each other and carry out
the supporting, protective and secretory functions. The basal cells are small and low;
they lie on the basement membrane with a wide base, their nucleus makes up the
lower row of the epithelium. These are undifferentiated cells of the neuroectodermal
origin; they may give rise to the olfactory and supporting cells. The olfactory receptor
cells are an exception among the neurons as they are renewed every 30–35 days due
to the multiplication of the basal cells.
The larynx is a hollow tube; its basis is composed of the hyaline and elastic
cartilages. At the entrance to the larynx the epiglottis made up of elastic cartilage is
placed. The epithelium of the mucosa is stratified squamous nonkeratinized. The
lamina propria contains many elastic fibers, has salivary glands, lymphoid follicles
and a laryngeal tonsil. In the middle of the larynx the mucosa forms two pairs of
folds. The lower pair is true vocal folds; the upper pair is false (vestibular) folds. In
the true vocal folds there are skeletal muscles (vocal muscles). When they contract
the elastic fibers (vocal ligaments) of the folds are stretched. The false folds have no
muscles. Normally they are not used in speech, only if the true ones have been
removed. The vocal folds have a lot of blood vessels, so they can easily swell in
children. It may cause false croup in the first years of life. The submucosa is absent.

76
In the fibro-cartilaginous tunic the skeletal muscles are attached to the outer and
inner surfaces of cartilages. The outside layer is the adventitia.
The trachea is a hollow tube, 2–2,5 cm in diameter, 11 cm long. The tracheal
wall has a structure typical for the airways. The mucosa epithelium has ciliary, goblet
and endocrine cells. They secrete peptide hormones and biogenic amines. The
muscular lamina is absent, but in the lamina propria there are separate circular
bundles of smooth muscle cells and a lot of longitudinal elastic fibers (elastic
lamina). The submucosa has serous and mucous mixed glands. The fibro-
cartilaginous tunic consists of a dense connective tissue and 16–20 unclosed hyaline
cartilage rings. Free ends of the cartilage rings are on the posterior surface, against
the esophagus, and are connected with a bundle of a smooth muscle called the
tracheal muscle. The perichondrium of hyaline rings is fused with a dense connective
tissue. Unclosed cartilaginous rings facilitate the passage of the bolus through the
esophagus.
Bronchi. The trachea divides into two major (primary) bronchi – right and left.
They are large first-order bronchi, which begin the bronchial tree. They branch into
large 2nd-order bronchi: extra-pulmonary lobar (secondary) bronchi, then into zone
bronchi, which enter the lungs and branch into segmental (tertiary) bronchi (10 in
each lung). The intrapulmonary part of the bronchial tree begins with them. The
segmental bronchi branch into medium and small bronchi. Small bronchi branch into
bronchioles, which end with terminal bronchioles. On the terminal bronchioles the
lung lobes are located; there are about 20 thousand of them. The formation of the
bronchial tree completes by the time of birth, but the formation of new branches
continues for a few years (at the time when a child begins to walk, and in puberty).
Organic specificities of the bronchi. The bronchial wall is composed of four
layers. The major (primary) bronchi are 15 mm in diameter. Muscular lamina
appears in the mucous membrane, which has an inner circular layer and an indefinite
longitudinal layer consisting of individual bundles of muscle cells. When the
muscular lamina contracts, shallow folds are formed. The fibro-cartilaginous tunic
has closed cartilaginous rings.
The large 2nd-order bronchi (lobar, zonal and segmental) have a diameter of 5–
10 mm. The muscular lamina is thicker and bundles of muscle cells have an obliquely

77
circular direction that provides bronchoconstriction and shortening of the length of
bronchi. The number of submucosal glands decreases; the hyaline cartilage has a
form of separate plates.
The middle bronchi have a diameter of 2–5 mm. The height of the ciliated cells
and the number of goblet cells of the mucous epithelium decreases. The muscular
lamina is thicker and the submucosal glands are fewer in number. The size and the
number of plates of hyaline cartilage are reduced, and the elastic cartilage appears.
The small bronchi are 1–2 mm in diameter. The epithelium becomes double-
row ciliated and contains few goblet cells. The muscular lamina of mucosa is
powerful, so the bronchial lumen is stellate, deep folds of mucosa are clearly visible.
Glands and cartilage plates are gradually disappearing.
The terminal bronchioles have a diameter of less than 0,5 mm and a single-
layer ciliated epithelium. There are 5 types of cells: 1) ciliary cells, 2) poorly
differentiated cells without cilia, 3) secretory Clara cells, which are involved in the
metabolism of the surfactant, 4) endocrine cells which produce bombesin, calcitonin,
serotonin, 5) brush border cells with microvilli (chemoreceptors). The lamina propria
contains longitudinal elastic fibers and individual bundles of smooth muscle cells
between them.
As the bronchial tree branches out, the diameter of the bronchi, the ciliated
epithelium height, the number of nuclei rows, the number of goblet cells, the number
of glands in the submucosa, and the amount of hyaline cartilage in the fibro-
cartilaginous tunic decrease, but the elastic cartilage appears. The small bronchi have
a thicker muscular lamina and no cartilage and glands.
The LUNGS consist of the intrapulmonary part of the bronchial tree and the
respiratory part. The structural and functional unit of the respiratory part is the
pulmonary acinus. Acini are located on the branches of the terminal bronchioles.
Each lobe of the lung contains 12–18 pulmonary acini. The terminal bronchiole
branches dichotomically: into the 1st, 2nd, 3rd-order respiratory bronchioles, each of
which branches into two alveolar ducts. Each alveolar duct ends with two alveolar
sacs. All parts of the acinus have alveoli in their walls. The alveoli are the bubbles of
0,2–0,1 mm in diameter. The total area of the alveoli is 100–120 m². In the
respiratory bronchioles there are few alveoli. Between the alveoli there is always a

78
part of the bronchiole wall. The epithelium of the respiratory bronchioles is cubic
and without cilia. Smooth myocytes form separate circular bundles under them.
Individual alveoli are located in the walls and open into the lumen of the bronchioles.
Alveolar ducts have a lot of alveoli, but between the alveoli 2–3 cubic epithelial cells
and slim bundles of smooth muscle cells are saved. They function as thickenings,
supporting the tubular form of the alveolar duct. The walls of the alveolar sacs
consist only of the alveoli.
The efficiency of gas exchange depends on the work of 3 main structures:
1) the alveolar epithelium, 2) the surfactant lining the cavity of the alveoli, 3)
the inter-alveolar septa.
The inter-alveolar septa are thin layers of the connective tissue between the
alveoli. They perform five functions:
1) provide the elasticity of the alveoli walls, since they have elastic fibers
surrounding alveoli and promoting an exhalation;
2) make up the acinus frame with the help of collagen and reticular fibers;
3) perform the protective function with the help of macrophages, which are in
the septa and may come out into the lumen of the alveoli;
4) provide the most efficient gas exchange, since narrow blood capillaries
densely surrounding the alveoli pass in the septa; each capillary has a diameter of 5–7
mcm and is bordered with two alveoli; there erythrocytes are located in a row;
5) do not allow the wall of the acinus to collapse during a bronchial
obstruction, creating a possibility of air penetration from one acinus into another; the
septum has thin acellular areas (inter-alveolar Kohn pores), 10–15 mcm in diameter,
through which the alveoli of the adjacent acini perform the air exchange.
The alveolar epithelium lines the cavity of the alveoli. It consists of two cell
types: 1st type – respiratory cells, 2nd type – and big alveolar cells (secretory
alveolocytes). Respiratory cells have a size of 6–10 mcm, are elongated, flattened;
the nucleated sections have a thickness of 5–6 microns, the processes – 0,2 microns.
In the cytoplasm there are small mitochondria and vacuoles; on the free surface there
are microvilli. These cells are able to suck the air from the lumen of the alveoli.
During a bronchiole obstruction the air is sucked from the alveoli, the alveoli
collapse, and atelectasis develops. It predisposes the organism to pneumonia.

79
Secretory cells are larger, with short processes, contain more mitochondria, better
developed EPR, many vacuoles and membrane bodies. These cells produce
phospholipids and glycoproteins of the surfactant.
The surfactant covers the alveolar epithelium and prevents the alveoli from
sticking together. It prevents development of the edema, since the fluid does not
come out of the tissue into the alveoli. The surfactant contains 2 phases: the surface
phase (membranous, consisting of a phospholipid monolayer) and a deeper phase (the
hypophase, composed of glycoproteins). The bronchial epithelium has secretory cells
that produce enzymes breaking down the surfactant. Within an hour 10–40 % of the
surfactant is renewed.
The air in the alveolar cavity is separated from the blood by means of the air-
blood barrier composed of four parts: 1) the surfactant layer, 2) the anucleate part of
the respiratory alveolocytes (0,2 mcm), 3) the merging basement membrane of the
respiratory cells and the capillary endothelium (0,1 mcm), 4) the anucleate portion of
the capillary endothelium (0,2 microns). The total thickness of the barrier through
which the gas exchange is performed is 0,2–0,5 microns.
The blood supply of the lungs is carried out by two systems: through the
vessels of the systemic and pulmonary circulation. The vessels of the systemic
circulation are the bronchial arteries and veins; they pass only in the walls of the
bronchi, nourishing them. The vessels of the pulmonary circulation are the pulmonary
arteries, capillaries of the interalveolar septa and the pulmonary veins; they carry out
gas exchange. In the walls of the intrapulmonary bronchi there are numerous
anastomoses between the branches of the bronchial artery and the pulmonary artery.

