FSAEI HE I.M.

Sechenov First MSMU MOH Russia (Sechenovskiy University)

Department of histology, cytology, and embryology

T. V. Boronikhina, V.L. Goryachkina,

M.Y. Ivanova, S. L. Kuznetsov,
and A. N. Yatskovskiy

HISTOLOGY, CYTOLOGY, AND EMBRYOLOGY

TEXT with CONTROL PROBLEMS, CONTROL TESTS and PICTURES

Moscow, 2018
T. V. Boronikhina, V.L. Goryachkina, M.Y. Ivanova, S. L. Kuznetsov, and A. N. Yatskovskiy
HISTOLOGY, CYTOLOGY, AND EMBRYOLOGY:
TEXT with CONTROL PROBLEMS, CONTROL TESTS and PICTURES, 2018. – … p.
The English version was edited by E.V. Babchenko

© T. V. Boronikhina, V.L. Goryachkina, M.Y. Ivanova, S. L. Kuznetsov, and A. N. Yatskovskiy

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 CONTENTS:
Cytology
Epithelial Tissues
Blood and Lymph
Connective Tissues
Skeletogenic Tissues: Cartilage and Bone Tissues
Muscle Tissues
Nervous Tissue
Nervous System: Peripheral Nervous System and Spinal Cord
Nervous System: Brain
Primary Sentient Sense Organs: Organ of Vision and Organ of Smell
Secondary Sentient Sense Organs: Organ of Hearing, Organ of Equilibrium, and Organ of
Taste
Cardiovascular System
Central Organs of Hemopoiesis: Red Bone Marrow and Thymus
Peripheral Organs of Hemopoiesis and Immunogenesis
Endocrine System
Digestive System: Oral Cavity and Esophagus
Digestive System: Stomach and Small Intestine
Digestive System: Large Intestine, Liver, and Pancreas
Respiratory System
Integumentary System: Skin and Appendages
Urinary System
Male Reproductive System
Female Reproductive System: Ovaries
Female Reproductive System: Reproductive Cycle, Uterus, Oviducts, Vagina, and
Mammary Glands
Human Embryology: Initial Stages of Embryonic Development
Human Embryology: Embryonic Period, Provisory Organs, and Placentation
Control Problems: Answers and Explanations
Control Tests: Key

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 1. CYTOLOGY

Cytology is a science studying the structure, biochemistry, and functioning of cells.

According to the cell doctrine postulated by Schleiden and Schwann (1839), a cell is
morphofunctional unit of all living things and all tissues of multicellular organisns. Cells are
different in shape (rounded, cuboidal, columnar, flat, fusiform, and with processes) that reflects
the cell fuction. Each cell consists of the cytoplasm and the nucleous as well as is surrounded by
the cell membrane.

Cell membrane
The cell membrane received the name plasmalemma (derived from the Greek lemma
meaning bark) for its resemblance to the bark of trees. The plasmalemma is not visible under the
light microscope, because its total thickness is about from 8 to 10 nm. Under the electron
microscope (EM), it appears as if it is formed of three layers: the outer dark layer, the inner dark
layer, and the middle light layer. That is why it was called the trilaminar membrane. Sometimes
(with low resolution of EM) we can observe only a dark line.
The cell membrane is formed of phospholipids, proteins, and carbohydrates. The
poshospholipid molecule is composed of two parts: hydrophobic and hydrophilic parts. The outer
dark layer and the inner dark layer of the cell membrane are due to the presence of phospholipids.
Large integral proteins are situated between phospholipids. They extend from one side of the
membrane (the outer dark layer) to the other (the inner dark layer). Large integral proteins play an
important role in cell metabolism, regulation, and integration. They can serve as receptors of
enzymes, a pump, or any combination of these functions. Peripheral proteins are superficially
distributed in the outer and inner lipid layers. Cholesterol molecules are present in the cytoplasmic
aspect of the plasmalemma. Some carbohydrates are attached to large integral proteins
(glycoproteins) and phospholipids (glycolipids). Glycolipids and glycoproteins form the outer
layer of the cell membrane called glycocalyx. This outer layer may be very thick or thin, depending
on the cell function.
The cell membrane is a dynamic system; it participates in the functional and metabolic
activities of the cell. The plasmalemma bounds cells insulating them from surrounding medium.
It takes part in cell recognition, intercellular adhesion (aids in holding adjacent cells together), and
cell adhesion to extracellular matrix. It serves as receptor sites for hormones, neurotransmitters,
and growth factors.The cell membrane participates in formation of some organelles (cilia, flagella)
and in movement of motile cells (formation of pseudopodia). In neurons, the cell membrane
conducts nerve impulses.

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 The main function of the plasmalemma is transport of substances from environment into the
cell cytoplasm and back. There are various mechanisms of this transport. Passive transport or
diffusion is tipical for small molecules such as oxygen, carbon dioxide, essential ions, and some
waste. Active transport is typical for large molecules such as sugar, amino acids, and fatty acids.
This transport mechanism requires energy. Selective transport is closely associated with receptors
on the outer surface of the cell membrane allowing it to select and determine which materials can
enter or leave the cell. Vesicular transport is typical for solid particles (bacteria, cell debris) or
bulk fluid. If substances enter the cell, this transport is endocytosis, which can be either
phagocytosis (for solid particles) or pinocytosis (for bulk fluid). In phagocytosis, a solid particle
comes in contact with the cell membrane that gradually surrounds the particle, forming a
phagosome. The phagosome is pinched off from the cell membrane and moves inside the
cytoplasm. In pinocytosis, the plasmalemma invaginates to form small pits or caveolae, which
gradually separate from the cell membrane. They have been referred to as pinocytosis vesicles. If
substances leave the cell, this vesicular transport is exocytosis (release of secretory products).
The cell membrane is continually pumping sodium ions to the outside of the cell. As a
result the concentration of sodium is higher in the tissue fluid than in the cytoplasm. The
concentration of potassium ions is higher in the cytoplasm than in the tissue fluid. The sodium–
potassium pump is responsible for the cell membrane polarization: the outer surface of the
plasmalemma is charged positively whereas its inner surface bears a negative charge.
Plasmalemma modifications
To perform functions, plasmalemma forms modifications on the apical, basal, and lateral
surfaces of cells. Microvilli and cilia are apical membrane modifications.
Microvilli are finger-like projections of the apical membrane of certain cells. They have
similar sizes and shapes regardless of the cell type. Microvilli contain actin microfilaments, which
are anchored to the plasma membrane at the microvillus tip and extend to the apical pole of the
cell. Microvilli increase the area surface of the apical cell membrane to activate its transport
function. For example, multiple microvilli on the apical surface of the intestinal epithelial cells
(brush border) make absorption more intensive.
Cilia are true motile organelles. They are finger-like projections of the apical membrane of
certain cells containing specifically arranged microtubules: nine double peripheral microtubules
and a pair of central microtubules. Cillia are organelles associated with the extracellular transport
of material such as mucus. They are present on the apical pole of the epithelial cells lining the
trachea and bronchi as well as the oviducts and uteres.
Basal striation (infolding) is basal membrane modification. It includes vertical membrane
folds extending into the cytoplasm and numerous mitochondria vertically arranged between folds.

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This structure is typical for cells characterized by active transport through their basal portion, such
as epitheliocytes of the renal convoluted tubules and the salivary gland striated ducts. Basal
plasmalemma of some epithelial cells forms hemidesmosomes to attach the cells to the basement
membrane (see below).
Cellular junctions are plasmalemma modifications on the lateral cell surface. There are
several types of cellular junctions.
Junctions of adherent type provide lateral attachment of cells. In this type of junction, there
is no direct contact between the cell membranes; they are separated by a wide intercellular space
(about 20 nm) filled with adhesive material. The varieties of the adherent junctions are as folowes:
zonula adherens (a girdle ribbon-like junction of epithelial cells), macula adherens or desmosome
(local junction most developed in the epithelia), hemidesmosomes (only on the basal part of the
epithelial cells), and fascia adherens (located only between the cardiac muscle cells).
Junctions of occluding type are so-called the tight junctions. It is created by local sealing of
the plasma membranes of the adjacent cells. These junctions prevent the passage of substances
through intercellular spaces. They are typical for epithelial cells.
Junctions of communicative type are called the gap junctions or nexuses. In this junction,
two parallel, closely apposed plasma membranes are separated by a gap of 2nm. Many channels
consisting of proteins connexons pierce the site of the gap junction. Nexuses allow small molecules
and ions to pass directly from cell to cell without entering the extracellular space. These junctions
are located between epithelial cells, smooth muscle cells, cardiomyocytes, and neurons.

Cytoplasm
The outer and generally larger part of the cell is called cytoplasm. Cytoplasm contains
organelles and inclusions suspended in the cytoplasmic matrix (cytosol, hyaloplasm).
Organelles
The organelles are constant obligatory cytoplasmic structures having distinctive morphology
and performing specific functions.Organelles are described as membranous (membrane-limited)
and nonmembranous.The membranous organelles include rough endoplasmic reticulum (rER),
smooth endoplasmic reticulum (sER), Golgi apparatus, mitochondria, lysosomes, and
peroxisomes.The nonmembranous organelles include ribosomes, centrioles, microtubules, and
filaments.
Rough endoplasmic reticulum (rER). Under EM, rough endoplasmic reticulum appears as
a series of interconnected, membrane-limited flattened sacs called cisternae and tubules with
ribosomes on the membrane exterior surface. Under the light microscope (LM), rER is basophilic
due to the presence of the ribosomes. rER synthesizes proteins of three types: secretory products

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(foe export), lysosomal enzymes, and membrane proteins. Also, rER accumulates and transports
its products. rER is well-developed in serous glandulocytes (pancreatic acinar cells), fibroblasts of
connective tissue, which produce proteins of the extracellular matrix (collagen, elastin, etc.), and
plasma cells, which secrete immunoglobulins (antibodies).
Smooth endoplasmic reticulum (sER). The sER consists of short anastomosing tubules
that are not associated with ribosomes. This organelle synthesizes lipids, cholesterol, steroid
hormones, and carbohydretes (glycogen, mucus). sER is well-developed in the adrenal cortex cells
producing steroid hormones, in the liver cells producing glycogen, cholesterol, and blood
lipoproteins. Like rER, tubules of sER accumulate and transport synthesized products.
In the hepatocyte, sER is involved in detoxification of various substances (toxins, certain
drugs). In muscle tissues, sER serves for calcium ion storage that is necessasery for contractions.
Golgi apparatus includes numerous dictyosomes, each of which consists of flattened
saccules, vesicles, and vacuoles. The saccules are arranged in a stack exhibiting two faces: the
convex forming (cis) face associated with small transfer vesicles and the concave maturing (trans)
face associated with vacuoles. Golgi apparatus takes part in secrition. It accumulates and modifies
products, packs it in membrane, and releases secretory granules. The transfer vesicles convey
products synthesized in rER or sER to the forming face of the saccule stack. Secretory granules
(vacuoles) arise on the saccule stack maturing face. In the same way, Golgi apparatus forms
lysosomes. Additionally, complex molecules, such as glycoproteins, lipoproteins, and glycolipids,
are created on Golgi apparatus membranes.
Mitochondria can be elliptical, ovoid, spherical, discoidal, rod-shaped, etc. It is very
difficult to observe them under LM, because they measure from 0.2 to 2 nm in width and from 2
to 7 nm in length. It is necessary to use special staining to identify them with LM. In case like that,
mitochondria are seen to be rods or threads. Each mitochondrion is covered with two membranes:
the outer membrane is smooth and surrounds the organelle; the inner membrane forms folds termed
cristae, which project into the inner chamber or mitochondrial matrix.
The main function of mitochondria is known to produce energy for cells, namely,
mitochondria provide aerobic stage of energy metabolism: Krebs cycle and oxidative
phosphorylation occur here. The outer membrane is thought to play a role in controlling the
movement of substances into and out of the mitochondria, including release of ATP. The enzymes
for the Krebs cycle are housed in mitochondrion matrix. The enzymes for oxidative
phosphorylation are located on the inner membrane cristae. Toward the matrix, the inner
membrane encloses elementary particles that are the sites of oxidative enzyme localisation. The
synthesis of ATP from ADP takes place here. Mitochondrial matrix also contains DNA,
ribosomes, the enzymes of fatty acid oxidation, granules with Ca++ and Mg++ ions.

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 Mitochondria are found in large numbers in metabolically active aerobic cells (hepatocytes,
cardiac muscle cells, neurons). Cells with low metabolic activity (lymphocytes) or anaerobic cells
(fibroblasts) contain few mitochondria.
Lysosomes are granule-like organelle from 25 nm to 0.05 mcm in diameter. They are
surrounded by a unit membrane and containing hydrolytic enzymes (proteases, acid phosphotase,
etc.). The lysosome varies in number greatly from one cell to another, depending on its type and
function. Lysosomes are involved in intracellular digestion; they may interact with the material
brought into the cell from the outside or with broken down organelles. Lysosomes are very
important for the defense of the body against certain bacterial invaders.
Morphofunctionally, lysosomes can be subdivided into primary lysosomes and secondary
ones. The lysosomes that bud off the maturing face of Golgi apparatus stack are termed primary
lysosomes. They contain only enzymes; they are not yet involved in the digestive activity. The
fusion of primary lysosomes with phagosomes results in the formation of secondary lysosomes
that contain both the digestive enzymes and the material to be digested. Secondary lysosomes
measure from 0.5 to 1.5 µm in diameter. When secondary lysosomes cannot digest the materials,
they turn into debris-filled vacuoles that are called residual bodies (telolysosomes, tertiary
lysosomes) that may remain in the cell throughout its life ("the age pigment" or lipofuscin granules
in neurons).
Thus, lysosomes play a significant role in breaking down different materials in the cells.
The absence of certain lysosomal enzymes leads to the pathological accumulation of residual
bodies, resulting in lysosomal storage diseases. More than 20 storage diseases due to the deficient
activity of lysosomal enzymes have been identified.
A contrasting group of lysosomal diseases is due to the intracellular break up of lysosomes.
For example, in gout, leukocytes engulf urate crystals form in the synovial cavities and other
connective tissue spaces. These crystals result from the genetically induced high level of uric acid
in the body fluids. As urate crystals become incorporated into secondary lysosomes, they disrupt
the lysosomes. The leukocytes are destroyed, and the enzymes released into the tissues induce
inflammation characteristic of uratic arthritis.
Peroxisomes (microbodies) are enclosed by a unit membrane and contain nearly 20
enzymes (catalase, peroxidase, etc.). They measure from 0.2 to 0.8 mcm in diameter. Peroxisomes
generate hydrogen peroxide as an oxidation product; then, enzyme catalase breaks it down to
oxygen and water, because hydrogen peroxide is quite toxic to cells.
Peroxisomes are capable of production of dissipated energy, generating heat. It takes place
during the oxidation of various substrates by molecular oxygen. Peroxisomes are involved in the
metabolism of purine bases (parts of nucleic acids). Human peroxisomes metabolize purines to

8
uric acid, the final product of purine metabolism. High levels of uric acid cause gout, a painful
disease with joint inflammation and chalky deposits.
Peroxisomes possess enzyme alcohol dehydrogenase and thereby degrade alcohol,
reducing the degree of intoxication and alcohol-induced liver damage. Peroxisomes contain
enzymes of gluconeogenesis, the transformation of amino acids and fatty acids to carbohydrates.
Glucocorticoids, adrenal cortex hormones, regulate this procces.
Ribosomes are small clumps consisting of rRNA and proteins. Each ribosome includes two
subunits. The small subunit contains one rRNA molecule and 24 different proteins; the large
subunit contains two molecules of rRNA and 40 proteins. In translation, molecule of mRNA passes
through the cleft between subunits. Both small and large subunits are manufactured in the
nucleolus, leave the nucleus via nuclear pores, and enter the cytoplasm where they combine
together and with mRNA to synthesize proteins.
Ribosomes may occur free in the cytoplasm or be attached to the membrane of rER
(described above). Free ribosomes are scattered freely in the cytoplasm and are responsible for its
diffuse basophilia. Young growing cells contain many free ribosomes. Free ribosomes exist as
monoribosomes in out of working and as polyribosomes (polysomes) in complex with mRNA.
Under EM, polysomes are spiral in shape. Free ribosomes synthesize proteins, which are necessary
for the cell itself (enzymes, nucleolar proteins, hemoglobin in erythrocytes, keratins in epithelial
cells).
Centrioles are paired rod-shaped organelles located close to the nucleus in the center of a
cell. This part of the cell is called the centrosome (the cell center, centrosphere). Each centriole
consists of nine triplets of microtubules oriented parallel to a long axis of the organelle. In resting
cells, the centrioles are arranged at right angles to each other but are not connected. Centrioles are
surrounded by dense material (centriolar satellites) connected with each triplet. The centriolar
satellites appear to be the actual points of polar attachment of the microtubules of the mitotic
spindle.
Centrioles play an important role in cell division (both mitosis and meiosis). Centrioles
duplicate themselves in the G2 period of the mitotic cycle. Each pair of centrioles migrates to
opposite poles of the dividing cell and induce the formation of the mitotic spindle. Centrioles are
involved in shortening of the spindle microtubules during anaphase.
Out of division, centrioles are responsible for formation of cytoskeleton microtubules,
ciliogenesis in ciliated cells, and development of axonemes of the spermatozoon tails.
Microtubules are long cylindrical structures formed of globular protein known as tubulin.
Most of the microtubules are anchored in a region near centrioles, from which they radiate.
Microtubules are found in mitotic spindle, centrioles, cilia, cilium basal bodies, and in the sperm

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axoneme. Microtubules freely located in the cytoplasm are elements of the cytoskeleton.
Microtubules maintain the cell shape, provide intercellular transport, are responsible for beating
of cilia and flagella, cell movement, and migration of chromosomes in division.
Filaments are thread-like organelles consisting of proteins. There are two groups of
filaments: microfilaments and intermediate filaments.
Microfilaments are composed of protein actin. Actin microfilaments are present in all cell
types like the main component of cytoskeleton. In nonmuscle cells, actin may constitute up to 10%
of the total protein. Microfilaments often grouped as bundles close to the cell membrane forming
undermembranous layer of the plasmalemma. In this localization, microfilaments take part in
movement of the plasmalemma in endocytosis and exocytosis, in anchorage and displacement of
the membrane proteins, and migration of cells. Microfilaments are found in the cellular junctions
of adherent type and in microvilli. In muscle cells and fibers, actin filaments combined with
myosin filaments organize specific myofibrils.
Intermediate filaments consist of different proteins having tissue specificity. There are five
major classes of intermediate filaments. Keratin filaments occur in epithelial cells as
tonofilaments; vimentin filaments are primarily present in connective tissue cells; desmin filaments
are abundant in smooth muscle cells; neurofilaments are present in neurons; glial filaments are
present in neuroglial cells. Intermediate filaments are components of cytoskeleton and take part in
coordination of the of organelle activity.
Inclusions
The inclusions are isolated clusters of some substences in the cytoplasm performing specific
functions. Compared with organelles, inclusions are not constant and obligatory cytoplasm
components. They lack morphology and appear like droplets (lipids), granules (proteins), or
clumps (glycogen). Some inclusions, for example, secretory granules, are membrane-enclosed.
Glycogen may be seen under LM only after special fixation and staining procedures. Under EM,
glycogen appears as granules of 25 to 30 nm in diameter and clusters of such granules. The liver
and striated muscle fibers contain large amounts of glycogen.
Lipid inclusions are stored in adipose cells as unit large drop (in white adipose cells) or as
numerous small droplets (in brown adipose cells). Fat sometimes accumulates in hepatocytes and
other types of cells.
The most important human pigment is hemoglobin, an iron-containing protein of
erythrocytes. Myoglobin, the pigment with similar structure and function, exists in muscle cells
and fibers, imparting them red color. Melanin is usually a brown-to-black pigment found chiefly
in the skin, hair, eyes, and in the substantia nigra of the brain.

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 Nucleus
The nucleus is a membrane-limited cell compartment that contains genetic information. The
nucleus functions to keep genetic information (due to DNA content), to realize genetic information
(in transcription), and to transmit genetic information (by cell divisions). The nucleus regulates
the cell growth, differentiation, maturation, and functioning.
The nucleus consists of nuclear envelope, chromatin, the nucleolus (or nucleoli), nuclear
skeleton, and nucleoplasma.
Nuclear envelope appears as a single line under LM. Under EM, two membranes can be
observed: outer and inner. The space between the membranes was termed the perinuclear space.
The outer membrane has many ribosomes on its surface and is continuous with the rER cisternae.
The inner membrane lies adjacent to the fibrous nuclear lamina. This lamina contains special
filaments and provides internal support for chromatin, chromatin-associated proteins, the inner
nuclear membrane, and nuclear pores.
Nuclear pores are seen as round or octagonal interruptions of the nuclear envelope. They
may occupy from 3% to 35% of the nuclear surface. Each nuclear pore contains the protein pore
complex consisting of 8 peripheral granules, which form the so-called annulus, and a central
granule termed the pore diaphragm. From the pores, the filamentous material extends into both the
cytoplasm and the nucleus. Nuclear pores regulate the passage of substances between the nucleus
and cytoplasm. Some nuclear proteins (histones, lamines), enzymes, nucleotids are transported
from the cytoplasm to the nucleus. All kinds of RNA and subunits of ribosomes leave the nucleus
to function in the cytoplasm.
In cell division, the nuclear envelope breaks into vesicles, which reconstitute the nuclear
envelope at the end of the anaphase and in the telophase.
Chromatin is a complex of DNA and proteins; it keeps genetic information. Chromatin
proteins include basic proteins called histones and other nonhistone proteins. These proteins take
part in DNA condensation and regulate DNA activity. The length of DNA strand is about two
meters that is why DNA undergoes condensation (stranding) to be packed in the nucleus. Histones
take part in the first steps of condensation; nonhistone proteins provide the following steps.
The chromatin visible under LM as dense clumps is condensed chromatin called
heterochromatin. The chromatin invisible under LM is decondensed chromatin called
euchromatin. Euchromatin is active form of chromatin; it participates in transcription.
Euchromatin predominates in metabolically active cells (neurons). Heterochromatin is non-
working form of chromatin. Marginal heterochromatin is found at the periphery of the nucleus;

11
central heterochromatin is scattered as irregular clumps; perinucleolar heterochromatin surrounds
the nucleolus. Heterochromatin predominates in metabolically inactive cells (lymphocytes).
In cell division, chromatin is transformed to chromosomes. DNA strands connected with
chromatin proteins undergo the largest condensation and are arranged to form in series
chromonemma, chromatid, and chromosome. Each chromosome consists of two chromatids as a
result of DNA reduplication in S period of the mitotic cycle.
Nucleolus is a part of nucleus responsible for formation of ribosomal subunits. Nuclei may
contain one or more nucleoli. Nucleolus is composed of a portion of chromosome (nucleolus
organizer) surrounded by rRNA and proteins. The nucleolus proteins are ribonucleoproteins and
enzymes (RNA polymerase), which take part the synthesis of rRNA and subunit arrangement.
Nucleolus basophilia is due to the presence of RNA and DNA.
The EM shows filamentous material (pars fibrosa) and granular material (pars granulosa)
of the nucleolus. The pars fibrosa consists of dense filaments about 5 nm thick, predominantly
situated in the interior of the nucleolus. The pars granulosa consists of small particles from 10 to
15 nm in diameter. Perinucleolar heterochromatin surrounds of the nucleolus.
Nuclear skeleton is a sponge structural framework consisting of proteins. It is formed by
microfibers (from 2 to 3 nm in thickness) associated with microfibrils (from 20 to 30 nm in
diameter). Both of them are connected with the nucleolus, the inner membrane, the lamina fibrosis,
and the nuclear pores. The nuclear cytoskeleton is believed to play a role in the arrangement of the
chromatin in chromosomes in cell divisions.
Nucleoplasm (matrix) consists of nucleoproteins and a number of enzymes, which
participate in the DNA and RNA synthesis.

Mitotic division
Mitosis consists of fore phases (indirect division): prophase, metaphase, anaphase, and
telophase.
In the mitotic prophase, chromosomes are condensed and become visible in light
microscope; the nucleolus disappears; the nuclear envelope undergos disorganization and breaks
into vesicles. Chromosomes directly lie in the cytoplasm. Centrioles migrate to the opposite cell
poles.
In the mitotic metaphase, chromosomes are assembled on the equatorial (metaphase) plate;
centrioles induce mitotic spindle formation. Spindle microtubules are attached to a chromosome
at the kinetochore.
In the mitotic anaphase, chromatids are separated from each other and move to the opposite
cell poles.

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 In the mitotic telophase, chromosomes are decondensed; the nucleolus re-appears; the
nuclear envelope is restored; the cytoplasm undergoes division (cytotomia, cytokinesis). The
absence of cytoplasmic division results in multinuclear cell formation.
Mitotic division results in increase in the number of cells, production of two identical
daughter cells, and maintainance of the diploid number of chromosomes.

The cell cycle

The cell cycle is the lifespan of a cell that begins with its appearance (as a result of maternal
cell division) and ends with its division into two daughter cells or its death. The cell cycle includes
the followings events: the mitotic cycle, cell differentiation, cell functioning, and cell death.
The mitotic cycle consists of mitosis and mitotic interphase dividing into 3 phases: G1, S,
and G2 phases. The interval after mitosis is called G1 phase. During this phase, the daughter cells
grow, synthezis protein (enzymes) and RNA, and form plasmalemmal receptors. During the S
phase, DNA reduplication, hystone synthesis, and self-replication of centrioles occur. The interval
between the S phase and mitosis is called G2 phase. The synthesis of proteins tubulins for the
mitotic spindle and accumulation of ATP occur during this phase.
The majority of the cells have to differentiate after mitosis. The beginning of differentiation
is associated with the cell leaving the cycle. As a rule, cells leave the cycle from the G1 phase;
some cells leave the cycle from the G2 phase. In the latter case, the cell becomes polyploid.
In initial differentiation, cells can return into the mitotic cycle and divide. Young cells are
characterized by high proliferative (mitotic) activity. In final differentiation, mature cells can not
re-enter the cycle and lose capacity to divide.
Stem cells (reserve cells) exist in the G0 phase (phase of rest) and very rarely re-enter the
cycle. After stem cell division, one daughter cell starts to differentiate; the other one remains in
G0 phase, becoming new stem cell to maintain the stem cell population.
In tissues, aggregate of cells capable of proliferation is called cambium. It includes rarely
dividing stem cells and young undifferentiated cells with high mitotic activity. In all tissues, highly
differentiated and mature cells lack proliferative ability.
The tissues of the adult body are classified into three populations: static, stable, and renewing
according to their cambial cell activity. Static cell populations are devoid of cambial cells and
never display mitotic divisions (neurons, cardiac muscle cells). Stable cell populations have
inactive cambium, whose cells episodically divide (glandular epitheliocytes, smooth muscle cells).
Renewing cell populations are characterized by very active cambium and demonstrate abundance
of dividing cells (covering epithelium).

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 Every cell has its own program of activity and death. Nuclear DNA contains a lethal gene or
the gene of death. When this gene is expressed (activated), the DNA is destroyed and
undergos fragmentation; the nucleus is broken into fragments; the cell decreases in volume; the
plasmalemma forms numerous vesicles (blebbing); the cell is broken in membrane-bounded
apoptotic bodies. Inflammation never occurs. This process is called apoptosis. Apoptosis is a
normal process of programmed cell death. This mechanism of death is induced in cells when they
are damaged, useless to the body, or dangerous. In the second type of cell death called necrosis,
the cell membrane is ruptured, the cell becomes swollen, and a severe inflammatory reaction
develops.

CONTROL PROBLEMS

1. The concentration of some ions outside a cell is lower than that in the cell cytoplasm. Can
the ions pass through the plasmalemma into the cell?
2. The cells cultivated in vitro are attached to the substratum and to each other. What cellular
structures provide the attachment?
3. The experiments with tissue cultures revealed that the cells did not respond to the
influence of the hormone studied. Give an explanation to the experimental results.
4. When a wound heals, it becomes full of cells and fibers. How do these cells and fibers
appear in the healing wound?
5. A healing wound is rich in collagen fibers and the cells containing numerous lysosomes
and phagosomes. Is it true that the cells take part in collagen fiber production?
6. Young growing cells are known to be characterized by the basophilic cytoplasm. Give an
explanation to this phenomenon.
7. The action of ionizing radiation results in the destruction of cell organelles. How do these
cells utilize the organelle residues?
8. There are three cell populations in the lymph node: the cells rich in free ribosomes, the
cells with numerous lysosomes, and the cells with a large amount of the rough endoplasmic
reticulum. Which cells increase in number when the blood level of immune proteins (antibodies)
considerably rises?
9. Histologists studying malignant cells revealed numerous keratin filaments in the cell
cytoplasm. What type of tissue did the malignant cells arise from?
10. The histological slide shows several neurons with large light nuclei and marked
nucleoli. Assess the level of protein synthesis in these cells.
11. A cell enters mitotic division. Does protein synthesis occur in the dividing cell?

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 12. The cytophotometric investigation revealed one-nucleated and binucleated tetraploid
cells in the liver. What are the mechanisms of the appearance of these polyploid cells?
13. Forensic experts established that the blood smear they examined belonged to a female.
What led them to this conclusion?
14. The investigators observed and described two types of cell death in a tissue culture. In
the first type, the cell membrane is ruptured, the cell becomes swollen, and a severe inflammatory
reaction develops. The second type of death is characterized by DNA fragmentation, a decrease in
cell volume, plasmalemma blebbing, and the formation of membrane-bounded bodies causing cell
breakage. Inflammation does not occur. What are the two types of cell death?

CONTROL TESTS

Directions: each of the following statements contains five suggested completions. Choose
the one that is best in each case.
1. Each of the following statements concerning the plasmalemma is true, EXCEPT: A –
includes elementary cell membrane; B – its supermembranous layer consists of glycolipids and
glycoproteins; C – its submembranous layer contains filaments and microtubules; D – is a semi-
permeable cell boundary; E – is not an obligatory cell component.
2. The plasma membrane functions are as follows, EXCEPT: A – is a selectively permeable
barrier; B – is the site for hormone receptors; C – provides cell-to-cell interaction; D – is the
primary protein synthesis site; E – takes part in the active and passive transport.
3. Each of the following statements concerning the microvilli is true, EXCEPT: A – are
plasmalemma projections; B – contain microtubules; C – amplify cell surface area; D – form the
brush border of intestinal epithelium; E – contain microfilaments.
4. Each of the following statements concerning the cilia is true, EXCEPT: A – are
plasmalemma projections; B – contain nine peripheral doublets and the central pair of
microtubules; C – are not visible in light microscope; D – their basal bodies are similar to
centrioles; E – are movable organelles.
5. The intercellular junction where ionic channels pierce the adjacent membranes is called:
A – desmosome; B – nexus; C – tight junction; D – synapse; E – lateral interdigitations.
6. The disk-shaped intercellular junction where a dense plaque with filaments is present on
the cytoplasmic surface of each opposing plasma membrane is called: A – desmosome; B – nexus;
C – tight junction; D – synapse; E – lateral interdigitations.
7. The intercellular junction that blocks the substance access to the intercellular space is
called: A – desmosome; B – nexus; C – tight junction; D – synapse; E – lateral interdigitations.

15
 8. Each of the following statements concerning the mitochondria is true, EXCEPT: A – have
a double-membrane structure; B – its inner membrane infolds to form cristae; C – its matrix
contains enzymes of Krebs’ cycle; D – its cristae contain enzymes of the electron-transport chain;
E – are not able to produce ATP.
9. The cytoplasm basophilia is inherent in cells that: A – have cilia; B – accumulate lipids;
C – actively synthesize proteins; D – accumulate glycogen; E – synthesize mucus.
10. The microfilaments are composed of the following proteins: A – actin; B – desmin; C –
keratin; D – vimentin; E – integrin.
11. These filaments belong to the population of intermediate filaments, EXCEPT: A –
tonofilaments; B – neurofilaments; C – actin filaments; D – glial filaments; E – desmin filaments.
12. Each of the following statements concerning the nuclear envelope structure is true,
EXCEPT: A – consists of two membranes separated by the perinuclear space; B – contains nuclear
pores providing communication between the nucleus and cytoplasm; C – its outer membrane is
studded with ribosomes; D – its inner membrane has a fibrous lamina anchoring chromatin; E –
its outer membrane is continuous with Golgi apparatus.
13. Each of the following statements concerning chromatin is true, EXCEPT: A –
euchromatin is a lightly stained and dispersed; B – heterochromatin is a densely stained and
condensed; C – heterochromatin takes part in transcription; D – two types of chromatin may be
transformed one into another; E – the abundance of euchromatin gives evidence of intense protein
synthesis.
14. Each of the following statements concerning the nucleolus functions is true, EXCEPT:
A – the nucleolar organizer region contains genes encoding mRNA; B – rRNA is synthesized and
assembled into ribosome subunits; C – ribosome subunits leave the nucleus through nuclear pores;
D – in the cytoplasm, ribosomes either assemble into polysomes or bind to rER; E – the number
and size of nucleoli give evidence of intense protein synthesis.
15. Each of the following statements concerning mitosis is true, EXCEPT: A – results in the
production of two identical daughter cells; B – is direct cell division; C – equally divides
chromosomes between daughter cells; D – maintains the diploid number of chromosomes; E –
consists of four phases.
16. Each of the following statements concerning the mitotic spindle is true, EXCEPT: A –
contains microtubules; B – its components are attached to a chromosome at the kinetochore; C –
is responsible for chromosome movement in the anaphase; D – is formed before chromosome
condensation; E – centrioles take part in its formation.
17. The following cytoplasmic components are inclusions, EXCEPT: A – lipid droplets; B
– glycogen clumps; C – lysosomes; D – mucous granules; E – protein granules.

16
 Directions: one or more of the given statements or completions is/are correct. Choose the
answer: A – if only 1,2, and 3 are correct; B – if only 1 and 3 are correct; C – if only 2 and 4 are
correct; D – if only 4 is correct; E – if all are correct.
18. The glycocalyx is composed of: (1) glycoproteins (2) cholesterol (3) glycolipids (4)
glycogen
19. The rER synthesizes: (1) secretory proteins (2) cell membrane proteins (3) lysosome
enzymes (4) cytosol proteins
20. The abundance of rER in the cytoplasm can be identified by: (1) diffuse basophilia (2)
acidophilia (3) absence of staining (4) local basophilia
21. The functions of sER are as follows: (1) lipid metabolism (2) carbohydrate metabolism
(3) detoxification (4) release and recapture of calcium ions in muscles
22. The following statements regarding the Golgi apparatus are true: (1) consists of several
disk-shaped saccules arranged in a stack (2) its cis (convex) face is associated with small vesicles
from ER (3) its trans (concave) face is associated with vacuoles (4) it is abundant in secretory cells
23. The following statements regarding the Golgi apparatus functions are true: (1)
accumulates, modifies, and packs secretory products (2) forms primary lysosomes (3) takes part
in the synthesis of lipoproteins, glycoproteins, and glycolipids (4) manufactures membrane
proteins
24. The lysosome membranes and lysosome enzymes are formed in: (1) rER (2) sER (3)
Golgi apparatus (4) free ribosomes
25. The following statements regarding the lysosome functions are true: (1) protect cells
from waste products accumulation (2) degrade aged organelles (3) take part in phagocytosis (4)
provide autolysis
26. The following statements regarding the peroxisome are true: (1) is a spherical structure
surrounded by unit membrane (2) its matrix contains the enzyme catalase (3) its catalase converts
hydrogen peroxide to water and oxygen (4) is derived from rER
27. The following statements regarding the centrioles are true: (1) exist as a pair of cylinder-
like structures oriented at right angles to one another (2) each centriole has nine peripheral
microtubule triplets but lacks the central pair (3) before cell division, they replicate themselves by
forming procentrioles (4) during cell division, separate and migrate to the cell poles
28. The cytoskeleton includes: (1) actin filaments (2) intermediate filaments (3)
microtubules (4) centrioles

17
 29. The following statements regarding the microtubule functions are true: (1) are parts of
the cytoskeleton (2) form the mitotic spindle (3) take part in intracellular transport and cell
movement (4) constitute cilia, flagella, and centrioles
30. The cells containing a lot of free ribosomes synthesize: (1) secretory proteins (2) cytosol
proteins (3) cell membrane proteins (4) proteins for cell growth and differentiation
31. The following events take place in the G1 period of the mitotic interphase: (1) intense
protein synthesis (2) DNA reduplication (3) daughter cell growth (4) self-replication of centrioles
32. The following events take place in the S period of the mitotic interphase: (1) DNA
reduplication (2) daughter cell growth (3) self-replication of centrioles (4) intense energy
production
33. The following events take place in the G2 period of the mitotic interphase: (1) intense
energy production (2) ATP accumulation (3) intense tubulin synthesis (4) DNA reduplication
34. The following events take place in the mitotic prophase: (1) chromosome condensation
(2) nucleolus disappearance (3) nuclear envelope disorganization (4) centriole migration to the
opposite cell poles
35. The following events take place in the mitotic metaphase: (1) chromosome condensation
(2) chromosome assembling on the equatorial plate (3) nucleolus disappearance (4) the mitotic
spindle formation
36. The following events take place in the mitotic anaphase: (1) chromosome condensation
(2) nucleolus disappearance (3) the mitotic spindle formation (4) movement of chromatids to the
opposite cell poles
37. The following events take place in the mitotic telophase: (1) chromosome
decondensation (2) nuclear envelope restoration (3) nucleolus re-appearance (4) cytoplasm
division
38. The absence of cytoplasmic division (cytokinesis) in mitosis results in: (1) cell death (2)
generation of a subsequent mitosis (3) formation of haploid cell (4) formation of multinuclear cell

18
 FIGURES

Fig. 1.1. Plasmalemma molecular organization.

I – supramembranous layer (glycocalyx); II – lipid bilayer; III – submembranous layer (cytoplasm
cortical layer); 1 – integral proteins; 2 – semi-integral proteins; 3 – peripheral proteins; 4 –
phospholipids; 5 – cholesterol; 6 – glycolipids; 7 – glycoproteins.

Fig. 1.2. Cytoplasm

A – intracellular digestion: 1 – phagocytosis; 2 – pinocytic vesicle; 3 – phagosome; 4 – primary
lysosome; 5 – phagosome and lysosome fusion; 6 – digestive vacuole; 7 – residual body; 8 –
exocytosis; 9 – Golgi apparatus; 10 – mitochondrion; 11 – rER; 12 – lysosome and autophagosome
fusion; 13 – autodigestive vacuole. B – participation of rER and Golgi apparatus in secretion: 1 -
rER; 2 – transport vesicles; 3 – Golgi apparatus; 4 – secretory granules; 5 – exocytosis (excretion
of secretory granule).

19
 .
Fig. 1.3. Nucleus ultrastructure
1 – decondensed chromatin (euchromatin); 2 – condensed chromatin (heterochromatin); 3 –
nucleolus; 4 – nuclear envelope; 5 – nuclear pore; 6 – nucleoplasm.

Fig. 1.4. Cell cycle

M – mitosis; G1 – premitotic period; S – synthetic period; G2 – postmitotic period; D1 – initial
stages of differentiation; D2 – final stages of differentiation; F – cell functioning; G0 – period of
rest (stem cell existence).

20
 Fig. 1.5. Mitosis
I – prophase: 1 – centrioles; 2 – nucleus; 3 – chromosomes; II – early metaphase: 1 – mitotic
spindle; 2 – spindle threads attached to chromosome kinetochores; III – metaphase; IV –
anaphase; V – early telophase; VI – late telophase.

21
 2. EPITHELIAL TISSUES

Histology is the science studying the tissues. Tissues are aggregates of cells and extracellular
material organized to perform distinctive functions. There are four basic tissue groups: epithelial
tissues; a group of internal medium tissues including blood, lymph, and all types of connective
tissues; muscular tissues; and nervous tissue.
The epithelial tissues or epithelia are a diverse group of tissues, including covering epithelia,
which, cover or line body surfaces and cavities, and glandular epithelia, which form exocrine and
some endocrine glands. Epithelia function as interfaces between different biological
compartments. As such, epithelia mediate a wide range of activities such as external (between the
body and environment) selective transport, secretion, and physical protection. All these major
functions may be exhibited at a single epithelial surface. For example, the epithelial lining of the
small intestine is primarily involved in absorption of the products of digestion, but the epithelium
also protects itself from intestinal contents by the secretion of a surface coating of mucus.
Epithelia are cellular tissues, they consist of only cells, which are arranged in layers, and
lack exstracelular matrix. All epithelia are supported by a basement membrane. Basement
membranes separate epithelia from underlying supporting tissues and are never penetrated by
blood vessels; epithelia are thus dependent on the diffusion of oxygen and metabolites from
adjacent supporting tissues, usually, loose connective tissue.
The classification of epithelia is based on: (1) the number of cell layers: a single layer of
epithelial cells is termed simple epithelium, whereas epithelia composed of several layers are
termed stratified epithelia, and (2) the shape of the component cells: this is based on the appearance
in sections taken at right angles to the epithelial surface. In stratified epithelia, the shape of the
outermost layer of cells determines the descriptive classification. Cellular outlines are often
difficult to distinguish, but the shape of epithelial cells is usually reflected in the shape of their
nuclei.
Epithelia may be derived from any germ layer: ectoderm, mesoderm or endoderm, but never
originate from the mesenchyme.

Covering epithelial tissues

Simple epithelia. Epithelium is simple if all its cells rest on the basement membrane.
Simple squamous epithelium is composed of flattened, irregularly shaped cells forming a
continuous surface. The term “squamous” derives from the comparison of the cells to the scales
of a fish. Like all epithelia, this delicate lining is supported by an underlying basement membrane.
The basement membrane is rarely thick enough to be seen under LM. Simple squamous epithelium

22
is found to line the surfaces involved in transport of gases (as in the lung alveoli) or fluids (as in
the mesothelium). The mesothelium forms the delicate lining of the pleural, pericardial, and
peritoneal cavities where it permits the passage of tissue fluid into and out of these cavities.
Reflecting the minimal metabolic activity of these cells, the nuclear chromatin is condensed and
the cytoplasm contains few organelles.
Simple cuboidal epithelium represents an intermediate form between simple squamous and
simple columnar epithelium. The distinction between tall cuboidal and low columnar epithelium
is often very slight. In section perpendicular to the basement membrane, the epithelial cells appear
square, leading to its traditional description as cuboidal epithelium; on surface view, however, the
cells are actually polygonal in shape. The nucleus is usually rounded and located in the centre of
the cell. Simple cuboidal epithelium usually lines small ducts and tubules, which may perform
excretory, secretory, or absorbtive functions; examples are the small collecting ducts of the kidney,
salivary glands, and the pancreas.
Simple columnar epithelium is similar to simple cuboidal epithelium, except that the cells
are taller and appear columnar in sections at right angles to the basement membrane. The height
of the cells may vary from low to tall columnar, depending on the degree of functional activity.
The nuclei are elongated and may be located at the base, in the centre or, occasionally, in the apical
part of the cytoplasm. This is known as polarity. Simple columnar epithelium is most often found
on highly absorptive surfaces such as in the small intestine, although it may constitute the lining
of highly secretory surfaces such as that of the stomach. Simple columnar ciliated epithelium as a
type of simple columnar epithelium is traditionally described separately because of the presence
of surface specializations called cilia on the apical surface of the majority of the cells (the
epithelium of the oviducts or uterus). Among the ciliated cells there are some nonciliated cells,
which usually perform a secretory function.
Cilia are much larger than microvilli and are visible under LM. Each cillium consists of a
finger-like projection of the plasma membrane, its cytoplasm containing a motile specialization of
the cytoskeleton. Each cell may have up to 300 cilia that, along with those of other cells, beat in a
wavelike manner, generating a current, which propels fluid or minute particles over the epithelial
surface. Simple columnar ciliated epithelium is not common in humans, except in the female
reproductive tract.
Another variant of simple columnar epithelium is described in which the majority of the
cells are also usually ciliated. The term pseudostratified is derived from the appearance of this
epithelium in section, which conveys the erroneous impression that there is more than one layer
of cells. In fact, this is a true simple epithelium, since all the cells rest on the basement membrane.
The nuclei of these cells, however, are disposed at different levels, thus creating the illusion of

23
cellular stratification. Not all the ciliated cells extend to the luminal surface; such cells are capable
of cell division, providing replacements for lost or damaged cells.Pseudostratified columnar
ciliated epithelium may be distinguished from true stratified epithelia by two characteristics.
Firstly, the individual cells of the pseudostratified epithelium exhibit polarity. Secondly, cilia are
never present on stratified epithelia. Pseudostratified epithelium lines the larger airways of the
respiratory system in mammals and is therefore often referred to as respiratory epithelium.
Stratified epithelia. Stratified epithelia consist of two or more layers of cells, but only one
of them (a basal layer) rests on the basement membrane. They mainly perform a protective
function, and the degree and nature of the stratification is related to the kinds of physical stresses
to which the surface is exposed. The classification of stratified epithelia is based on the shape and
structure of the surface cells, since the cells of the basal layer are usually cuboidal in shape.
Stratified squamous epithelium consists of a variable number of cell layers, which exhibit
transition from a cuboidal or columnar basal layer to a flattened surface layer. The basal cells
divide continuously. During the process, the cells undergo first maturation, then degeneration. The
surface cells show the process of degeneration; this is particularly evident in the nuclei, which
become progressively condensed (pyknotic) and flattened before ultimately disintegrating.
Stratified squamous epithelium is well adapted to withstand abrasion, since the loss of
surface cells does not compromise the underlying tissue. It is poorly adapted to withstand
desiccation. This type of epithelium lines the oral cavity, pharynx, esophagus, anal canal, uterine
cervix and vagina, i.e., the sites, which are subject to mechanical abrasion but which are kept moist
by glandular secretion.
The specialized form of stratified squamous epithelium constitutes the epithelial surface of
the skin (epidermis) and is adapted to withstand the constant abrasion and desiccation, to which
the body surface is exposed. During maturation, the epithelial cells undergo a process called
keratinization, resulting in the formation of a tough, non-cellular surface layer, consisting of the
protein named keratin. Keratinization may be induced in normally non-keratinizing stratified
squamous epithelium such as that of the oral cavity when it is exposed to excessive abrasion or
desiccation.
Transitional epithelium is a form of stratified epithelium that lines the urinary tract in
mammals where it is highly specialized to accommodate a great degree of stretch and to withstand
the toxicity of urine. This epithelial type is so named, because it has some features, which are
intermediate (transitional) between stratified cuboidal and stratified squamous epithelia. In the
contracted state, transitional epithelium appears to be about four to five cell layers thick. The basal
cells are roughly cuboidal, the intermediate cells are polygonal, and the surface cells are large and

24
rounded and may contain two nuclei. In the stretched state, transitional epithelium often appears
only two or three cells thick.
The intercellular, luminal, and basal surfaces of epithelial cells exhibit a variety of
specializations. Intercellular surfaces of epithelial cells are linked by several different types of
membrane and cytoskeletal specializations. These cell junctions permit the epithelia to form a
continuous cohesive layer, in which all of the cells “communicate” and cooperate to meet the
particular functional requirements of the epithelium.
Occluding junctions, also known as tight junctions, are located immediately beneath the
luminal surface of simple columnar epithelium (e.g., intestinal lining), where they seal the
intercellular spaces so that the luminal contents cannot penetrate between the lining cells. Each
tight junction forms a continuous circumferential band or zonule around the cell and is thus also
known as a zonula occludens.
Adhering junctions tightly bind the constituent cells of the epithelium together and act as
anchorage sites for the cytoskeleton of each cell so that the cytoskeletons of all cells are effectively
linked into a single functional unit. Adhering junctions are of two morphological types. Deep to
the tight junctions of columnar epithelial cells, an adhering junction forms a continuous band (the
zonula adherens) around the cell, providing structural reinforcement to the occluding junction.
Secondly, adhering junctions in the form of small circular patches or spots called desmosomes (the
macula adherens) are circumferentially arranged around columnar cells deep to the continuous
adhering junction. The combination of the zonula occludens, the zonula adherens, and
circumferentially arranged desmosomes is known as the ajunctional complex. Desmosomes (spot
adhering junctions) are also widely scattered elsewhere in epithelial intercellular interfaces,
binding the whole epithelial mass into a structurally coherent whole.
Adhering junctions and communicating junctions are not exclusive to epithelia and are also
present in cardiac and visceral muscle where they appear to serve similar functions.
The luminal surfaces of epithelial cells may incorporate two main types of specialization:
cilia and microvilli. Cilia are relatively long, motile structures, which are easily resolved by light
microscopy. In contrast, microvilli are short, often extremely numerous projections of the plasma
membrane, which cannot be individually resolved under LM.
The basal surfaces of epithelial cells and underlying supporting tissues is marked by a non-
cellular structure known as the basement membrane, which provides structural support for
epithelia and constitutes a selective barrier to the passage of materials between the epithelium and
supporting tissue. The basal plasma membranes of some simple epithelia, which are very active in
ion transport (e.g., the cells of the kidney tubules), exhibit deep basal folds. These greatly enhance
surface area and provide an arrangement, by which the energy-producing mitochondria can be

25
situated in intimate association with the plasma membrane. Hemidesmosomes, a variant of the
desmosome, are present on the inner aspect of the basal plasma membrane adjacent to the basement
membrane and provide a means of anchorage of the cytoskeleton to the basement membrane and
underlying supporting tissue.

Glandular epithelia and glands

The epithelium, which is primarily involved in secretion, is often arranged into structures
called glands. Glands are the invaginations of epithelial surfaces, which are formed during
embryonic development by proliferation of epithelium into the underlying tissue. The glands,
which maintain their continuity with the epithelial surface, discharging their secretion onto the
free surface via a duct, are called exocrine glands. In some cases, the glands have no ducts. The
secretory products of such glands, known as endocrine glands, pass into the bloodstream. Their
secretions are known as hormones. Nevertheless some endocrine glands develop by migration of
epithelial cells without the formation of a duct. Exocrine glands may be broadly divided into
simple and compound glands.
Simple glands are defined as those with a single, unbranched duct. The secretory portions of
simple glands have two main forms, tubular or acinar (spherical), which may be coiled and/or
branched. Compound glands have a branched duct system, and their secretory portions have
morphological forms similar to those of simple glands.
The simplest exocrine glands are goblet cells. Goblet cells are modified columnar epithelial
cells, which synthesize and secrete mucus. They are scattered among the cells of simple epithelial
linings of the respiratory and intestinal tracts. The distended apical cytoplasm contains a dense
aggregation of mucigen granules, which, when released by exocytosis, combine with water to form
the viscous secretion called mucus. Mucigen is composed of a mixture of neutral and acidic
proteoglycans and therefore can readily be demonstrated by the PAS method, which stains
mucigen crimson. The “stem” of the goblet cell is occupied by a condensed nucleus and crammed
with other organelles involved in mucigen synthesis.
Simple tubular glands have a single, straight tubular lumen into which the secretory products
are discharged. Sweat glands are almost the only example of simple coiled tubular glands. Each
consists of a single tube, which is tightly coiled in three dimensions. Portions of the gland are thus
seen in various planes of section. Sweat glands have a terminal secretory portion lined by simple
cuboidal epithelium, which gives way to a excretory duct lined by stratified cuboidal epithelium.
Simple branched tubular glands are found mainly in the pyloric part of the stomach. They
are mucus-secreting glands. Each gland consists of several tubular secretory portions, which

26
converge into a single, unbranched duct of a wider diameter; it is also lined by mucus-secreting
cells. Unlike the cells of the small and large intestines, these mucous cells are not goblet-shaped.
Simple branched acinar gland consists of several secretory acini, which empty into a single
excretory duct. Sebaceous glands provide a good example of this type of the gland. Their mode of
secretion is holocrine, i.e., the secretory product, sebum, accumulates within the secretory cells
and is discharged by degeneration of the cells.
Brunner’s glands of the duodenum are the example of compound branched tubular glands.
Their duct system is branched, thus defining the glands as compound glands. The secretory
portions have a tubular form, which is branched and coiled.
Compound acinar glands are those in which the secretory units are acinar in form and drain
into a branched duct system. This type of glands consists of numerous acini, each of which drains
into a minute duct. These minute ducts, which are just discernible in the centre of some acini, drain
into a system of branched excretory ducts of increasing diameter and are lined by simple cuboidal
epithelium. The pancreas is a good example of this type of glands.
Compound tubulo-acinar glands have three types of secretory units, namely, branched
tubular, branched acinar, and branched tubular with acinar end-pieces called demilunes. The
submandibular salivary gland is the classic example. It contains two types of secretory cells,
mucus-secreting cells and serous cells; the former stain poorly, but the latter, which have a protein-
rich secretion (digestive enzymes), stain strongly due to their large content of rough endoplasmic
reticulum. Generally, the mucous cells form tubular components, whereas the serous cells form
acinar components and demilunes.
There are three modes of discharge of secretory products from the cells. Merocrine – the
secretion may occur by exocytosis from the cell apex into a lumen, so neither the cell membrane
nor the cytoplasm become part of the secretion. This is the usual mode of secretion of all gland
cells. Apocrine – a small portion of the apical part of cytoplasm is released along with the secretory
product. This is an unusual mode of secretion and applies to lipid secretory products in the breasts
and some sweat glands. Holocrine secretion involves the discharge of whole secretory cells with
subsequent disintegration of the cells to release the secretory product. Holocrine secretion occurs
principally in the sebaceous glands. In general, all glands have a continuous basal rate of secretion,
which is modulated by nervous and hormonal influences. The secretory portions of some exocrine
glands are embraced by contractile cells, which lie between the secretory cells and the basement
membrane. The contractile mechanism of these cells is thought to be similar to that of muscle
cells. These cells are called myoepithelial cells.
Endocrine glands are ductless glands. The secretory products diffuse directly into the
bloodstream. The secretory products are known as hormones and control the activity of cells and

27
tissues usually far removed from the site of secretion. Most endocrine glands consist of clumps or
cords of secretory cells surrounded by a rich network of small blood vessels. Each clump of
endocrine cells is surrounded by a basement membrane, reflecting its epithelial origin. Endocrine
cells release hormones into the intercellular spaces from which they diffuse rapidly into
surrounding blood vessels.

CONTROL PROBLEMS

1. Absorption is the main function of the small intestine lined with the epithelium. What
type of epithelia is adequate to this function?
2. The brush border on the epithelial cells of the small intestine can be destroyed in some
diseases (sprue). What cell functions are impaired in this case?
3. There are two epithelia in the histological section of an organ. One of them covers the
surface of the organ; the other epithelium is located in the wall depth of the organ. Specify the
epithelia and suggest their functions.
4. The cells of the stratified squamous keratinized epithelium are cultivated in two flasks.
One of them contains the stratum basale cells; the other flask contains the stratum lucidum cells.
Which of the flasks will contain proliferating cells?
5. The stratified squamous keratinized epithelium covers the skin. Are there any
differences in the structure of the epithelium covering the thick (hairless) skin and the epithelium
covering the thin skin?

CONTROL TESTS

Directions: each of the following statements contains five suggested completions. Choose
the one that is best in each case.
1. Each of the following statements concerning the mesothelium is true, EXCEPT: A – is
derived from mesoderm; B – is simple; C – its cells are squamous; D – not each of its cells reaches
the lumen; E – lines the peritoneal cavity.
2. Each of the following statements concerning the pseudostratified epithelium is true,
EXCEPT: A – all its cells rest on the basement membrane; B – all its cells reach the apical surface;
C – contains goblet cells; D – is ciliated; E – contains short (basal) cells.
3. Each of the following statements concerning the basement membrane is true, EXCEPT:
A – separates epithelium from the underlying connective tissue; B – is absent in some epithelia; C

28
– contains type lV collagen and laminin; D – serves for epithelial cell attachment; E – takes part
in nutrition of epithelium.
4. The cardinal features of the epithelia are as follows, EXCEPT: A – form the stroma of
organs; B – look like sheets; C – are derived from all germ layers; D – regenerate intensively; E–
their cells are polarized.
5. The epithelia are simple if: A – their cells are polarized; B – their cells form sheets; C –
all their cells rest on the basement membrane; D – not all their cells reach the apical surface; E –
their cells are continuously sloughed.
6. The epithelia are stratified if: A – their cells are continuously sloughed; B – their cells
form sheets; C – their cells are polarized; D – all their cells can divide; E – not all their cells are
in contact with the basement membrane.
7. Each of the following statements concerning the stratified squamous nonkeratinized
epithelium is true, EXCEPT: A – contains the spinulate cell layer; B – contains the basal layer
with stem cells; C – contains the superficial layer of flat anucleate cells; D – its superficial cells
are continuously sloughed; E – lines the oral cavity, the esophagus, the rectum, and the vagina.
8. Each of the following statements concerning the stratified transitional epithelium is true,
EXCEPT: A – is capable of keratinization; B – consists of the basal, intermediate, and superficial
layers; C – changes the number of its layers, depending on the degree of stretching; D – its
superficial cells are dome-shaped; E – lines the urinary system organs.
9. The criteria of the exocrine gland classification are as follows, EXCEPT: A – branching
of the duct; B – the number of secretory portions; C – the shape of secretory portions; D – contact
of cells with the basement membrane; E – the mode of secretion.
10. Each of the following statements concerning a compound branched tubuloalveolar gland
is true, EXCEPT: A – its duct branches; B – its secretory portions are numerous; C – it has one
secretory portion; D – its secretory portions may be flask-like; E – its secretory portions may be
tube-like.

Directions: one or more of the given statements or completions is/are correct. Choose the
answer: A – if only 1,2, and 3 are correct; B – if only 1 and 3 are correct; C – if only 2 and 4 are
correct; D – if only 4 is correct; E – if all are correct.
11. The following characteristics of the epithelia are true: (1) line internal and cover external
body surfaces (2) are avascular (3) rest on the basement membrane (4) abound in the extracellular
substance

29
 12. The following statements regarding the stratified squamous keratinized epithelium are
true: (1) its basement membrane is sinuous (2) covers the skin (3) its basal layer contains stem
cells (4) its superficial cells are flat and anucleate
13. The stratified squamous keratinized epithelium from the thin skin in comparison with
the same epithelium from the thick skin is characterized by the following: (1) lacks the stratum
lucidum (2) contains the poor-developed stratum granulosum (3) contains the thin stratum
corneum (4) lacks the stratum spinosum
14. The epithelia are specialized for the following functions: (1) mechanical and chemical
protection (2) outer exchange (3) secretion (4) maintenance of homeostasis
15. The epithelium lining the intestine is characterized by the following features: (1) contains
goblet cells (2) is simple columnar (3) has the brush border (4) is specialized for absorption
16. The specializations of epithelial cells on the apical surface are as follows: (1)
hemidesmosomes (2) microvilli (3) nexuses (4) cilia
17. The specializations of epithelial cells on the basal surface are as follows: (1)
hemidesmosomes (2) desmosomes (3) plasma membrane infoldings (4) nexuses
18. The specializations of epithelial cells on the lateral surface are as follows: (1) tight
junctions (2) desmosomes (3) nexuses (4) hemidesmosomes
19. The following statements regarding the apocrine mode of secretion are true: (1) inheres
in some sweat glands (2) inheres in the mammary gland (3) is characterized by releasing the apical
cell cytoplasm with secretory material (4) its mechanism is exocytosis
20. The following statements regarding the merocrine mode of secretion are true: (1) is
characterized by releasing the apical cell cytoplasm with secretory material (2) inheres in
sebaceous glands (3) is characterized by releasing the entire cell with secretory material (4) its
mechanism is exocytosis
21. The following statements regarding the holocrine mode of secretion are true: (1) inheres
in sebaceous glands (2) its mechanism is exocytosis (3) is characterized by releasing the entire cell
with secretory material (4) inheres in sweat glands
22. In embryogenesis the epithelia are derived from: mesoderm (2) ectoderm (3) endoderm
(4) mesenchyme

30
 FIGURES

Fig. 2.1. Structure of various types of epithelial tissue

A – simple squamous epithelium; B – simple cuboidal epithelium; C – simple columnar
epithelium: a – striated epithelium of the small intestine; b – mucous epithelium of the stomach;
D – simple pseudostratified ciliated epithelium; E – stratified squamous nonkeratinized
epithelium; F - stratified squamous keratinized epithelium; G – stratified transitional epithelium:
a – stretched; b – unstretched; 1 – basement membrane; 2 – brush border; 3 – ciliated cells; 4 –
intercalated cells; 5 – basal cells; 6 – goblet cells (unicellular endoepithelial glands); 7 – basal
layer; 8 – intermediate layer; 9 – superficial layer; 10 – stratum spinosum; 11 – stratum
granulosum; 12 – stratum lucidum; 13 – stratum corneum; 14 – blood capillaries in loose
connective tissue.

31
 Fig. 2.2. Classification of the exocrine glands
A – simple nonbranched tubular; B – simple nonbranched alveolar; C – simple branched tubular;
D – simple branched alveolar; E – compound branched tubuloalveolar; 1 – ducts; 2 – secretory
portions.

Fig. 2.3. Modes of secretion

A – merocrine mode: a – by diffusion; b – by exocytosis; B – apocrine mode: a – microapocrine;
b – macroapocrine; C – holocrine mode; 1 – secretory material; 2 – secretory cells accumulated
secretion.

32
 3. BLOOD and LYMPH

Blood, lymph, and all types of connective tissue constitute the group of internal medium
tissues. The tissues of this group are characterized by the following features: they originate from
mesenchyme, display a variety of cells, contain a well-developed extracellular matrix, and
maintain body homeostasis.
Blood is a liquid tissue, which circulates throughout the body in the closed system of vessels.
Its volume in an average adult is approximately 5 liters. The predominant function of blood is
transport. Blood carries gases, nutrients, waste products, hormones, antibodies, and electrolytes
throughout the body. Blood is involved in defence reactions of the body, such as phagocytosis,
immunity, inflammation, and blood clotting. Blood also helps maintain homeostasis in the body,
regulates the osmotic and acid–base balance as well as body temperature.
Blood is composed of formed elements suspended in the fluid intercellular material known
as plasma. The relative volume of the formed elements and plasma is about 40 to 45% and 55 to
60%, respectively. This value is called a hematocrit.
Plasma is the fluid extracellular amorphous ground substance of blood. Plasma contains
water (90%), organic substances: proteins, hormones, glucose, cholesterol (9%), and inorganic
salts (1%). Albumins, globulins, and fibrinogen are the important blood proteins. The plasma
composition is studied in the course of biochemistry.
Formed elements are the major area of interest in histology. They include erythrocytes
(postcellular structures), leukocytes (true cells), and platelets (cell fragments). The number of
formed elements in a certain blood volume is called the blood formula or hemogram. Each cubic
millimetre of blood contains from 4 to 5 million erythrocytes, from 4,000 to 9,000 leukocytes, and
from 180,000 to 320,000 platelets. Each liter of blood contains from 4 to 5×1012 erythrocytes, from
4 to 9×109 leukocytes, and from 180 to 320×109 platelets.
The morphology of the blood formed elements is studied in blood smears. The specimens
are not embedded in paraffin and sectioned. A drop of blood is placed directly on a slide and spread
thinly over the surface of the slide, with the edge of another slide to produce a monolayer of cells.
This preparation is air-dried and stained according to Romanovsky–Giemsa method, with the use
of two dyes: azure II and eosin. On the basis of their appearance after staining, white blood cells
are divided into granulocytes and agranulocytes.
Blood is a readily available specimen that can be withdrawn from a patient without any
complications. Blood chemistry and blood cytology reveal much about the patient’s health. These
examinations are not too difficult, and all patients undergo them at the beginning of treatment.

33
 Erythrocytes
Erythrocytes are the most prevalent cells in peripheral blood: each cubic millimetre of blood
contains approximately 5×106 these formed elements; each liter of blood contains from 4 to 5×1012
erythrocytes. Erythrocytes are produced in the red bone marrow from stem cells; their life span is
approximately 120 days in the circulation. Erythrocyte destruction occurs in the spleen, and,
partially, in the liver.
Erythrocytes are biconcave discs, measure from 7 to 8 µm in diameter, and stain from light
salmon to pink in the blood smear. The biconcave-disc shape considerably enlarges the aggregate
surface area of all erythrocytes. The immense capacity of blood to bind and transport gases is
partially due to the tremendous surface area of erythrocytes. Erythrocytes are extremely elastic
and deform readily when passing through the smallest blood vessels.
Erythrocytes are surrounded by a typical plasma membrane. On the external surface of
plasmalemma, the determinants for the A, B, and O blood groups, as well as the Rh-factor, reside.
The ultrastructure of erythrocytes is not rich: neither organelles nor nuclei are present in the mature
erythrocyte, except for microfilaments of the proteins spectrin and actin. These proteins are
associated with the internal aspect of the cell membrane and serve as cytoskeleton for erythrocytes,
maintaining their morphology. Since erythrocytes do not possess mitochondria, their energy
requirements are met by glycolysis. Nuclei and organelles are lost during erythropoiesis in the
bone marrow to clear erythrocyte cytoplasm for hemoglobin. About one-third of the erythrocyte
mass is hemoglobin (Hb), a protein composed of four globin chains and an iron-containing
porphyrin called heme. When hemoglobin is not present in sufficient amount, either because the
normal amount in each cell is decreased or because the amount in each cell is sufficient but the
cells are reduced in number, the condition clinically shows up as anaemia.
There are several types of normal hemoglobin in humans known as A1, A2 (adult), and F
(fetal) hemoglobin. The types of hemoglobin depend on the amino acid sequences of polypeptide
chains. HbA1 is the predominant type in adult blood. HbF is the principal form of hemoglobin in
the fetus (in adult only 2%), and its persistence in a high percentage in the adult is indicative of
certain forms of anaemia. Additionally, abnormal hemoglobin, such as HbS, may also be present
in the human population. HbS is the result of a genetic alteration (point mutation) that causes
sickling of the red blood cells. This abnormality in shape occurs in sickle cell anaemia.
Peripheral blood contains immature erythrocytes called reticulocytes, which contain
aggregated reticular clusters of ribosomes. Reticulocytes comprise about 1% of all erythrocytes in
the blood. Some hemolytic diseases and bleeding cause an abundance of reticulocytes.
Erythrocytes transport oxygen from pulmonary alveoli to peripheral tissues and carbon
dioxide from peripheral tissues to pulmonary alveoli. In the lungs, a region of high partial pressure

34
of oxygen, hemoglobin preferentially picks up oxygen to form oxyhemoglobin. In the peripheral
tissues, a region of high partial pressure of carbon dioxide, oxyhemoglobin releases its oxygen,
exchanging it for carbon dioxide, to form carbhemoglobin. Carbon monoxide also binds to the
hemoglobin molecule to form carboxyhemoglobin. This bond is much more tenacious than that of
oxygen and may cause the death of an individual. The erythrocyte plasma membrane also takes
part in the transport of amino acids and polypeptides.