Questions for self-control:

1. What non-respiratory functions do you know?
2. Name the distinctive features of the organ structure of the respiratory tract.
3. Name the tunics of the respiratory tract wall.
4. What is the structural and functional unit of the respiratory part?
5. What is the surfactant?

80
 Lecture 12. URINARY SYSTEM
The urinary system performs 5 functions: 1 – urinary excretion of useless body
substances, 2 – participation in water-salt metabolism, 3 – maintaining acid-base
homeostasis, 4 – endocrine function, 5 – hematopoietic function (it produces
erythropoietin; in the fetus and in newborns kidneys have hematopoiesis foci). The
urinary system includes the urine-producing organs: kidneys and the urine tract,
which consists of collecting tubes, papillary tubules, cups, a pelvis, ureters, a bladder,
a urethra.
KIDNEYS are bean-shaped paired organs with a gate on the concave side.
Through the gate the renal artery enters the kidney, while the renal vein and the
ureter leave it. There are renal cups and a pelvis at the gate. The kidney has a
connective tissue capsule. It is covered with adventitia and an adipose tissue, and in
front – with mesothelium. Under the capsule lies a dark renal cortex, and in the
middle of the kidney there is a light renal medulla that forms 8–12 lobes – renal
pyramids. The tip of each pyramid is called renal papilla. The renal cortex contains
renal corpuscles and enters the medulla in the form of renal columns. The renal
medulla enters the cortex in the form of medullary rays. In adults, there is a cortical
cortex under the capsule where renal corpuscles are absent.
The structural and functional unit of the kidney is the NEPHRON. It is a
complex epithelial tubule, which begins with a capsule surrounding the vascular
glomerulus. Together they form a renal corpuscle. The nephron consists of 5 parts: 1
– a capsule of renal corpuscles, 2 – a proximal tubule, 3 – a nephron loop (Henle’s
loop), 4 – a distal tubule, 5 – a short connecting tubule, linking the nephron and the
collecting duct. Urine is produced in two stages: filtration and reabsorption. The
primary urine is filtered through the capillaries of the vascular glomerulus into the
cavity of the renal corpuscle capsule. From the capsule it passes to other parts of the
nephron where reabsoption occurs. It is absorption of useful substances from the
primary urine into the blood. The renal corpuscle has two poles: 1 – a vascular pole,
where the afferent arteriole enters the renal corpuscle and the efferent arteriole exits
from it, 2 – a urinary pole, where the nephron capsule passes to the proximal tubule.
The proximal and distal tubules are presented with convoluted tubules, and the

81
nephron loop with straight tubules. From the nephron the secondary urine is
collected in the collecting tubule which begins the urinary tract.
According to the location and structure the nephrons are divided into two
types: 1 – short cortical nephrons – fully located in the renal cortex, so that the loop
tubules and collecting tubes form the medullary rays; 2 – long juxtamedullary
nephrons – their corpuscle and renal convoluted tubules are located in the renal
cortex, and straight tubules in the renal medulla.
Blood circulation in the kidney
About 1700 litres of blood brought by the renal artery (arteria renalis) pass
through the kidney per day. It branches into the interlobar arteries extending between
the pyramids toward the corticomedullary junction. Here the interlobular arteries
divide to form the arcuate arteries, which divide into two branches. The first branch
is the straight true arteries which go to the renal medulla. They branch into the
medullar networks of peritubular capillaries that entwine the straight tubules and
merge into the straight veins leading to the arcuate veins. The second branch is the
radial interlobular arteries which go to the renal cortex and branch into the
intralobular arteries, and then into the afferent arterioles, which enter the renal
corpuscles and divide into 70–100 anastomozing capillaries to form a plexus of
capillary loops called the vascular glomeruli. Here the blood is filtered, and
afterwards it leaves the glomerular capillaries via the efferent arterioles. The
capillaries of the vascular glomeruli form the wonderful arterial network (rete
mirabile). It bears this name because it lies between two arterioles: afferent and
efferent.
In the cortical nephrons the diameter of the efferent arteriole is almost twice as
small as that of the afferent arteriole that impedes the outflow of blood from the renal
corpuscle and creates high pressure (70–90 mm / Hg) (millimeter of mercury) in the
vascular glomeruli, which is necessary for urine filtration. The efferent arterioles
branch again to form the secondary peritubular capillary network of the cortex. Then
blood goes into the interlobular or stellate veins, which lie under the capsule and
empty into the interlobular veins. Then blood goes to the arcuate veins, to the
interlobar veins, and then into the renal vein.

82
 In juxtamedullar nephrons the diameters of afferent and efferent arterioles are
the same, so in the vascular glomeruli the pressure is not high, and filtration is absent.
The primary urine is not formed. Normally, they discharge an excess blood through
the arteriovenous anastomoses like a shunt. Their efferent arterioles pass into the
false straight arteries that go to the renal medulla, turn back and go to the straight
veins entering the arcuate veins. Only some of these arteries form a peritubular
capillary network. At the increased blood pressure, as a result of hard muscular work,
or a stress, these nephrons come into play.
Microscopic structure of the nephron
The capsule of the nephron has a shape of a double-walled concave glass. It
consists of the parietal and visceral layers and the cavity between them. The parietal
layer is formed with the flattened cubic nephrocytes. The visceral layer is formed
with podocytes and penetrates between the capillary loops. Podocytes are large cells
with processes, a light cytoplasm, and a few organelles. The body of the cell is 15–20
mcm, the large primary processes (cytotrabeculi) extend from the body. Each primary
process gives rise to many short secondary processes – cytopedicles (pedicelli, little
foot), which are attached to the thick basement membrane (90 nm), common for the
podocytes and endothelium. Between the cytopedicels there are gaps that
communicate with the capsular cavity, and the capillary endothelium has fenestrae.
Only the common basement membrane of the endothelium and podocytes forms a
continuous blood-nephridial barrier between blood and the capsular cavity. The
endothelium, basement membrane, and podocytes make up the renal filtration
barrier, impermeable for blood cells and large proteins. Through this barrier and
under a high pressure the filtration of water and dissolved substances with the
molecular weight less than 70 kiloDalton from blood plasma into the capsular cavity
is continuously performed in the vascular glomeruli. These are salts, sugars, amino
acids, simple proteins, partially lipids. The filtrate is filtered through the gaps
between the podocytes, enters the capsule cavity and forms the primary urine – 100–
170 liters per day. Then, the primary urine enters the proximal part where
reabsoption begins.
The proximal tubule has a convoluted part around the renal corpuscle and a
straight part, which passes into the Henle’s loop. It has the outer diameter of 50–60

83
mcm and a narrow lumen. The Henle’s loop is lined with high cubic cells with murky
oxyphilic cytoplasm. There are a lot of inclusions and lysosomes, well-developed
GrEPR, mitochondria there. The border between cells is unvisible. The cells have a
basal striation and a brush border of microvilli on the apical surface. The brush
border has a high ATPhase activity that provides energy for active transportation of
substances. The nephrocytes of proximal tubules are very active. Through them
reabsorption of 60 % water, glucose, amino acids, proteins, Na from the urine to
blood is performed. Normally, the daily urine contains no more than 150 mg of
protein. Besides, here nephrocytes secrete difficult soluble substances (creatinine,
uric acid, antibiotics) into the urine, so the tubular lumen often contains a precipitate.
As a result, sugar and protein disappear from the urine, so it becomes
hypotonic and moves into the straight descending tubule of the Henle's loop. It is
narrow, d=13 mcm, lined with flattened cubic nephrocytes, has a free lumen. The
cells are passive, organelles and microvilli are poorly developed, the cytoplasm is
clear, the basal striation is absent. The substances reabsorbed in the proximal tubules
create hypertonic environment around the descending tubule that draws out water of
the tubule. There is a passive diffusion of 30 % water from the urine in the tissues
and blood. It enhances ADH (vasopressin) of the pituitary gland, that activates
hyaluronidase and causes depolymerization of the basement membrane, reduction of
the epithelium and formation of intercellular gaps.
As a result of water diffusion, the concentration of electrolytes in the urine
increases, the urine becomes hypertonic again and moves upward into the ascending
straight tubule of Henle’s loop, d=30 micrometers. It has cubic epithelium with
visible boundaries of cells and a basal striation. The brush border is absent. The
cytoplasm is turbid at first, but near the distal end it becomes light. Here reabsoption
of electrolytes, mainly, of K, Na and Cl (but not water !!!) occurs. Then the urine
enters the convoluted distal tubule, d=20–50 mcm, which winds around the renal
corpuscle like a proximal tubule. Here the selective reabsorption of Na takes place,
so its cells have receptors for aldosterone, which increases blood pressure and Na
reabsoption. The distal tubule has a smooth lumen, cubic epithelium. A light
cytoplasm with a basal striation and the brush border is absent. A short connecting
tubule leads the urine out of the nephrons into the collecting tubes. They constitute