Platelets
A cubic millimetre of blood contains from 180,000 to 320,000 platelets; each liter of blood
contains from 180 to 320×109 platelets. Platelets are not cells: they are cell fragments derived from
megakaryocytes in the bone marrow. Megakaryocytes are giant polyploid cells. When platelets
are formed, small bits of cytoplasm are separated from the peripheral regions of the
megakaryocyte. The life span of platelets is less than 2 weeks in circulation, and they are destroyed
in the spleen and in the liver.
Platelets are lenticular in shape and measure 2 to 4 µm in diameter. In blood smears, they
appear as round or oval particles that may be clustered in small or large masses. Platelets are
surrounded by the plasma membrane that has deep surface invaginations connected with a tubular
system, which probably functions in sequestering calcium ions. Platelets have a central
granulomere, which stains purple in blood smears, and a peripheral hyalomere, which stains
faintly. The hyalomere is rich in microfilaments and microtubules. The small bundles of these
cytoskeletal elements lie just beneath the plasmalemma and encircle the periphery of the platelet,
maintaining its morphology. The granulomere is composed of α-granules, dense bodies,
occasional mitochondria, a few lysosomes, and clusters of glycogen particles. The α-granules are
from 300 to 500 nm in diameter, contain fibrinogen, platelet thromboplastin, and the growth factor.
The dense bodies are from 250 to 300 nm in diameter; contain pyrophosphate, ADP, ATP,
serotonin, and calcium ions.
Platelets are important for blood coagulation and clot formation. When the wall of a blood
vessel is cut or broken, platelets adhere to the ruptured end of the vessel. The platelets will
aggregate into a platelet clot at the site of vessel injury and will release, among other substances,
serotonin and thromboplastin. Serotonin, a potent vasoconstrictor, causes the vascular smooth
muscle cells to contract, thereby reducing the local blood flow at the site of injury. Thromboplastin
initiates the series of reactions that leads to the formation of a fibrin clot. Thromboplastin
transforms prothrombin into thrombin, and the latter, in turn, transforms fibrinogen into fibrin.
These reactions require the presence of calcium ions. Platelets aggregate rapidly, adhering to each
other and to fibrin. Masses of aggregated platelets and fibrin are the basis for clots. After the

35
definitive clot has been formed, platelets bring about clot retraction, probably as a function of actin
filaments in the hyalomere. Finally, after the clot has served its function, platelets are presumably
responsible for clot dissolution, probably by releasing lysosomal enzymes into the clot.
Thromboplastin is present in the plasma as well as in the platelets. Platelet-free blood
coagulates, though much more slowly, and lymph, which has no platelets, coagulates too.
Pathologically, the platelets may agglutinate and give rise to colourless intravascular clots
or thrombi. Deficiency of circulating platelets is clinically known as thrombocytopenia and
characterised by slow blood coagulation.

Leukocytes
A cubic millimetre of blood contains from 4,000 to 9,000 leukocytes; each liter of blood
contains from 4 to 9×109 leukocytes. They are true cells, containing nuclei and organelles in their
cytoplasm. Leukocytes are movable, they can move like an amoeba. White blood cells must be
regarded as transitional cells in the blood; they leave the blood through the walls of capillaries and
venules to enter the connective tissue, where they perform their specific functions. Leukocytes
participate in protective reactions of the body, such as immunity and inflammation.
Leukocytes are subdivided into two groups: granulocytes and agranulocytes depending on
the presence or absence of specific granules in their cytoplasm. Granulocytes include neutrophils,
eosinophils, and basophils. Agranulocytes include lymphocytes and monocytes. The percentage
of various leukocytes is called the leukocytic formula: neutrophils constitute from 60 to 75%,
eosinophils constitute from 2 to 5%, basophils constitute from 0.5 to 1%, lymphocytes constitute
from 19 to 37%, and monocytes constitute from 3 to 11%.
Neutrophils are the most common leukocytes in normal human peripheral blood; they
comprise about 60 to 75% of all leukocytes. Neutrophils are round cells 12 to15 µm in diameter.
The nucleus has three to five lobes connected to each other by thin threads of chromatin. The
cytoplasm contains two types of membrane-bounded granules: primary (nonspecific, azurophilic)
and secondary (specific) granules. The azurophilic granules, which appear early in granulopoiesis
and occur in all granulocytes as well as in monocytes and lymphocytes, are lysosomes.
Primary granules comprise about 20% of the granule population, stain with azure, are visible
under LM, and are diagnostic for neutrophils. These granules are lysosomes, which contain various
hydrolytic enzymes that function in phagocytosis. They also contain the enzyme myeloperoxidase,
producing bactericidal molecular oxygen from hydrogen peroxide (H2O2).
Specific granules (secondary) comprise about 80% of the granule population, are small (0.1
to 0.2 µm in diameter), do not stain well, and are not visible under LM. They contain bactericidal
substances, namely, lysozyme, phagocytin, collagenase, and alkaline phosphatase. Specific

36
granules also contain the protein lactoferrin, which binds ferric ions required for bacterial
multiplication.
The neutrophil cytoplasm includes a few mitochondria, a small Golgi apparatus, little
endoplasmic reticulum, and occasional free ribosomes. Glycogen deposits are plentiful. The life
span of neutrophils is less than 1 week.
The neutrophil functions are the phagocytosis and destruction of bacteria; hence, neutrophils
are microphagocytes. Neutrophils form the first line of defence during acute inflammation.
Bacteria can be phagocytosed after opsonization. During opsonization, microorganisms are
coated with immunoglobulin or complement proteins. Neutrophils recognize the immunoglobulin
coating on the opsonized bacterium rather than a component of the bacterial cell wall itself. Thus,
opsonization facilitates the phagocytosis of bacteria by neutrophils.
Neutrophils migrate from the bloodstream between endothelial cells to enter the connective
tissue. Neutrophils first adhere to bacteria and then engulf them in the membrane-bound
phagosome. Phagosomes fuse with secondary granules, and bactericidal substances kill the
bacteria. Then primary granules release their hydrolytic enzymes into phagolysosome, digesting
the microorganisms. Ultimately, neutrophils may kill themselves. The accumulation of dead
neutrophils, macrophages, microorganisms, and tissue fluid constitutes pus.
Immature neutrophils have C-shaped or S-shaped nuclei and are named band neutrophils.
Under normal conditions, no more than 5% of band forms are seen in smears. But if there is a great
need for neutrophils in the body, e.g., in cases of infection and inflammation, band neutrophils
increase in number. This increase is called “a shift in the leukocytic formula to the left”.
Basophils comprise from 0.5 to 1% of all leukocytes. Often, several hundred white blood
cells must be examined in the blood smear before one basophil is found.
Basophils are round cells from 8 to 10 µm in diameter. The basophil has an S-shaped nucleus
that is frequently masked by numerous large specific granules. Primary (azurophilic) granules are
also present. Specific granules are large (0.5 to 1.3 µm in diameter), membrane-bounded, spherical
structures. They contain heparin, histamine, peroxidase, and slow-reacting substance of
anaphylaxis (SRS-A). These granules stain metachromatically with the mixture of dyes used to
stain blood smears. Metachromasia means a change in colour. This is a property of structures to
change the colours of dyes, usually basic dyes. In our case, specific basophilic granules change
the blue colour of azure for cherry. This property is considered to belong to heparin.
The basophilic plasmalemma contains IgE receptors. When these receptors bind the
immunoglobulin complex to specific antigens, the basophils degranulate to produce allergic
reactions and, in extremely severe cases, anaphylactic shock.

37
 Basophils regulate tissue homeostasis and contribute to inflammation by releasing
histamine, heparin, SRS-A, and the eosinophil chemotactic factor.
Eosinophils comprise from 2 to 5% of all leukocytes. Eosinophils are round cells, from 10
to 14 µm in diameter. The eosinophilic nucleus has two or three lobes. The cytoplasm contains
relatively few organelles and many glycogen deposits. The specific granules are plentiful, and a
few azurophilic granules are also present. Specific granules are large, ellipsoidal, membrane-
bounded, and stain reddish orange. The electron micrographs depict an elongated crystalline core
in these granules. The contents of specific granules are lysosomal enzymes, peroxidase, and the
major basic protein. Primary granules are few in number. They contain acid phosphatase,
arylsulfatase, and other hydrolytic enzymes.
Eosinophils inactivate histamine and the slow-reacting substance of anaphylaxis released by
basophils at inflammation sites. Eosinophils are implicated in inactivating and killing parasitic
agents. The major basic protein from crystalloid has a poorly understood antiparasitic function.
Eosinophils are believed to phagocytose antibody–antigen complexes too. Allergic reactions and
parasite invasions cause an increase in the number of eosinophils in the blood.
Lymphocytes comprise from 19 to 37% of all leukocytes; they are the most common
agranulocytes. They are round, small cells, from 8 to 10 µm in diameter. Lymphocytes have a
round deeply staining nucleus that occupies most of the cell volume and a narrow rim of the light
blue cytoplasm at the periphery.
Three groups of lymphocytes can be identified according to size: small, medium, and large.
In the bloodstream most lymphocytes are small-sized (more than 90%) or medium-sized.
The ultrastructure of lymphocytes is not rich: small lymphocytes possess a few
mitochondria, a poorly developed Golgi apparatus, and a rough endoplasmic reticulum, but contain
numerous free ribosomes. A few lysosomes (azurophilic granules) are also present.
There are two types of lymphocytes: T and B lymphocytes. They are classified according to
their specific surface determinants and their site of differentiation. T lymphocytes are thymus-
dependent. They have membrane-bound receptors, unique cell surface proteins (not antibodies)
that appear during cell maturation in the thymus. These surface molecules are required to facilitate
the recognition or binding of T cells to foreign antigens. B lymphocytes are so named, because
they were first recognized as a separate population in the bursa of Fabricius in birds; while human
B lymphocytes develop in the red bone marrow. B lymphocytes have plentiful immunoglobulins
on the external surface of the plasma membrane that function as antigen receptors.
There is a third group of lymphocytes, the so-called null cells, possessing no surface
determinants. The null lymphocytes may include cells that are circulating hemopoietic stem cells
or natural killer cells. These cell types are indistinguishable in blood smears or tissue sections;

38
immunocytochemical staining for different types of receptors on their cell surface must be used to
identify them.
Lymphocytes are the key cells in the immune system. T lymphocytes are primarily
responsible for cell-mediated immunity, whereas B lymphocytes provide humoral immunity.
When lymphocytes first encounter a specific antigen, they are stimulated to undergo several
mitotic divisions and then differentiation into effector cells, i.e., the cells with specific functions.
B lymphocytes differentiate into plasma cells. Plasma cells abound in rER and are involved in
antibody production. T lymphocytes differentiate into cytotoxic T lymphocytes (killer, helper, and
suppressor). Some B and T cells do not undergo differentiation into effector cells but serve as
long-lived memory cells, circulating lymphocytes that can respond more rapidly to their specific
antigen.
Monocytes comprise from 3 to 11% of all leukocytes. Monocytes are the largest of all
circulating cells (from 12 to15 µm in diameter). The monocyte has an acentric, kidney-shaped
nucleus. In contrast to lymphocyte chromatin, monocyte chromatin stains uniformly, revealing a
delicate network. The cytoplasm of monocytes is blue with numerous azurophilic granules. They
are primary lysosomes containing peroxidase, acid phosphatase, and arylsulfatase among other
enzymes.
The life span of monocytes is probably less than 3 days in the bloodstream. Monocytes are
direct precursors of macrophages. Monocytes migrate into connective tissue and differentiate into
macrophages. In the peripheral blood, they are in transit from the bone marrow to the body tissues,
where they will differentiate into the various phagocytes of the mononuclear phagocytic system,
i.e., the connective tissue macrophages (histiocytes), osteoclasts, alveolar macrophages,
perisinusoidal macrophages in the liver (Kupffer cells), and macrophages of the lymph nodes,
spleen, and bone marrow. During inflammation, the monocyte leaves the blood vessel at the site
of inflammation, transforms into a tissue macrophage, and participates in the phagocytosis of
bacteria, other cells, and tissue debris. The monocyte–macrophage also plays an important role in
immune responses by concentrating antigen and presenting modified antigens to lymphocytes to
facilitate antibody production by immunocompetent cells. The monocyte–macrophage can secrete
many substances: interferon, pyrogen, lysozyme, etc.

Lymph
Lymph, like blood, consists of fluid plasma in which various elements are suspended. Red
blood cells and platelets are entirely absent, and granulocytes are few in number, the chief cellular
elements are lymphocytes. The lymph plasma is similar to that of blood, but it is of less fixed
constitution. It carries carbonic acid but very little oxygen.

39
 During digestion, the lymphatics of the intestine become filled with a large amount of fat
globules in chylomicrons. The lymph assumes white colour and is known as chyle. Many of the
fat globules are removed before the lymph reaches the bloodstream.

CONTROL PROBLEMS

1. The patient’s blood test revealed 2.5×1012/L of erythrocytes and 12% of reticulocytes.
What term is used to describe these blood formula changes? What are the possible causes of the
condition?
2. The blood of two patients is being tested. One of the patients lives in a highland area;
the other patient is a lowlander. What differences may be found in the hemograms of patients
living in highlands and lowlands? Explain your answer.
3. A blood smear shows leukocytes with round heterochromatic nuclei and a narrow rim
of the light blue cytoplasm. In accordance with the leukocytic formula they account for about 35%
of all leukocytes. What blood formed elements are described? Does their number correspond to
the physiological norm?
4. The clinical blood test revealed 63% of neutrophils, 9% of eosinophils, 22% of
lymphocytes, and 6% of monocytes. Does the leukocytic formula correspond to the physiological
norm? If it does not, what are the possible causes of the formula alterations?
5. A child blood smear is being examined. The leukocytic formula reveals 30% of
neutrophils and about 60% of lymphocytes. How would you assess this result?

CONTROL TESTS

Directions: each of the following statements contains five suggested completions. Choose
the one that is best in each case.
1. Each of the following statements concerning the erythrocytes is true, EXCEPT: A – are
7-8 µm biconcave discs; B – contain cytoskeletal microfilaments; C – lack nuclei and organelles;
D – are cell fragments; E – contain hemoglobin.
2. Each of the following statements concerning the platelets is true, EXCEPT: A – contain
small dense nuclei; B – are megakaryocyte fragments; C – are surrounded by the plasma
membrane; D – exhibit hyalomere and granulomere; E – contain serotonin and thromboplastin.

40
 3. Each of the following statements concerning the leukocytes is true, EXCEPT: A – are
motile; B – function in loose connective tissue; C – have nuclei and cytoplasm; D – all of them
are capable of phagocytosis; E – take part in defence reactions.
4. Each of the following statements concerning the neutrophils is true, EXCEPT: A – their
nuclei consist of 3-5 lobes; B – contain azurophilic granules; C – contain specific granules; D –
comprise 6-8% of all leukocytes; E – are microphagocytes.
5. The azurophilic (primary) granules occurring in all kinds of leukocytes contain: A –
histamine; B – hydrolytic enzymes; C – heparin; D – bactericidal substances; E – thromboplastin.
6. Each of the following statements concerning the band neutrophils is true, EXCEPT: A –
are mature neutrophils; B – have horseshoe-shaped nuclei; C – comprise about 5% of all
neutrophils; D – their increase in number is called “a shift in the leukocytic formula to left”; E –
they increase in number in inflammatory conditions.
7. Each of the following statements concerning the basophils is true, EXCEPT: A – comprise
0.5-1% of all leukocytes; B – their nuclei are masked by granules; C – their specific granules stain
metachromatically; D – their granules contain heparin and histamine; E – they are macrophage
precursors.
8. Each of the following statements concerning the monocytes is true, EXCEPT: A – are the
largest circulating blood cells; B – have kidney-shaped nuclei; C – contain specific granules; D –
contain azurophilic granules; E – comprise 3-11% of all leukocytes.
9. The following blood cells are direct macrophage precursors: A – lymphocytes; B –
basophils; C – eosinophils; D – monocytes; E – neutrophils.
10. Each of the following statements concerning the lymphocytes is true, EXCEPT: A – are
small, medium-sized, and large; B – comprise 60-70% of all leukocytes; C – have large round
nuclei; D – have narrow rims of the light blue cytoplasm; E – are divided into T and B
lymphocytes.
11. The blood cells responsible for humoral immunity and converting to plasma cells are as
follows: A – T lymphocytes; B – basophils; C – monocytes; D – neutrophils; E – B lymphocytes.
12. The blood cells primarily responsible for cell-mediated immunity are as follows: A – T
lymphocytes; B – eosinophils; C – B lymphocytes; D – basophils; E – neutrophils.

Directions: one or more of the given statements or completions is/are correct. Choose the
answer: A – if only 1,2, and 3 are correct; B – if only 1 and 3 are correct; C – if only 2 and 4 are
correct; D – if only 4 is correct; E – if all are correct.

41
 13. The following statements regarding the reticulocytes are true: (1) are immature red blood
cells (2) contain reticular clusters of ribosomes (3) comprise about 1% of all erythrocytes (4)
increase in number in cases of bleeding or hemolysis
14. The erythrocyte functions are as follows: (1) oxygen transport (2) blood coagulation (3)
carbon dioxide transport (4) phagocytosis of bacteria
15. The platelet functions are as follows: (1) gas transport (2) blood coagulation (3)
phagocytosis of bacteria (4) clotting
16. In embryogenesis blood originates from: (1) mesoderm (2) ectoderm (3) endoderm (4)
mesenchyme
17. The neutrophil functions are as follows: (1) histamine inactivation (2) release of
histamine (3) macrophagocytosis (4) phagocytosis and destruction of bacteria
18. The eosinophil functions are as follows: 1) histamine inactivation (2) release of histamine
(3) inactivation and killing of parasitic agents (4) secretion of immunoglobulins
19. The following statements regarding the eosinophils are true: (1) their nuclei have 2-3
lobes (2) lack primary granules (3) their specific granules contain the crystalline core (4) comprise
20-30% of all leukocytes
20. The pathological processes causing an increase in the number of blood eosinophils are
as follows: (1) bleeding (2) allergic reactions (3) hemolytic diseases (4) parasite invasion
21. Agranulocytes include the following leukocytes: (1) lymphocytes (2) basophils (3)
monocytes (4) eosinophils
22. Granulocytes include the following leukocytes: (1) neutrophils (2) basophils (3)
eosinophils (4) monocytes
23. The key cells of the immune system are the following blood formed elements: (1) T
lymphocytes (2) neutrophils (3) B lymphocytes (4) basophils
24. Lymphocytes are classified into T and B types according to: (1) surface determinants (2)
ultrastructure (3) site of differentiation (4) shape

42
 FIGURES

Fig. 3.1. Ultrastructure of leukocytes and platelets

A – neutrophil; B – eosinophil; C – basophil; D – lymphocyte; E – monocyte; F – platelet; 1 –
nucleus; 2 – rER; 3 – Golgi apparatus; 4 – mitochondria; 5 – specific granules; 6 – primary
granules; 7 – lysosomes; 8 – dense bodies; 9, 10 – tubular system; 11 – microtubules.

43
 4. CONNECTIVE TISSUES

Connective tissues are the tissues of mesenchymal origin. They belong to the group of
internal medium tissues. Connective tissues provide structural and metabolical support for other
tissues and organs throughout the body. Connective tissues mediate the exchange of nutrients,
metabolites and waste products between tissues and blood (internal exchange). Some connective
tissue cells defend organism against pathogens microorganisms because they take part in immune
reactions and phagocytosis. Connective tissues perform repairative function: tissue defects
(wounds) are usually closed by connective tissue scars. Note that the processes of tissue repair are
largely a function of connective tissues. Connective tissues take part in organ morphogenesis
forming capsules of many organs and trabeculae inside the organs.

Classification
Connective tissues are classified on connective tissues proper and skeletogenic tissues
(cartilaginous and bony tissues). The group of connective tissues proper includes fibrous
connective tissues and spesial connective tissues. Fibrous tissues are loose, dense irregular, and
dense regular connective tissues. Special connective tissue group contains adipose tissues (white
and brown), reticular tissue, and embryonic mucoid tissue existing in the umbilical cord.

Extracellular matrix
Connective tissues consist of cells and extracellular matrix.The extracellular matrix includes
the ground substance and fibers: collagen fibers, elastic fibers, and reticular fibers. The
extracellular matrix is important for permeability, spatial organization, and mechanical stability of
connective tissues.
The ground substance is more developed in the loose connective tissue; it is mainly
composed of proteoglycans and hyaluronic acid. Proteoglycans are large molecules. They are
composed of core proteins to which glycosaminoglycans (GAGs) are covalently bound. GAGs are
large polysaccharides, which maintain turgor and determine the diffusion of substances through
extracellular matrix. They can be divided into four groups: (1) hyaluronic acid, the main
component of connective tissue; (2) chondroitin sulfate identified in cartilages, bones, blood
vessels, in the skin, and cornea; (3) dermatan sulfate mostly found in the skin, blood vessels, heart
valves, tendons, and the lung; (4) keratan sulfate and heparan sulfate located in cornea and
cartilage; heparan sulfate is found in the lamina lucida of basement membrane. GAGs have the
following properties: the high negative charge and strongly hydrophilic behavior, with the
exception of hyaluronic acid, covalently bound to proteins to form proteoglycans. Besides GAGs,

44
the ground substance contains glycoproteins. They serve as adhesive molecules between the cells
and extracellular scaffold. There are some types of glycoproteins in connective tissues: fibronectin
(surface glycoprotein of fibroblasts, has affinity to collagen), laminin (a major component of the
basement membranes), entactin (also a component of the basement membranes).
The extracellular matrix includes three types of fibers, two of which collagen fibers and
reticular fibers are composed of fibrillar protein – collagen. The collagens are a large family of
proteins, which can aggregate to produce either filaments, fibers, or meshwork, which then
interacts with other proteins to provide support in the extracellular matrix. There are at least 20
types of collagen polypeptids (α-chains). They form different fibers. For example, type I collagen
forms large bundles of collagen fibers. Their distribution is the skin, dermis, tendons, bone,
ligaments, cornea, and loose connective tissue. Type II collagen forms small bundles of collagen
fibers. Their distribution is hyaline and elastic cartilage, vertebral disks, and vitreous of eye. Type
III collagen forms reticular fibers; they are situated in the blood vessels, bone marrow, spleen,
lymph nodes, lung, and the liver. Type IV collagen forms sheet-like layers in basement membranes
and the lens capsule.
The formation of collagen fibers involves series of events, some of which occur inside the
cell, while other events occur outside the cell. Intracellular events include the uptake of amino
acids (proline, lysine, etc.) by endocytosis, resulting in the production of polypeptide chains in the
rER. A number of modifications of the polypeptide chains occur within the cisternae of rER and
the Golgi complex. The resultant molecules are called procollagen. Then packing of the
procollagen into secretory vesicles occurs inside the cell. These secretory vesicles move to the
plasma membrane and leave the cell by means of exocytosis. Extracellular events include the
formation of tropocollagen and the aggregation of tropocollagen into collagen fibers. Collagen
fibers have a 68-nm banding pattern. This banding pattern is a reflection of the arrangement of
tropocollagen in forming the fibril. Tropocollagen measures about 300 nm long with a head and a
tail. In forming a fibril these molecules become aligned head to tail in overlapping rows with a
gap between the molecules within each row. Thus, collagen fibers consist of bundles of fine
collagen fibrils.
Elastic fibers provide tissues with the ability to respond to stretch and distension. They are
thinner than collagen fibers. Elastic fibers are composed of elastin and microfibrils. The protein
elastin is rich in proline and glycine but is poor in hydroxyproline. Microfibrils are fibrillar
glycoprotein. Elastin is synthesized by the same pathway as collagen.

Connective tissue cells

45
 Connective tissues contain diverse cells, the main of which are cells of the fibroblast family.
The fibroblast is a spindle-shaped or stellate cell. Its nucleus has a regular elliptic contour and
sparse and scattered chromatin. The ultrastructural organization of the fibroblast reflects its
function. The fibroblast contains well-developed rER, on which the precursor polypeptides of
collagen, elastin, proteoglycans, and glycoproteins are synthesized. Besides rER, it contains many
free ribosomes, a well-defined Golgi apparatus, mitochondria, fat droplets, and primary and
secondary lysosomes. Additionally, the bundles of actin microfilaments are prominent; they are
implicated in cellular motility. The function of the fibroblasts is to produce substances of
extracellular matrix.
When the fibroblasts become less active during adult life, their nuclei undergo condensation
and their cytoplasms appear less basophilic, they are then reffered to as fibrocytes. The fibrocyte
is a more elongated cell than the fibroblast, contains decreased amounts of rER and other
organelles.
The fibroblast family includes myofibroblasts. This cell looks like a fibroblast, contains rER,
Golgi complex, and mitochondria. In addition, it contains bundles of longitudinally disposed actin
filaments and dense bodies similar to those observed in smooth muscle cells. The myofibroblast
plays a role in the contraction of wounds and may synthesize collagen fibers.
Macrophages are the next type of connective tissue cells. They are long-lived actively
phagocytic cells, widely distributed throughout the body. They are derived from the blood
monocytes. Monocytes leave the bloodstream and migrate to the tissues to turn into macrophages.
Macrophages and their precursors are assigned to the “mononuclear phagocyte system”. It includes
histiocytes of connective tissues, the liver Kupffer cells, alveolar macrophages of the lung, bone
tissue osteoclasts, microglial cells of the CNS, macrophages of the bone marrow, spleen, lymph
nodes, and serous cavities. The minimal criteria for inclusion in this system are: the derivation
from the red bone marrow, characteristic cell structure, high level of phagocytic activity.
It should be noted that the Russian scientist Elie Mechnikoff was the first who described the
phagocytic cells. More than 100 years ago (1882) he found that vertebrates possessed two types
of cells able to fight invading organisms. These cells are microphages (small eaters) now known
as neutrophils and macrophages (big eaters). The latter include monocytes and phagocytosing
cells.
The main features of macrophages are abundant lysosomes and phagolysosomes, and
numerous folds or fingerlike processes. Moreover macrophage contains a relatively large Golgi
apparatus, mitochondria, sER, and rER, and well-developed cytoskeletal elements. Bundles of
actin-rich microfilaments are involved in adhesion, endocytosis, and movement.

46
 Note that macrophages can secrete a variety of important molecules. Secretory products of
macrophages include enzymes (lysosomal hydrolases, neutral proteinases, lysozyme), coagulation
factors (V, VII, IX, X), molecules that regulate cell activities and cell proliferation (interferon,
interleukin 1, the tumor necrosis factor, the angiogenesis factor). Among other macromolecules,
there are endogenous pyrogens, a fever mediator, and apolipoprotein E playing an important role
in the transport of cholesterol and triglycerides to the liver.
It should be noted that macrophages take part in the immune response. The participation of
macrophages in the immune response involves the processing and presentation of antigens to
lymphocytes. Macrophages “present” antigens on their surface. A macrophage-bound antigen
serves as a trigger in the proliferation of lymphocytes. For this reason this process was termed
antigen-dependent proliferation and differentiation of lymphocytes, resulting in the appearance of
effector cells: T-killers, T-helpers, T-suppressors, and plasma cells.
Plasma cells are antibody-producing cells derived from B-lymphocytes. A plasma cell
contains a well-developed rER and Golgi apparatus, few lysosomes and mitochondria. LM shows
radially arranged clumps of dense heterochromatin adjacent to the nuclear membrane. This
arrangement of chromatin gives the cartwheel appearance to the nucleus. In addition, the well-
developed Golgi region gives the light macula appearance near the nucleus.
Mast cells have been described in 1877 by Paul Erlich and named them "mast" cells (the
German for “feeding”). He observed the granules within these cells and presumed that they
represented stored nutrients; hence, he named them "mast". As a rule, mast cells are located around
blood vessels. They are numerous in the dermis and in the connective tissue of the mucous lining
of the respiratory and digestive tract, connective tissue of the lungs, and the serosal lining of the
peritoneal cavity. They take part in the metabolism of heparin, histamine, and other factors
producing allergic reactions. Mediators produced by human mast cells are histamine (increases
capillary permeability, contracts smooth muscle cells, and stimulates mucus secretion), heparin
(anticoagulant), eosinophil chemotactic factors (attract eosinophils and neutrophils), SRS-A
(contracts smooth muscle cells).
The allergic reaction is known to be mediated by IgE. They are produced by plasma cells in
response to certain antigens called allergens. Mast cells and basophils have a high affinity for IgE.
IgE attaches to mast cells, but the antigen-combining sites of antibody molecules are exposed. If
the antigens re-enter the body again, they react with these sites. The combination of antigen with
IgE triggers the release of mediators (degranulation), producing allergic disease. The extremely
severe allergic reaction may causes anaphylactic shock. More than 100 years ago it was found that
the second injection of an antigen had harmful effect, and indeed could be fatal. In 1893, this effect
was called anaphylaxis (the Greek ana – again; aphylaxis – defenseless). Anaphylaxis is easily

47
demonstrated in guinea pigs. If a guinea pig is injected a particular antigen and then after 10 to 14
days is injected the same antigen, it goes into what is called anaphylactic shock. This is manifested
by difficulty in breathing and a rapid pulse rate; moreover, the animal may die from an inability
to breathe. The reason for respiratory failure is that the smooth muscle cells of small bronchi
become so contracted that their lumen is too narrow to permit an adequate volume of air to enter
and, in particular, to leave the lung. Another effect observed in anaphylaxis is that venules and
capillaries become dilated and leaky so that the plasma escapes from them. As a result, blebs of
plasma may form in the loose connective tissue directly under the epithelium. This phenomenon
was called urticaria.
Reticular cells manufacture reticular fibers. Reticular cells have prosseses and with reticular
fibers constitute the reticular tissue from group of special connective tissue. Reticular tissue forms
the stroma of hemopoietic organs (the bone marrow, spleen, lymph nodes) and takes part in
hemopoiesis, creating the microenvironment for developing blood formed elements.
Pigment cells or melanocytes produce and accumulate melanin. They are located in the
skin connective tissue and also in the epidermis; they defend the skin against ultraviolet.
Melanocytes are only connective tissue cells arised from the neural crest.
Endothelial cells, pericytes, and adventitial cells form capillary wall and belong to
connective tissue. Additionally, all blood leucocytes function in connective tissue, as noted above.
.
Many kinds of cells are widely distributed in loose connective tissue. In its matrix, the
ground substance is abundant and occupies more volume than the fibers. The fibers are thin and
relatively sparse. Loose connective tissue is located under epithelia and around blood vessels. Its
main function is exchange of metabolites between blood and tissues (internal exchange). In dense
connective tissue, the cell population is sparse (usually represented by only one cell type). In its
matrix, there is relatively a small amount of ground substance, collagen fibers are predominant
and arranged in thick bundles. If the bundles of fibers are oriented in various directions the tissue
is irregular (the reticular layer of the skin). If the bundles of fibers are oriented in parallel rows to
each other the tissue is regular (tendons, ligaments). The main function of dense connective tissues
is mechanical support.

Adipose tissues
The adipose tissue is divided into two types: white and brown. White adipose tissue is
composed of large fat cells or adipocytes. Each cell contains one flattened nucleus and a large
single lipid droplet. If hematoxylin and eosin are used for staining, a hole will be seen instead of

48
a lipid droplet. If special staining is used, the lipid droplet stains orange (Sudan III) or black (Sudan
IV).
It is noteworthy that fat cells are organized into groups called lobules. The lobules of fat
cells are separated by partitions of loose connective tissue; they have been called septa. This
connective tissue conducts blood vessels and nerves into adipose tissue. The white adipose tissue
is present in the following fatty areas: under the skin (hypodermis), in the mammary glands and
gluteal region (females), around the kidney and blood vessels, in the mesentery, omentum, and the
abdominal wall.
Note that the white adipose tissue can be divided into two functional kinds: storage adipose
tissue with fat readily available for energy production (adipose tissue of the hypodermis,
mesenteries, omenta, retroperitoneum), and structural adipose tissue with the role of an elastic pad,
mechanical support and protection (adipose tissue in the orbits of the eye, articulations, palms,
soles, cheeks, etc.). The structural adipose tissue remains practically unchanged during fasting.
White adipocytes have membrame receptors for hormones (insulin, glucagon, and adrenalin),
which regulate cell lipid metabolism. The white adipose tissue performs many functions: fat
storage, thermoisolation, binding of water, elastic pad, mechanical support, and replacement of
involuted organs (thymus, red bone marrow).
Brown adipose tissue appears brown, because its cells are rich in cytochrome pigments. This
tissue is highly vascularized: every cell is surrounded by 3 to 5 blood capillaries. The brown
adipose tissue has lobular organization. It is formed of small polygonal cells called brown
adipocytes.The adipocytes nucleus is located in the cell center, the cytoplasm is filled with many
lipid droplets and numerous mitochondria. The peculiarity of the metabolism of these cells is to
produce the heat energy. In hibernating animals and laboratory rodents, the brown adipose tissue
is found around the thorax, near the thyroid gland and kidney. In humans, this tissue is present in
large amounts in newborns. It is located in the axillae, at the nape, in the posterior triangle of the
neck, in the vicinity of the thyroid gland, carotid arteries, and renal hilus.

CONTROL PROBLEMS

1. Two types of connective tissues are visible in a histological section. One of them
contains relatively fewer fibers but a lot of the amorphous ground substance. The matrix of the
other tissue is rich in collagen fiber bundles arranged parallel to each other. What types of
connective tissue are represented in the slide?

49
 2. There are collagen, elastic, and reticular fibers in the connective tissue matrix. What
types of fibers stain with Eosin? What histological methods are employed to reveal the other types
of fibers?
3. A sting of a bloodsucking insect results in the development of swelling. Explain the
phenomenon if it is known that the insect saliva contains the enzyme hyaluronidase.
4. Vitamin C deficiency results in scurvy characterized by bleeding gums, loose teeth, and
poor bone growth. Explain the mechanism of vitamin C participation in the development of the
symptoms.
5. The histological slides stained with Sudan to reveal lipids show two types of adipose
cells. The first type is round cells with flattened nuclei; the cytoplasm appears as a thin rim around
a large lipid droplet. The second type is polyhedral cells with round nuclei and a cytoplasm with
abundant small fat droplets. Specify the cells and suggest their functions.
6. Immune reactions are characterized by increased blood levels of immunoglobulins
(antibodies). What connective tissue cells produce immune proteins? What is the origin of these
cells?
7. Patients with type I diabetes quickly lose their weight. Explain the pathogenesis of the
symptom on the basis of the effect of insulin on the white adipose cells.
8. Melanocytes (pigment cells) are found in both the skin epidermis and dermis. Why is
the tumor arising from the cells (melanoma) classified as the nervous tissue tumor?

CONTROL TESTS

Directions: each of the following statements contains five suggested completions. Choose
the one that is best in each case.
1. The connective tissue functions are as follows, EXCEPT: A – exchange between a body
and the environment; B – immune and phagocytic defence; C – exchange between blood and
tissues; D – support; E – repair.
2. Each of the following statements concerning the loose connective tissue is true, EXCEPT:
A – contains relatively fewer fibres, but more amorphous ground substance; B – its fibres are
arranged in parallel bundles; C – contains various cells; D – is located under epithelia and around
blood vessels; E – is mainly specialized for the transport function.
3. Each of the following statements concerning the fibroblasts is true, EXCEPT: A – include
fibroclasts, myofibroblasts, and fibrocytes; B – are predominant cells in connective tissues; C –
contain granules with heparin and histamine; D – contain well-developed rER and Golgi apparatus;
E – manufacture the extracellular matrix precursors.

50
 4. Each of the following statements concerning the macrophages is true, EXCEPT: A – arise
from blood monocytes; B – contain numerous primary and secondary lysosomes; C – belong to
the mononuclear phagocyte system; D – have variable shape, because they move in connective
tissues; E – manufacture antibodies.
5. Each of the following statements concerning the mast cells is true, EXCEPT: A – abound
in metachromatic granules; B – contain heparin and histamine; C – are located near the blood
vessels; D – manufacture collagen precursors; E – are involved in inflammatory and anaphylactic
reactions.
6. Each of the following statements concerning the plasma cells is true, EXCEPT: A –
manufacture collagen fibres; B – arise from activated B lymphocytes; C – are ovoid in shape; D –
have acentric nuclei; E – contain a lot of rER.
7. Each of the following statements concerning the white adipose cells is true, EXCEPT: A
– have a thin rim of cytoplasm; B – contain numerous mitochondria; C – possess flattened nuclei;
D – contain a single fat drop; E – are responsible for the fat storage.
8. Each of the following statements concerning the brown adipose cells is true, EXCEPT: A
– generate heat; B – contain numerous mitochondria; C – have round active nuclei; D – contain
many small fat droplets; E – their narrow cytoplasm possesses few organelles.
9. Each of the following statements concerning the reticular connective tissue is true,
EXCEPT: A – forms the stroma of hemopoietic organs; B – consists of reticular cells and reticular
fibres; C – is the embryonic connective tissue; D – its fibres are argyrophilic; E – creates the
microenvironment for hemopoietic cells.
10. Each of the following statements concerning the mucous connective tissue is true,
EXCEPT: A – is the embryonic connective tissue; B – is located in the umbilical cord; C – contains
a jelly-like matrix; D – generates heat in infants; E – is specialized for amortization.
11. In embryogenesis the all types of connective tissue originate from: A – neural tube; B –
mesenchyme; C – ectoderm; D – endoderm; E – notochord.
12. Specialized connective tissues are as follows, EXCEPT: A – mucous tissue; B – reticular
tissue; C – dense regular tissue; D – white adipose tissue; E – brown adipose tissue.

Directions: one or more of the given statements or completions is/are correct. Choose the
answer: A – if only 1,2, and 3 are correct; B – if only 1 and 3 are correct; C – if only 2 and 4 are
correct; D – if only 4 is correct; E – if all are correct.
13. The connective tissue extracellular matrix is composed of: (1) collagen fibres (2)
amorphous ground substance (3) elastic fibres (4) blood vessels

51
 14. The following statements regarding the collagen fibres are true: (1) are composed of
tropocollagen (2) have great tensile strength (3) are eosinophilic (4) electron micrographs reveal
their cross-banding pattern
15. The following statements regarding the elastic fibres are true: (1) require special staining
to be observed by light microscopy (2) are coiled and branching (3) are able to stretch (4) consist
of procollagen
16. The following statements regarding the reticular fibres are true: (1) mostly consist of
type III collagen (2) are stained by silver impregnation (3) are located in the stroma of hemopoietic
organs (4) are secreted by reticular cells
17. The amorphous ground substance of the loose connective tissue matrix includes: (1)
glycosaminoglycans (2) proteoglycans (3) glycoproteins (4) water
18. The following statements regarding the dense irregular connective tissue are true: (1)
contains more fibres but less amorphous ground substance (2) its fibres are oriented in different
directions (3) is located in the dermal reticular layer (4) forms organ capsules
19. The following statements regarding the dense regular connective tissue are true: (1)
contains more fibres but less amorphous ground substance (2) its fibres are arranged in parallel
bundles (3) forms tendons and ligaments (4) contains various cells
20. The macrophages are specialized for the following functions: (1) phagocytosis of
bacteria, foreign particles, and cell debris (2) presentation of antigens to lymphocytes (3) release
of interleukin, pyrogen, and other substances (4) manufacture of collagen fibres
21. The following statements regarding the plasma cells are true: (1) have basophilic
cytoplasm (2) light areas with Golgi apparatus are adjacent to their nuclei (3) manufacture
antibodies (4) release histamine and heparin
22. The connective tissue cells that make up the capillary wall are as follows: (1) pericytes
(2) mast cells (3) endothelial cells (4) reticular cells
23. The following statements regarding the brown adipose tissue are true: (1) forms the
stroma of hemopoietic organs (2) is found in infants as well as in hibernating animals (3) is the
embryonic connective tissue (4) has a rich vascular supply
24. The following statements regarding the pigment cells are true: (1) are responsible for the
synthesis and storage of melanin (2) arise from the neural crest (3) cluster in the dermis of coloured
skin areas (4) are involved in immune reactions

52
 FIGURES

Fig. 4.1. Connective tissue cells

A – fibroblast; B – macrophage; C – plasma cell; D – mast cell; E – capillary cells; 1 – nucleus;
2– rER; 3 – mitochondria; 4 – centriole; 5 – lysosome; 6 – Golgi apparatus; 7 – microvilli; 8 –
phagosome; 9 – metachromatic granules; 10 – degranulation; 11 – pericyte; 12 – endothelial cell;
13 – adventitial cell.

Fig. 4.2. Connective tissue cells (continuation)

53
F – white adipose cells; G – brown adipose cells; 1 – nucleus; 3 – mitochondria; 14 – lipid droplets.

54
 5. SKELETOGENIC TISSUES: CARTILAGE AND BONE TISSUES

Cartilage tissues
There are three types of cartilage tissues: hyaline, elastic, and fibrocartilage tissues.
Hyaline cartilage tissue is the most common cartilaginous tissue in the body. It is located
is the nose, larynx, trachea, and bronchi. It forms the cartilaginous parts of the ribs. It covers the
articular surfaces of bones and can be found at the epiphyseal plates in the bones of growing
children. Hyaline cartilage tissue forms the skeleton of the fetus. The matrix of hyaline tissue
appears glassy in the living state; the name hyaline is derived from the Greek “hyalos” meaning
“glassy”.
Hyaline cartilage tissue has a unique matrix and characteristic cells. The cartilage matrix is
firm but pliable. It is composed of amorphous ground substance, type II collagen fibrils, and elastic
fibrils. Collagen fibrils are prevalent and constitute about 40% of the total matrix, but they are not
discernible in histologic sections, because the fibrils are very fine and have the same refractive
index as the amorphous substance. The amorphous ground substance is rich in proteoglycans,
hyaluronic acid, chondroitin sulphates, and keratan sulphate. The matrix adjacent to chondrocytes
(the capsular matrix) is poor in collagen, but rich in glycosaminoglycans, and stains deeply
basophilic. The cartilage matrix is highly hydrated. Much of this water is tightly bound to the
proteoglycan aggregates, which explains the resilience of cartilage. Some of the water is loosely
bound, providing high matrix permeability.
Cartilage tissues lack blood vessels. Nutrients, waste materials, and hormones pass to and
from the cells via diffusion, except high molecular weight proteins, e.g., immunoglobulins.
Therefore, cartilage transplantation in humans is successful: the engraftment is easy and the
homografts are long-lasting. With age, the matrix composition changes, its permeability may
become worse. As a result, the cells hypertrophy and die, and the matrix becomes calcified.
Chondrogenic cells differentiate into chondroblasts. Chondroblasts secrete extracellular
matrix and are capable of mitotic division. Chondroblasts surrounded by their secretion are called
chondrocytes. Condrocytes are mature cartilaginous cells. They are proliferous cells and retain
secretory activity. Located superficially, young chondrocytes are ovoid and positioned so that their
longitudinal axes lie parallel to the cartilage surface. Located deeper, they are more spherical and
arranged in groups of four to eight cells, the so-called isogenous groups. The isogenous group cells
result from successive mitotic divisions of one chondrocyte and cannot be dispersed in the dense
matrix.
Chondroblasts and chondrocytes have the fine structure typical of cells that synthesize large
amounts of proteins and polysaccharides to be secreted from the cells. The electron micrographs

55
display an abundant rough endoplasmic reticulum, an extensive Golgi apparatus, and numerous
mitochondria. Chondrocytes contain many cytoplasmic vacuoles with collagen precursors and
glycoproteins. Chondrocytes also have large amounts of nutrients such as lipid droplets and
glycogen deposits, because they exist so far from blood vessels.
Cartilage tissues form organs, the cartilages. Each cartilage is subdivided into young
cartilage and mature cartilage, as well as is surrounded by the perichondrium (except at articular
surfaces). The young cartilage is the periphery of the organ containing young chondrocytes. The
mature cartilage occupies the center of the organ and contains isogenous groups. The
perichondrium is connective tissue envelope composed of an outer fibrous layer and an inner
cellular layer. The fibrous layer contains type I collagen and elastic fibrils, fibroblasts, and blood
vessels. The cellular layer contains the chondrogenic cells and chondroblasts. The perichondrium
provides cartilage with nutrients and takes part in cartilage growth.
There are two mechanisms of cartilage growth, the so-called appositional and interstitional
growth. The appositional growth occurs from chondrogenic cells differentiating into
chondroblasts, forming a new layer of matrix around the periphery of the existing cartilage. The
interstitial growth is the process that forms new cartilage within the cartilage mass by chondrocyte
divisions and chondrocyte matrix secretion.
Elastic cartilage tissue is found in cartilades of the ear, the auditory tube, the epiglottis, and
parts of the larynx. The matrix of elastic cartilage tissue is identical to that of hyaline one, but it
contains a rich network of elastic fibers that imparts to it a yellowish colour. Under LM, untreated
elastic cartilage appears similar to hyaline cartilage. However, special stains reveal elastic fibers
composed of elastin. Elastic cartilage possesses a perichondrium with chondroblasts, its
chondrocytes form isogenous groups. It does not degenerate as readily as hyaline cartilage: the
matrix of elastic cartilage never undergoes calcification.
Fibrocartilage tissue exists in the annulus fibrosus of intervertebral disks, the pubic
symphysis, in the menisci of the knee joint, and in the junctions between large tendons and the
articular cartilage in large joints. It does not occur alone, it serves as a transition between hyaline
cartilage and connective tissue. The fibrocartilage extracellular matrix contains fewer
glycosaminoglycans and by far more collagen fibers than hyaline cartilage tissue. Collagen fibers
are arranged in parallel bundles, like a tendon. The fibrocartilage chondrocytes lie in longitudinally
disposed columns between collagen bundles.

56
 Bone tissues and bones
Bone tissue consists of mineralized matrix and characteristic cells. Bone tissue exists in
organs, bones. Bone as an organ includes bone tissue, periosteum, endosteum, blood vessels,
articular cartilages, and bone marrow, both red and yellow.
The bone serves as a support for the body and provides for attachment of muscles. It also
protects the central nervous system and vital organs and contains bone marrow, which functions
in hemopoiesis. The bone is an important calcium reserve, containing about 99% of the body’s
calcium, an element essential for muscle contraction, enzymatic activities, transmission of nerve
impulses, cell adhesion, and blood coagulation.
The bone tissue matrix contains organic and inorganic portions. The organic portion is
composed of about 95% type I collagen and amorphous ground substance. The latter contains
chondroitin sulphates, keratan sulphate, and osteomucoid, e.g., protein differing from collagen.
The inorganic portion represents about 50% of the dry weight of the matrix and is composed of
calcium, phosphorus, bicarbonate, citrate, magnesium, potassium, and sodium. The extracellular
matrix also contains hydroxyapatite crystals [Ca10(PO4)6(OH)2], which are formed of calcium and
phosphorus.
Both bone matrix components work synergistically to produce the extraordinary tensile
strength and flexibility of bone. If the organic matrix is removed from a bone, the remaining
mineralized bone is extremely brittle. If the mineral component of the bone is removed by
prolonged exposure to acid, the bone becomes rubbery.
The mineralized bone matrix prevents free diffusion; therefore, in contrast to cartilaginous
tissues, bone tissue is not avascular. The blood vessels entering the periosteum and endosteum
penetrate the bone matrix via Volkmann’s canals, which run perpendicularly to the haversian
canals that they interconnect.
The periosteum is a noncalcified connective tissue layer covering bone on its external
surfaces, except articular regions. It is composed of an outer fibrous and an inner cellular layers.
The outer layer consists mostly of a dense connective tissue containing blood vessels; the inner
layer is more cellular and contains osteogenic cells and osteoblasts. Periosteum collagen fibers,
the so-called Sharpey’s fibers, penetrate the bone matrix and attach the periosteum to bone. The
periosteum is a source of osteogenic cells and provides bone with blood supply.
The endosteum is a specialized connective tissue lining the marrow cavities of bone. It
contains the same elements as the periosteum but is thinner. The endosteum also supplies
osteogenic cells and osteoblasts for growth and repair.

57
 Osteogenic cells are derived from embryonic mesenchyme. Osteogenic cells are spindle-
shaped cells in the periosteum and endosteum that are capable of differentiating into osteoblasts.
A low O2 tension may cause these cells to be transformed into chondrogenic cells.
Osteoblasts are derived from osteogenic cells. Osteoblasts secrete the organic portion of the
bone matrix and take part in matrix mineralization. On the bone surface, osteoblasts may resemble
a cuboidal layer as they begin to secrete the organic matrix. Later, as the matrix synthesis declines,
they assume a flattened morphology. Osteoblasts contain cytoplasmic processes that bring them
into close contact with other osteoblasts and osteocytes. The electron micrographs reveal in their
cytoplasm a well-developed rough endoplasmic reticulum, Golgi apparatus, and numerous
granules containing the precursors of glycosaminoglycans. The matrix secretion entraps the
osteoblast in a lacuna with its cytoplasmic processes. Ceasing its secretory function, it changes its
morphology and becomes an osteocyte.
Osteocytes are derived from osteoblasts. These mature bone cells housed in their own
lacunae maintain communication with each other via gap junctions between their narrow
cytoplasmic processes extending through the canaliculi. The nutrients and metabolites within
canaliculi nourish and maintain these cells. The electron micrographs display, in contrast to
osteoblasts, increased amounts of condensed nuclear chromatin, reduced amounts of rough
endoplasmic reticulum, and a small Golgi apparatus in osteocytes. Osteocytes do not manufacture
the bone matrix, but they maintain bone homeostasis.
Osteoclasts are multinucleated giant cells, possessing as many as 50 nuclei. They are
derived from the blood monocytes and responsible for bone resorption and remodelling. The
osteoclasts are located in their own lacunae, e.g., depressions located on the bone surface. These
lacunae result from the osteolytic activities of osteoclasts. The electron micrographs display a
ruffled border in osteoclasts. The ruffled border is composed of plasma membrane finger-like
evaginations along the lacunar surface. Active bone resorption occurs here. The function of
osteoclasts is osteolysis, effected by creating an acidic environment that decalcifies the surface
bone layer. Acid hydrolases, collagenases, and proteolytic enzymes then degrade decalcified
material, and the cell resorbs the organic and inorganic residues of the bone matrix.
There are two types of bone tissues: coarsely bundled bone tissue (primary, immature) and
lamellar bone tissue (secondary, mature).
The coarsely bundled bone tissue matrix contains thick bundles of collagen fibrils, which
lie in different directions with osteocytes between them. This type of bone tissue occurs mostly in
embryogenesis. Later, the immature bone tissue is remodelled and replaced by secondary bone
tissue, except in certain places such as the tooth sockets, the skull suture lines, and the insertion
sites of tendons.

58
 The lamellar bone tissue replaces primary bone. Its collagen is arranged parallel to each
other in lamellae (from 3 to 7µm thick). The osteocytes in lacunae are located between the lamellae
and occasionally within them.
The lamellar bone tissue forms two types of bone substance: spongy and compact bone
substance. The spongy substance is found at the epiphyses and within the diaphyses of long bones,
in flat and short bones. The lamellae of spongy substance are irregularly arranged. Spongy bone
is filled with spaces that are interconnected. These spaces in long bones often contain bone
marrow, which may be either red (containing hemopoietic cells) or yellow (containing primarily
fat). The compact substance is found at the diaphyses of long bones, in flat and short bones. The
compact bone matrix is arranged in osteons or haversian systems. The osteon is cylindrical and
composed of 4 to 20 concentric lamellae, surrounding a Haversian canal that transmits blood
vessels, nerves, and some loose connective tissue with osteoblasts and osteoclasts.
In the diaphyses of long bones, lamellae exhibit a special arrangement: there are outer
circumferential lamellae and inner circumferential lamellae, as well as typical osteons, and
interstitial lamellae between osteons. The perforating canals (Volkmann’s) are the communication
channels between the haversian systems, the periosteum, and the marrow cavity.

Osteogenesis - bone histogenesis or bone development

The bone tissue is derived from embryonic mesenchyme and develops in one of two ways:
intramembranous bone formation involves development within a layer of condensed mesenchyme;
and endochondral bone formation occurs via a cartilage model that is replaced by bone tissue.
Bone remodelling continues throughout life.
Intramembranous bone formation (direct osteogenesis) is typical of flat bone
development. It begins when mesenchymal cells condense to form a primary ossification centre,
from which osteoblasts differentiate and begin to secrete the matrix. The osteoblasts are trapped
by their own matrix and become osteocytes. The osteoblasts and bone matrix with entrapped
osteocytes constitutes a bone trabecula. Bone trabeculae calcify and join together. The primary
bone forms first and is later replaced by the secondary bone. Blood vessels invade the area at the
time when undifferentiated mesenchymal cells give rise to the bone marrow cells.
Endochondral bone formation (indirect osteogenesis) is typical of long bone development.
It begins in the hyaline cartilage model. A primary centre of ossification occurs at the midriff of
the diaphysis of the cartilage model. The vascularization of the perichondrium at the midriff of the
cartilage model causes the transformation of chondrogenic cells into osteogenic cells, which in
turn differentiate into osteoblasts. The osteoblasts elaborate the bone matrix on the cartilage core
beneath the perichondrium, now known as the periosteum. The new bone appears as the

59
subperiosteal collar (or cuff), is named the perichondral bone, and is formed similar to
intramembranous bone formation. In histologic sections, the perichondral bone matrix stains
acidophilic.
The chondrocytes within the cartilage model hypertrophy and begin to degenerate, the
cartilaginous matrix undergoes calcification. The periosteal bud – osteogenic cells, osteoclasts,
and blood vessels from the bone collar – penetrates the cartilage model. Osteoclasts begin to resorb
the mineralized cartilage matrix, and osteoblasts elaborate and calcify the bone matrix, forming a
calcified cartilage–calcified bone complex, the so-called endochondral bone. In histologic
sections, the calcified cartilage stains basophilic, while the calcified bone stains acidophilic.
The bone collar becomes thicker and elongates toward the epiphysis. The osteoclasts resorb
the endochondral bone, establishing the primitive marrow cavity. The processes recur and spread
toward the epiphysis, where the secondary centre of ossification occurs. The sequence of events is
similar, but not identical, to that occurring at the primary centre. The ossification begins when
osteogenic cells from the blood and adjacent periosteum invade the epiphysis and differentiate into
osteoblasts that elaborate the bone matrix to replace the disintegrating cartilage.
The remaining cartilage now possesses two areas: an articular surface that will remain
through life and the epiphyseal plate that will be replaced by bone when growth ceases. The
epiphyseal plate continues to grow by adding new cartilage at the epiphyseal end while it is being
replaced by bone at the diaphyseal end. The diaphyseal bone becomes continuous with epiphyseal
bone at about 20 years of age, as the epiphyseal plate ceases to grow and is replaced. In histologic
sections, the epiphyseal plate appears as a zone of cell proliferation: rapid mitotic divisions give
rise to rows of isogenous cell groups. This zone is called the columnar cartilage.

Influence on bones
Nutrition greatly affects bone development. Low-protein diets result in a deficiency of amino
acids essential for collagen synthesis by osteoblasts. Lack of calcium, either from a low intake or
inadequate absorption by the small intestine (due to lack of vitamin D) results in poorly calcified
bone, which leads to rickets in children and osteomalacia in adults.
Vitamin D is also necessary for ossification, and hypervitaminosis D causes bone resorption.
Vitamin A deficiency inhibits bone formation and growth, while excessive amounts of vitamin A
accelerate the ossification of the epiphyseal plates. In either case, smaller stature results. Vitamin
C is necessary for collagen formation; its deficiency results in scurvy, characterized by poor bone
growth and inadequate repair after fractures.
Parathyroid hormone activates osteoclasts that resorb and release calcium, thus elevating the
blood calcium levels. Calciotonin inhibits matrix resorption and prevents the release of calcium,

60
thus decreasing the blood calcium levels. The pituitary growth hormone stimulates epiphyseal
cartilage growth, so that its excess produces a giant, while its lack produces a dwarf. Acromegaly,
a disease characterized by very thick long bones in adults, results from an excess of the growth
hormone. Sex hormones affect bone growth by influencing epiphyseal ossification. In excess, a
small stature develops; in deficiency, a tall stature results.

CONTROL PROBLEMS

1. There is a histological section of the hyaline cartilage stained with Hematoxylin and
Eosin. The section periphery is pink and subdivided into two layers: the outer layer is dense, the
inner layer is looser. What part of cartilage is described? What tissues does it consist of? What is
the layer where the chondrogenic cells and chondroblasts are located?
2. There are three histological slides of different cartilage types. Two of them stain with
Hematoxylin and Eosin, the third slide stains with Orcein. Which of the cartilage matrix fibrils do
these methods detect? Identify the cartilage type in which the fibrils are revealed?
3. There are two slides of bone tissues. The first slide demonstrates bundles of collagen
fibrils in the bone matrix. The second slide reveals collagen arranged in lamellae. Specify the bone
tissue types and indicate their localization.
4. An electron micrograph of the bone tissue shows two cells. One of them contains plenty
of rough endoplasmic reticulum and is surrounded by collagen fibrils. The other bone cell
possesses narrow processes extending through the mineralized matrix; the cytoplasmic organelles
are sparse. Specify the cells and suggest their functions.
5. An electron micrograph of bone tissue reveals a multinucleated giant cell located in a
depression of the bone surface. The cell plasmalemma forms a ruffled border, and the cytoplasm
contains numerous lysosomes. Specify the bone cell and determine its functions. Name the blood
formed element the bone cell originated from. What body system does the bone cell belong to?
6. The histological slide of the developing tubular bone reveals two regions of ossification.
In one of them, the bone matrix stains strongly eosinophilic. In the other region of ossification, the
bone matrix includes basophilic areas. Specify the regions of ossification and explain why they
look differently.

CONTROL TESTS

Directions: each of the following statements contains five suggested completions. Choose
the one that is best in each case.

61
 1. Each of the following statements concerning the hyaline cartilage location is true,
EXCEPT: A – covers articular surfaces of bones; B – forms the fetal skeleton; C – constitutes bone
epiphyseal plates; D – forms the auditory tube; E – is found in the respiratory tract.
2. Each of the following statements concerning the hyaline cartilage matrix is true, EXCEPT:
A – is firm and pliable; B – abounds in elastic fibres; C – contains type II collagen fibrils; D – is
highly permeable; E – is impermeable for immunoglobulins.
3. Each of the following statements concerning the perichondrium is true, EXCEPT: A –
provides nutrition for cartilages; B – its outer layer is fibrous; C – its inner layer is cellular; D – is
avascular; E – provides appositional growth of cartilages.
4. Each of the following statements regarding the chondroblasts is true, EXCEPT: A –
originate from chondrogenic cells; B – are located in the inner perichondrium layer; C – are
arranged in isogenous groups; D – synthesize the cartilage matrix; E – are capable of division.
5. Each of the following statements regarding the chondrocytes is true, EXCEPT: A – arise
from chondroblasts; B – can form isogenous groups; C – are capable of division; D – take part in
the cartilage matrix synthesis; E – are located in the inner perichondrium layer.
6. Each of the following statements concerning the periosteum is true, EXCEPT: A –
contains osteocytes; B – is composed of fibrous and cellular layers; C – contains osteogenic cells
and osteoblasts; D – provides blood supply to bones; E – provides growth and repair of bones.
7. Each of the following statements concerning the osteoblasts is true, EXCEPT: A – are
derived from osteogenic cells; B – are located in the inner periosteum layer; C – produce the
organic portion of bone matrix; D – possess the ruffled border; E – contain well-developed rER
and Golgi apparatus.
8. Each of the following statements concerning the osteocytes is true, EXCEPT: A – produce
the organic portion of bone matrix; B – differentiate from osteoblasts; C – house in their own
lacunae; D – possess narrow cytoplasmic processes; E – maintain bone homeostasis;
9. Each of the following statements concerning the osteoclasts is true, EXCEPT: A – are
multinucleated giant cells; B – are located near the blood vessels; C – have the ruffled border; D
– possess osteolytic activity; E – are derived from osteocytes.
10. Each of the following statements concerning the coarsely bundled bone tissue is true,
EXCEPT: A – is a primary immature bone tissue; B – contains thick bundles of collagen fibrils;
C – occurs mostly in adult body; D – is replaced by lamellar bone tissue; E – is located near the
skull sutures, in tooth sockets, and at insertion sites of tendons.
11. Each of the following statements concerning the osteon is true, EXCEPT: A – is a
morphostructural unit of the compact bone substance; B – is composed of 4-20 concentric

62
lamellae; C – contains a central canal; D – is avascular; E – contains osteocytes in lacunae between
lamellae.
12. The bone tissue embryonic origin is: A – notochord; B – mesenchyme; C – ectoderm; D
– endoderm; E – neural crest.
13. In contrast to the perichondral bone, the endochondral bone contains: A – residues of
calcified cartilage; B – bone matrix; C – osteoblasts; D – osteocytes; E – osteoclasts.
14. The epiphyseal plate function is: A – formation of the perichondral collar; B – formation
of periosteal buds; C – formation of the cartilage model; D – calcification of the bone matrix; E –
bone growth.

Directions: one or more of the given statements or completions is/are correct. Choose the
answer: A – if only 1,2, and 3 are correct; B – if only 1 and 3 are correct; C – if only 2 and 4 are
correct; D – if only 4 is correct; E – if all are correct.
15. The following characteristics of the perichondrium are true: (1) surrounds cartilages,
except articular surfaces (2) consists of two layers (3) is a connective tissue envelope of cartilages
(4) contains blood vessels, chondrogenic cells, and chondroblasts
16. The following characteristics of the hyaline cartilage are true: (1) lacks blood vessels (2)
contains zones of young cartilage and mature cartilage (3) undergoes age-related regressive
changes (4) its matrix can become mineralized
17. The cartilages grow: (1) not at all (2) only interstitially (3) only appositionally (4)
interstitially and appositionally
18. The following statements regarding the elastic cartilage are true: (1) is found in the
auricle, the auditory tube, and the epiglottis (2) abounds in elastic fibres (3) never undergoes
calcification (4) lacks the perichondrium
19. The following statements regarding the fibrocartilage are true: (1) its collagen fibres are
arranged in parallel bundles (2) exists in intervertabral disks (3) is found at the junction sites
between tendons and articular cartilage (4) its chondrocytes lie between collagen bundles
20. The following statements regarding the bone matrix are true: (1) prevents free diffusion
(2) contains type I collagen (3) contains calcium, phosphorus, and bicarbonate (4) abounds in
elastic fibres
21. The following statements regarding the lamellar bone tissue are true: (1) replaces primary
bone (2) is immature bone tissue (3) forms spongy and compact bone substance (4) its collagen
fibres are arranged in coarse bundles

63
 22. The following statements regarding the bone spongy substance are true: (1) is found in
the epiphysises of long bones (2) its lamellae are irregularly arranged (3) contains bone marrow
(4) contains osteons
23. The following statements regarding the bone compact substance are true: (1) is found in
the diaphysis of long bones, in flat and short bones (2) is avascular (3) its lamellae are arranged in
osteons (4) contains bone marrow
24. Haversian canal contains: (1) blood vessels (2) nerves (3) some loose connective tissue
4) few osteoblasts and osteoclasts
25. The following statements regarding the intramembranous bone formation are true: 1) is
direct bone formation (2) is characteristic of long bone development (3) is characteristic of flat
bone development (4) is indirect bone formation
26. The endochondral bone formation begins in: (1) the epiphysis of the cartilage model (2)
epiphyseal plates (3) mineralized cartilage (4) the perichondrium of the cartilage model diaphysis
27. The following structures are formed in the endochondral bone formation: (1)
endochondral bone (2) perichondral bone (3) periosteal buds (4) epiphyseal plates
28. The following structures make up the arrangement of the long bone diaphysis: (1) osteons
(2) outer circumferential lamellae (3) interstitial lamellae (4) inner circumferential lamellae

FIGURES

64
Fig. 5.1. Types of cartilaginous tissues and cartilages
A – hyaline cartilage; B – elastic cartilage; C – fibrocartilage; D – histogenesis of cartilaginous
tissue; E – chondrocytes structure; 1 – perichondrium: a – outer fibrous layer; b – inner cellular
layer; 2 – young chondrocytes; 3 – cartilage matrix; 4 – isogenous groups of chondrocytes; 5 –
elastic fibers; 6 – chondroblasts; 7 – collagen fibers; 8 – mitochondrion; 9 – nucleus; 10 – rER; 11
– glycogen inclusions; 12 – Golgi apparatus.

65
 Fig. 5.2. Bone cells and bone tissue types
A – osteocytes; B – osteoblasts; C – osteoclast; D – coarsely bundled bone tissue; E – lamellar
bone tissue; 1 – osteocytes; 2 – bone lamellae.

6. MUSCLE TISSUES

66
 Muscle tissues are responsible for movements of the body and for changes in the size and
shape of internal organs. Muscle tissues are classified on the basis of their appearance. Two
different types of muscle tissues are recognized: striated muscle tissue and smooth muscle tissue.
Striated muscle tissue is subclassified on the basis of its location: skeletal muscle tissue and cardiac
muscle tissue.

Skeletal muscle tissue

Skeletal muscle tissue is responsible for voluntary movement under the influence of the
somatic nervous system. Skeletal muscle tissue is composed of parallel striated muscle fibers,
surrounded and held together by loose connective tissue. Tendons or some other arrangements of
collagenous fibers attach to the ends of these fibers.
Every muscle fiber is cylindrical in shape, from 10 to 100 nm in diameter and several
centimeters in length. Each muscle fiber is a multinucleated structure formed by fusion of
individual cells (myoblasts) in the process of development. Each muscle fiber is surrounded by the
sarcolemma. It consists of two layers: the plasmalemma (inner layer) and the basement membrane.
Satellite cells are interposed between the basement membrane and plasmalemma. They are stem
cells. These cells are in the G0 phase. They can prolifarate after injury to give rise to myoblasts.
Numerous mitochondria, nuclei, and Golgi apparatus are located beneath the sarcolemma.
Many nuclei are situated under the plasmalemma of a muscle fiber. Each muscle fiber has
hundreds of myofibrils running parallel along its length. If hematoxilin and eosin are used, muscle
fibers stain pink due to the presence of numerous myofibrils. About 80% of sarcoplasm (derived
from the Greek sarcos meaning flesh) is occupied by myofibrils separated from each other by
mitochondria and sarcoplasmic reticulum. A considerable amount of glycogen, free ribosomes,
and a variable number of lipid droplets can be found in sarcoplasm. Each myofibril has
characteristic banding patterns (dark and light bands). When observed under polarized light, the
dark-staining bands are birefringent (anisotropic), while the light-staining ones are isotropic.
Accordingly, the dark bands are called A-bands (A stands for “anisotropic”) and the light ones, I-
bands (I stands for “isotropic”). Owing to these alternations of dark and light bands, transverse
striations in a muscle fiber can be seen with light microscope. In addition, fine dark lines called Z-
lines can be seen bisecting the light band (I-band). The Z-lines divide each myofibril into numerous
contractile units, called sarcomeres, arranged end to end. The sarcomere is the functional unit of a
myofibril.
Each myofibril consists of two types of filaments: thick and thin filaments. A-bands are
composed of thick filaments; I-bands are composed of thin filaments. Note that both thick and thin
filaments have some overlapping only in the peripheral regions of A-bands. The region of A-band,

67
where thick and thin filaments do not overlap, was called H-bands. It should be noted that both
ends of thick filaments, however, have only one end free; the other is attached to a Z-line. Thus,
the thin filaments extend from each Z-line toward the middle of the sarcomere, where they project
in between the thick filaments so as to interdigitate with them. A dark line can be seen in the center
of an A-band. It was called M-line. The M-line is formed of a thickened segment of myosin
filaments. The special protein myomesin holds myosin filaments in the region of the M-line.
Each thick filament is composed of myosin molecules in a great number. Myosin molecule
consists of two polypeptide heavy chains and four light chains. Two stranded heavy chains form
the tail (or backbone) of myosin molecule; peripheral parts of heavy chains and light chains form
two global heads. Myosin head represents an active part of myosin molecule, since it contains
ATP- binding site, actin-binding site, and demonstrates ATPase activity. The myosin molecule
has two hinge regions: near the head and at some distance from the head. These hinges permit the
heads to move during relaxation. The myosin head is believed to oscillate back and forth.
Each thin filament is composed of three proteins: actin, troponin, and tropomyosin. Each
thin filament is formed by the polymerization of many single molecules of globular actin. Some
globular actins have special active sites for the binding of myosin heads. Tropomyosin winds
around an actin filament to stabilize it and to prevent the interaction between myosin heads and
actin. The troponin complex is attached to tropomyosin. The troponin complex consists of three
polypeptides named troponin T, I, and C. Note that the troponin C region binds Ca++ ions.
In addition to myosin, actin, tropomyosin, and troponin, some accessory proteins are also
present. Titin (or connectin) runs parallel to the filament array and links the ends of the thick
filaments to Z-disk. Desmin filaments link adjacent myofibrils to each other and maintain their
register. Also, they link myofibrils to the cell membrane.
Myofibrils are surrounded by the sarcotubular network or sarcotubular system. It consists of
two types of tubules: L-tubules and T-tubules. L-tubules are the tubules of smooth sarcoplasmic
reticulum running parellel or longitidinally to myofibrils. L-system tubules open into terminal
cysternae (enlargements of sarcoplasmic reticulum). The latter are continuous and completely
surround each myofibril. Two adjacent cisternae do not communicate, since between them a T-
tubule is interposed to form a triad. The T-tubules are transversely oriented canalicular
invaginations of the plasma membrane. Triads are located at the levels of the A-I band junctions.
As T-tubules are connected with the extracellular space, some nutrients pass across T-
tubules from the extracellular space into the fiber. The nutrients enter the sER owing to the
presence of triads. T-tubules conduct waves of depolarization directly to terminal cisternae. L-
system, primary terminal cisternae, functions as a reserve of Ca++. Also, it takes part in
transportation of nutrients from the triad into the fiber as well as production of glycogen and lipids.