84
the renal medulla and medullar rays, which have a wide lumen and high cubic or
cylindrical epithelium containing light and dark cells. Light cells (principal cells)
have a watery cytoplasm. They absorb water and produce hormone prostaglandin-E2
(PG-E2), which regulates the local blood flow. These cells have receptors for ADH
(antidiuretic hormone, or vasopressin), which reduces the amount of urine, enhancing
reabsoption of water. Dark cells (intercalated cells) acidify the urine (like the parietal
cells of the stomach), that ensures its bactericidal action.
The volume of the secondary (final) urine is 1–1,5 liters. It is acidified, has a
high concentration of urea and creatinine sulfates. Reabsorption of substances in the
kidney is limited (the amount of glucose cannot exceed 170 mg, the excess of glucose
is excreted with the urine at diabetes). Aldosterone regulates absorbtion of Na, and
ADH – absorption of water. Small doses of adrenaline (in stress) cause a spasm of the
efferent arterioles and enhanced filtration, and high doses (in shock, or at a hard
trauma) cause a spasm of both efferent and afferent arterioles. Then filtration stops
and an acute renal failure develops, which can lead to death.
The ENDOCRINE APPARATUS regulates a blood flow and urine production.
It consists of 4 units: 1 – the juxtaglomerular apparatus (JGA), it produces renin,
which increases blood pressure; 2 – the prosteglandin apparatus, it allocates
prostaglandin, which dilates blood vessels and reduces blood pressure; it is
represented with the light nephrocytes of collecting tubes and the interstitial cells in
the medulla; 3 – the kallikrein apparatus, it is represented with the distal tubule cells
and produces kallikrein, which regulates the production of renin and prostaglandins,
increases a blood flow and urine output; 4 – the erythropoietin apparatus, it is
represented with the cells of the vascular glomerular mesangium (lactic sells) which
secrete erythropoietin. Mesangium is the ground substance of the connective tissue
and the fibroblast- and macrophage-like cells, in pathology they produce collagen,
and the glomerule is sclerosed.
Juxtaglomerular apparatus (JGA) consists of 3 types of cells: dense macula
cells, juxtaglomerular cells and juxtavascular Gurmagtig cells. The dense macula
cells have receptors for Na, narrow and high. They lie in the wall of the distal tubules
which is adjacent to the vascular pole between the afferent and efferent arterioles.
Under them the basement membrane is thin, sometimes absent, and there are gaps

85
between the cells. The juxtaglomerular cells (JG-cells) are large, with a bright
nucleus and oxyphilic granules of secretion. They lie in the middle tunic of the
afferent arterioles, instead of smooth muscle cells. They produce renin breaking
down the plasma protein hypertensinogen to form the inactive hormone angiotensin-
1 which is activated into angiotensin-2 in the lungs. It stimulates the production of
aldosterone, raises blood pressure, increases absorption of water and Na.
Gurmagtig’s cells have processes and lie in the triangle between the dense macula,
afferent and efferent arterioles. With the exhaustion of JG-cells they can produce
renin.
In newborns the kidney is round and has short ducts, so the cortical cortex is
absent, and the renal corpuscles are small and lie densely. The inner layer of the
corpuscle capsule does not penetrate between the loops of capillaries. The basement
membrane is thin, the podocytes are not formed. In the proximal tubules the brush
border and basal striation are not developed. Water filtration and reabsorption are
weak, demand for water is high, and the urine contains sugar and protein. Na
reabsorption is more intensive than in adults. It can be a cause of edema. Sensitivity
of kidney to aldosterone is decreased, and to ADH is absent. The podocytes are
formed by 1 year of life, the basement membrane and the fenestrated endothelium by
5 years.
The urinary tract consists of ureters which take the urine from the renal pelvis,
a urinary bladder and a urethra. They have somewhat similar histologic structure,
with the walls containing three tunics: mucosa, submucosa, muscular and adventitia,
except for the upper part of the bladder that is covered with serosa. The mucosa of
these organs is lined with a unique stratified transitional epithelium called the
urothelium which contains three types of cells forming two layers. Small basal cells
and columnar cells rest on the basement membrane and form the pseudostratified
epithelial layer. The secondary superficial layer consists of very large bulbous cells
called the umbrella cells. They protect the underlying cells from cytotoxic effects of
hypertonic urine. When the bladder is empty, the mucosa is highly folded and the
urothelium has thick pseudostratified first epithelial layer and bulbous umbrella cells.
When the bladder is full, the mucosa is smooth, the urothelium is thinner, the first

86
epithelial layer becomes a simple epithelium and the umbrella cells (the secondary
layer) are flatter.
Development of the urinary system
The urogenital (urinary) system develops from the mesoderm in three stages.
First, the pronephros (the head kidney) is formed, then the mesonephros (the primary,
or trunk, kidney) appears, and, finally, the metanephros (the final, secondary kidney)
develops. The pronephros is laid from 8–10 front nephrotoms; it consists of
protonephridia, lives for about a month, and then resolves. The mesonephros
develops at the 2nd month from 25 trunk nephrotoms and consists of metanephridia.
One end of the metanephridial canals open into the Wolff’s duct, and the other end
invaginates into the lumen of the canals and forms a bilayer capsule with the vascular
glomerulus. The mesonephros acts up to 4–5 months and participates in the formation
of gonads. Simultaneously with the resorption of mesonephros the secondary kidney
(metanephros) is laid from unsegmented mesoderm of the nephrogenic germ in the
caudal part of the embryo. In the urogenital sinus two Wolff’s ducts grow together
and create the cranial protrusion to form the bladder, ureter, renal pelvis and calyx.
From the calyx the epithelial cords grow radially into the nephrogenic germ. From
these cell cords the collecting tubules develop. They are the inducers of the formation
of nephrons in the nephrogenic germ. First, the epithelial buds are formed in the
germ, then they stretch into sealed tubules with a lumen. The distal end of such a
tubule is converted into a double-walled cup. The vascular glomeruli grow into such
cups. Then the partition between the lumen of the tubule and the collecting tubes
bursts open and nephrons begin to work. Under the influence of radiation, alcohol,
etc., this partition does not burst open, so the polycystic kidney is formed. It can later
turn into the hydronephros.

Questions for self-control:

1. What functions does the urinary system perform?
2. What is the structural and functional unit of the kidney?
3. Describe the blood circulation in the kidney.
4. Describe the microscopic structure of the nephrons.
5. What cells are related to the endocrine apparatus of the kidney?

87
 Lecture 13. DEVELOPMENT of REPRODUCTIVE SYSTEM.
MALE REPRODUCTIVE SYSTEM
The reproductive system develops with the urinal system in parallel and
consists of gonads and accessory organs. The gonads in men are testes, in women
ovaries. In the gonads reproductive cells are formed and sexual hormones are
produced. Additional organs in men are the accessory glands, excretory genital ducts
and supporting sexual organs. Additional organs in women are the uterine tubes,
uterus, vagina and vulva. The development undergoes 3 stages: 1 – laying of the
indifferent genital germ, 2 – sexual differentiation of the genital germ, 3 –
development and maturation of sex (reproductive) cells.
Stage 1. Laying of the indifferent genital germ occurs indifferently at 1 month
of development, i.e., it happens in the same way both in males and in females. From
the mesonephros (Wolff’s duct), parallel to it, the paramesonephros (Muller’s duct)
splits. On the medial surface of the mesonephros the celomic epithelium grows and
forms two genital ridges – the germs of gonads. The primary reproductive cells
(gonoblasts) migrate into these ridges. They are laid in the blood islets of the yolk sac
wall from the mesenchyme. Gonoblasts are large and round cells, with plenty of
glycogen and RNA. From the epithelium of genital ridges the genital cords with
gonoblasts grow into the mesonephros.
Stage 2. Sexual differentiation of the genital germ begins at the 2nd month of
development and is determined with the presence or absence of Y-chromosome that
encodes the gene of the peptide hormone Inhibin-1.
In boys at 6 weeks of development the epithelial cells of the genital ridges and
cords begin to produce hormone Inhibin-1, that inhibits the cell proliferation of
Muller’s duct and mesenchyme at the base of the mesonephros. As a result, Wolff’s
duct is preserved and differentiates into the appendage of the testis and excretory
genital ducts. Muller’s duct is reduced, leaving only the upper and lower parts
developing into the vestigial organs – Morgan’s vial and the prostate (male) utricle.
At 3 months of development the prostate gland (prostata) is laid around the male
utricle as an outgrowth of the epithelium of the proximal part of the urethra.
88
 In girls sexual differentiation of the genital germ begins later: at 7–8 weeks of
development. Y-chromosome is absent, so Inhibin-1 is not produced. The
mesenchyme at the base of the mesonephros grows intensely and forms the
mesovarium, from which the ovarian medulla will develop. The growing
mesenchyme eliminates the ends of the genital cords and tubules of the mesonephros
and separates the mesonephros from the genital germ. Afterwards the mesonephros is
reduced, and Muller’s duct continues to differentiate: the upper part forms the
fallopian (uterine) tubes, the ends of which turn into the funnels (infundibulum) with
fimbriae. The distal ends of these tubes thicken and grow together forming the uterus
and vagina. At incomplete fusion of Muller’s ducts the pathology of development
appears: a two-horned uterus, a double uterus or a double vagina.
MALE REPRODUCTIVE SYSTEM
In boys the genital ridges differentiate into testes. Inside the genital ridge the
mesenchyme grows between the genital cords. Then it grows from inside under its
epithelium and forms a layer of a dense connective tissue which differentiates into the
testis capsule – the tunica albuginea. On the inner surface of the testis the albuginea
expands to form the mediastinum. The genital cords stop growing into the genital
ridges, but in the interior of the ridges they continue growing, elongate and form the
convoluted seminiferous tubules of the testis, 70–80 cm long. They are separated with
the septa, which depart from the mediastinum and divide the testis into 100–250
testicular lobules. Each lobule consists of 1–4 convoluted seminiferous tubules. Near
the mediastinum the tubules become straight, then they enter the mediastinum and
pass into the tubules of the rete of testicle (rete testis).
In the seminiferous tubules the epithelial cells differentiate into the supporting
cells (sustentocytes), and the gonoblasts differentiate into gonocytes, and then into
spermatogonia. Between the tubules the mesenchyme develops into a loose collagen
tissue, forming the interstitium of testis. The interstitial Leydig’s cells appear there by
2 months of development. These cells are large, oval or polygonal, with an oxyphilic
cytoplasm containing glycogen, glycoproteins and large lipid secretion granules.
They are arranged in groups and secrete male sex hormone (testosterone) into the