68
 Contractile mechanism: the sliding filament model
Every striated muscle fiber is innervated by the terminal branch of a motoneuron. It is located
in the spinal cord and the brain stem. The terminal part of a nerve fiber (axon) contacts with the
surface of a muscle fiber forming a myoneural junction. It was called the motor end plate. When
the wave of depolarization reaches the terminal part of the axon, the vesicles that contain
acetylcholine fuse with the plasmalemma and empty their contents into the cleft.
Acetylcholine reacts with receptors that are situated on the muscle fiber plasmalemma. It is
noteworthy that part of acetylcholine will be destroyed by the enzyme acetylcholinesterase to
prevent continued stimulation. When acetylcholine combines with receptors, the sarcolemma
permeability increases to create membrane depolarization. The wave of depolarization moves
inside the fiber and reaches the terminal cisternae, which contain a high concentration of Ca++ ions
and have electrically sensitive Ca++ ions channels in their wall. Membrane excitation of the T-
tubule system causes these Ca++ ion channels to open, thus allowing Ca++ ions to enter the
sarcoplasm and to reach troponin (a special site for binding Ca++ ions). When Ca++ ions come into
contacts with troponin, the latter pulls tropomyosin, thus changing its disposition, and the active
sites of actin become liberated from the tropomyosin block. The heads of myosin bind with the
active sites of actin to form cross-bridge complexes. The complex contraction causes the actin
filaments to slide along the length of myosin filaments. This process is repeated many times during
the contraction, causing individual sarcomeres to shorten. Sarcoplasmic reticulum rapidly pumps
the Ca++ ions back into L-tubules, and the contraction ceases. This mechanism of contraction was
termed the sliding filament mechanism of contraction.
It will be interesting for future doctors to know that in myasthenia gravis characterized by
muscular weakness (the Greek mys meaning muscle; asthenia, weakness), the plasmalemma of
muscle fibers has fewer receptors. The receptors are attacked by antibodies to produce autoimmune
reaction. As a result, the muscle can respond to the nerve stimulus by only a feeble contraction.
Skeletal muscle as an organ consists of striated muscle fibers held together by connective
tissue. Every muscle fiber is surrounded by a delicate layer of loose connective tissue called
endomysium. Capillaries and nerves run in parallel to muscle fibers. Each fiber is provided with
several capillaries. The perimysium is a thicker connective tissue layer that surrounds groups of
fibers. Larger blood vessels and nerves travel in the perimysium. The epimysium is the sheath of
dense connective tissue surrounding the whole muscle.
Muscle fibers are divided into three types: red (type I, slow-twitch fibers), white (type IIa,
fast-twitch, fatigue-resistant fibers), and white (type IIb, fast-twitch, fatigue-sensitive fibers). Note
that the red fibers show a high level of oxidative metabolism; type IIa fibers, oxidative and

69
glycolytic metabolism; type IIb fibers, only glycolytic metabolism. Some muscles have the same
proportion of type 1 and type 2 fibers. In general, muscles that maintain posture (e.g., calf muscles)
have a high proportion of type I fibers, while muscles used for a short burst of power abound in
type II fibers. Thus, skeletal muscles consist of a mixture of different types of fibers, and the
pattern often reflects the activity of the muscle.
Muscle fibers are innervated by somatic motor neurons. The single motor neuron may
innervate from 1 to 2000 fibers to form the motor unit. The structure, histochemistry, and
physiology of a muscle fiber depend on innervation. Thus, red muscle fibers are innervated by
small motoneurons, white muscle fibers – by large motoneurons.
Muscles contain stretch receptors. Sensory fibers provide information on the tension of
skeletal muscle from two sources: (a) encapsulated nerve ending responding to stretch in the
tendon associated with a muscle; (b) spiral nerve endings in muscle spindles sensitive to stretch
and tension. The muscle spindle is composed of a fusiform capsule of dense connective tissue
surrounding a group of 8 to 15 thin fibers termed intrafusal fibers. Two types of intrafusal fibers
are distinguished: those with a fusiform shape and a central arrangement of nuclei (nuclear bag
fibers) and those of uniform width with dispersed nuclei (nuclear chain fibers). Specialized motor
nerve fibers innervate the intrafusal fibers. The spiral nerve endings are wrapped around the
intrafusal fibers and form special sensory afferent fibers running back to the spinal cord.

Cardiac muscle tissue

Cardiac muscle tissue is composed of cells called cardiomyocytes. Cardiac muscle cells are
mononuclear. Their nuclei are placed centrally. Between cardiomyocytes there is a very thin layer
of loose connective tissue and a rich capillary blood supply. Cardiomyocytes appear to branch and
anastomose with neighboring cells. Cardiac muscle cells are linked into long functional fibers by
specialized cell junctions, which anchor each cell to its neighbor. Intercellular junctions, which
can be seen under LM as straight lines running transversely across the fibers, are termed
intercalated disks. This disk contains three types of junctions: (1) desmosomes, (2) fascia adherens,
i.e., adherent-type junctions anchor the actin filaments of myofibrils to the end of the cell; (3) gap
junctions (nexuses) facilitate the passage of membrane excitation.
Ultrastructurally, cardiac muscle cells contain myofibrils, a lot of mitochondria, well-
developed sER, and T-tubules. Myofibrils of cardiomyocytes are virtually identical to those in
skeletal muscle fibers. The molecular basis and mechanism of the cardiac muscle contraction is
similar to that of the skeletal muscle fibers.
Besides contractile (tipical) cardiomyocytes there are conducting (atypical) cells, which
make up the autonomic impulse-generating system of the heart. The atypical cells are larger than

70
contractile muscle cells, have few myofibrils and mitochondria, lack T-tubules but contain a large
amount of glycogen.These cells are anaerobes and get energy by glycolysis.
The cytoplasm of some atrial cardiomyocytes has electron-dense granules, a well-developed
rER and Golgi complex. These cells produce polypeptide hormone the so-called atrial natriuretic
factor (ANF).
There is no population of stem cells in cardiac muscle tissue; therefore, regeneration
following damage cannot occur. Destroyed cardiac muscle cells are replaced by connective tissue.

Smooth muscle tissue

Smooth muscle tissue forms contractile portions of the wall of most hollow viscera (e.g.,
gut, urinary bladder, and uterus), as well as contractile elements in blood vessels. It is also found
as organized muscle bundles in the iris and ciliary body of the eye, as a thin sheet in the skin of
the scrotum (the dartos muscle) and some bundles of smooth muscle cells in association with hair
follicles (arrector pili muscles).
Smooth muscle tissue is composed of smooth muscle cells. These cells are spindle-shaped,
contain one rod-shaped centrally located nucleus, and lack transverse striations. Each smooth
muscle cell is surrounded by the basement membrane. Owing to the presence of the basement
membrane, smooth muscle cells are anchored together. Gap junctions (nexuses) connect the
adjacent cells at the defect in the basement membrane. Small groups of smooth muscle cells are
organized into bundles by loose connective tissue containing blood vessels and nerves
(perimysium).
Ultrastructurally a smooth muscle cell contains mitochondria, the Golgi apparatus, scattered
profiles of rER, and free ribosomes. These organelles are mostly confined to a conical region at
each pole of the nucleus. The rest of the cytoplasm is occupied largely by thin filaments. Thin
filaments are composed of actin (an isoform specific to smooth muscle cells) and tropomyosin.
There is no troponin in smooth muscle cells in contrast to striated muscle fibers. Characteristic
dense bodies are distributed throughout the cytoplasm. The thin filaments appear to be inserted
into these dense bodies. Some dense bodies are directly connected with the plasmalemma. The
dense bodies contain α-actinin and are evidently comparable to Z-lines of the skeletal muscle. The
intermediate filaments are also inserted into the dense bodies.
Thick filaments of the smooth muscle cells are composed of myosin, but of a different type
to that of skeletal muscle fibers. These type of myosin can only bind to actin if its light chains
become phosphorylated; this phenomenon does not occur in skeletal muscle fibers.

71
 Smooth muscle cells have no T-system. A large number of pinocytic vesicles are associated
with the sarcolemma and sER. The vesicles and sER sequester the calcium that is released to
stimulate contraction.
The contraction mechanism of smooth muscle cells differs from that of striated muscle
fibers. The contractile proteins are arranged in a criss-cross lattice inserted circumferentially into
the cell membrane. Due to such an arrangement of the contractile proteins, contraction results in
shortening of the cell; it assumes a globular shape in contrast to its elongated shape in the relaxed
state. The next feature of the contractile mechanism is associated with the control of Ca++ ion
movement. In a relaxed smooth muscle cell, free Ca++ ions are normally sequestered in the sER
throughout the cell. When the membrane is excited, free Ca++ ions are released into the cytoplasm
and bind to the protein called calmodulin (calcium-binding protein). The calcium–calmodulin
complex then activates an enzyme called myosin light chain kinase. The latter phosphorylates the
myosin light chains. When these are phosphorylated, the myosin heads can react with actin and
permit it to bind to actin. Actin and myosin interact by filament sliding to produce contraction in
a way similar to that for skeletal muscle.
Smooth muscle cells are specialized for slow, prolonged contraction without fatigue.
Contraction of smooth muscle cells is under the regulatory control of the autonomic nervous
system. Nerve terminals are located at a considerable distance from smooth muscle cells. However,
not all smooth muscle cells are exposed directly to the nerve terminals. The contraction of smooth
muscle cells is propagated from cell to cell via gap junctions. The smooth muscle cell contraction
may also be stimulated by hormones.
Smooth muscle cells have a well-developed rER and Golgi apparatus and secrete the
extracellular matrix: collagen, elastin, and other matrix components
Smooth muscle tissue contains cambiall cells and may respond to injury by undergoing
mitosis. Additionally, there are regularly replicating populations of smooth muscle cells. For
example, smooth muscle cells in the uterus proliferate during the menstrual cycle and pregnancy.

CONTROL PROBLEMS

1. The histological section of an organ demonstrates two cellular tissues. In one of them,
each cell is surrounded by the basement membrane. In the other tissue, the cells rest on the
basement membrane. Identify the tissues seen in the slide.
2. The electron micrograph shows some cells tightly adjacent to each other and joined
together by numerous desmosomes. The second electron micrograph shows other cells also

72
adjacent to each other, but separated by the basement membrane and joined together by numerous
gap junctions (nexuses). What tissues do these cells belong to?
3. The histological section of muscle tissue stained with Iron hematoxylin reveals
crossbanding striations. What additional morphological features enable us to identify the cardiac
muscle tissue?
4. The electron micrograph of the skeletal muscle fiber reveals a small cell found between
the plasmalemma and the basement membrane. Identify the cell and suggest its function.
5. There are two electron micrographs of the skeletal muscle fibers. In one of them, thin
myofilaments deeply penetrate into the A bands so that the I bands considerably decrease in size.
In the other micrograph, the I bands are wide. Explain the functional state of the muscle fibers.
6. The electron micrograph of the transverse section of skeletal muscle fibers shows a thick
myofilament surrounded by six thin ones. What sarcomere band was crosscut?
7. There are two slides demonstrating regeneration of muscle tissues. One of them shows
fibroblast-like cells. The other slide shows tube-like structures with several nuclei centrally
arranged in a chain. Which one demonstrates regeneration of the skeletal muscle tissue?

CONTROL TESTS

Directions: each of the following statements contains five suggested completions. Choose
the one that is best in each case.
1. Each of the following statements concerning the skeletal muscle tissue is true, EXCEPT:
A – is derived from the myotome; B – consists of striated muscle fibres; C – connective tissue
surrounds each fibre; D – possesses satellite cells; E – muscle fibres are joined by intercalated
discs.
2. Each of the following statements concerning the smooth muscle tissue is true, EXCEPT:
A – is derived from the mesenchyme; B – consists of muscle fibres; C – consists of muscle cells;
D – its cells lack cross striation; E– its contraction is involuntary.
3. Each of the following statements concerning the cardiac muscle tissue is true, EXCEPT:
A – consists of muscle symplasts; B – consists of muscle cells; C – is striated; D – is derived from
the mesoderm; E – its cells are joined by intercalated discs.
4. Each of the following statements concerning the striated myofibril is true, EXCEPT: A –
consists of thick and thin filaments; B – contains actin and myosin; C – includes myoglobin; D –
has dark and light bands; E – is subdivided into sarcomeres.
5. The main stages of the skeletal muscle tissue embryonic development are as follows,
EXCEPT: A – myoblasts arise from the myotome; B – myoblasts arise from the sclerotome; C –

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myoblasts fuse; D – myotubes result from fusion of myoblasts; E – muscle fibres differentiate
from myotubes.
6. Each of the following statements concerning the sarcotubular system is true, EXCEPT: A
– includes T tubules; B – includes sER (L tubules); C – forms triads; D – produces proteins; E –
contains terminal cisterns.
7. Each of the following statements concerning the smooth muscle cell is true, EXCEPT: A
– contains one nucleus; B – is surrounded by the basal lamina and reticular fibres; C – contains
actin and myosin; D – is joined with other cells by nexuses; E – contains T tubules.
8. Each of the following statements concerning the red muscle fibres is true, EXCEPT: A –
contain a large amount of myoglobin; B – possess numerous mitochondria; C – are rich in
oxidative enzymes; D – are adapted to fast short-lived contractions; E – show mild ATP-ase
cytochemical staining.
9. Each of the following statements concerning the white muscle fibres is true, EXCEPT: A
– contain a large amount of glycogen; B – contain few mitochondria; C – are adapted to slow
repetitive contractions; D – show marked ATP-ase cytochemical staining; E – are not rich in
oxidative enzymes.
10. The typical cardiac muscle cells contain the following structures, EXCEPT: A – one or
two nuclei; B – many mitochondria; C – striated myofibrils; D – T tubules; E – pinocytotic
vesicles.
11. The muscle cells producing hormones are: A – atypical cardiac myocytes; B – smooth
myocytes; C – atrial myocytes; D – satellite cells; E – none of them.
12. Each of the following statements concerning the striated myofibril structure is true,
EXCEPT: A – A band is anisotropic; B – I band is isotropic; C – Z line bisects I band; D – H zone
transects I band; E – H zone has a dark M line in its centre.
13. Each of the following statements concerning striated myofibrils is true, EXCEPT: A –
include thick and thin filaments; B – lack crossbanding; C – run parallel to the long axis of fibre
through its entire length; D – are held by intermediate filaments from desmin and vimentin; E –
are surrounded by the sarcoplasmic reticulum.
14. Each of the following statements concerning striated myofibrils is true, EXCEPT: A – I
band contains only thin filaments; B – thin filaments anchor at Z line; C – A band contains both
thin and thick filaments in 6 to 1 ratio; D – M line is formed by the midpoints of thick filaments;
E – H zone contains only thin filaments.

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 Directions: one or more of the given statements or completions is/are correct. Choose the
answer: A – if only 1,2, and 3 are correct; B – if only 1 and 3 are correct; C – if only 2 and 4 are
correct; D – if only 4 is correct; E – if all are correct.
15. The characteristics of the skeletal muscle as an organ are true: (1) is formed of striated
fibres (2) contains the endomisium (3) contains the perimysium (4) contains the epymysium
16. The following statements regarding a sarcomere are true: (1) is a distance between two
successive Z lines (2) is a functional unit of striated myofibrils (3) is similarly arranged in skeletal
tissue and cardiac muscle (4) includes 0.5 of I band + A band + 0.5 of I band
17. The cross striation of muscle fibres is due to: (1) cross disposition of myofibrils (2) the
presence of dark and light bands (3) the presence of many nuclei (4) alternation of dark and light
bands
18. The following statements regarding the atypical cardiac muscle cells are true: (1) contain
few myofibrils (2) contain many glycogen granules (3) contain few mitochondria (4) make up the
heart impulse-generating system
19. The following statements regarding the repair of skeletal muscle fibres are true: (1)
satellite cells divide (2) myoblasts arise from satellite cells (3) myoblasts fuse to form myotubes
(4) myotubes differentiate to muscle fibres
20. The following statements regarding the satellite cells of the skeletal muscle tissue are
true: (1) are stem cells (2) exist in G0 phase (3) take part in muscle repair (4) are located between
the basement membrane and the muscle fibre plasmalemma
21. The following statements regarding the T tubules of striated muscle fibres are true: (1)
are plasmalemma invaginations (2) take part in the release of calcium ions (3) are located between
adjacent terminal cisterns (4) take part in the diad formation
22. The intercalated disks of the cardiac muscle cells have the following specializations: (1)
sites of myofibril attachment (2) desmosomes (3) interdigitations (4) gap junctions
23. The following statements regarding the smooth muscle cells are true: (1) are fusiform
(2) contact by gap junctions (3) produce reticular fibrils (4) lack sarcolemmal vesicles
24. The following statements regarding the cytoplasmic and peripheral densities of the
smooth muscle cells are true: (1) are analogous to Z lines (2) contain α-actinin (3) function as
myofilament attachment sites (4) facilitate the spread of excitation
25. The following statements regarding the sarcolemmal vesicles (caveolae) of the smooth
muscle cells are true: (1) are present along the periphery of the cell cytoplasm (2) are associated
with sER (3) are associated with the cell membrane (4) function to take up and release calcium
ions

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 26. The following statements regarding the smooth muscle tissue regeneration are true: (1)
smooth muscle cells can divide (2) minor wounds heal by new smooth muscle cells (3) large
defects are closed by connective tissue (4) regeneration is not possible at all
27. The following statements regarding the cardiac muscle tissue regeneration are true: (1)
cardiac muscle cells can divide (2) the cardiac muscle lacks capacity for reparative regeneration
(3) minor wounds heal by new muscle cell production (4) any defect is closed by connective tissue
scar

FIGURES

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 Fig. 6.1. Muscle tissues
A, B – smooth myocytes; C – smooth myocyte ultrastructure: 1, 2 – dense bodies; 3 – nexus; 4 –
pinocytic vesicles; 5 – basal membrane; 6 – nucleus; 7 – Golgi apparatus; 8 – myofilaments; D –
skeletal muscle fibers; E – cardiac muscle tissue; F – skeletal muscle fiber ultrastructure: 1 –
satellite cell; 2 – T-tubule; 3 – myofibrils; 4 – Z-line; 5 – glycogen; 6 – L-tubules; 7 – mitochondria;
8 – nucleus; 9 – triade; 10 – basal membrane; 11 – tendon collagen fibers.

7. NERVOUS TISSUE

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 Nervous tissue is cellular tissue; it lacks extracellular matrix and consists of only cells of
two principal types: nerve cells (neurons) and supporting cells (glia).

Neurons
The neuron or nerve cell is a functional unit of the nervous tissue. Nerve cells are specialized
to receive stimuli and to conduct electrical impulses to other parts of the system. They are arranged
as an integrated communications network, with several neurons in a chain-like fashion typically
involved in sending impulses from one part of the system to another. The specialized contacts
between neurons that provide information from one neuron to the next one in the chain are called
synapses.
There are more than ten billion neurons in the human nervous system. Although nerve cells
show the greatest variety of sizes and shapes of any group of cells in the body, they fall into three
general categores:
• sensory neurons that convey impulses from receptors to the central nervous system;
• motor neurons that convey impulses from the central nervous system or from ganglia to
effector cells;
• intermediate, also called central neurons, that form a communicating and integrating
network between sensory and motor neurons. It is estimated that more than 99.9% of all neurons
belong to this integrating network.
All neurons have a cell body and processes that are named axon and dendrites. The cell body
of the neuron contains the nucleus and those organelles that maintain the nerve cell. The processes
extending from the cell body constitute a structural characteristic common for all neurons. Most
neurons have only one axon, usually the longest process extending from the cell. Some axons may
be more than one meter long. A neuron usually has many dendrites. These processes are shorter
and, usually, thiner than axons.
Neurons are classified on the basis of the number of processes extending from the cell body.
Thus, multipolar neurons have one axon and two or more dendrites. Bipolar neurons have one
axon and one dendrite. A special type of a bipolar neuron that is called the pseudounipolar neuron
has one process that divides close to the cell body into two long processes: an axon and a dendrite.
Sensory neurons usually are pseudounipolar, less often they are bipolar. Motor neurons are
multipolar, and intermediate neurons may be either bipolar or multipolar.
The physiologic direction of impuls conduction is from dendrites to the cell body and, then,
from the cell body to an axon.

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 The cell body of a neuron has the characteristics of a protein-secreting cell. The cell body
or perikaryon is part of the cell surrounding a large, euchromatic nucleus with a prominent
nucleolus. Nerve cell perikarya demonstrate blue clumps named Nissl bodies. They stain intensely
with basic dyes and metachromatically with thionine dyes. Nissl bodies are the rough endoplasmic
reticulum. The perikaryon also contains numerous mitochondria, a large perinuclear Golgi
apparatus, lysosomes, microtubules, neurofilaments, vesicles, and inclusions. Nissl bodies, free
ribosomes, and, occasionally, the Golgi complex extend into the dendrites but not into the axon.
This helps to distinguish between axons or dendrites.
Dendrites are neuronal processes that receive stimuli from other nerve cells or from the
environment. Generally, dendrites are located near the cell body. They have fewer diameters than
axons. They are unmyelinated; usually form extensive arborizations called dendritic trees.
Dendritic trees significantly increase the receptor surface of neuron.
Axons are neuronal processes that transmit impulses to other neurons or to effector cells.
There is only one axon for each neuron, and it may be extremely long. Some axons may travel
more than a meter to reach their effector targets. Some neurons of the central nervous system, in
contrast, have a short axon. An axon may give rise to a recurrent branch near the cell body and to
other collateral branches. The beginning of an axon from the cell body is known as the axon
hillock.
The region of the axon between the apex of the axon hillock and the beginning of the myelin
sheath is called the initial segment. The initial segment is the site at which an action potential is
generated in the axon. The action potential is stimulated by impulses carried to the axon hillock
on the membrane of the cell body after impulses have been received on the dendrites or the cell
body itself.
Axons in the nervous system may be myelinated (with a myelin sheath) or less often
unmyelinated (without this sheath).
Substances needed in the axon are synthesized in the cell body and require transport to those
sites. This process is called axonal transport. The axonal transport is a bidirectional mechanism.
The first type may be described as anterograde transpor, which carries material from the
perikaryon to the periphery. The second type is retrograde transport, which carries material from
the axon terminal and the dendrites to the perikaryon.
Neurons lack cambial cells (static population) and proliferative activity. If a cell body is
damaged the neuron dies. In contrast, if processes are cut they may regenerate.

Glial cells

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 The supporting cells are designated glial cells or neuroglia. Glail cells are nonconducting
cells that are in intimate physical contact with neurons and carry out attending functions. There
are two types of neuroglia: macroglia and microglia. Macroglial cells are divided into three types:
oligodendrocytes, astrocytes, and ependymal cells (ependyma). Oligodendrocytes are the cells that
provide protection for neuronal cell bodies and processes. Astrocytes are the cells that provide
physical and metabolic support for the neurons. Ependymal cells form the epithelium-like lining
of the brain ventricles and the spinal canal. Macroglial cells are derived from neuroectoderm.
Microglial cells are the phagocytic cells of the central nervous system. They are phagocytes
and are normally present only in small numbers in the adult central nervous system (CNS). They
proliferate and become actively phagocytic only in regions of injury and disease. They are derived
from blood monocytes and considered to be part of the so-called mononuclear phagocytic system.
Oligodendrocytes exsist in both the central and peripheral nerves systems. They surround
neurons providing metabolic support, take part in nerve fiber formation and their regeneration. In
the peripheral nervous system (PNS) there are two types of oligodendrocytes: some of them cover
the neuron processes and are named Schwann cells or lemmocytes; the other cells cover the bodies
of the neurons and are named satellite cells.
Astrocytes are the largest of the neuroglial cells. They exist only in the CNS. There are two
types of astrocytes: (1) protoplasmic astrocytes, which lie in the gray matter and (2) fibrous
astrocytes, which lie more often in the white matter. Astrocytes have processes that extend between
blood vessels and neurons. The ends of the processes form end feets that may cover a large area
of the outer surface of a blood vessel or the axolemma. Astrocytes are now thought to maintain
the microenvironment of the neurons and to play a role in formation of the blood–brain barrier.
Ependyma or ependymal cells line the fluid-filled cavities of the central nervous system.
They are cuboidal to columnar cells that have the morphologic and physiologic characteristics of
fluid-transporting cells. The modified ependymal cells and associated capillaries are called the
chorioid plexus.

Nerve fibers
Nerve fibers are the neuron processes (axis cylinders) enclosed by oligodendrocytes in the
CNS and lemmocytes (Shwann cells) in the PNS. The main function of glial sheathes is electrical
isolation of the process plasmalemma. The nerve fibers may be myelinated or unmyelinated.
The myelinated fibers are rapid and conduct impulses at a rate of 80 to120 m/s. Each fiber
includes an axis cylinder (usually an axon). In the PNS, an axon invaginates plasmalemma of
Schwann cell and dives to its cytoplasm. The axis cylinder is enclosed by the lemmocyte
membrane, whose overlying duplicature forms a mesaxon. The Schwann cell rotates, and the

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mesaxon wraps around the axis cylinder to create the myelin sheath. The myelin sheath consists
of compacted layers of the lemmocyte mesaxon (or plasma membrane) and is rich in lipids. The
cytoplasm of the Schwann cell is extruded to periphery, forming the outer sheath called the
neurilemma, but is preserved in Schmidt-Lanterman clefts. Fanctionally, clefts are nutrition
cannals. The myelin sheath is segmented, because it is formed by numerous Schwann cells
arranged along the axon. The junction of adjacent Schwann cells is devoid of myelin and called
the node of Ranvier. The axolemma at the node displays a unique electron density and provides
saltatory conduction of nervous impulses. In the CNS, an oligodendrocyte forms multiple
processes to myelinate several nearbay axons.
The unmyelinated fibers are slow and conduct impulses at a rate of 8-10 m/s. Each fiber
includes several axis cylinders (usually dendrites), so it is called cabale type fiber. The axis
cylinders are enclosed by invaginations of the lemmocyte plasmalemma. The Schwann cells are
elongated in parallel to the long axis of the processes, and the processes fit into grooves on the
surface of the cell. The lips of the groove are closed forming a mesaxon.
In the PNS, nerve fibers are enveloped by the endoneurium consisting of basal lamina and
reticular fibers. The endoneurium components are manufactured by lemmocytes.

Synapses
Neurons communicate with other neurons and with effector cells by means of synapses.
Synapses are specialized junctions between neurons that facilitate transmission of impulses from
one neuron to another. Synapses also occur between axons and effector cells, such as muscle and
gland cells. Synapses between neurons may be classified as: axodendritic, occurring between axon
and dendrites; axosomatic, occurring between axon and the cell body; axoaxonic, occurring
between axons; dendrodendritic, occurring between dendrites.
Synapses may also be classified as chemical or electrical. In chemical synapses, neurons
and their processes are closely apposed. Usually, only the 20 to 30 nm intercellular space separates
them. A typical chemical synapse consists of:
• a presynaptic knob (presynapse), which is at the end of the neuron process from which
neurotransmitter is released;
• a synaptic cleft, i.e., the 20 to 30 nm space that the neurotransmitter must cross;
• a postsynaptic membrane (postsynapse), which has receptor sites on the plasma
membrane the neurotransmitter interacts with;
• a parasynapse or synaptic glial cells, which insulate the synaptic cleft and take part in the
neurotransmitter elimination.

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 Electrical synapses, which are common in lower vertebrates and invertebrates, are gap
junctions that permit movement of ions between cells and, consequently, permit direct spread of
current from one cell to another. Mammalian equivalents of electrical synapses include the nexuses
(the gap junctions) in the smooth and cardiac muscle tissues.
Synapses are not resolvable in routine light microscopy preparations. Silver precipitation
staining method (Golgi method) not only demonstrates the overall shape of some neurons but also
shows synapses on the neuron surface. Typically, an axon makes several of these button-like
contacts with neurons. Often, the axon travels along the surface of the neuron, making several
synaptic contacts called “button in passing.” The axon then continues to end finally as a terminal
twig with an enlarged tip (“terminal button”) or the end bulb. The number of synapses on a neuron
or its processes, which may vary from just a few to tens of thousands per neuron, appears to be
directly related to the number of impulses that the neuron is receiving and processing.
Synaptic transmission
The presynaptic component or the end bulb of the axon is characterized by the presence of
synaptic vesicles, membrane-limited structures that range from 30 to 100 nm in diameter and
contain a neurotransmitter. There are also numerous small mitochondria and a layer of dense
material, the presynaptic density, on the cytoplasmic side of the presynaptic membrane.
The synaptic cleft separates the presynaptic membrane from the postsynaptic membrane.
The postsynaptic component, i.e., a portion of the plasma membrane of the second neuron, is
characrerized by the presence of a layer of dense material, the postsynaptic density, on the
cytoplasmic side of the membrane. It contains neurotransmitter-binding receptors.
The transmitter release is regulated by the calcium channels in the postsynaptic membrane.
When a nerve impulse reaches the postsyneptic membrane, the voltage reversal across the
membrane produced by the impulse, colloquially called depolarization, causes the voltage-gated
calcium membrane channels to open. The influx of calcium from the space causes the synaptic
vesicles to migrate to, and fuse with, the presynaptic membrane, thereby releasing the transmitter
into the synaptic cleft by exocytosis. The transmitter diffuses across the synaptic cleft. Receptors
on postsynaptic membrane bind the neurotransmitter, causing the channels to open in that
membrane, which allows ions to enter the neuron. This ion flux causes the voltage reversal
(”depolarization”) in the postsynaptic membrane, thereby generating a second nerve impulse.
The neurotransmitter release by the presynaptic component can cause either excitation or
inhibition at the postsynaptic membrane. In excitatory synapses, a neurotransmitter causes local
reversal of the voltage of the postsynaptic membrane to a threshold level that leads to the initiation
of nerve impulse. In inhibitory synapses, the neurotransmitter release hyperpolarizes the
postsynaptic membrane, making the generation of the nerve impulse more difficult.

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 The ultimate generation of a nerve impulse in a postsynaptic neuron is dependent on the
summation of excitatory and inhibitory impulses reaching that neuron. In this manner, the reaction
of a postsynaptic neuron (or target organ, i.e., a muscle or a gland cell) may be very precisely
regulated. The function of synapses is not simply to transmit impulses in an unchanged manner
from one neuron to another. Rather, synapses allow for the processing of neural input. Typically,
the impulse passing from the presynaptic to the postsynaptic neuron is modifided at the synaptic
station by other neurons that, although not in direct pathway, nevertheless have access to the
synaptic station. These other neurons may influence the membrane of the presynaptic neuron or
the postsynaptic neuron and facilitate or inhibit the transmition of impulses.
A number of molecules that serve as transmitters have been identified in various parts of the
nervous system. The most common transmitters are acetylcholine (ACh) and norepinephrine (NE).
ACh is a transmitter between axons and striated muscle at the neuromuscular junction. ACh and
NE serve as transmitters between axons and effectors in the autonomic nervous system. Other
commonly found transmitters are gamma-aminobutyric acid (GABA), dopamine, serotonin,
glutamic acid, and glycine. Recently, several small peptides have also been shown to act as
synaptic transmitters. Among these are substance P, hypothalamic releasing hormones,
enkephalins, etc.
Special enzymes, acetylcholinesterase and catecholaminetranspherase, associated with the
postsynaptic membrane, rapidly degrade ACh and NE, respectively. The transmitters may also be
reincorporated into vesicles in the presynaptic component by endocytosis. The degradation or
recapture of neurotransmitters is necessary in order to limit the duration of stimulation or inhibition
of the postsynaptic membrane.

Nerve endings
There are two types of nerve endings: efferent and afferent. The efferent nerve endings or
motor endings are the contacts between the axon of a motor (efferent) neuron and target cells.
There are special synapses: axomuscular, axovascular, and axoglandular synapses, in which the
postsynaptic membrane is the target cell cytolemma.
Afferent (sensory) endings or receptors are specialised structures, located at the distal tips
of sensory neurons dendrites. Although receptors may have many different structures, they have
one basic characteristic in common. They are able to initiate a nerve impulse in response to a
stimulus. Numerous types of receptors may be classified as exteroceptors, enterocepters, and
proprioceptors.
Exteroceptors react to stimuli from the external environment (temperature, touch, smell,
sound or light, etc.). Enteroceptors react to stimuli from within the body (the degree of filling or

83
stretch of the alimentary canal, bladder, and blood vessels). Proprioceptors also react to stimuli
from within the body, providing sensation of the body position and muscle tone and movements.
The simplest receptor is a bare dendrite, called a nonencapsulated (free) ending. Free
receptors are found in epithelia, connective issue, and in close association with hair follicles. But
most sensory nerve endings acquire connective tissue capsules or sheaths of varying complexity.
Sensory nerve endings with connective tissue sheaths are called encapsulated endings. Many of
these encapsulated endings are mechanoreceptors in the skin and joint capsules (the end bulb of
Crause, Ruffini’s corpuscles, Meissner’s corpuscles and Pacini’s corpuscles). Neuromuscular
spindles are encapsulated sensory endings in skeletal muscle. Functionally related to Golgi tendon
organs are encapsulated tension receptors found at muscle–tendon junctions.

The origin of the nervous tissue cells

All the elements of nervous tissue derive from the cells of the neural tube and the neural
crest.
The central nervous system neurons derive from the cells of the neural tube. These cells are
called neuroblast. After the developing nerve cells have migrated to their predestined location in
the neural tube and have differentiated into mature neurons, they no longer divide. Astrocytes and
oligodendrocytes also derive from the cells of the neural tube (glioblasts), but studies with tritiated
thymidine indicate that these neuroglial cells may undergo a slow turnover. As noted above,
microglia derives from the mononuclear cells of blood along with other macrophages of the body.
The PNS ganglion cells derive from the neural crest and undergo several stages in their
development. At the beginging there is a proliferation of ganglion precursor cells in the neural
crest; then the cells migtrate from the neural crest to their future ganglionic site. Then a second
wave of mitosis begins at the site followed by the development of processes that reach the taget
tissues and sensory territories. During the second mitotic wave, more cells are produced than are
needed. Those that do not make functional contact with target tissues undergo cell death.
Olygodendrocytes of the PNS (satellite cells and lemmocytes) also arise from the neural crest.

CONTROL PROBLEMS

1. There is a neuron in a slide stained with Toluidine blue. The neuronal perikaryon and
some processes contain dark blue clumps. Identify the clumps and the neuronal processes in which
the blue clumps are revealed.

84
 2. A student attempts to find “neurofibrils” in the neurons in a slide stained with
Hematoxylin and Eosin. Help the student. Explain why the term “neurofibrils” is in inverted
commas.
3. A microphotograph shows a neuron and numerous glial cells surrounding the neuron
soma and its processes. Which of the glial cells are lemmocytes and which of them are satellites?
4. There are two slides of nerve fibers cut across. The axis cylinder in the first slide stained
with Osmic acid is light and its sheath is black. The axis cylinder in the second slide stained with
Silver nitrate is black and its sheath is white. What types of nerve fibers are represented in the
slides? Specify the visible sheaths.
5. A microphotograph demonstrates a synapse. The right synaptic part contains small
vesicles, whereas the left synaptic part contains no vesicles. Where is the presynapse? Indicate the
direction in which the synapse conducts nerve impulses.
6. A patient became paralyzed. Which of the neurons of the reflex arch are damaged in this
case?
7. Two patients do not respond when a doctor pricks their hands with a needle. One of them
feels pain but cannot jerk his hand away. The second patient does not feel pain on pricking. Which
neurons of the reflex arch are damaged to cause these conditions?

CONTROL TESTS

Directions: each of the following statements contains five suggested completions. Choose
the one that is best in each case.
1. The following organelles are plentiful in the neuron cytoplasm, EXCEPT: A – Golgi
apparatus; B – mitochondria; C – microtubules and microfilaments; D – centrioles; E – rER.
2. Nissl bodies seen by light microscopy as basophilic clumps are: A – sER; B – Golgi
apparatus; C – mitochondria; D – microtubules; E – rosettes of polysomes and rER.
3. The neurofibrils seen by light microscopy are the fixation artefact and represent
aggregated: A – mitochondria; B – Golgi apparatus; C – microtubules and microfilaments; D –
rER; E – sER.
4. Each of the following statements concerning the axon is true, EXCEPT: A – lacks rER
and polysomes; B – lacks mitochondria; C – contains many microtubules; D – demonstrates axonal
transport; E – conducts impulses away from the soma.
5. Each of the following statements concerning the synapses is true, EXCEPT: A – transfer
impulses from one neuron to another; B – are chemical and electrical; C – interact with stimuli

85
and generate nervous impulses; D – are axodendritic, axosomatic, and axoaxonic; E – may be
exciting and inhibitory.
6. Each of the following statements concerning the chemical synapse is true, EXCEPT: A –
its presynapse contains vesicles with a neurotransmitter; B – its presynaptic membrane is
thickened; C – its postsynaptic membrane has receptors; D – has a synaptic cleft; E – lacks glial
cells.
7. The following glial cells belong to the macroglia, EXCEPT: A – oligodendrocytes; B –
protoplasmic astrocytes; C – glial macrophagocytes; D – fibrous astrocytes; E – ependymal cells.
8. The glial cells arising from the blood monocytes are: A – microglia; B – oligodendrocytes;
C – protoplasmic astrocytes; D – fibrous astrocytes; E – ependymal cells.
9. The glial cells lining the brain ventricles and the spinal canal are: A – microglia; B –
oligodendrocytes; C – protoplasmic astrocytes; D – fibrous astrocytes; E – ependymal cells.
10. The glial cells forming sheaths around neuronal processes in the nerve fibres are: A –
protoplasmic astrocytes; B – fibrous astrocytes; C – microglia; D – oligodendrocytes
(lemmocytes); E – ependymal cells.
11. Each of the following statements concerning the myelinated fibres is true, EXCEPT: A
– their outer sheath is neurilemma; B – contain several axis cylinders; C – their inner sheath is
myelinated; D – conduct impulses at a rate of 80 to120 m/s; E – possess nodes of Ranvier.
12. Each of the following statements concerning the myelinated sheath is true, EXCEPT: A
– includes several layers of the lemmocyte plasma membrane; B – has lipoprotein organization
with lipid predominance; C – contains nucleus and organelles of Schwann cell; D – is formed by
mesaxon winding around the axis cylinder; E – possesses Schmidt-Lanterman clefts.
13. Each of the following statements concerning the receptors is true, EXCEPT: A – are
terminal modifications of sensory neuron dendrites; B – are the motor nerve endings; C – if they
contain only neuron process, they are free; D – if they contain glial cells, they are nonfree; E – if
they are enclosed by connective tissue capsules, they are encapsulated.
14. Each of the following statements concerning the lamellar (Pacinian) corpuscle is true,
EXCEPT: A – is a deep pressure receptor; B – contains the inner flask with a sensory fibre; C –
contains the outer flask from glial cells; D – is the motor nerve ending; E – possesses connective
tissue capsule from multiple layers.

Directions: one or more of the given statements or completions is/are correct. Choose the
answer: A – if only 1,2, and 3 are correct; B – if only 1 and 3 are correct; C – if only 2 and 4 are
correct; D – if only 4 is correct; E – if all are correct.

86
 15. According to the morphological classification the neurons are: (1) multipolar (2) bipolar
(3) pseudounipolar (4) sensory
16. According to the functional classification the neurons are: (1) sensory (2) motor (3)
associative (4) bipolar
17. In embryogenesis the CNS and PNS neurons develop from: (1) mesenchyme (2) neural
tube (3) mesoderm (4) neural crest
18. In embryogenesis the CNS and PNS glial cells arise from: (1) neural tube (2) neural crest
(3) mesenchyme (4) mesoderm
19. The following statements regarding the dendrites are true: (1) are numerous or single (2)
conduct impulses toward the soma (3) have spines (4) have extensive arborizations
20. The following statements regarding the axon are true: (1) is always single (2) is the
longest and thickest neuronal process 3) branches to form collaterals (4) branches at its end
21. The chemical synapses transfer impulses in one direction because: (1) their presynapse
has vesicles with a neurotransmitter (2) they are nexuses (3) their postsynaptic membrane has
receptors (4) they are only exciting
22. The following statements regarding the regeneration of the nervous tissue are true: (1)
neurons are unable to divide (2) glial cells can divide (3) neuron processes can regenerate (4) the
neuronal soma can regenerate after injury
23. The following statements regarding the glial cells are true: (1) take part in neuron
nutrition (2) participate in regeneration of nerve fibres (3) form a protective barrier around neurons
(4) maintain electrolyte balance
24. The glial cell functions are: (1) support and defence of neurons (2) transport of
substances from blood (3) formation of nerve fibre sheaths (4) conduction of nervous impulses
25. The following statements regarding the unmyelinated fibres are true: (1) contain several
axis cylinders (2) their sheaths are formed by lemmocytes (3) conduct impulses at a rate of 8 -10
m/s (4) possess nodes of Ranvier
26. The following statements regarding the node of Ranvier are true: (1) lacks myelin (2) is
the site between adjacent Schwann cells (3) provides saltatory conduction of nervous impulses (4)
contains Schwann cell nucleus
27. The following statements regarding the Schmidt-Lanterman cleft are true: (1) is the site
between adjacent Schwann cells (2) is a myelin portion where the lemmocyte cytoplasm is
preserved (3) provides saltatory conduction of impulses (4) is nutrition canal
28. The following statements regarding the motor end plate are true: (1) contains
acetylcholine as a neurotransmitter (2) is formed by ending of the motor neuron axon (3) exists on
skeletal muscle fibres (4) contains glial cells

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 FIGURES

Fig. 7.1. Morphologic and functional classifications of neurons

A – pseudounipolar sensory neuron; B – bipolar intercalated neuron; C – multipolar motor
neuron; 1 – neuron perikaryon (cell body); 2 – dendrites; 3 – receptor; 4 – axons; 5 – synapses; 6
– effecter (motor ending); 7 – skeletal muscle fiber.

Fig. 7.2. Glial cells in the nervous system

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I – CNS gray matter; II – CNS white matter; III – PNS organs; 1 – ependymal cells; 2 – blood
vessel; 3 – protoplasmic astrocyte; 4 – neuron; 5 – microglial cell; 6 – oligodendrocyte; 7 –
fibrous astrocyte; 8 – lemmocyte (Schwann cell); 9 – satellite cells.

Fig. 7.3. Development and structure of the myelinated nerve fibers

A – cross sections of a myelinated nerve fiber at different stages of development: 1 – simple
mesaxon; 2 – axis cylinder; 3 – lemmocyte (Schwann cell) cytoplasm; 4 – spiral mesaxon. B –
longitudinal section of a myelinated nerve fiber: 1 – mesaxon; 2 – axis cylinder; 3 – myelin (
Schmidt-Lanterman) cleft; 4 – node of Panvier; 5 – lemmocyte (Schwann cell) cytoplasm; 6 –
lemmocyte nucleus.

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 Fig. 7.4. Myelinated (A) and unmyelinated (B) nerve fibers
1 – axis cylinders; 2 – myelin; 3 – lemmocyte nucleus; 4 – microtubules; 5 – microfilaments; 6 –
mitochondria; 7 – mesaxon; 8 – endoneurium.

Fig. 7.5. Motor ending on a skeletal muscle fiber (the motor end plate)
1 – lemmocyte; 2 – lemmocyte nucleus; 3 – lemmocyte plasmalemma; 4 – axoplasm; 5 –
axolemma; 6 – postsynaptic membrane ( muscle fiber plasmalemma); 7 – axon mitochondria; 8 –
synaptic cleft; 9 – muscle fiber mitochondria; 10 – synaptic vesicles; 11 – presynaptic membrane
(axolemma); 12 – muscle fiber cytoplasm; 13 – muscle fiber nucleus; 14 – myofibril.

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 Fig. 7.6. Sensory neurons and receptors
A – free receptor in the epidermis; B – encapsulated receptor in the dermis; 1 – receptor
connective tissue capsules; 2 – receptor glial cells; 3 – sensory neuron myelinated dendrites; 4 –
sensory neuron cell body; 5 – sensory neuron myelinated axon; 6 – the spinal cord.

8. NERVOUS SYSTEM: PERIPHERAL NERVOUS SYSTEM and SPINAL

CORD

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 The nervous system allows for rapid response to external stimuli. The nervous system
evolved from the simple neuroeffector system of lower animals. In primitive nervous systems,
only simple receptor–effector reflex loops exist in response to external stimuli. In higher animals,
the nervous system retains capability of responding to stimuli from external environment through
the action of effector cells (such as skeletal muscle), but the neuronal responses are more varied.
They range from simple reflexes that require only the spinal cord to complex operations of the
brain that bring to bear the memory of past experiences. In higher animals, the nervous system
also regulates the function of internal organs. This part of the nervous system is the autonomic
nervous system.
The nervous system consists of all the nervous tissue in the body. It can be divided into the
central nervous system (CNS) and peripheral nervous system (PNS). The CNS consists of the brain
and the spinal cord, located in the cranial cavity and vertebral column, respectively. The PNS
consists of cranial and spinal nerves (motor, sensory, and mixed), ganglia (collections of nerve
cells outside the CNS), and nerve endings: motor (effectors) and sensory (receptors). The effecror
region of the nervous system is functionally divided into the somatic part (is voluntary, innervates
skeletal muscles) and the autonomic part (is unvoluntary, innervates smooth muscles, cardiac
muscles, and glands). The autonomic nervous system is classified into sympathetic and
parasympathetic divisions.
The cell bodies of the main somatic motor neurons are located in the CNS (the spinal cord
and brain stem). Their axons leave the CNS and travel in peripheral nerves to the skeletal muscles
that they innervate. The autonomic motor neurons are located in the autonomic ganglia of the PNS.
The sensory region of the nervous system is not subdivided and serves for both the somatic
and autonomic parts.

Peripheral nervous system organs

Nerves
The nerves are made up of many nerve fibers that carry sensory and motor (effector)
information between CNS and the organs and tissues of the body. The neuron cell bodies, which
processes form the peripheral nerves, may be located in the CNS or in peripheral ganglia.The
ganglia contain clusters of neuronal cell bodies and nerve fibers leading to and from them.
The peripheral nerve bulk consists of nerve fibers (mylineted and unmylinated) and
connective tissue sheathes helding fibers together. The connective tissue is organized into three
distinctive components: endoneurium, perineurium, and epineurium. The endoneurium constitutes
the connective tissue associated with individual nerve fibers, forming the nerve fascicles.

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 The perineurium is a specialized connective tissue surrounding nerve fascicles. It serves as
a semipermeable barrier. It may be one or more cell layers. The cells of these layers are squamous
in shape. They contain actin microfilaments and are contractile. Each layer exhibits an external
(basal) lamina on both surfaces. Collagen fibrils are present between the cell layers, but fibroblasts
are typically absent. The perineurium forms the blood–neural barrier regulating the
microenvironment within the fascicles of nerve fibers in peripheral nerves.
The epineurium consists of dense connective tissue that surrounds and binds together nerve
fascicles into a common bundle. It forms the peripheral nerve capsule. Adipose tissue is often
associated with the epineurium in the larger nerves.
The nerves have their blood vessels in the epineurium and the perineurium. The
endoneurium depends on diffusion from and to the blood vessels through the perineurium.
Nervous ganglia
The ganglia contain clusters of neuronal bodies and nerve fibers. The cell bodies in the
ganglia may belong to sensory neurons (somatic and visceral afferents) or they may belong to
motor neurons (visceral efferents) of the ANS, sensory and motor (autonomic) ganglia,
respectively.
The peripheral nervous ganglia are made up of the large neuronal cell bodies and numerous
nerve fibers as well as oligodendrocytes: the satellite cells surround the neuronal cell bodies,
lemmocytes surround neuron processes. The glial cells help to establish and maintain a controlled
microenvironment around the ganglion neurons. Minimum amount of the connective tissue,
playing the role of the ganglion capsule and stroma, also is present.
Sensory ganglia are associated with either the spinal cord dorsal roots (dorsal root or spinal
ganglia) or the cranial nerves (sensory cranial ganglia). Sensory neurons are situated in the PNS,
but close to the CNS. They belong to both the somatic and autonomic nervous systems.
The dorsal root ganglia have a special structure. The neuronal cell bodies are located on the
periphery of the organ; the central region is occupied by numerous nerve fibers. These ganglia
contain a unique type of neurons – pseudounipolar sensory neurons. The neuron dendrites extend
to periphery as a part of the mixed spinal nerves and terminate with receptors; their axons extend
to the spinal cord forming the dorsal roots. In the spinal cord, the axons form many branches, some
of which establish synapsis with neurons in the gray matter; some branches enter the dorsal
columns of the white matter forming sensory ascending tracts. All the processes (both axnons and
dendrites) are myelinated.
Autonomic ganglia are associated with the nerve autonomic branches. They are extramural
ganglia (paravertabral and prevertebral) and intramural nervous ganglia, which are situated within

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the organs. The first of them may be sympathetic and parasympathetic, the second group belongs
to the parasympathetic system.
Autonomic ganglia are motor gandlia because they contain the cell bodies of the autonomic
motor (effector) neurons. Accoding morphological classification, these neurons are multipolar.
Their dendrites branch within the ganglion; their axons leave the ganglion (the postganglionic
fibers) and reach muscles or glands that they innervate. All the processes (both axnons and
dendrites) are unmyelinated, which explainas slower reaction of the autonomic system in
comparison with the somatic part on the external stimuli. The preganglionic fibers (the axons of
the autonomic intermediate neurons) enter the ganglion and synapse on the motor neurons.
Autonomic ganglia contain glial cells (satellite cells and lemmocytes) and poor connective
tissue stroma. Extramural ganglia are surrounded by a dense connective tissue capsule that is
comparable to and continuous with the epineurium of the nerves.
The intramural ganglia located in tube-like organs (the digestive tract, oviducts, ureters)
belong to the metasympathetic system. They contain apart from motor neurons a small amount of
sensory and intermediate cells. These neurons constitute the local reflex arches providing the organ
peristaltic movements.

Spinal cord
The spinal cord is an organ of the CNS. It is a cylindrical structure that is cranially
continuous with the brain. It is divided into 31 segments (8 cervical, 12 thoracic, 5 lumbar, 5 sacral,
and 1 coccygeal). Each segment is connected to a pair of spinal nerves. Each spinal nerve is joined
to its segment of the spinal cord by two roots grouped as the posterior (dorsal) or anterior (ventral)
roots.
In cross section, the spinal cord exhibits a butterfly-shaped gray inner substance. It is divided
into the anterior, lateral, and posterior horns. The spinal canal passes through the central part (gray
commissure) of the gray matter. It contains the cerebral-spinal fluid (CSF). The gray matter is
surrounded by a white peripheral substance, the white matter. It is divided into the anterior, lateral,
and posterior columns.
The gray matter contains neuronal cell bodies, neuron processes (mainly dendrites), glial
cells, and blood vessels.
All the gray matter neurons are multipolar. In the anterior horns, the motor neurons of the
somatic reflex arc are situated. Their axons leave the spinal cord through the ventral root, become
a component of the mixed spinal nerve of that segment and innervate the skeleton muscles. The
axons are myelinated; near the muscle fibers, they divide into numerous terminal branches that
form a neuromuscular synapsis or effector called the motor end plate.

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 In laterale horns (from CVIII to LII segments), the intermediate neurons of the sympathetic
reflex arches are housed. Their axons leave the spinal cord as the components of ventral spinal
roots and establish synapses with the motor neurons in the sympathetic ganglia.
The posterior horns contain intermediate neurons of the somatic reflex arches. Their axons
either synapse with the gray matter neurons or enter the white matter to form tracts.
Functionally related groups of nerve cell bodies in the gray matter are called nuclei. In
context, the term nucleus means a cluster or group of neuronal cell bodies plus fibers and neuroglia.
The nuclei of the CNS are the morphologic and functional equivalents of the PNS ganglia.
Synapses occur only in the gray matter.
There is variety of glial cells in the gray matter: protoplasmic astrocytes, oligodendrocytes,
ependymal cells lining the spinal cord canal, and microglial cells.
The white matter is composed of myelinated axons, glial cells, and blood vessels.
Functionally related bundles of axons in the white matter are called tracts. The own spinal cord
tracts conduct impulses between segments; they consist of axons of the spinal cord intermediate
neurons. These tracts surround the gray matter. The ascending tracts conduct impulses up from the
spinal cord to the brain; they include axons of the spinal cord intermediate neurons (in the anterior
and lateral columns) and axons of the dorsal root ganglion neurons (in the posterior columns). The
descending tracts conduct impulses down from brain to the spinal cord. They consist of the brain
neuron axons and travel both in the anterior and lateral columns of the spinal cord white matter.
The glial cells of the white matter are as follows: fibrouse astrocytes, oligodendrocytes, and
microglial cells. Blood vessels enter the white matter from the pia mater (the innermost the spinal
cord connective tissue membrane).

Somatic and autonomic reflex arches

A reflex arc is a chain of neurons conducting impulses from a receptor to an effector. The
simple reflex arc consists of sensory, intermediate, and motor neurons.
The sensory neurons of the somatic reflex arc situated in the dorsal root ganglion, the
intermediate neurons - in the spinal cord posterior horns, and the motor neurons - in the spinal cord
anterior horns. The somatic reflex arches may include only two neurons: the sensory and motor
neurons (the knee and elbow arcs).
The autonomic reflex arc sensory neurons are located in the dorsal root ganglion too. The
sympathetic intermediate nervous occupi the spinal cord lateral horns; the parasympathetic
intermediate neurons form nuclei in the spinal cord sacral segments and in the brain stem. The
motor neurons are situated outside the CNS in the autonomic ganglia. The autonomic reflex arc

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consists of minimal three neurons; its effector part is bi-neuronal including intermediate and motor
neurons.
Both somatic and autonomic reflex arches may be longer on account of the spinal cord tracts
and the brain neurons.

CONTROL PROBLEMS

1. An investigator has been set the task to study sensory (afferent) neurons in the peripheral
nervous system. What PNS organs are they found in? What morphological type do the sensory
neurons belong to?
2. An investigator has been set the task to study the motor (efferent) neurons innervating the
skeletal muscles and the neurons innervating the smooth muscle cells. What organs are the neurons
located in? What morphological type do the efferent neurons belong to?
3. The microscopic examination of the spinal cord dorsal root reveals myelinated nerve
fibers. What is the organ the myelinated fibers arise from? What neuronal processes form axis
cylinders in the fibers? What neurons do the processes belong to?
4. The microscopic examination of the spinal cord ventral root reveals myelinated nerve
fibers. What processes form axis cylinders in the myelinated fibers? What neurons do the processes
belong to?
5. The spinal cord dorsal root has been experimentally cut. What is the fate of the cut
myelinated fibers in the root portion connected with the spinal cord and in the root portion
connected with the spinal ganglion?
6. The spinal cord ventral root has been experimentally cut. What nerve endings (receptors
or effectors) stop functioning as result of cutting?
7. There is an intramural nerve ganglion and an extramural nerve ganglion with multipolar
neurons. What functions do the ganglia perform? What types of neurons according to the
functional classification do the ganglia contain?
8. The histological microphotograph demonstrates postganglionic nerve fibers. Are the
fibers myelinated? What processes form the axis cylinders in the fibers? What neurons do the
processes belong to?
9. The microscopic examination of the spinal cord reveals degeneration of the posterior
column nerve fibers. What neurons have been damaged to cause degeneration? What neuron
processes form the axis cylinders in the posterior column nerve fibers?

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 FIGURES

Fig. 8.1. Somatic reflex arc

1 – receptors; 2 – sensory neuron dendrite; 3 – sensory (afferent) neuron cell body; 4 – sensory
neuron axon; 5 – associative (intercalated) neuron cell body; 6 – associative neuron axon; 7 –
motor (efferent) neuron cell body; 8 – motor neuron axon; 9 – motor end plate; 10 – the dorsal
root ganglion; 11 – dorsal root of the spinal cord; 12 – ventral root of the spinal cord; 13 – the
spinal nerve. (Reprinted with permission from Юшканцева С.И., Быков В.Л. Гистология,
цитология и эмбриология. Краткий атлас. С-Пб.: Издательство "П-2", 2007.)

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 Fig. 8.2. Autonomic reflex arc
1 – receptors; 2 – sensory neuron dendrite; 3 – sensory (afferent) neuron cell body; 4 – sensory
neuron axon; 5 – associative (intercalated) neuron cell body; 6 – associative neuron axon; 7 –
motor (efferent) neuron cell body; 8 – motor neuron axon; 9 – motor endings on smooth muscle
cells and glands; 10 – the dorsal root ganglion; 11 – dorsal root of the spinal cord; 12 – ventral
root of the spinal cord; 13 – autonomic ganglion; I, II, III – local reflex arch. (Reprinted with
permission from Юшканцева С.И., Быков В.Л. Гистология, цитология и эмбриология.
Краткий атлас. С-Пб.: Издательство "П-2", 2007.)

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 Fig. 8.3. Motor neurons and motor endings (effectors)
A – the motor end plate on the skeletal muscle fiber; B – effector on the smooth muscle cell;
1 – axons; 2 – presynapse; 3 – mitochondria; 4 – synaptic vesicles; 5 – presynaptic membrane; 6
– synaptic cleft; 7 – postsynaptic membrane; 8 – postsynapse; 9 – muscle fiber nucleus; 10 –
myofibrils; 11 – smooth muscle cell nucleus; 12 – motor neuron in the spinal cord anterior horn;
13 – motor neuron in the autonomic ganglion; 14 – autonomic intercalated neuron (sympathetic)
in the spinal cord lateral horn; 15 – the spinal cord dorsal root; 16 – the dorsal root ganglion

Fig. 8.4. Spinal cord

A – the white matter; B – the gray matter; C – the autonomic ganglion; D – motor endings; 1 –
somatic motor nucleus in the anterior horn; 2 – autonomic (sympathetic) associative nucleus in
the lateral horn; 3 – associative nucleus in the intermediate zone; 4-5 – associative nuclei in the
posterior horn.
10. NERVOUS SYSTEM: BRAIN

99
 The brain includes the brain stem, the cerebellum, and the cerebral hemispheres. All the
brain parts are made up of the white matter and gray matter in a specific arrangement. The gray
matter exists as nuclei within the white matter and as the cotex in the cerebellum and cerebrum.
The brain gray matter (both the nuclei and cortex) consists of neuron cell bodies, dendrites,
axons, glial cells, and blood vessels. It is a site of synapses.
The white matter contains the neuron axons in the myelinated nerve fibers, the associated
glial cells, and blood vessels. The axons travel from one part of the nervous system to another.
Whereas many of the axons going to or coming from a specific location are grouped into bundles
called tracts.
The kinds of nervous cells found in the gray matter vary according to which part of the brain
is being examined. Majority of them are multipolar intermediate neurons but the brain stem houses
nuclei of the somatic motor neurons (analogies of the spinal cord anterior horns) and nuclei of the
parasympathetic intermediate neurons. Glial cells are represented by the astrocytes (protoplasmic
and fibrous), oligodendrocytes, and microglia, the CNS macrophages. The brain ventricles contain
CSF and are lined by the ependymal cells.

Cerebellum
The cerebellum coordinates muscular activity and maintains posture and equilibrium. The
cerebellum consists of the white matter core and the gray matter in the form of cortex and four
pairs of nuclei in the central position. Afferent and efferent fibers pass to and from the brain stem
via inferior, middle, and superior cerebellar peduncles.
There are three layers in the cerebellar cortex. The uppermost of them is the molecular layer.
It includes the stellate and basket neurons as well as large numbers of unmyelinated nerve fibers.
The middle layer is the ganglionic layer. It has a single layer of huge neurons called Purkinje
cells. Purkinje cells have large pear-shaped cell bodies and an extensively branching dendritic
system, which arborizes into the outer molecular layer. Purkinje cell axons extend down through
the granular cell layer, enter the white matter, and terminate in the cerebellum nuclei forming
synapses on the nuclear neurons.
The innermost cortical layer is the granulear layer. It contains numerous neurons called the
granule cells and Golgi cells scattered in the superficial part of the granule cell layer. The granule
cells have small round cell bodies and short dendrites; their axons pass to the molecular layer
where they bifurcate to run parallel to the cortex surface (“parallel fibers”). The axons synapse
with the dendrites of Purkinje cells, basket cells, and Golgi cells.

100
 Purkinje cells are called efferent neurons because their axons conduct impulses away from
the cortex. Eventually, these impulses reach the somatic motor neurons in the brain stem and the
spinal cord. The rest cerebellar neurons serve Purkinje cells: the stellate and basket cells connect
them across a folium and inhibit; the granule neurons connect Purkinje cells along a folium and
excite. The granule neurons are the only exiting cells in the cerebellum cortex.
Afferent fibers conduct impulses towards the cerebellum cortex from the brain stem and then
pass via the white matter core to make complex connections with the cortical neurons. The
climbing fibres terminate in the molecular layer and synapse with Purkinje cell dendrites. The
mossy fibers terminate in the granular layer and synapse with the granule cell dendrites. Slightly
above this contact, Golgi cell axon forms inhibitory synapse on the granule cell dendrite. This
triple synaptic complex is called the cerebellar island.
The cerebellar efferent fibers are the Purkinje cell axons, which pass down through the
granular layer into the white matter where they synapse in the central nuclei of the cerebellum.

Cerebral cortex
The cerebral hemispheres consist of a convoluted cortex of gray matter overlying the central
medullary mass of white matter, which contains nuclei of the gray matter. The white matter
consists of myelinated nerve fibers conducting impulses between different parts of the cortex and
to and from other parts of the CNS.
The cerebral cortex neurons are multipolar intermediate. Histologically, they are divided
into several different morphological types depending on the cell body shape. The pyramidal cells
are the most numerous of them and characteristic only for the cerebral cortex. Their cell bodies
are triangular in shape; dendrites arborize from the cell top and lateral surfaces; axon arises from
the broad basal body part. Pyramidal cells may be small, medium, large, and huge (about 120-µm)
in size.
The cortical neurons are arranged in layers. In the neocortex, there are six layers differing in
neuron morphology, size and population density.
The most superficial layer is the molecular layer (1). It contains relatively few neurons and
large numbers of glial cells and nerve fibers. The fibers are dendrites and axons of cortical neurons
making synapses with one another. The deeper layer is the outer granular layer (2). A dense
population of small pyramidal cells and stellate cells make up this thin layer, which also contains
various axons and dendritic connections from other layers. The next layer is the pyramidal layer
(3). It is broad and mainly contains pyramidal cells of medium size. The inner granular layer (4)
consists of densely packed stellate cells. The ganglionic layer (5) includes large or huge pyramidal
cells and smaller numbers of stellate cells.The name of the layer originating from the huge

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pyramidal cells (Betz cells) of the motor cortex. The deepest layer is the multiform layer (6).This
is so named for the wide variety of differing morphological forms found in this layer. It contains
numerous small pyramidal cells, as well as stellate cells, especially superficially, and fusiform
cells in the deeper part.
The afferent fibers of the cerebral cortex are axons of neurons, which cell bodies lying
elsewhere in the brain: either in other region of the cortex (cortico-cortical fibers) or in the
thalamus (thalamo-cortical fibers). These fibers enter the cortex from the white matter, vertically
pass, and branch in the first, second, and forth cortical layers forming horizontal nerve plexuses.
The efferent fibers are axons of pyramidal cells of mainly the third and fifth cortical layers.
They form tracts connecting either different regions of the cortex or the cortical areas with other
parts of the CNS (for example, the pyramidal tract passes through the brain stem to the spinal cord
and synapses with the anterior horn motor neurons).
The synaptic interconnections within the cortex are exceedingly complex, with any one
neuron synapsing with several hundred others. However, there are several basic principles of
cortical organization and function. The functional units are disposed vertically, corresponding to
the general orientation of axons and major dendrites. The afferent fibers generally synapse high in
the cortex with the dendrites of neurons, the cell bodies of which lie in deeper layers of the cortex.
The efferent pathways tend to give off branches, which pass back into more superficial layers to
communicate with their own dendrites via interneuronal connections involving other cortical cell
types.
There are two types of the cerebral cortex: (1) granular type or sensory cortex with the 2nd
and the 4th well-developed layers and (2) agranular type or motor cortex with the 3rd and the 5th
well-developed layers.

Connective tissue of the central nervous system

Three sequential connective tissue membranes, the meninges, cover the brain and spinal
cord. The dura mater is the outermost layer. The arachnoid layer lies beneath the dura. The pia
mater is a delicate layer resting directly on the surface of the brain and spinal cord.
In the cranial cavity, the thick layer of connective tissue that forms the dura mater is
continuous at its outer surface with the periosteum of the skull. Within the dura mater, there are
spaces lined by endothelium (and backed by periosteum and dura mater, respectively) that serve
as the principal channels for the blood returning from the brain. These venous sinuses receive
blood from the principal cerebral veins and carry it to the internal jugular veins. In the spinal canal,
the vertebrae have their own periosteum, and the dura mater forms a separate tube surrounding the
spinal cord.

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 The arachnoid makes delicate trabeculae between the dura and pia mater on the surface of
the brain and spinal cord. The space bridged by these trabeculae is the subarachnoid space; it
contains CSF.
The pia mater is also a delicate connective tissue layer. It lies directly on the surface of the
brain and spinal cord; its blood vessels enter the brain and spinal cord to supply them. The surface
of the spinal cord and the brain is covered by a membrane formed by the processes of astrocytes
and the basement membrane that separate them from the pia mater. It is called the external glial
membrane.

Blood–brain barrier
There are many blood vessels in both the central and peripheral nervous systems. The blood
vessels are separated from the nervous tissue by the interposition of basal laminae and the
processes of astrocytes. In the central nervous system, the boundary between the blood vesseles
and nervous tissue is so strong that many substances that readily leave the blood vessels to enter
other tissues do not normally enter the nervous tissue. This construction in the central nervous
system is known as the blood–brain barrier.
The blood–brain barrier restricts the passage of substances from the circulation to the CNS
parenchyma. It is formed by the astrocytes processes, covering all blood vessels inside the brain
tissue and by the complex of tight junctions existing between the endothelial cells of the blood
vessels of the brain. These junctions prevent the passage of solutes and fluid from the lumen to the
extravascular space via the intercellular space of endothelium.
Some parts of the CNS, however, are not isolated from substances carried in the blood. These
may be areas of the brain in which sampling of materials circulating in the blood is necessary to
regulate neurosecretory control of parts of the nervous system and of the endocrine system.

Choroid plexus
The choroid plexus is a vascular structure in the four ventricles of the brain and is responsible
for the production of cerebrospinal fluid. It drains from the interconnected ventricular cavities via
three channels connecting the fourth ventricle with the subarachnoid space that surrounds the CNS.
The cerebrospinal fluid is produced at a constant rate and is reabsorbed from the subarachnoid
space into the superior sagittal venous sinus via finger-like projections called arachnoid villi.