89
blood which is activated in the prostate gland, causes hypothalamus masculinization
(reconstruction by the male pattern) and affects the development of the secondary
sexual characteristics and reproductive cells.
From Wolff’s duct the epididymal duct (ductus epididimidis) differentiates at
the end of the 2nd month. This duct forms the body and the tail of the epididymis; the
vas deferens (ductus deferens) with vial and seminal vesicles extends from it. With
the time the mesonephros tubules connect with the rete testis, turn into the efferent
tubules of the testis (ductuli efferentes testis) and form the head of the epididymis.
The vas deferens becomes ductus ejaculatorius in the prostate, which opens into the
ductus urethra. On the front edge of the urogenital sinus the penis is laid from the
mesenchyme of the genital tubercle.
Up to 5 months of development the gonocytes actively multiply and close the
lumen of the seminiferous tubules. Then the epithelium of the rete testis begins to
produce the hormone Inhibin-2, which suppresses the production of FSH by the
pituitary gland and the reproduction of gonocytes. By birth Inhibin-3 begins to be
produced. It inhibits only the production of FSH and has no influence upon the
gonocytes. In newborns the seminiferous convoluted tubules have no lumen. Its
epithelium has only two kinds of cells – sustentocytes and spermatogonia.
Stage 3. Development and maturation of reproductive cells takes place after
birth. By 7–8 years of age the lumen appears in the seminiferous convoluted tubules,
and at puberty spermatogenesis begins.
Normal spermatogenesis needs the temperature less than that of the body, so in
all mammals testes with epididymis are placed outside the body and are located in the
scrotum. At delayed lowering of the testes into the scrotum cryptorchidism develops,
spermatogenic epithelium atrophies. Testes in the scrotum are mobile, because they
are covered with the serous membrane which secretes liquid in some places and
absorbs it in others. At cooling and viral diseases, liquid absorption is disturbed, so
hydrocele may develop.
In the body of the mature man spermatogenesis occurs constantly and wavily.
In different parts of the convoluted seminiferous tubule there are different phases of

90
spermatogenesis. The spermatogenetic cells lie in layers in the loops made by
processes of sustentocytes, composing spermatogenic epithelium. Sustentocytes
(Sertoli’s cells) lie on the basement membrane of tubules. They are large and have
processes. The nucleus lies in the basal part. It is large, bright, and polygonal, with
nucleoli. The cytoplasm contains many inclusions of protein, lipid, and carbohydrate.
The apical surface of Sertoli’s cells has receptors for androgens and FSH. They
synthesize the androgenbinding protein that delivers testosterone from the blood to
the spermatids. There are light and dark sustentocytes. Bright cells secrete Inhibin-2,
which inhibits secretion of pituitary FSH and proliferation of spermatogonia. Dark
cells secrete estrogens that stimulate proliferation of spermatogonia. Sustentocyte
functions: 1) to deliver the active testosterone that stimulates spermatozoon
development, 2) the trophic function, 3) the endocrine function (Inhibin-2 and
estrogen), 4) to secrete seminal fluid, 5) phagocytosis of waste products of
spermatogenic cells, 6) to be a part of the blood-testis barrier.
Spermatogenesis consists of 4 periods: reproduction, growth, maturation and
formation. During the reproduction period diploid spermatogonia are divided at
mitosis. The spermatogonia are in the lower layer of the spermatogenous epithelium
near the basement membrane and capillaries. There are 2 groups of spermatogonia.
Group A: stem and halfstem cells. Stem cells are dark, they divide very rarely and
maintain their population indefinitely. Halfstem cells are light, often divide, a
division takes place in 75 days. Group B: spermatogonia beginning to differentiate.
After the division they form a chain (syncytium), they enter the period of growth and
differentiate into primary spermatocytes. They occupy the second layer of the
epithelium. These cells pass the complete interphase before meiosis – they increase
their size by 2–3 times and double the DNA. Chromosomes are highly condensated
and form bivalents, so the chromatin of the nucleus looks like large clumps. The
growth period ends with the prophase of the 1st meiotic division. At the gestation
period the primary spermatocytes undergo the whole meiosis. After the 1st division
two secondary spermatocytes are formed. They are a half size and have a light
nucleus with a haploid set of doubled chromosomes. They occupy the third layer of

91
the epithelium. Soon they divide during the second division into the haploid
spermatids – small cells with a dense nucleus. They occupy the top layer and do not
divide. These cells enter the period of formation or spermatogenesis, and under the
influence of testosterone they are transformed into spermatozoa. Spermatozoon has 4
sections: the head, the neck (a communicating part), the body, and the tail
(flagellum). The head contains a nucleus covered with acrosome (the extremity body)
at the front. Acrosome is formed of Golgi’s complex and contains enzymes that
dissolve the oocyte tunics. The cell center is located behind the nucleus, forming the
neck. The cell center forms an axis of the flagellum. Near the neck, around the axis
the mitochondria are helically arranged forming the body of spermatozoon, and the
rest of cytoplasm with an axis forms the flagellum.
Spermatogenic epithelium has antigenic properties. Thus, it is separated from
blood with the blood-testis barrier, which consists of tight junctions of the lateral
processes of sustentocytes, the wall of the seminiferous tubules, interstitium and
capillary endothelium. With the destruction of the barrier the autoimmune reaction
develops to destroy the cells of spermatogenesis (for example, in parotitis). The wall
of the seminiferous tubule has myoid cells. They contract rhythmically helping to
remove the sperm from the seminiferous tubules into the straight tubules, and from
them into the rete testis.
12–18 efferent tubules go out of the rete testis forming the head of the
epididymis of the testis. All excretory genital ducts have a 3-layered wall: mucous,
muscular and adventitia. Efferent tubules are uneven lumen. They are lined with a
single-layer epithelium containing 2 kinds of cells: prismatic ciliated cells and
glandular cubic cells producing a little acidic secret. Then the sperm moves into a
very convoluted ductus epididymis, which forms the body and the tail of the
epididymis. It has a smooth lumen and is lined with double-row epithelium with
stereocilia (glued cilia). Ductus epididymis produces the acid secretion that
suppresses metabolism and immobilizes spermatozoa. Here, they can accumulate and
persist for a long time. From the epididymis the spermatozoa enter the ductus ( vas)
deferens with a strong 3-layer muscular tunic. The ductus deferens is a part of the

92
spermatic cord, which also includes the testicular artery, the pampiniform plexus and
nerves. This duct enters the prostate to form the ejaculatory duct with a thin muscular
tunic. It opens into the urethra.
The additional glands open into the excretory genital ducts. These glands are
the seminal vesicles, the prostate gland and the bulbourethral (Kupfer’s) gland. The
seminal vesicles open into the ampule of the ductus deferens in front of the prostate.
They are lined with a single- or double-row prismatic glandular epithelium. Their
secretion comprises 60 % of sperm; it is mucous, weakly alkaline, rich in fructose. It
dissolves glycocalyx of spermatozoa and gives them mobility. The activation of
sperm called capacitation occurs.
The PROSTATE GLAND is located at the exit of the urethra from the bladder.
It performs exo- and endocrine functions. The endocrine function is activation of
testosterone. The glandular cell turns TS into dihydroTS; through the nuclear
receptors it activates the cell to secretion and through the blood gets to the testes and
activates spermatogenesis. The exocrine function is production of weakly acid
secretion. It contains a citric acid, enzymes, ATP, makes up 20 % of sperm, liquefies
sperm and increases spermatozoon motility. The prostate consists of 2 lobes
connected with the isthmus. Its basis is formed of the connective tissue with bundles
of smooth muscle cells; between them 40–50 prostatic glands are located. They are
branched tubuloacinar glands. They are lined with a single layer of a single- or multi-
row glandular epithelium and open into the urethra, near the semen tubercle. By the
size and location the glands are divided into 3 groups: 1 (transition zone) – around the
urethra 5 % of mucous small glands, which often develop adenomas, 2 (central zone)
– in the middle 25 % of submucosal glands with longer ducts, 3 (peripheral zone) –
on the periphery 70 % of main glands with still longer ducts. With age, as a result of
stagnation the secretion may thicken and form small spherical concretions called
corpora amylacea. They can turn into prostate stones. Semen tubercle acts in the
lumen of the urethra. There are a lot of nerves and veins which are overflown with
blood during erection. The tubercle covers through the urethra, preventing the leaking
of semen into the bladder. Behind the semen tubercle there is the male or prostate