CONTROL PROBLEMS

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 1. There are axodendritic synapses in the cerebellar cortex, in which the afferent mossy
fibers form the presynaptic component. What structures form the postsynaptic component of the
synapses? Which of the cerebellar cortex layers do the mossy fibers terminate in?
2. There are axodendritic synapses in the cerebellar cortex, in which the afferent climbing
fibers form the presynaptic component. What structures form the postsynaptic component of the
synapses? Which of the cerebellar cortex layers do the climbing fibers terminate in?
3. The microphotograph shows a large pear-shaped neuron of the brain. The neuron soma is
surrounded by the nerve fibers that form the basket-like synapses. What part of the brain does the
neuron belong to? What neurons form the basket-like synapses on the neuron soma? How do the
basket-like synapses influence the neuron?
4. The microphotograph demonstrates a 120-µm pyramidal neuron of the brain. The neuron
axon arising from the soma extends into the brain white matter. What part of the brain does the
pyramidal neuron belong to? What tracts do the pyramidal neuron axons make up? What part of
the spinal cord may the pyramidal tracts terminate in?
5. There is a histological slide of the cerebral cortex in which the 2nd and the 4th layers are
well-developed. Name the cerebral cortex layers. What type of the cerebral cortex does this region
belong to? What function does this type of the cerebral cortex perform?
6. There is a histological slide of the cerebral cortex in which the 3rd and the 5th layers are
well-developed. Name the cerebral cortex layers. What type of the cerebral cortex does this region
belong to? What function does this type of the cerebral cortex perform? What tracts arise from this
type of the cerebral cortex?
7. The animal developed paralysis of the hind legs (movements became impossible) due to
damage to neuron axons at the medulla oblongata level. What part of the brain are the neurons
with damaged axons located in? What tracts fail to conduct impulses as a result of the traumatic
injury?

CONTROL TESTS

Directions: each of the following statements contains five suggested completions. Choose the one
that is best in each case.
1. Each of the following statements concerning the spinal ganglion is true, EXCEPT: A – contains
pseudounipolar neurons; B – is associated with the spinal cord ventral root; C – its neuron dendrites form
part of the spinal nerve; D – its neuron dendrites possess receptors; E – its neurons are surrounded by
satellite cells.

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 2. The dorsal root of the spinal cord is formed by: A – the axons of motor neurons of the spinal cord;
B – the dendrites of neurons of spinal ganglia; C – the dendrites of motor neurons of the spinal cord; D –
the axons of neurons of spinal ganglia; E – the axons of interneurons of the spinal cord.
3. Each of the following statements concerning the autonomic ganglia is true, EXCEPT: A – contain
multipolar neurons; B – the axons of their neurons are unmyelinated; C – the axons of their neurons end on
skeletal muscles; D – contain oligodendrocytes; E – preganglionic fibres form synapses on their neurons.
4. The gray matter of the spinal cord consists of the following structures, EXCEPT: A – connective
tissue trabeculae; B – multipolar neurons; C – astrocytes; D – oligodendrocytes; E – microglia.
5. The white matter of the spinal cord consists of the following structures, EXCEPT: A – astrocytes;
B – microglia; C – myelinated fibres; D – multipolar neurons; E – oligodendrocytes.
6. Each of the following statements concerning the cerebellar cortex is true, EXCEPT: A – its
molecular layer contains stellate and basket cells; B – lacks blood vessels; C – its granular layer contains
granule cells and Golgi cells; D – its middle layer contains Purkinje cells; E – contains protoplasmic
astrocytes, oligodendrocytes, and microglia.
7. Each of the following statements concerning Purkinje cells from the cerebellar cortex is true,
EXCEPT: A – are located in single layer; B – their dendrites arborize in the molecular layer; C – their axons
enter the white matter; D – are pyramidal in shape; E – conduct impulses away from the cortex.
8. The cerebellar cortex neurons exciting Purkinje cells are: A – granule cells; B – basket cells; C –
Golgi cells; D – stellate cells; E – pyramidal cells.
9. The cerebellar cortex neurons connecting Purkinje cells along a folium are: A – basket cells; B –
pyramidal cells; C – stellate cells; D – Golgi cells; E – granule cells.
10. The cerebellum white matter contains the following structures, EXCEPT: A – mossy afferent
fibres; B – climbing afferent fibres; C – efferent fibres; D – glial cells; E – ependymal cells.
11. The mossy afferent fibres enter the cerebellar cortex and synapse with the dendrites of: A – basket
cells; B – Purkinje cells; C – stellate cells; D – granule cells; E – Golgi cells.
12. The climbing afferent fibres enter the cerebellar cortex and synapse with the dendrites of: A –
basket cells; B – Purkinje cells; C – stellate cells; D – granule cells; E – Golgi cells.
13. Each of the following statements concerning efferent fibres of the cerebral cortex is true,
EXCEPT: A – are the axons of pyramidal cells from the 3rd and the 5th layers; B – convey impulses to the
cortex; C – may end in the same hemisphere; D – may end in the other hemisphere; E – may leave the brain
and enter the spinal cord.
14. Each of the following statements concerning afferent fibres of the cerebral cortex is true,
EXCEPT: A – convey impulses to the cortex; B – end and branch in the 1st, 2nd, and the 4th layers; C – carry
impulses away from the cortex; D – form transversal plexuses; E – synapse with cortex interneurons.

Directions: one or more of the given statements or completions is/are correct. Choose the answer: A
– if only 1,2, and 3 are correct; B – if only 1 and 3 are correct; C – if only 2 and 4 are correct; D – if only
4 is correct; E – if all are correct.

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 15. The peripheral nerves are composed of: 1) nerve fibres (2) epineurium (3) perineurium (4)
endoneurium
16. The ventral root of the spinal cord is formed by: (1) the axons of motor neurons of the spinal cord
(2) the axons of sensory neurons of spinal ganglia (3) the axons of autonomic interneurons of the spinal
cord (4) the dendrites of sensory neurons of spinal ganglia
17. The following statements regarding the spinal cord neurons are true: (1) are multipolar (2) are
motor and associative (3) their axons may leave the spinal cord through the ventral root (4) their axons may
extend from the gray matter into the white matter
18. The white matter of the spinal cord is formed by axons of neurons from: (1) spinal cord (2) spinal
ganglia (3) brain (4) autonomic ganglia
19. The following statements regarding the gray matter of the spinal cord are true: (1) its anterior
horns contain motor somatic neurons (2) its posterior horns contain interneurons for sensory impulses (3)
its lateral horns contain autonomic interneurons (4) its commussure contains the central canal
20. The following statements regarding the white matter of the spinal cord are true: (1) its posterior
columns contain ascending sensory tracts (2) its anterior columns contain mainly descending motor tract
(3) its lateral columns contain both ascending and descending tracts (4) its blood vessels extend from the
spinal cord pia mater
21. The cerebellar cortex is composed of the following layers: (1) molecular (2) of Purkinje cells (3)
granular (4) pyramidal
22. The cerebellar cortex neurons connecting Purkinje cells across a folium are: (1) granule cells (2)
stellate cells (3) Golgi cells (4) basket cells
23. The cerebellar cortex neurons inhibiting Purkinje cells are: (1) stellate cells (2) basket cells (3)
Golgi cells (4) granule cells
24. The following statements regarding the cerebellar islands are true: (1) are located in the granular
layer of the cortex (2) contain synapses between mossy fibres and granule cell dendrites (3) contain
synapses of Golgi cell axons with granule cell dendrites (4) contain Purkinje cell axons
25. The cerebral cortex includes the following layers: (1) molecular (2) external granular (3) external
pyramidal (4) layer of Purkinje cells
26. The cerebral cortex includes the following layers: (1) internal granular (2) internal pyramidal (3)
multiform (polymorphic) (4) molecular
27. The following statements regarding the granular type of the cerebral cortex are true: (1) contains
a well-developed external granular layer (2) contains a well-developed internal granular layer (3) is
characteristic of sensitive areas of the cortex (4) contains a well-developed internal pyramidal layer
28. The following statements regarding the agranular type of the cerebral cortex are true: (1) contains
a well-developed external pyramidal layer (2) contains a well-developed internal pyramidal layer (3) is
characteristic of motor areas of the cortex (4) contains a well-developed molecular layer

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 FIGURES

Fig. 9.1. Cerebellar cortex neural organization

I – molecular layer; II – ganglionic layer; III – granular layer; 1 – stellate cell; 2 – basket cell; 3
– Purkinje cell; 4 – granule cell; 5 – Golgi cell; 6 – sensory neuron of the dorsal root ganglion; 7
– mossy afferent fiber; 8 – motor neuron of the spinal cord; 9 – sensory neuron of the vestibular
ganglion; 10 – climbing afferent fiber; 11 – granule cell axon; 12 – Purkinje cell axon; 13 –
Purkinje cell dendrites; 14 – basket cell axon.

Fig. 9.2. Cerebral cortex

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A – neuron arrangement (cytoarchitecture); B - fiber arrangement (myeloarchitecture); I –
molecular layer; II – external granular layer; III – external pyramidal layer; IV – internal
granular layer; V – ganglionic (internal pyramidal) layer; VI – multiform (polymorphic) layer; 1
– pyramidal cells; 2 – stellate cells; 3 – polymorphic cells; 4 – tangential nerve fiber plexuses; 5
– afferent fibers; 6 – efferent fibers.

11. PRIMARY SENTIENT SENSE ORGANS: ORGAN of VISION and

ORGAN of SMELL

The sense organs are divided into two types: primary and secondary sentient sense organs,
depending on the nature of their receptor cells. The primary sentient sense organs include the organ
of vision, the eye, and the organ of smell, the olfactory epithelium; their receptor cells are neurons.
The secondary sentient sense organs include the organs of hearing and equilibrium, the ear, and
the organ of taste, the taste buds; their receptors are epithelial cells called neuroepithelial cells.
The sense organ is the peripheral part of the analyzer; its functions are interaction between
receptors and stimuli and generation of nervous impulses. The middle part of the analyzer is the
sensory nerve that transmits these impulses to the brain to be processed. The central part of the
analyzer is the area of the cerebral cortex that is responsible for association and analysis of
information. Damage to any part of the analyzer may result in the loss of sense.

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 Organ of vision, the eye
The eye is the visual organ located in the skull bony orbit. The eye converts light to nervous
impulses and transmits these impulses to the brain for processing. The eyeball is composed of
three tunics: the sclera, the vascular tunic, and the retina.
The sclera is the outer tunic of the eye, consists of relatively avascular dense regular
connective tissue. The sclera covers the posterior five-sixths of the eye, maintains the shape of the
eyeball, and serves as an attachment site for extrinsic oculomotor muscles. The oculomotor
muscles permit the eye to rotate freely and to change the visual fields. The anterior aspect of the
sclera is transparent and is known as the cornea, whose junction with the sclera is marked by the
limbus.
The cornea is the highly modified anterior portion of the outer tunic of the eye. It is slightly
thicker than the sclera and has a smaller radius of the curvature. The cornea’s high refractive index
and small radius of the curvature make it extremely important in image formation. The cornea is
composed of five layers: epithelium, Bowman’s membrane, stroma, Descemet’s membrane, and
endothelium.
The corneal epithelium is classified as stratified squamous nonkeratinized epithelium. It has
a remarkable capacity for healing and regeneration. Minor wounds are closed by cell migration;
larger wounds are healed by mitosis in the basal layers and the new cell production. The superficial
layer of the corneal epithelium is bathed by tears, keeping the cornea moist and protecting it from
dehydration. The tears also contain lysozyme, an antibacterial agent. The corneal epithelium is
highly innervated; it contains several free nerve endings that, when stimulated, cause the blinking
reflex: the eyelids close, protecting the cornea, and plentiful tears begin to flow. Bowman’s
membrane (the anterior border membrane) rests under the corneal epithelium. It is a homogenous
noncellular layer composed of interlacing collagen fibers and extracellular substances. Bowman’s
membrane provides form, stability, and strength to the cornea. The corneal stroma is the thickest
corneal layer, comprising about 90% of the corneal thickness. The stroma is formed by fibroblasts,
many layers of collagen bundles, and an amorphous ground substance rich in chondroitin sulfates
and keratan sulfate. The stroma lacks blood vessels. Descemet’s membrane is an extremely thick
basement lamina separating the stroma from the endothelium lining the cornea. This membrane
probably is the basement membrane of, and is secreted by, the corneal endothelium. The
endothelium lines the posterior aspect of the cornea and is composed of simple squamous cells
exhibiting numerous pinocytotic vesicles. The endothelium continually resorbs fluid from the
stroma, thus contributing the transparency of the cornea.

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 The cornea is supplied by diffusion. The centre of the cornea receives nutrition from the
aqueous humor in the anterior chamber of the eye; the periphery receives nutrition from the blood
vessels in the limbus. Corneal homografts are used with considerable success, because the cornea
does not contain any blood vessels or typical lymphatics.
Corneal transparency is due to the regular arrangement of its fibrous elements, the unique
composition of glycosaminoglycans, and the lack of blood vessels.
The cornea and the sclera join at the limbus. The anatomy of this region is complex, and the
area is quite significant clinically. The structures regulating the outflow of aqueous humor from
the eye are located here. They are the trabecular meshwork and the canal of Schlemm. These two
structures drain fluid from the anterior chamber of the eye into the venous system. Obstructions
that prevent drainage of aqueous humor from the eye may cause an increase in the intraocular
pressure, which is a characteristic feature of a severe common disease called glaucoma.
The vascular layer of the eye (the uvea) is the middle layer of the eye whose three parts are
the choroid, the ciliary body, and the iris.
The choroid is a thin layer just beneath the sclera. It consists of loose connective tissue,
contains many blood vessels and numerous melanocytes. The melanocytes absorb light and impart
to the choroid black colour in histologic sections. The choroid is composed of three layers: the
outer layer of arterioles and venules, the middle capillary layer, and the inner layer called Bruch’s
membrane. Bruch’s membrane is a thin structure; it is composed of a central core of elastic fibers
that are bordered on the one side by the endothelium basal lamina and on the other side by the
basal lamina of the retinal pigment epithelium.
The ciliary body is the region of the vascular tunic located between the visual retina and the
iris. The ciliary body is wedge-shaped and completely encircles the lens. Numerous long radially
arranged ciliary processes project from the thick ciliary body toward the lens. Suspensory
ligaments arise from the ciliary processes and insert into the lens capsule, serving to anchor it in
place. The ciliary body is composed of loose connective tissue, melanocytes, and blood vessels.
The main mass of the ciliary body, except the ciliary processes, consists of muscles of
accommodation called the ciliary muscles.
The inner surface of the ciliary body is lined with pigmented layer of the retina. This layer
lacks photoreceptors and extends anteriorly as the ciliary epithelium. The ciliary epithelium
consists of two cell layers: the outer unpigmented layer and the inner layer rich in melanin. The
epithelial cells lining the ciliary processes transport the blood plasma components to the posterior
chamber, forming the aqueous humor. The aqueous humor nourishes the lens and the other inner
structures of the eye and then flows over the lens, through the pupil, through the trabecular

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meshwork into the anterior chamber, and then through the canal of Schlemm into the eye venous
system.
The accommodation is the focus on a close object; it is a function of the ciliary muscles.
Contraction of the ciliary muscles reduces tension on the suspensory ligaments attached to the
lens, and the lens becomes more convex. This allows the lens to focus images of nearby objects
on the retina. Abnormalities in contraction of ciliary muscles may cause either myopia or
hypermetropia. Accommodation is gradually lost with advancing age due to the loss of the lens
elasticity, which results in presbyopia.
The iris is the most anterior extension of the choroid, separating the anterior and posterior
chambers one from another. The posterior surface of the iris rests on the lens forming an adjustable
opening, the pupil. The main mass of the iris consists of a loose, highly pigmented connective
tissue containing many blood vessels. The anterior surface of the iris is covered with a simple layer
of pigment cells; its deep surface is covered with a double-layer pigment epithelium. The
melanocytes in the stroma and pigment cells of the epithelium prevent light from entering the
interior of the eye, except via the pupil. The iris has colour. The hue of colour depends on the
amount of melanocytes and the quantity of melanin in them. If only a few melanocytes are present,
the eyes are blue; increasing amounts of pigment impart darker colours to the eyes.
The pupil (the iris aperture) varies in size with the amount of light in the environment. The
muscle dilating the pupil is arranged radially around the pupil; when it contracts, due to stimulation
by sympathetic nerve fibers, the pupil dilates. The muscle constricting the pupil is arranged in
concentric rings around the pupillary orifice, and when it contracts, due to stimulation by
parasympathetic nerve fibers, the pupil constricts. Thus, the pupillary muscles regulate the amount
of light entering into the eye.
The lens is a biconvex transparent flexible structure located directly behind the pupil. The
lens is held in place by the suspensory ligaments that arise from the ciliary body and insert upon
the lens equator. The suspensory ligaments keep tension on the lens, enabling it to focus on distant
objects. A degree of the lens convexity depends on the contraction or relaxation of ciliary muscles.
The lens consists of three parts: the lens capsule, the subcapsular epithelium, and the lens
fibers. The lens capsule is a basement membrane, produced by the underlying anterior epithelial
cells and lens fibers. The subcapsular epithelium is located only on the anterior surface of the lens.
It is composed of a single cuboidal cell layer. The lens fibers are highly modified elongated cells
that differentiate from the subcapsular epithelium. The mature lens fibers lack both nuclei and
organelles, but are filled with proteins called crystallins. New lens fibers are added at the equator,
but this function diminishes with increasing age. Cataract is opacity of the lens. Pigments or other
substances can accumulate in the lens fibers, and vision is impaired.

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 The vitreous body is the refractile gel filling the cavity between the lens and the retina. It is
composed mostly of water, collagen, and hyaluronic acid. The vitreous body also contains few
hyalocytes that secrete the collagen and hyaluronic acid. The collagen fibers in the vitreous body
lack the usual collagen periodicity. The remnant of the embryonic hyaloid artery forms the hyaloid
canal through the middle of the vitreous body.
The retina is the innermost tunic of the eye that is responsible for photoreception. The retina
has two main components: the pigmented retina (outer layer) next to the choroid and the neural
retina (inner layer) next to the vitreous body. Detachment of the retina occurs when the neural and
pigmented retinae become separated from each other. Since the nervous portion of the retina
depends on nutrients from the choroid diffusing through the pigmented epithelium of the retina, a
detached nervous portion undergoes degenerative changes unless it is successfully restored to its
normal position.
The pigmented retina or pigment epithelium consists of a layer of columnar cells firmly
attached to Bruch’s membrane. The junctional complexes (desmosomes, gap junctions, tight
junctions) attach the lateral borders of these cells together. This tightly joined layer of cells
probably is a barrier between the blood and the neural retina. The cells of the pigment epithelium
exhibit basal invaginations that contain basally located mitochondria, suggesting their involvement
in ion transport. The long microvilli extend from the apices of the pigment epithelial cells and
sheathe the tips of the rods and cones. The cells of pigment epithelium phagocytose the shed tips
of the outer segment of rods and cones. The melanin granules are found both apically and in cell
processes. The melanin synthesized by the pigment cells absorbs light after the rods and cones
have been stimulated. The pigment epithelium functions in esterification and the transport of
vitamin A, which is necessary for visual pigment formation by the rods and cones.
The neural retina consists of neurons, glial cells (Müller cells), and blood vessels. The latter
enter the retina via the optic disk and supply its inner portion; the outer portion is supplied by
diffusion from the choroid. The retinal neurons are at least of five types: the photoreceptor cells,
bipolar cells, ganglion cells, horizontal cells, and amacrine cells. The photoreceptors, bipolar cells,
and ganglion cells synapse with each other in a strict sequence and constitute the retinal neural
chain that is the initial link of the optic tract. The horizontal and amacrine cells form horizontal
bonds within the retinal layers and connect neurons with each other in a lateral fashion.
The neural retina includes two types of photoreceptor neurons called rods and cones. The
rods and cones have a nuclear region, dendrites from two parts – the outer and inner segments, and
a short axon forming a synaptic region. Their specialized dendrites, either rod-shaped or cone-
shaped, interdigitate with microvilli of the pigment epithelium cells; the axons form a synaptic
contact with bipolar and horizontal cells.

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 The outer segments of the rod and cone dendrites are photoreceptors. They contain multiple
layers of stacked plasma membranes and are rich in the photoreceptive pigments – rhodopsin in
rods and iodopsin in cones. The outer membrane structures are eventually shed and subsequently
phagocytosed by the pigment epithelium. The inner segments of each rod and cone contain a
concentration of mitochondria and other organelles. The inner segment is a metabolic centre of a
photoreceptor cell. It produces proteins that migrate to the outer segment, where they become
incorporated into the membranes. The outer and inner segments are separated by a constriction
that contains an incomplete cilium (without the two central microtubules) that terminates in a basal
body within the inner segment.
The number of rods is about 120 million in each human retina. The rods are long, slender
cells containing hundreds of stacks of flat close membranous disks in their outer segment. The
disks are not continuous with the plasma membrane of the rod cells. The rods contain rhodopsin
in their disks and are the receptors sensitive to light of low intensity (twilight or night vision); they
are responsible for black-white vision. Some rods may form synapses with one bipolar cell and
give rise to summation.
The number of cones is about 7 million in each human retina. They are photoreceptor cells
similar to rods, except for a cone-shaped outer segment. Their outer segments possess
invaginations of the plasma membrane (not disks) filled with the photosensitive pigment iodopsin.
Their inner segments contain a large lipid drop surrounded by numerous mitochondria known as
ellipsoid. The cones are sensitive to bright light and responsible for colour vision (day vision). The
cone synapses individually with the bipolar cell. Iodopsin is located in different amounts in various
types of cones, making the cone most sensitive either to the red, green, or blue region of the visual
spectrum, thus accounting for the three types of cones. Congenital absence of certain types of
cones results in daltonism, i.e., colour blindness.
The outer segments of rods and cones face the back of the eyeball so that light passes through
the inner layers of the retina before reaching the photosensitive region of these cells; it is the so-
called inverted type of the retina.
The molecule of photosensitive pigments rhodopsin and iodopsin is composed of opsin,
integral transmembrane protein, and retinal, an aldehyde form of vitamin A. Light interacts with
photopigments in the disks of the rods or invaginations of the cones, and retinal becomes
dissociated from opsins, which permits the diffusion of bound calcium from the membrane into
the cytoplasm of the outer segment. The excess of calcium ions acts to hyperpolarize the cell by
inhibiting the entrance of sodium ions into the cell (closing sodium channels). Ionic alterations
generate the electrical activity in the entire cell. Reassembly of retinal and opsins is an active
process occurring in the dark. It is accompanied by the recapture of calcium ions by the

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membranous disks or invaginations, with subsequent reopening of sodium channels, and a
reestablishment of the normal resting membrane potential.
The layers of the retina are complex and are 10 in number. They are (from outside inward):
(1) the pigment epithelium; its basement membrane is a part of Bruch’s membrane, as described
above;
(2) the layer of rods and cones consists of the outer segments of photoreceptor cells and microvilli
of the pigment epithelial cells that invest the tips of the rods and cones;
(3) the external limiting membrane is a region characterized by junctional specializations between
Müller (glial) cells and the photoreceptors;
(4) the outer nuclear layer where the nuclear regions of the rods and cones are located;
(5) the outer plexiform layer where synapses occur between the axons of the photoreceptor cells
and bipolar and horizontal cells; the synapses between the photoreceptor and the bipolar cells are
the first synapses of the optic tract, the horizontal cells synapse with numerous rods and cones in
a lateral fashion;
(6) the inner nuclear layer contains the cell bodies of bipolar cells, horizontal cells, amacrine cells,
and Müller cells;
(7) the inner plexiform layer where synapses occur between the axons of bipolar cells and the
dendrites of ganglion cells (the second synapses of the optic tract); the amacrine cell processes
connect the bipolar cells with ganglion cells in a lateral fashion;
(8) the ganglion cell layer contains the ganglion cell bodies – the final neurons in the retinal neural
chain;
(9) the optic nerve fibre layer consists of the unmyelinated axons of ganglion cells, which form
the fibers of the optic nerve; at the optic disk, each fibre acquires a myelin sheath;
(10) the inner limiting membrane represents termination of the Müller cell processes and their
associated basement membranes.
The optic disk is the area of the retina where the optic nerve pierces the sclera and leaves the
eye. Neither the rods nor cones are present in the region of the optic disk; therefore, this retinal
area lacks visual activity. The fovea centralis is the region of the retina that is responsible for the
greatest visual activity. It is a depression in the posterior wall of the retina containing only cones.
There are three functional apparatus in the eye. The refractive apparatus of the eye includes
the cornea, the aqueous humor in the anterior and posterior chambers of the eye, the lens, and the
vitreous body. All these structures are transparent; they pass the light through themselves and
refract it. The accommodative apparatus of the eye includes the iris and the ciliary body,
possessing intrinsic muscles. These muscles adjust the aperture of the iris, regulating the amount
of light entering into the eye, and alter the lens convexity permitting accommodation for close

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vision. The receptive apparatus of the eye includes only the neural retina that contains
photoreceptor neurons, namely, the rods and cones. These specialized cells encode the various
patterns of the image for transmission to the brain via the optic nerve.
Embryonic development of the eye
The eye develops initially as the optic vesicle from the forebrain (prosencephalon) – the
anterior part of the anterior cerebral vesicle of the embryo. The optic vesicle subsequently
invaginates to form a double-layer optic cup. The outer layer of the cup develops into the
pigmented layer of the retina, whereas the inner wall of the cup becomes the neural retina; the
attachment stalk of the optic vesicle develops into the optic nerve. At the same time the thickened
ectoderm in front of the optic cup bulges inward to form the lens vesicle. The lens vesicle is then
separated from the ectoderm from which it arose. The formation of the lens provides an example
of embryonic induction.
The neuromesenchyme (derived from the neural crest) surrounding the developing eye gives
rise to both the sclera and vascular tunic (except for the ectodermal corneal epithelium) including
the smooth muscles of the iris and ciliary body. The actively growing cells of the developing eye
require a special blood supply and this is provided, as the eye forms, by the hyaloid artery.

Organ of smell, the olfactory epithelium

The olfactory epithelium is located on the roof of the nasal cavity, on either side of the nasal
septum, and onto the superior nasal conchae. The olfactory mucosa has a pseudostratified ciliated
columnar epithelium, which makes the mucosa quite tall. This epithelium is modified for olfaction.
The olfactory epithelium contains three cell types: olfactory, supporting, and basal cells.
The olfactory cells are bipolar neurons. Their modified dendrites are characterized by a
bulbous projection (olfactory knob, olfactory vesicle), from which several cilia extend. The
olfactory cilia are nonmotile and very long; they contain membrane-bound chemoreceptors, which
recognize the structural differences of odoriferous substances. Serous glands in the mucosa
moisten these cilia to dissolve the chemicals of inspired air. The interaction between receptors and
stimulant molecules causes depolarization of the olfactory cell membrane, with subsequent
generation of an action potential. Compared to other animals, the human olfactory cells have
relatively short cilia, which results in a rather poorly developed sense of smell. For example, cats,
which have a keen sense of smell, have cilia that are up to 80 µm long .
Numerous unmyelinated axons of the olfactory cells form bundles called fila olfactoria,
which pass through the cribriform plate of the ethmoid bone to the brain and synapse with neurons
in the olfactory bulb.

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 The supporting cells have apical microvilli and a well-developed Golgi complex and look
like secretory cells. Supporting cells provide mechanical and metabolic support to the olfactory
cells. They function in a manner comparable with glial cells.
The basal cells rest on the basal lamina but do not extend to the surface, forming an
incomplete layer. Basal cells are undifferentiated and are believed to be regenerative both for
olfactory and supporting cells. Olfactory cells have a normal life span of about a month. If injured,
they are quickly replaced. Olfactory cells appear to be the only neurons that are replaced during
postnatal life.
The lamina propria of the olfactory mucosa contains many veins, unmyelinated nerves, and
Bowman’s glands. Bowman’s glands produce a watery serous secretion that is released onto the
olfactory epithelium surface via narrow ducts. The olfactory stimuli dissolve in this material, attain
the olfactory cell cilia, and then are carried away by the secretion to prepare the receptors for new
stimuli.

CONTROL PROBLEMS

1. The microphotograph shows a photoreceptor cell with a stack of flat membranous disks
in its outer segment. Name the photoreceptor cell. Which of the photosensitive pigments do the
disks contain? What light intensity is the photoreceptor cell sensitive to? Which kind of vision is
the photoreceptor cell responsible for?
2. The microphotograph shows a photoreceptor cell with numerous membranous
invaginations in its outer segment. Name the photoreceptor cell. Which of the photosensitive
pigments do the invaginations contain? What light intensity is the photoreceptor cell sensitive to?
Which kind of vision is the photoreceptor cell responsible for?
3. The lens is a biconvex transparent structure. If the lens focuses on distant objects, it
becomes flatter. If the lens focuses on close objects, it becomes more convex. Specify the
phenomenon. What eyeball structures cause the lens convexity to alter?
4. Vitamin A deficiency results in the impairment of twilight and night vision called night
blindness. Explain the pathogenesis of the disease.
5. Albinism (congenital lack of pigmentation (whiteness) of the hair, skin, eyes, etc.) is
characterized by day blindness, i.e., an impairment of vision in bright light. Explain why the
absence of melanin in the eye structures causes day blindness.
6. There are two histological slides of the retina. In the first slide, the melanin granules are
in the pigment epithelium cell bodies. In the second slide, the melanin granules are in the pigment

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epithelium cell processes. Which lighting condition (light or darkness) does each of the slides
correspond to?
7. Mountaineers are often blinded by Alpine snow when they climb to the top of the
mountain. Explain the phenomenon.
8. Patients with profuse discharge from the mucous membrane of the nose partially lose the
sense of smell. Explain the phenomenon.

CONTROL TESTS

Directions: each of the following statements contains five suggested completions. Choose
the one that is best in each case.
1. Each of the following statements concerning the cornea is true, EXCEPT: A – is
transparent; B – is avascular; C – receives nutrition by diffusion; D – is composed of five layers;
E – contains numerous melanocytes.
2. Each of the following statements concerning the corneal epithelium is true, EXCEPT: A
– is stratified squamous nonkeratinized; B – is transitional; C – is bathed by tears; D – is highly
innervated; E – arises from ectoderm.
3. Each of the following statements concerning the ciliary body is true, EXCEPT: A – is
avascular; B – is a modification of the eye vascular tunic; C – has processes with suspensory
ligaments; D – contains intrinsic muscles; E – takes part in accommodation.
4. Each of the following statements concerning the iris is true, EXCEPT: A – is a
modification of the eye vascular tunic; B – blocks light entering except via the pupil; C – lacks
colour; D – contains intrinsic muscles; E – regulates the amount of light entering the eye.
5. Each of the following statements concerning the photoreceptors is true, EXCEPT: A – are
bipolar neurons; B – form synapses with amacrine cells; C – their dendrites have the outer and
inner segments; D – their axons synapse with bipolar cells; E – their cell bodies constitute the
retinal outer nuclear layer.
6. Each of the following statements concerning the rods is true, EXCEPT: A – number about
120 million; B – their outer segments include flat membranous disks; C – contain rhodopsin; D –
are responsible for black-white vision; E – are excited by bright light.
7. Each of the following statements concerning the cones is true, EXCEPT: A – their outer
segments contain plasma membrane invaginations; B – their inner segments contain an ellipsoid;
C – are excited by low-intensity light; D – are responsible for colour vision; E – contain iodopsin.
8. The retinal inner nuclear layer contains nuclear regions of the following cells, EXCEPT:
A – bipolar cells; B – ganglion cells; C – horizontal cells; D – amacrine cells; E – Muller cells.

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 9. The retinal ganglion cell layer contains the cell bodies of: A – photoreceptors; B –
horizontal cells; C – amacrine cells; D – bipolar cells; E – ganglion neurons.
10. The retinal optic nerve fibre layer contains the axons of neurons: A – amacrine; B –
ganglion; C – bipolar; D – horizontal; E – photoreceptor.
11. The optic nerve is composed of: A – photoreceptor dendrites; B – bipolar cell axons; C
– amacrine cell dendrites; D – ganglion cell axons; E – horizontal cell axons.
12. The retinal external and internal limiting membranes are formed by the processes of: A
– glial cells; B – photoreceptors; C – amacrine cells; D – ganglion cells; E – horizontal cells.
13. Each of the following statements concerning the pigmented epithelium is true, EXCEPT:
A – consists of columnar cells; B – its cells have processes investing the outer segments of
photoreceptors; C – contains melanin granules; D – contains the photosensitive pigment; E – is the
outermost retinal layer.
14. Each of the following statements concerning the pigmented epithelium functions is true,
EXCEPT: A – transports vitamin A and nutrients from the choroid; B – phagocytoses shed tips of
rods and cones; C – absorbs light; D – takes part in light adaptation; E – transmits nervous
impulses.
15. Each of the following statements concerning the olfactory cells is true, EXCEPT: A –
are bipolar neurons; B – their dendrites are characterized by bulbous projections; C – the cilia
extend from their olfactory knobs; D – they are mechanoreceptors; E – their unmyelinated axons
are gathered into the fila olfactoria.