93
utericle, which opens onto the surface of the semen tubercle. It often develops
metaplasia and tumor. With age, the testosterone level declines. It may lead to the
development of prostatic hyperplasia and adenomas. In hyperfunction the prostate
produces a lot of active testosterone. It causes a spasm of the dermal vessels of the
parietal part of the head and baldness. In hypofunction testosterone is inactive. It is
produced in a greater amount, so hypergonadoidism develops.
Bulbourethral glands are tubuloacinar glands, which open into the prostatic
urethra. Secreting units have swellings and are lined with cuboidal epithelium;
sometimes they contain crystal-like inclusions. The secretion is mucous, thick,
weakly alkaline, it lubricates the surface of the urethra.
Thus, in the formation of sperm testis, epididymis and additional glands are
involved; the final pH of sperm is 7,05–7,07.
Endocrine regulation of the mail reproductive system
The hypothalamus has two centers of regulation of sexual functions. The
higher center in men is suppressed by testosterone. The lower center produces GnRH
and creates a continuous secretion of LH and FSH. FSH stimulates secretion of
estrogen and inhibin by sustentocytes that regulate reproduction of spermatogonia.
LH stimulates secretion of testosterone by Leydig’s cells and sperm maturation.

Questions for self-control:

1. What are the stages of development of the reproductive system?
2. Name the tubules of the testes.
3. What functions do the sustentocytes perform?
4. Name the spermatogenesis periods.
5. What cells produce testosterone?
6. Name the endocrine and exocrine functions of the prostate.

94
 Lecture 14. Female reproductive system
In girls the 2nd stage of sexual differentiation of the genital germ begins later –
by 7–8 weeks of embryogenesis. Y-chromosome is absent, so inhibin-1 is not
produced. The mesenchyme at the base of mesonephros grows intensively and forms
mesovarium, from which the ovarian medulla will develop. The growing
mesenchyme eliminates the ends of the genital cords and tubules of mesonephros and
separates the mesonephros from the genital germ. Later the mesonephros is reduced,
and Muller’s ducts continue to differentiate: the upper part forms the fallopian
(uterine) tubes, the ends of which are converted into the infundibulum with fimbriae
(fringed). The distal ends of these tubes thicken and grow together forming the uterus
and vagina. In case of incomplete fusion of Muller’s ducts pathologies of
development appear: two-horned uterus, double uterus or double vagina.
By the 8th week of embryogenesis the ovarian cortex begins to be formed in the
genital ridges. The genital cords with gonocytes grow from the epithelium into the
genital ridges. Between them the mesenchyme grows into the genital ridges and
crushes the genital cords into the cellular islets – oviparous globes. Each globe
contains epithelial cells and follicular gonocytes. Oogonia are formed of them. The
genital cords grow into the ovary up to 1 year of age, and then the mesenchyme forms
the tunica albuginea, which prevents the ingrowth of cords into the ovary.
Immediately after the formation of oviparous globes OOGENESIS begins. The
reproduction period lasts for 3–4 months of embryogenesis. It is an active
multiplication of oogonia by mitosis. The period of growth begins at the 3rd month –
gradually oogonia differentiate into the primary oocytes. They are surrounded with a
protective sheath of follicular cells which form the follicle. Oocyte and follicle
growth run in parallel to each other and are divided into the small and great growth
periods. During the oocyte small growth period a primary oocyte passes the
interphase before meiosis, accumulates yolk and increases by 2–3 times in diameter.
Then the oocyte doubles the DNA and enters the meiotic division prophase
(chromosomes enter crossingover). The oocyte is surrounded with one layer of flat
follicular cells that form the primordial follicle around it. Follicular cells inhibit

95
meiosis, so chromosomes in the oocyte remain in the crossingover state till puberty.
During the follicle small growth period the oocyte accumulates yolk and increases to
the final size of 120–130 microns. Follicular cells become cubic and together with
oocytes begin to secrete proteoglycans to form a transparent secondary oocyte shell –
zona pellucida. This is called the primary follicle. Follicular cells proliferate, form
two layers, and the follicle is called the primary growing follicle. By birth many
follicles die, and 300–400 thousand primordial and primary follicles retain there.
They supply reproductive cells during all reproductive period. Up to 3 years old,
there are remnants of oviparous globes with 2–3 oogonia and without oogonia.
The oocyte and follicle great growth period begins after 3 years of age, but up
to 12–13 years the pituitary gland releases little LH, so growing follicles do not
mature. They get exposed to atresia (involution). At their place cysts with fluid are
often formed.
The OVARIES are oval in shape, weighing 5–7 g, 3–5 cm long, 1,5–3 cm
wide, 0,7–1,5 cm thick. They are covered with tunica albuginea, thinner than in the
testis, in order not to impede ovulation. Albuginea is covered with the serous
membrane, and the outer surface of the ovary – with 1 layer of cubic fetal genital
epithelium rings. Under the tunica lies the cortical substance of the follicles and the
medulla of the loose connective tissue is in the ovary center.
The follicle great growth period begins at 3 years. All primary follicles grow.
Their oocyte does not grow, but continues to accumulate yolk and forms cortical
granules of glycoproteins. Follicular cells proliferate to form multiple layers. The
first layer of prismatic cells with long processes is called the radiant crown – corona
radiata, – the oocytes linked with these cells are sent through the genital tract. The
cellular processes of the corona radiata penetrate through the zona pellucida into
plasmolemma of the oocyte and deliver it nutrition. The rest layers of follicular cells
form the granular shell – zona granuloza. Around the follicle the connective tissue
forms the follicular shell – theca folliculi, –composed of 3 layers: 1 – the basal
membrane of the follicular epithelium, 2 – theca interna of the loose connective
tissue with vessels and interstitial cells, similar to Leydig cells of the testes, 3 – theca

96
externa of the dense connective tissue. Interstitial cells in the ovaries secrete
testosterone that penetrates through the basal membrane into the follicular cells
which convert it into estrogens. Thus from the age of 3 the female hormones appear
in girls’ blood. At pathology the sprouting interstitial cells form a tumor –
disgerminoma. It secretes a lot of testosterone, which leads to masculinization of the
female body (restructuring by the male pattern).
Under the influence of FSH, the follicle cells of the granular (follicular) layer
begin to secrete liquor folliculi with estrogen and gonadocrinin inhibiting the growth
of neighboring follicles. The liquor pushes the follicular cells, forming a cavity called
antrum. Such a follicle is called the secondary growing (antral) follicle. It is able to
continue to develop only after puberty. The oocyte of the secondary growing follicle
is pushed to the wall of the follicle, surrounded with the follicular cells that form
cumulus oophorus (small hillock). This follicle is 1,2–1,5 cm in diameter and is
called tertiary (mature, preovulatory, or graafian (Graaf’s)) follicle. The oocyte in
the follicle is separated from the antigen with the blood-ovarian barrier which
includes the capillary endothelium, a layer of the connective tissue and the follicular
epithelium with the basement membrane.
The primary oocyte enters the gestation period of ovogenesis after ovulation.
Only 400–500 follicles reach ovulation. Other follicles undergo the degenerative
process called atresia under the influence of gonadocrinins. The atretic body is
formed, where oocyte and follicular cells die, zona pellucida shrinks, swells and is
saved for a long time, and interstitial cells proliferate and produce testosterone.
Eventually atretic bodies are dissolved.
Ovulation is the rupture of the theca folliculi and tunica albuginea and the exit
of oocyte into the abdominal cavity. Ovulation occurs cyclically. In humans usually
only one follicle ovulates; it is called dominant. Sometimes two of them can ovulate
as well. Mature Graaf’s follicle is ready to ovulate because its theca becomes thinner
and is easily torn under the pressure of liquor. Pituitary emits ovulatory quota of LH
which activates hyaluronidase. It causes depolymerisation of the ground substance in
the theca folliculi and tunica albuginea of the ovaries, where edema and hyperemia of

97
the vessels occur. It leads to bursting of the shells and releasing of the oocyte into the
abdominal cavity. With a frequent inflammation of the ovaries their tunica albuginea
may thicken hampering the ovulation, and ovarian cysts are formed. During ovulation
in the fallopian tubes the vessels are also overflown with blood. The fallopian tubes
become elastic and cover the ovary tightly with its funnel-shaped opening – the
infundibulum, – which catches up the oocyte with its fimbriae (fringe), and the oocyte
falls into the tube. In the infundibulum of the fallopian tube follicular cells of the
corona radiata are not able to block meiosis. Immediately after ovulation the oocyte
enters the gestation period of ovogenesis, during which it completes meiosis. After
the first division a large secondary oocyte and a small reduction-body (polar body)
are formed. The both cells have a haploid set of doubled chromosomes. After the
second division the secondary oocyte produces the second reduction-body (polar
body) and a mature ovum. The period of formation is absent in ovogenesis. In the last
division the two centrioles move away in the reduction-body which eliminates the
further division of the ovum if fertilization has not occurred. When sperm fertilizes
the ovum, the spermatozoon brings centrioles to the ovum and provides the
subsequent division of the zygote. The reduction-bodies are resorbed, but at
pathology the reduction-body can also be fertilized, which will result in an ugly
tumor – teratoma.
After ovulation, the follicular cavity collapses, being filled with a blood clot.
At this place the corpus luteum is formed. It develops in four stages. 1st stage –
proliferation and vascularization, when the preserved follicular cells proliferate
rapidly; between them grows the loose connective tissue with vessels. 2nd stage –
glandular metamorphosis, – develops under the influence of LH. Follicular cells
accumulate lipochrom and turn into lutein cells, the forming body becomes yellow.
3rd stage – prosperity: under the influence of LH and prolactin the lutein cells produce
progesterone that prepares the genital tract for the development and preservation of
pregnancy and at the same time inhibits the growth of follicles and production of
estrogen. If a pregnancy takes place, the corpus luteum is called the corpus luteum of
pregnancy. It grows up to 5 cm in diameter and functions for 2–3 months. If a

98
pregnancy does not occur, the corpus luteum is called menstrual. It is small (2 cm in
diameter), functions about 2 weeks, and then regresses. 4th stage – involution: the
lutein cells stop producing progesterone, then they die; in the place of the corpus
luteum the scar connective tissue is left (corpus alticans).
The GENITAL TRACT consists of the uterine tubes (fallopian tubes, or
oviducts), uterus and vagina. The oviduct is a paired tube 7–14 cm long. It has a wall
of 3 layers: mucous, muscular and serous. The mucous layer forms strongly
branching folds to ensure contact with the ovum and the embryo. It is covered with a
single-layer prismatic epithelium of ciliated cells and glandular cells which produce
mucous secretion. After ovulation decidual cells appear in the lamina propria. The
muscular tunic contains a lot of blood vessels and two layers of smooth muscle: inner
circular and outer longitudinal. Due to its peristalsis the embryo moves to the uterus.
The uterus is a hollow muscular organ in which a fetus develops. It has a wall
of 3 tunics: mucous – endometrium, muscular – myometrium, and the outer –serous
(perimetrium). In the uterus body and fundus adventitia (the parametrium) is the
dense connective tissue wich forms ligaments in the cervix (neck) of the uterus. The
endometrium consists of simple prismatic epithelium and lamina propria. The
epithelium forms crypts, simple straight tubular glands which appear by 4 years. At
the premenstrual period cilia appear in the epithelium, and in the lamina propria –
decidual cells producing sex hormones and prolactin. There are two layers in the
endometrium distinguished by functions: functional and basal. The functional layer is
thick. It changes during the menstrual cycle, pregnancy, and later is rejected. The
basal layer is thin and fused with the myometrium. It contains the bottoms of the
uterine glands. It remains almost unchanged after menstruation or childbirth. Due to
it regeneration of the entire endometrium is performed.
The myometrium is made up of 3 layers of smooth muscle. The inner
submucosal layer is oblique longitudinal. The middle vascular layer is oblique
circular and contains a lot of large vessels with a spiral course. The external
supervascular layer is oblique longitudinal. Smooth muscle cells of the myometrium
have organic specificity – they can form processes and increase in length up to 500

99
microns. Due to hypertrophy of the myometrium the uterus increases the weight from
50 g to 1 kg during pregnancy. After childbirth, the uterus involution develops and
the uterus mass restores.
The blood supply of the uterus is abundant and has its organic specificities: 1)
the arteries of the vascular layer of the myometrium have a spiral course; 2) small
arteries of the submucosal layer of the myometrium have no adventitia, thus their
muscular tunic is fused with the myometrium. The myometrium is reduced after the
placental separation. The small arteries are clamped and the bleeding stops. After
complicated labor uterine atony may develop: blood vessels open and bleeding starts;
3) two kinds of arteries enter the endometrium: straight arteries fall into the basal
layer, helical arteries with progesterone receptors fall into the functional layer.
Ovarian-menstrual cycle
The ovarian-menstrual cycle is a cyclical change in the female reproductive
organs regulated by the hypothalamic-pituitary-epiphysis system. The pineal gland
secretes antigonadotropin and melatonin. Antigonadotropin weakens the LH secretion
by the pituitary gland. Melatonin depresses the secretion of gonadotropins. During
daytime the secretion of melatonin is more intensive and the secretion of sex
hormones is less, and vice versa at night. In stress, under the action of epinephrine
(adrenaline) production of melatonin is increased and genital hypofunction can
develop.
There are 3 phases of the ovarian-menstrual cycle: menstrual, post-menstrual
(proliferative), premenstrual (functional).
The menstrual phase lasts for 1–4 days and is accompanied by bleeding; 30–40
ml of blood is lost. Before the beginning of menstruation the functional layer of the
endometrium is rejected, as the corpus luteum stops producing progesterone that
causes a spasm of spiral arteries and ischemia, and then necrosis of the functional
layer of the endometrium. The vessels become brittle, relaxed, overflown with blood
and finally burst. Thus bleeding takes place; the dead functional layer is rejected and
washed away with blood. The whole cavity of the uterus becomes an open wound;
leucocytes become activated to fight infections. Straight arteries of the endometrium

100
do not respond to the lack of progesterone, so the basal layer is not rejected and due
to it the functional layer will be restored. During menstruation the organism has
almost no sex hormones, since the corpus luteum progesterone suppresses the growth
of follicles and production of estrogen. Afterwards it ceases to function itself.
The postmenstrual (proliferative) phase takes place from the 4–5th day to the
11th day after the beginning of the menstrual phase. The lack of sex hormones
stimulates the pituitary gland to secrete FSH, which activates the growth of follicles
in the ovaries and production of estrogen and gonadocrinine. The larger follicle
grows quickly and inhibits the growth of the neighboring follicles by its
gonadocrinine. Thus this follicle develops into Graafian follicle. The growing
follicles produce a lot of ESTROGEN which stimulates a rapid recovery of the
functional layer of the endometrium.
With increased estrogen levels the secretion of pituitary FSH decreases by the
11th day, but the secretion of LH increases. A period of relative rest lasts from the
11th to the 14th days after the beginning of the menstrual phase. The endometrial
growth slows down: it has been restored, the glands are long, narrow and secrete
little, and cilia appear in the epithelium. The secretion of LH and prolactin by the
pituitary increases by the 14th day. It activates the superior ovulatory center of the
hypothalamus. It works only in women and stimulates the pituitary gland to release
LH ovulatory quota. Ovulation takes place. The remnants of the ruptured follicle are
transformed into the corpus luteum which begins to produce progesterone.
The third phase of the cycle, premenstrual (functional) phase, develops under
the influence of PROGESTERONE from the 14th to 28th day after the beginning of
the menstrual phase. The uterus is preparing to receive the embryo. Luteum
progesterone inhibits the secretion of FSH and LH, but not prolactin. The prolactin
level increases. It supports secretion of progesterone. Under the action of these
hormones the endometrial thickness is doubled due to the swelling of the connective
tissue. The glands become crimped, wide, with ciliated cells, and produce a lot of
mucus. The connective tissue cells accumulate glycogen, and decidual cells appear.
They secrete sex hormones and prolactin. Sex hormones inhibit the lymphocyte

101
response; prolactin increases the survival of cells. If fertilization does not occur, the
corpus luteum undergoes involution and menstruation occurs. In pregnancy the
functional phase lasts for 6–8 weeks until the formation of the placenta. The signal of
pregnancy is implantation of the embryo in the uterine wall (on the 7th day).
In the fallopian tubes during the premenstrual phase the mucosa becomes
similar to the endometrium, the decidual cells appear, and a tube may take a
developing embryo (abdominal pregnancies).

Questions for self-control:

1. What features of oogenesis do you know?
2. What is the follicle atresia?
3. What are the tunics of the oocyte?
4. What is ovulation?
5. What structures does the genital tract consist of?
6. What tunics of the uterine wall do you know?

102
 Lecture 15. HUMAN EMBRYOGENESIS
In humans, after ovulation in the upper third of the oviduct one ovum
(sometimes two) matures. It is oligolecithal, secondarily izolecithal, d=120–130 m,
surrounded with zona pellucida and corona radiata, and lives for 24 hours.
Spermatozoa live for 5 days in the acidic environment, one day in the alkaline one.
FERTILIZATION takes place in the upper third of the oviduct; it needs 60–
100 million spermatozoa. There are 3 phases in fertilization.
First phase – convergence of gametes. It is provided with the properties of
gametes and the reproductive tract. Spermatozoa are capable of rheotaxis (movement
against the flow of liquid), have positive chemotaxis to the ovum (which produces
gamons attracting them) and negative chemotaxis to the acidic environment of the
vagina, which drives them into a neutral environment of the cervix. With a lack of
progesterone the cervix environment may become alkaline and immobilize sperm. In
the female genital tract the capacitation (activation) of sperm finishes by the action of
their secretion. The uterus contracts and sucks the sperm. Then, due to the uterus
peristalsis, for the next two hours spermatozoa move to the upper third of the oviduct,
surround the ovum and begin to rotate it.
Second phase – penetration of sperm into the ovum. This process lasts for 10–
12 hours and begins with the acrosomal reaction. Enzymes that dissolve the corona
radiata and zona pellucida are released from the acrosome. Cytolemmae of gametes
merge, and the nucleus and centrioles of sperm enter the ovum cytoplasm, the tail is
lost. Monospermy is characteristic of humans, so only one spermatozoon penetrates.
Once the cortical reaction occurs in the ovum, the cortical granules release
glycoproteins and form fertilization membrane that prevents polyspermy.
Third phase – gamete fusion. It consists of 4 stages. 1st stage – two pronuclei,
2nd stage – synkaryon (dual nucleus), 3rd stage – nuclear fusion into a single diploid
nucleus. A single-celled embryo called a zygote is formed. 4th stage – ooplasmatic
segregation, implying movement of the zygote cytoplasm content and formation of
presumptive germs. Different portions of the zygote cytoplasm will be parts of
different blastomeres.
CLEAVAGE of the human zygote is complete, uneven, and asynchronous. It
starts at the end of the 1st day and takes place under the fertilization tunic. In 30 hours

103
after fertilization two blastomeres (dark and light) are formed. Dark blastomeres are
large; they are cleaved slowly and form the embryoblast, the material of the embryo
and extraembryonic organs. Light blastomeres are finer, and are cleaved quickly.
They grow around dark blastomeres and form the trophoblast. Up to the 4th day
fragmentation is slow, and 2, 3, 5, 7 blastomeres are formed, by the 4th day the
embryo contains 7–12 blastomeres. The first 8 blastomeres are pluripotent, and each
of them can give rise to the whole organism. Till the 5th day the cleavage goes fast,
and the embryo consists of 100–107 blastomeres that form a dense cell globule –
morula. Dark embryoblast blastomeres lie in the center of the morula (inside), and
light trophoblast blastomeres lie in one layer around embryoblasts (outside). The
trophoblast sucks fluid from the oviduct secretions and releases it inside the morula,
so the embryo becomes a vesicle called a blastocyst. Its wall is formed by the
trophoblast. The embryoblast forms the embryonic cell mass which lies in the
blastocyst cavity on the inner surface of the trophoblast. During cleavage the embryo
moves through the oviduct to the uterus. At the 5–6th day the embryo enters the
uterus. Until the 7th day the embryo floats in the secretions of the uterine glands, it is
the free blastocyst stage when the trophoblast prepares for implantation.
Implantation is the introduction of the embryo into the uterine wall. It begins
on the 7–8th day and continues for about 40 hours. By this time, the uterine glands
stop secreting, the uterus cavity becomes dry, the uterus contracts. The trophoblast
develops fast and includes 2 layers. The inner layer called cytotrophoblast consists of
dividing cells that replenish the outer layer called syncytiotrophoblast
(simplastotrofoblast). It is a supercellular multinucleous structure which forms strong
branching and anastomosing villi secreting enzymes. They dissolve the fertilization
tunic; the embryo is actively hatched out from under this tunic and penetrates into 1
or 2 adjacent uterine glands destroying the epithelium, connective tissue and blood
vessels of the endometrium by enzymes. Due to the vascular hemorrhage a blood clot
is formed over the embryo; later it is replaced with the connective tissue and the
epithelium is restored over it. Trophoblast villi float in the maternal blood, break
down nutrients, absorb cleavage products and O2. Furthermore, the
syncytiotrophoblast secretes hormones that support the corpus luteum of the mother`s
ovary to complete the formation of placenta.

104
 Gastrulation is performed in 2 stages: the first stage occurs before the
implantation, at the 6–7th day of the embryonic development, the second stage – at
the 15–17th day.
During the first stage of gastrulation the embryoblast splits up into two layers:
epiblast and hypoblast. The epiblast is adjacent to the trophoblast and contains the
material of ectoderm, a neural tube, mesoderm and a notochord. The hypoblast faces
the blastocyst cavity and contains the material of endoderm. From the 7th to 15th days
extraembryonic organs are laid. Embryoblast cells migrate into the blastocyst cavity
forming the trabecles of extraembryonic mesoderm. They grow to the trophoblast,
and by the 11th day they form a chorion. This chorion has villi on the entire surface.
Villi initially consist only of the trophoblast and are called primary villi. Later they
get extraembryonic mesoderm and are called secondary villi. By the 17th day vessels
grow into villi mesoderm and they become tertiary villi.
In the blastocyst cavity, between the mesoderm trabecles, cavities (lacunae)
with serous fluid are formed. They separate the embryoblast from the trophoblast.
The two cavities near the embryonic disc form the mesodermal germs of the amnion
(on the side of the epiblast) and the yolk sac (on the side of the hypoblast). By the
13–14th day they accumulate the epiblast and hypoblast forming the amniotic bubble
and the yolk sac. Ectoderm of the amniotic bubble fundus and endoderm of the yolk
sac roof compose the embryonic shield, the material of the embryo body. By the 14th
day the extraembryonic mesoderm chord grows from the embryonic shield towards
the trophoblast, forming the amniotic stem, which is the mesoderm germ of allantois.
By the 15th day the embryo has an embryonic shield and 4 extraembryonic organs.
The second stage of gastrulation starts. In the embryonic shield the epiblast
cells move like in the bird`s embryo and form the primary streak with Hensen's node
(primary bundle), and they produce the chord and the embryonic mesoderm. The
endoderm of the back part of the future primary intestine forms fingerlike protrusions
transformed into the epithelium of allantois. It grows into the amniotic stem which
will guide the ingrowth of vessels from the yolk sac to the chorionic villi. At the 17th
day the embryo`s nutrition and breathing are carried out through these vessels. By the
20th day the chord is formed, the neural plate is laid and the segmentation of
embryonic mesoderm and differentiation of somites in germs begin. From the 21st to

105
25th days the neural tube closes, the ganglion plate is segmented into the germs of the
spinal ganglia. From the 20th–21st day the separation of the embryo from the yolk sac
begins by means of trunk folds. They are formed on the edges of the embryonic
shield from the parietal layer of ectoderm and mesoderm that bend toward endoderm,
converge on the ventral side and merge, separating the embryo from the yolk sac. The
body of the embryo invaginates into the amniotic cavity. Endoderm merges with the
visceral layer of the mesoderm and forms the primary intestine connected to the yolk
sac with the yolk stalk, which is converted into the umbilical cord. At the 4th week the
ends of the intestine form mouth and anus; gill arches, jaws and limbs are laid. By
the 35th day the embryo has 43–44 somites. At the end of the second month
histogenesis and laying of almost all organs is completed. At 2,5 months of
development the embryo is 25 mm long, looks like a human being and from 3 months
is called a fetus.
From the 17th day PLACENTA develops in parallel to the embryo. From the 3rd
to 6th week placentation occurs (parts of the placenta formation). By the end of the
third month it is completely formed. The functional layer of endometrium is
transformed into decidua. It consists of 3 parts: 1) decidua basalis – a basic part
which will constitute the maternal part of the placenta; 2) decidua parietalis is a
parietal part lining the uterine wall free of the embryo; 3) decidua capsularis
separates the fetus from the uterus cavity. The decidua basalis and decidua capsularis
surround the chorion. The villi of the decidua capsularis are reduced (bald chorion)
and in the decidua basalis the villi grow strongly, forming a branched chorion. The
villi of the branched chorion are immersed into lacunae with the maternal blood;
some of them become an anchor, merging with the decidua basalis of the
endometrium. The placenta is disc-shaped, 15–18 cm in diameter, 2–3 cm thick,
weighs 600 g. It consists of 2 parts: fetal (part fetalis) and maternal (part uterina).
The fetus is connected to the placenta with the umbilical cord with the fetus vessels
(2 arteries, 1 vein). The umbilical cord is formed by the mucous connective tissue
with a high content of hyaluronic acid and water. It is covered with the double-
layered epithelium of the amnion.
The fetal part (part fetalis) of the placenta is a chorionic lamina with villi.
They contain branches of the umbilical vessels with the fetal blood and are composed

106
of the mucous connective tissue covered with the trophoblast. The external part of
chorionic lamina (facing the fetus) merges with the wall of the amnion covered with
the bilayer cubic epithelium. From inside the chorionic lamina is covered with the
trophoblast. Thousands of highly branched stem villi extend away from the chorionic
lamina. A one-stem villus forms the basis of one placental lobule. Till 2,5 months of
pregnancy the trophoblast (TPB) covering the villi is bilayer: the basal layer is
cytoTPB (Langhans’ cell layer), and the second layer is syncytioTPB. The cytoTFB is
composed of undifferentiated cells; due to their division the syncytioTPB is
replenished. In the second half of pregnancy the cytoTPB disappears because it is
used for the renewal of the syncytioTPB. The syncytioTPB performs 5 functions:
trophic, barrier, excretory, respiratory and endocrine. It produces 4 hormones:
1 – chorionic gonadotropin, like LH, stimulates the development of gonads
and adrenal glands of the fetus (Pregnancy Test is introduction of pregnant women’s
urine to female mice which stimulates ovulation in mice);
2 – progesterone maintains pregnancy and suppresses contraction of the
myometrium. It is produced from the 7th day of pregnancy, the maximum – by the
70th day, when the maternal corpus luteum stops working; the second maximum – at
the 230th–240th day (at the 7th month);
3 – placental lactogen, which is similar to prolactin. It prepares the maternal
mammary glands for lactation and stimulates the development of lungs and surfactant
in the fetus (at the lack of this hormone the fetal lungs are underdeveloped), the
maximum is secreted until childbirth;
4 – placental corticotropin, which determines the beginning of childbirth.
At the end of pregnancy the trophoblast of chorionic villi is gradually replaced
by oxyphilic homogeneous Langhans’ fibrinoid – the decay products of the
trophoblast and plasma proteins. The fibrinoid hinders the absorption of nutrients
from the maternal blood. If pregnancy is pathologically prolonged, the fibrinoid
accumulates Ca that creates a risk of fetal death.
The maternal part (part uterina) of placenta is composed of the basal lamina,
the connective tissue septa and lacunae with maternal blood. The basal lamina is a
basal endometrial decidua; there are many decidual cells, which are the main source
of prolactin during pregnancy. The basal lamina is covered with Rohr’s fibrinoid –

107
the decay products of immune complexes. At the places of attachment of anchor
chorionic villi to the basal lamina part of the trophoblast is shifted from the villi and
penetrates into the basal lamina, forming the peripheral trophoblast. It performs the
endocrine function only. From the basal lamina the septa extend, which separate
lacunae of maternal blood from each other and divide the placenta into lobules –
cotyledons. A cotyledon is a functional unit of the placenta. It consists of a lacuna
with blood and chorionic villi immersed into blood. At the edge of the placenta the
basal lamina fuses with the chorion and forms closing plates preventing the bleeding
of the lacunae.
The blood of the fetus and the mother is separated from each other by the
blood-placental barrier, which consists of the fibrinoid or TPB with the basement
membrane, connective tissue of villi and fetal capillary endothelium with basement
membrane.
Placental functions:
1. Trophic – cells of the part uterina accumulate glycogen, vitamins and salt
and give them to the fetus, and trophoblast digests and absorbs them.
2. Excretory – excretion of products of the fetus metabolism into the mother's
blood.
3. Respiratory – gas exchange between the mother’s blood of and that of the
fetus.
4. Endocrine – production of placental hormones.
5. Protective (barrier) – the placental barrier protection of the fetus from the
mother's immune system and inhibition of harmful substances. The placenta is unable
to inhibit penetration of gases, alcohol, drugs, nicotine, poisons, medicines,
antibodies, and infectious agents (viruses, protozoa, bacteria, including syphilis).
CRITICAL PERIODS IN THE HUMAN DEVELOPMENT and the effects of
environmental factors
Malformations can lead to miscarriage, stillbirth, and various diseases. This
problem was given a start in the work by Norman Gregg. He studied the mass
malformations in Australia in 1941 and found out that all the mothers of children
with deformities suffered rubella during pregnancy. Another wave of malformations

108
in Western Europe in the 1960-s was associated with using a hypnotic drug tolidamid
by pregnants.
It has been found out that during the formation of an organ its tissue cells
actively divide and differentiate, therefore they are especially sensitive to the harmful
factors and can be damaged by them. The cells of other organs, which are less active
in this period, may stay insensitive to the same factors. The periods of active
differentiation of cells, tissues, organs and systems are called critical periods. The
highest points of various organs differentiation occur in certain periods of
embryogenesis, so there is an exact schedule of critical periods. For example, the
rubella virus causes, according to the time of organ formations, diseases of eyes,
brain, heart, organs of hearing. Rubella reveales in the newborn if the mother was ill
before birth.
Malformations of the embryo up to 2,5 months (two months and a half) are
called embryopathy and those of the fetus from 2,5 months till birth – fetopathy.
There are 9 critical periods in the human development:
1. Progenesis. Harmful factors cause genetic and chromosomal genomic
mutations in the sperm and ovum.
2. Fertilization. Harmful factors cause acrosome defects, oligospermia
(ejaculate < 1 ml), azoospermia (no spermatozoa in ejaculate), abnormal fertilization
envelope, polyspermy (there may be even a teratoma). The risk of such mutations is
especially high at 40-50 year-old women.
3. Implantation period (the 7th–8th day of the development). Harmful factors
cause a delayed implantation, abnormal breathing and malnutrition, embryopathy or
death of the embryo.
4. Axial organs development and placenta formation period (the 3rd–8th week of
the development). Harmful factors cause detachment of the placenta and a threat of
miscarriage, the lack of the fetal limbs (the 5th–7th week) or heart (up to the 3rd week),
severe heart defects (up to the 8th week), the double eye, double nose, double face,
cleft lip and palate, lack of testis, uterus, kidneys, polycystosis and hydronephros.
5. Enhanced brain growth period (the 15th–20th week). Harmful factors may
cause development of oligophrenia, sensorineural deafness, encephalocele,

109
hydrocephalus, retinal cysts, violation of myelination, tumors from neuroblasts
(clinical manifestation at 6–8 years of age).
6. Main functional and genital systems formation period (the 20th–24th week).
Harmful factors may cause persistent functional disorders, heart defects, skeletal
deformities, hypothyroidism, cretinism, convulsions and death during birth, the
fusion of body parts in twins.
7. Birth period (normally 8 hours after birth). Harmful factors may cause fetal
hypoxia or asphyxia, irreversible damages of the heart, lungs, kidneys,
gastrointestinal tract, edema and hemorrhage in the brain, the child’s cerebral palsy or
death. Infections can cause a septic shock, meningitis, diseases of eye, skin, liver, etc.
8. Neonatal period (up to 1 year). In the early neonatal period adaptation of the
child may be accompanied by physiological jaundice, uric acid infarction, sexual
crises, and septic diseases. In the late neonatal period, hazards can cause disorders of
development, allergodermatoses, and rachitis.
9. Puberty period (11–16 years), or Neuroendocrine restructuring period.
Hazards (including infections, traumas, obesity) may cause puberty diseases
(dyspituitarism, cardiomyopathy, vascular dystonia, glaucoma, coronary cataracts,
and violation of hematopoiesis). In girls it may be expressed with anovulatory cycle,
premenstrual syndrome, adreno-genital syndrome.

Questions for self-control:

1. Name the stages of embryogenesis.
2. What is implantation and when does it occur?
3. What are the stages of gastrulation?
4. When does the placentation start? What parts does the placenta consist of?
5. What parts does the tunica decidua consist of?
6. What functions does syncytiotrophoblast perform?
7. What placental functions do you know?
8. Name the critical periods in the human development.

110
 Recommended literature
Basic:
1. Wheaterʼs Functional histology : a textbook and colour atlas / Ed. Barbara
Young, Geraldine OʼDowd, Phillip Woodford. – Ssixth edition. – Printed in the USA,
2014. – 452 p.
2. Histology, Cytology and embryology : textbook / Ed. Y. I. Afanasiev. –
Public., add. and proces. – M. : Medicine, 2006. – 768 p.
3. Atlas of microscopic and submicroscopic structure of cells, tissues and
organs : Study guidance / V. G. Eliseev, Y. I. Afanasiev, E. F. Kotovski, A. N.
Jackowski .– 5th publ., add. and proces. – M. : Medicine, 2004. – 448 p. : ill.

Additional :
1. Bykov V. L. Cytology and General histology. Functional morphology of
cells and tissues of human origin: a textbook / V. L. Bykov. – St. Petersburg : SOTIS
2007. – 520 p.
2. Garstukova L. G. Visual histology (General and private) : textbook / L. G.
Garstukova, S. L. Kuznetsov, G. V. Derevyanko. – M. : MIA, 2008. – 204 p.
3. Histology: Atlas for practical exercises: textbook / N. V. Boychuk, R. R.
Islamov, S. L. Kuznetsov, Y. A. Chelyshev. – M. : GEOTAR-MEDIA, 2008. – 160 p.
4. Kuznetsov S. L. Atlas of histology, cytology and embryology: Atlas :
textbook / S. L. Kuznetsov, N. N. Mushkambarov, L. V. Goryachkina. – 2 public.,
add. and process – M. : MIA, 2006. – 376 p.
5. Kuznetsov S. L. Histology, Cytology and embryology: textbook / S. L.
Kuznetsov, N. N. Mushkambarov. – M. : MIA 2007. – 600 p.

111
 Educational edition

Vasilieva Ludmila Sergeevna

Makarova Olga Alexandrovna
Dadueva Alexandra Sokratovna

Lecture notes on sections

«Special histology» and «Human embryogenesis»

Study guidance

112