Directions: one or more of the given statements or completions is/are correct. Choose the
answer: A – if only 1,2, and 3 are correct; B – if only 1 and 3 are correct; C – if only 2 and 4 are
correct; D – if only 4 is correct; E – if all are correct.
16. The following statements regarding the sclera are true: (1) consists of dense connective
tissue (2) maintains the eye shape (3) serves as the attachment site for oculomotor muscles (4) is
transparent
17. The following statements regarding the aqueous humor are true: (1) is produced by
ciliary processes (2) flows from the posterior eye chamber into the anterior eye chamber (3)
outflows via the canal of Schlemm into the eye venous system (4) is related to glaucoma
18. The following statements regarding the eye limbus are true: (1) contains the canal of
Schlemm (2) is corneal-scleral junction (3) its blood vessels provide corneal nutrition (4) contains
muscles of accommodation
19. The following statements regarding the choroid are true: (1) consists of loose connective
tissue (2) is highly vascular (3) contains numerous melanocytes (4) absorbs light

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 20. The following statements regarding the lens are true: (1) is an epithelial structure (2)
possesses its own capsule (3) consists of transparent fibres (4) is biconvex
21. The following statements regarding the vitreous body are true: (1) is refractile gel (2)
contains few hyalocytes (3) is composed of water, collagen, and hyaluronic acid (4) takes part in
accommodation
22. The following statements regarding the photoreceptors are true: (1) their inner segments
are cell metabolic centres (2) their tips are shed and phagocytosed (3) their outer segments face
the back of the eye (4) their axons synapse with horizontal cells and bipolar neurons
23. The following neurons of the retina constitute the initial link of the optic tract: (1)
photoreceptors (2) bipolar cells (3) ganglion cells (4) amacrine cells
24. The following neurons form horizontal bonds within the retinal layers: (1) Muller cells
(2) horizontal cells (3) bipolar cells (4) amacrine cells
25. The retinal layer of rods and cones consists of: (1) photoreceptor dendrites (2) cell bodies
of rods and cones (3) pigmented epithelium processes (4) axons of rods and cones
26. The retinal outer plexiform layer contains: (1) photoreceptor axons (2) bipolar cell
dendrites (3) horizontal cell processes (4) the first synapse of the optic tract
27. The retinal inner plexiform layer contains: (1) bipolar cell axons (2) ganglion cell
dendrites (3) the second synapse of the optic tract (4) amacrine cell processes
28. The following statements regarding the optic disk are true: (1) lacks rods and cones (2)
the optic nerve leaves the eye here (3) lacks visual activity (4) contains only two retinal layers
29. The following statements regarding the fovea centralis are true: (1) is a depression on
the posterior retinal wall (2) contains only cones (3) is a region of the greatest visual activity (4)
the optic nerve leaves the eye here
30. The olfactory epithelium consists of the following cells: (1) olfactory cells (2) basal cells
(3) supporting cells (4) glial cells
31. The following statements regarding the olfactory reception are true: (1) olfactory cilia
contain chemoreceptors (2) odoriferous substances dissolve in the olfactory gland secretion (3)
interaction between the olfactory molecules and receptors causes the cell membrane depolarization
(4) after interaction molecules are carried away by olfactory gland secretion to prepare receptors
for new stimuli

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 FIGURES

Fig. 10.1. Eyeball structure

I – eyeball: 1 – cornea; 2 – iris; 3 – ciliary body; 4 – sclera; 5 – retina; 6 – lens; II – retina layers:
1 – pigment epithelium; 2 – layer of rods and cones; 3 – outer nuclear layer; 4 – outer plexiform
layer; 5 – inner nuclear layer; 6 – inner plexiform layer; 7 – ganglion cell layer; 8 – optic nerve
fiber layer; III – the retina yellow sport: 1 – fovea centralis; 2 - retina layers; 3 – choroid; 4 –
sclera.

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 Fig. 10.2. Photoreceptor neurons
A – the rod; B – the cone; I – outer segments; II – connecting pieces; III – inner segments; IV –
cell bodies; V – axons; 1 – membranous disks (in the rod) or membrane invaginations (in the
cone); 2 – plasmalemma; 3 – cilia; 4 – ellipsoid (in the cone); 5 – mitochondria; 6 – endoplasmic
reticulum; 7 – nuclei; 8 – synapses.

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 Fig. 10.3. Olfactory epithelium
I – the olfactory epithelium; II – connective tissue (mucosa lamina propria); 1 – olfactory
neurons; 2 – dendrites; 3 – olfactory knob; 4 – axons; 5 – olfactory cilia; 6 – microvilli; 7 –
supporting cells; 8 – basal cells; 9 – basement membrane; 10 – fila olfactoria; 11 – olfactory
gland.

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 12. SECONDARY SENTIENT SENSE ORGANS: ORGAN of HEARING,
ORGAN of EQUILIBRIUM, and ORGAN of TASTE

The group of secondary sentient sense organs includes organ of hearing, organ of
equilibrium, and organ of taste. They contain epithelial receptor cells called neuroepithelial cells.
The sensory neuron dendrites (afferent fibers) synapse with the neuroepithelial cells, forming
afferent contacts that transmit impulses generating by receptor cells to the first neuron of
appropriate sensory tract. Thus, the sensory neurons of these organs are secondary sentient because
they do not interact with stimuli and receive information from receptor neuroepithelial cells.
Organ of hearing and equilibrium, the ear
The ear is the vestibulocochlear apparatus; it contains mechanoreceptors whose motion is
converted to electrical impulses, which are transmitted to the brain. The brain interprets the
impulses as sounds, a sense of the body’s position in space, or of the head movement. The ear has
three regions: the external ear, the middle ear, and the inner ear.
The external ear is composed of the auricle, the external auditory meatus, and the tympanic
membrane. The auricle contains irregular plates of the elastic cartilage tissue covered with thin
skin. The wall of the external auditory canal is composed of the elastic cartilage in the outer third
and the bone tissue in the inner two-thirds. The skin that lines the meatus is similar to the skin of
the auricle, but also contains a highly modified type of apocrine sweat glands called ceruminous
glands, which produce earwax (cerumen). The combined secretion of the sebaceous and the
ceruminous glands may accumulate, forming ceruminal plugs and keeping out sound waves.
The tympanic membrane separates the external auditory meatus and the tympanic cavity. Its
external surface is covered with a stratified squamous keratinized epithelium; its internal surface
is lined with a simple cuboidal epithelium. The tympanic membrane possesses fibroelastic
connective tissue interposed between these two epithelial coverings.
The middle ear contains the tympanic cavity, the auditory ossicles, and the auditory tube
(eustachian tube). The tympanic cavity is a small irregular space lying within the temporal bone.
The medial wall of the tympanic cavity possesses the oval window and the round window
separating the middle ear and the inner ear from each other. The cavity is lined with a simple
squamous epithelium and is air-filled, because it communicates with the nasopharynx via the
auditory tube. Any infection may reach the tympanic cavity from the upper respiratory tract.
Middle ear infections (tympanitis) are sometimes complications of head colds, particularly, in
children.

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 The auditory tube is lined with a pseudostratified ciliated columnar epithelium. Its lamina
propria has mucous glands and, in the medial portion, may be extensively infiltrated with
lymphocytes, which may form discrete nodules called the tubal tonsils.
The auditory ossicles include the malleus, incus, and stapes. The ossicles are arranged in
series: the malleus attached to the tympanic membrane articulates with the incus, which, in turn,
articulates with the stapes, which is attached to the oval window. The ossicles transmit movements
set up in the tympanic membrane by sound waves to the oval window. The latter transmits the
vibrations to the perilymph of the inner ear; thus, the amplitude of vibrations is decreased, but the
force is increased, because the ossicles are arranged to exert leverage.
The internal (inner) ear occupies a complex cavity in the petrous portion of the temporal
bone called the osseous (bony) labyrinth, which is divided into three parts: the cochlea, vestibule,
and semicircular canals. The cochlea is a spiral-shaped cavity with an axis formed by the pillar of
bone called the modiolus. The vestibule includes the saccule and utricle; the semicircular canals
are three in number and are oriented perpendicular to each other. Each semicircular canal possesses
a dilated region named the ampulla. The cochlea contains the organ of hearing known as the spiral
organ of Corti. The vestibule and semicircular canals contain the organ for detecting motion and
maintaining equilibrium.
All parts of the bony labyrinth are filled with perilymph. The bony labyrinth houses the
membranous labyrinth; it is contained within the bony labyrinth and is lined with the endothelium.
This closed system of membranous tubes and sacs is filled with a fluid termed endolymph, and, at
appropriate sites, sensory receptors are arranged inside these membranous structures. The
endolymphatic fluid and cellular debris are removed from the endolymph through the
endolymphatic duct to the subdural endolymphatic sac.

Organ of hearing
The cochlea is a bony tube that spirals 2.5 times around the modiolus, an osseous spiral core.
The cochlea has a broad base and tapers up like a cone. The cochlea houses the cochlear duct that
contains the spiral organ of Corti, which responds to various sound frequencies.
The cochlea has three compartments: the upper passage, the scala vestibuli; the lower
passage, the scala tympani; the intermediate passage, the cochlear duct (scala media). The cochlear
duct contains endolymph. The scala vestibuli and scala tympani are perilymphatic spaces. The
former ends at the oval window and the latter ends at the round window of the tympanic cavity.
The scala vestibuli and the scala tympani communicate with each other at the helicotrema – a small
opening located at the apex of the cochlea.

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 The cochlea is divided into three passages by the osseous spiral lamina, the vestibular
membrane, and the basilar membrane. The osseous spiral lamina is a lateral projection of the
modiolus. The periosteum of the spiral lamina upper lip is modified to form the spiral limbus. The
vestibular membrane extends between the spiral limbus and the wall of the cochlea; it is bordered
by the scala vestibuli (above) and the cochlear duct (below). The vestibular membrane is composed
of two layers of endothelial cells separated from each other by their intervening basal laminae.
One cellular layer faces and lines the scala vestibuli; the other layer faces and lines the roof of the
cochlear duct.
The basilar membrane is a thick membrane that extends between the spiral lamina and the
spiral ligament. The latter is the thickened periosteum of the cochlea on the outer wall of the
cochlear duct. The basilar membrane is bordered by the cochlear duct (above) and the scala
tympani (below). The basilar membrane is a thick layer of amorphous material that contains about
20,000 keratin-like fibrils. These fibrils project away from the spiral lamina and have proximal
free ends that may vibrate. The lower surface of the basilar membrane is lined with the endothelial
cells of the scala tympani; the upper surface of the basilar membrane contains the spiral organ of
Corti.
The lateral aspect of the cochlear duct, the spiral ligament, is lined with a modified
epithelium called the stria vascularis. The stria vascularis consists of a pseudostratified epithelium
and is vascularized by capillaries. The stria vascularis secretes endolymph and is involved in the
maintenance of the unusual ionic composition of this fluid, creating the hight positive charge called
the endolymphatic potential.
The epithelium of the stria vascularis extends onto the basilar membrane. The cells of
Claudius and the cells of Boettcher are present in the epithelium before it reaches the organ of
Corti. Numerous microvilli on the apical surfaces of these cells suggest that they have secretory
and/or absorptive functions.
The spiral organ of Corti lies upon the basilar membrane and is composed of many different
types of cells: two kinds of hair cells and six kinds of supporting cells. The hair cells are
neuroepithelial and are divided into the inner and outer hair cells. The inner hair cells are bulbous
in shape, their nuclei are basally located, and they contain many mitochondria concentrated around
the nucleus. Their free surface displays few elongated stiff stereocilia arranged in a straight line.
The inner hair cells are organized as a single cellular row along the entire length of the cochlea.
The outer hair cells are columnar in shape; their nuclei are round, basally located, and
surrounded by many mitochondria. Their free surface has many (approximately 100) long stiff
stereocilia that are arranged in a V-formation. The outer hair cells are organized in three or more
rows along the entire length of the cochlea.

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 Both inner hair cells and outer hair cells are associated with phalangeal cells and form
synaptic contacts with afferent and efferent nervous endings. The tips of the hair cells are
embedded in the tectorial membrane, which projects away from the spiral limbus into the scala
media. The tectorial membrane is a glycoprotein-rich viscous material; it is secreted by the
epithelium covering the spiral limbus.
The supporting cells of the organ of Corti are tall and slender and contain conspicuous
tonofibrils. Their apical surfaces contact with each other, hair cells, or both to form a continuous
surface called the reticular membrane. The supporting cells include the inner and outer phalangeal
cells, the inner and outer pillar cells, the border cells, and the cells of Hensen.
The inner and outer phalangeal cells are the supportive elements that are intimately
associated with the inner and outer hair cells, respectively. The phalangeal cells rest on the basilar
membrane. Each phalangeal cell has a cup-like indentation on its apical surface. The inferior third
of a hair cell rests in this depression. The apical portion of phalangeal cells expands into umbrella-
like phalangeal processes, which contact with the apical portions of the hair cells. The phalangeal
cells also support the slender nerve fibers that form synapses with the hair cells.
The inner and outer pillar cells possess a wide base and have elongated processes that contain
microtubules, intermediate filaments, and actin microfilaments. They both rest on the basament
membrane; their apices are intimately associated with each other. These cells enclose a space
called the inner tunnel of Corti. The inner tunnel contains afferent and efferent nerve processes
that pass through phalangeal cells and synapse with the hair cells.
The spiral organ of Corti contains two tunnels: the inner and outer tunnel. The inner tunnel
is enclosed by the inner and outer pillar cells, as described above. The outer tunnel is located
between the cells of Hensen and the outer hair cells. Both tunnels are filled with endolymph and
communicate with each other via intercellular spaces.
The cells of Hensen and border cells delineate the inner and outer borders of the spiral organ
of Corti. The outer border is made of the cells of Hensen; they are continuous with the cells of
Claudius. The inner border of the organ of Corti is made of the border cells that continue into the
region of the inner phalangeal cells.
The spiral ganglion is housed inside the spiral lamina and contains the cell bodies of afferent
bipolar neurons. The dendrites of these cells innervate the hair cells of the organ of Corti; their
axons make up the nerve fibers of the eighth cranial nerve and project into the central nervous
system.

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 Hearing
The vibration of the tympanic membrane is transmitted through the auditory ossicles to the
oval window and, thus, to the perilymph of the scala vestibuli and scala tympani. Vibrations in the
perilymph cause vibrations in the basilar membrane and its fibers. The fibers are thick and short
near the base of the cochlea; near the apex of the cochlea, they are longer and more slender. The
short fat fibers vibrate in resonance with high-frequency sounds; the long thin fibers vibrate in
resonance with low-frequency sounds. Thus, the maximum amplitude of the basilar membrane
displacement varies with the sound stimulus frequency.
The vibration is sensed by the hair cells as a result of their stereocilia, which are rigidly
supported at their base by the reticular lamina, becoming displaced with respect to the tectorial
membrane, in which their tips are embedded. This causes the hair cells to alter the pattern of
impulse activity in the afferent nervous fibers they contact with. It is noteworthy that some large
efferent nerve endings that contain synaptic vesicles are believed to transmit impulses to the hair
cells. Auditory impulses from the afferent endings on hair cells are carried by fibers toward nerve
cell bodies in the spiral ganglion. A single dendrite of an afferent neuron may have many branches
and so receives impulses from many hair cells. The bipolar cells of the spiral ganglion send their
axons (as the cochlear division of the auditory nerve) to end synaptically in the cochlear nuclei of
the brain stem.

Organ of equilibrium, the vestibular apparatus

The vestibular apparatus includes two maculae in the saccule and utricle, and three cristae
in the ampullae of the semicircular canals.
The maculae are specialized sensory regions located within the endolymph-filled cavities,
the saccule and utricle, occupying the bony vestibule. The maculae are composed of different
epithelial types: two types of neuroepithelial hair cells and supporting cells. The free surface of
the macula is covered with a gelatinous material probably secreted by the supporting cells and
containing small calcified particles called the otoliths. This gelatinous layer is termed the otolithic
membrane.
The neuroepithelial hair cells are of two types and distinguished primarily by their type of
afferent innervation, although they vary somewhat in shape too. Type I neuroepithelial hair cells
are bulbar in shape. Their expanded portion contains a round nucleus, numerous mitochondria,
and a well-developed Golgi apparatus. Their free surface displays from 50 to 100 elongated rigid
microvilli (stereocilia) arranged in a bundle and a single kinocilium located aside of the bundle.
The kinocilium has the typical microtubular arrangement of a cilium. The hairs of neuroepithelial

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cells do not freely float in the endolymph but are embedded in the otolithic membrane. The basal
portion of type I cells is almost completely surrounded by a cup-shaped afferent nerve ending.
Type II neuroepithelial hair cells are columnar in shape, possess basally located round nuclei,
and have many mitochondria and a well-developed Golgi apparatus. Their free surface displays
from 50 to 100 long rigid stereocilia arranged in a bundle and a single kinocilium located aside of
the bundle. The small afferent terminations make contact with the basal portion of these cells.
The supporting cells occupy the spaces between the hair cells. These cells are columnar in
shape; their nuclei are round and basally located. They possess many microtubules that project
from the base of the cell into an extensive terminal web.
The maculae in the utricule and saccule are sensors of gravity, vibrations, and linear
accelerations. The macula hair cells are stimulated by the otolith and the otolithic membrane
movements, which, in turn, are generated by the head movements. The macula is arranged
vertically in the saccule and horizontally in the utricle, so that the linear acceleration (positive or
negative) of the head in these two planes is detected by the central nervous system.
The semicircular ducts are located in the semicircular canals. They are three in number and
are oriented perpendicular to each other. The semicircular ducts contain endolymph that
communicates with that in the utricle and the saccule. Each duct possesses a dilated region, the
ampulla, which houses a crista, i.e., a sensory structure that resembles a macula. The crista is a
sensory receptor site composed of two types of neuroepithelial hair cells and supporting cells. The
free surfaces of these cells are covered with a thick glycoprotein layer called the cupula. The cupula
has a conical shape over the receptor cells and contains no otoliths.
The semicircular canals and the crista ampullaris are regarded as sensors of the angular
movements of the head and, hence, of the body as a whole. The cristae of the three semicircular
ducts are positioned perpendicular to each other; therefore, the angular accelerations along any of
the three axes is detected by the central nervous system. The nervous impulses that are generated
by the hair cells of the maculae and cristae are transmitted to the brain via the vestibular portion
of the acoustic nerve.

Organ of taste, the taste buds

The taste buds are small, intraepithelial structures containing specialized receptors, which,
when stimulated by contact with food, give rise to the nerve impulses that result in sensations of
taste. The taste buds are located on the lateral surfaces of the lingual papillae. The lingual papillae
are little projections of the mucous membrane on the dorsal surface of the tongue. Each papilla is
covered by stratified squamous epithelium and has a central primary papilla of the lamina propria.

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In all lingual papillae, connective tissue cores form secondary papillae, which interdigitate with
the overlying epithelium.
There are four types of papillae on the tongue: filiform, fungiform, foliate, and circumvallate.
The fungiform, foliate, and circumvallate papillae contain taste buds in their lateral epithelium.
The filiform papillae are covered by keratinized epithelium and do not contain taste buds.
Each taste bud is a group of epithelial cells arranged around a small central cavity called the
taste pit, like slices in an orange. A taste pore is located on the apical surface of the taste bud and
leads to the taste pit. In humans, the taste buds are composed of three different types of cells:
supporting (sustentacular), neuroepithelial, and basal cells. The neuroepithelial cells are taste
receptor cells; the sustentacular cells support them. The electron micrographs display long
microvilli on the apical surface of both the receptor cells and the sustentacular cells, which pass
through the taste pore to be bathed in saliva. These microvilli are described by light microscopists
as the taste hairs. The apical microvilli of neuroepithelial cells contain chemoreceptors that
function in the perception of the four taste sensations: salt, bitter, sweet, and sour. The nerve fibers
from the basal surface of the buds synapse with neuroepithelial cells.
In order to be tasted, substances must exist in solution and pass through the taste pores into
the taste pits. Here, the chemoreceptors are stimulated and generate impulses in the afferent nerve
fibers, which they synapse with.
Taste impulses from the anterior two thirds of the tongue are carried by the chorda tympani
division of the facial nerve and from the posterior third by the glossopharyngeal nerve.
Nonmyelinated afferent fibers of these nerves enter the proximal end of taste buds and synapse
with the neuroepithelial cells, as described above.
The average life span of neuroepithelial and sustentacular cells is as short as 10 days. Both
types of cells differentiate from the third kind found in a basal position in the taste bud – the basal
cells. Taste receptors are as vulnerable to hazards as the epithelium, in which they are located.
New receptor cells are formed continuously by differentiation of the basal cells in the taste buds.

CONTROL PROBLEMS

1. A student wrote in his project that the organ of hearing is secondary sentient, because it
develops from the otic vesicle. Is the student right?
2. A student studies the auditory conducting tract and hesitates to locate the first neuron
body. Where are the first auditory neurons located? Where do their dendrites and axons pass?
Identify the cells on which the dendrites form the afferent synapses?

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 3. The electron micrograph shows a neuroepithelial cell with the nerve fiber endings on its
basal portion. Name two types of the nerve fibers that innervate neuroepithelial cells. What
contacts do the nerve fibers form on the neuroepithelial cells?
4. The electron micrograph demonstrates a neuroepithelial cell with numerous stereocilia
and a single kinocilium on its apical surface. A student supposes that the cell belongs to the spiral
organ. Is he right?
5. The mode of action of a hearing-aid is based on the intensification of endolymph and
perilymph vibrations in the inner ear. Select in which cases the use of the hearing-aid is effective:
(1) the acoustic nerve damage, (2) ankylosis of the auditory ossicle, (3) the tympanic membrane
trauma, (4) the hair cell injury.
6. The patient’s perception of gravity is disturbed. Specify the receptor cells whose function
is lost.
7. One of the symptoms of gastrointestinal disorders is a “furred tongue.” Explain why the
sense of taste is impaired in this case?

CONTROL TESTS

Directions: each of the following statements contains five suggested completions. Choose
the one that is best in each case.
1. Each of the following statements concerning the cochlea is true, EXCEPT: A – is formed
by a spiral bony tube; B – contains the osseous core, modiolus; C – consists of the saccule and
utricle; D – houses the cochlear duct; E – contains the spiral organ of Corti.
2. The spiral ganglion is located in: A – scala media; B – spiral lamina of the modiolus; C –
scala vestibuli; D – tunnel; E –scala tympani.
3. The sensory neurons of the organ of hearing are located in: A – stria vascularis; B – spiral
ligament; C – tunnel; D – spiral ganglion; E – spiral organ.
4. Each of the following statements concerning the basilar membrane is true, EXCEPT: A –
separates the scala media and the scala vestibuli; B – consists of a thick layer of amorphous
material; C – contains keratin-like fibrils; D – the spiral organ is located on its upper surface; E –
separates the scala media and the scala tympani.
5. Each of the following statements concerning the stria vascularis is true, EXCEPT: A –
secrets endolymph; B – rests on the spiral ligament; C – consists of the psuedostratified epithelium;
D – is vascularized by capillaries; E – is a thickened periosteum of the spiral lamina.
6. The following cells of the spiral organ enclose the tunnel of Corti: A – outer hair cells; B
– outer phalangeal cells; C – pillar cells; D – inner hair cells; E – inner phalangeal cells.

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 7. Each of the following statements concerning the outer hair cells is true, EXCEPT: A – are
columnar in shape; B – are chemoreceptors; C – are arranged in three rows; D – their stereocilia
are arranged in V-formation; E – form point-like contacts with afferent fibres.
8. Each of the following statements concerning the inner hair cells is true, EXCEPT: A – are
arranged in a single row; B – are bulbous in shape; C – their stereocilia are arranged in a straight
line; D – are chemoreceptors; E – form cup-like contacts with afferent fibres.
9. Each of the following statements concerning the vestibular macula is true, EXCEPT: A –
contains supporting cells; B – contains two types of neuroepithelial cells; C – is covered with the
otolithic membrane containing otoliths; D – is a sensor of gravity; E – detects angular
accelerations.
10. Each of the following statements concerning the vestibular cristae is true, EXCEPT: A
– are three in number; B – their covering contains otoliths; C – are oriented perpendicular to each
other; D – are covered with the cupula; E – are the sensors of angular accelerations.
11. Each of the following statements concerning the vestibular neuroepithelial cells is true,
EXCEPT: A – are bulbar and columnar in shape; B – rest on supporting cells; C – possess
numerous stereocilia; D – lack the kinocilium; E – are mechanoreceptors.
12. Each of the following statements concerning the neuroepithelial cells of the taste buds is
true, EXCEPT: A – are not capable of renewal; B – are arranged around the taste pit; C – possess
microvilli on their apical surface; D – are chemoreceptors; E – synapse with afferent nerve fibres.

Directions: one or more of the given statements or completions is/are correct. Choose the
answer: A – if only 1,2, and 3 are correct; B – if only 1 and 3 are correct; C – if only 2 and 4 are
correct; D – if only 4 is correct; E – if all are correct.
13. The following statements regarding the modiolus are true: (1) is osseous (2) contains the
cochlear nerve (3) has a spiral lamina (4) is the cochlear axis
14. The following cochlear passages contain perilymph: (1) scala media (2) scala tympani
(3) cochlear duct (4) scala vestibuli
15. The following cochlear passages contain endolymph: (1) scala media (2) scala tympani
(3) tunnel of Corti (4) scala vestibuli
16. The following statements regarding the spiral lamina are true: (1) is a lateral projection
of the modiolus (2) contains the spiral ganglion (3) its thickened periosteum forms the spiral
limbus (4) has the upper and the lower lips
17. The spiral organ of Corti consists of the following cells: (1) phalangeal cells (2) pillar
cells (3) hair cells (4) neurons

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 18. The following statements regarding the phalangeal cells of the spiral organ are true: (1)
rest on the basement membrane (2) possess phalangeal processes (3) are supporting cells (4) have
cup-like depressions for hair cells
19. The tunnel of Corti contains: (1) perilymph (2) endolymph (3) keratin-like fibrils (4)
dendrites of sensory neurons
20. The following statements regarding the tectorial membrane are true: (1) consists of
glycoprotein-rich material (2) projects away from the spiral limbus (3) covers the hair cell tips (4)
contains afferent nervous fibres
21. The maculae of the vestibular apparatus are located in: (1) saccule (2) ampullae of
semicircular canals (3) utricle (4) cochlea
22. The cristae of the vestibular apparatus are located in: (1) saccule (2) utricle (3) cochlea
(4) ampullae of semicircular canals
23. The movements of the following structures stimulate the vestibular neuroepithelial cells:
(1) otoliths (2) cupula (3) otolithic membrane (4) tympanic membrane
24. The taste buds are located on the lateral surface of following lingual papillae: (1)
fungiform (2) foliate (3) circumvallate (4) filiform
25. The following statements regarding the taste buds are true: (1) consist of supporting,
neuroepithelial, and basal cells (2) contain taste pits (3) their taste pores open into the interpapillar
space (4) contains neurons
26. The following statements regarding the basal cells of the taste buds are true: (1) are stem
cells (2) give rise to supporting cells (3) give rise to neuroepithelial cells (4) are neurons

FIGURES

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 Fig. 11.1. Cochlear duct and spiral organ
I – cochlea appearance; II – cochlear duct (scala media): 1 – vestibular membrane; 2 – cochlear
duct filled with endolymph; 3 – stria vascularis; 4 – spiral ligament; 5 – basilar membrane
(tympanic wall); 6 – spiral organ; 7 – outer hair cells; 8 – inner hair cells; 9 – outer phalangeal
cells; 10 – outer and inner pillar cells; 11 – tunnel; 12 – inner phalangeal cells; 13 – afferent
neuron dendrites; 14 – afferent neurons of the spiral ganglion; 15 – spiral lamina; 16 – tectorial
membrane; III – outer (a) and inner (b) hair cells: 1 – stereocilia; 2 – organelles; 3 – nuclei; 4 –
synaptic vesicles; 5 – afferent and efferent nerve endings; 6 – cup-shaped synapse.

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 Fig. 11.2. Organ of equilibrium
I – parts of the inner ear: 1 – the semicircular canal ampullae; 2 – the utricle; 3 – the saccule. II –
the macula: 1 – neuroepithelial cells; 2 – supporting cells; 3 – nerve fibers; 4 – the otolithic
membrane; 5 – otoliths. III – neuroepithelial cells: 1 – type I cell; 2 – kinocilium; 3 – stereocilia;
4 – synapse; 5 – afferent nerve fiber; 6 – type II cell; 7 – supporting cell; 8 – efferent nerve
endings. IV – the crista: 1 – neuroepithelial cells; 2 – supporting cells; 3 – nerve fibers; 4 – the
cupula.

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 Fig. 11.3. Taste bud
1 – neuroepithelial receptor cell; 2 – supporting cell; 3 – basal cell; 4 – cells of the tongue
stratified epithelium; 5 – microvilli; 6 – nerve ending; 7 – nerve fiber; 8 – mucus; 9 – taste pore.

13. CARDIOVASCULAR SYSTEM

The сardiovascular (or circulatory) system is a transport system. There are two main
circulatory systems: the blood circulatory system and the lymphatic circulatory system. The blood
circulatory system carries oxygen, carbon dioxide, nutrients and metabolic breakdown products,
cells of the immune system, hormones and many other important substances. The lymphatic
system drains extracellular fluid from the tissues, returning it to the blood after having passed
through the lymph nodes.

Blood circulatory system

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 The blood circulatory system consists of the heart, arteries, veins, and vessels of
microcirculation. The microcirculatory bed includes arterioles, capillaries, venules, and arteriolo-
venular anastomoses or shunts.
General structure of the blood vessel wall
Blood vessel wall consists of three tunics, which vary in prominence in different vessel
types. These tunics are as follows: tunica intima, tunica media, and tunica adventitia.
The tunica intima is composed of a lining layer of highly specialized multifunctional
flattened cells termed endothelium. Endothelial cells rest on a basal lamina, under which there is
a very thin layer of loose connective tissue called subendothelial layer. In some arteries, the tunica
intima contains the internal elastic membrane.
Endothelium is highly specialized with endocrine, exocrine, cell adhesion, clotting, and
transport functions. Endothelium is a slowly renewing population of infrequently dividing cells.
Endothelial cells of veins have greater mitotic potential than those of arteries. Endothelial cells
produce some components of the basement membrane (proteoglycans, fibronectin, laminin, etc).
Endothelium is nonthrombogenic because it surface has a negative charge; blood platelets have a
negative charge, too; thus, they repel each other. Owing to its charge, the intact endothelium is not
attractive for blood cells. Conversely, subendothelial structures (especially collagen) are
thrombogenic and highly attractive for the blood cells. Hence, uninjured endothelium prevents
thromboformation.
Endothelium produces some substances that modulate blood coagulation and vasodilatation.
For instantce, endothelial cells produce prostacyclin, which inhibits platelet aggregation; nitric
oxide, which promotes vasodilatation and inhibits platelet adhesion and aggregation;
thromboplastin, which promotes blood coagulation; Willebrand factor promotes platelet adhesion
and activation of blood coagulation.
Endothelial cells take part in the regulation of the vascular tone. This regulation is associated
with the receptors on the endothelial surface.
Endothelial cells take part in capillary permeability. The exchange diffusion is possible due
to the high permeability of endothelium. Actually, the endothelial transport appears to be a very
complex process. Some molecules are delivered to the endothelial cell itself (pinocytosis), whereas
others are transported across the endothelial cells to the surrounding tissues (transcytosis). Some
molecules use both of these pathways.
The tunica media is composed of smooth muscle cells arranged circularly, a fine network
of collagen and elastic fibers, elastic membranes, and the ground substance containing
proteoglycans and glycoproteins.

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 The tunica adventitia is composed of loose connective tissue; smooth muscle cells may be
present, particularly in veins. The adventitia contains autonomic nerves, which innervate the vessel
smooth muscle cells, and small blood vessels, the vasa vasorum. The vasa vasorum send
penetrating branches into the tunica media.
Differences and peculiarities of the vessel structure depend on the hemodynamic conditions
(the blood pressure, blood speed, blood volume, diration of the blood stream, etc.).
Arteries
Arteries are classified into tree types: elastic arteries, muscular arteries, and mixed arteries.
Elastic (conducting) arteries are the aorta, brachiocephalic artery, and common carotid artery.
Muscular (distributing) arteries are large (from 2 to 10 mm in diameter) or small (from 0.1 to 2
mm in diameter) receiving blood from elastic arteries and distributing it to tissues and organs.
Mixed (conducting) arteries are transitional segments between elastic and muscular arteries. This
group includes: the axillary, external carotid, common iliac, and subclavian arteries.
The muscular artery tunica intima consists of a single continuous layer of squamous
endothelium cells lying on the basal lamina, subendothelial loose connective tissue, and prominent
internal elastic membrane. In small muscular arteries, the subendothelial layer is absent. Tunica
media is made up of several layers of helicoidally arranged smooth muscle cells. There are from
3 to 10 layers in small arteries and from 10 to 60 layers in large muscular arteries. A fine network
of collagen and elastic fibers as well as the ground substance containing proteoglycans and
glycoproteins surround muscle layers but smooth muscle cells predominate. Tunica externa
includes external elastic membrane, loose connective tissue, vasa vasorum, lymphatic, and nerve
fibers.
The elastic artery tunica intima consists of endothelium and the subendothelial layer of
loose connective tissue with longitudinally disposed bundles of smooth muscle cells. The inner
elastic membrane is absent but there are many bundles of elastic fibers instead of it. Tunica media
shows concentrically arranged fenestrated elastic membranes (from 50 to 70) interconnected by
elastic and collagen fibers, circumferentially disposed smooth muscle cells, and the ground
substance containing proteoglycans and glycoproteins. It should be noted that elastic structures
(fenestrated elastic membranes and elastic fibers) predominate. Tunica externa is from loose
connective tissue including vasa vasorum, lymphatic, and nerve fibers.
The mixed artery tunica intima is composed of endothelial cells, subendothelial layer of
loose connective tissue, and an inner elastic membrane. Tunica media consists of fenestrated
elastic membranes, smooth muscle cells, collagen and elastic fibers, and the ground substance.
Tunica externa is from loose connective tissue containing vasa vasorum, lymphatics, and nerve
fibers.

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 In arteries, vasa vasorum supply only tunica adventitia and external portion of tunica media,
whereas internal part of tunica media and tunica intima are supplied by diffusion from blood
stream.
Veins
From venules, the blood is collected in veins of increasing size: small, medium, and large
veins consistently. The veins are classified in two types: fibrous or unmuscular veins (they are
devoid of smooth muscle cells) and muscular veins. The muscular type is subdivided into the
following subtypes: with a small content of smooth muscle cells, with a moderate content of of
smooth muscle cells, and with a large content of of smooth muscle cells. The vein wall structure
conforms to the general three-layer arrangement in the circulatory system.
The wall of unmuscular veins consists of only two tunics. The tunica intima contains
endothelium resting on the basement membrane. The tunica media is absent. The tunica externa is
from loose connective tissue. This type of veins includes: meningeal and dural sinuses, veins of
the retina, bones, splenic trabeculae, the maternal part of placenta, and the nail bed.
The wall of muscular veins with a small content of smooth muscle cells consists of tree
tunics. The tunica intima is represented by endothelium on the basement membrane. The tunica
media contains either1or 2 circular layers of smooth muscle cells, the ground substance, collagen,
and elastic fibers. The tunica externa is from loose connective tissue.
In veins with a moderate content of smooth muscle cells, the tunica intima includes
endothelium on the basement membrane and a thin subendothelial layer. The tunica media contains
several layers of smooth muscle cells arranged in a circular fashion, the ground substance,
collagen, and elastin fibers. The tunica externa contains loose connective tissue and smooth
myocytes in longitudinal orientation.
In veins with a large content of smooth muscle cells, the tunica intima consists of
endothelium on the basement membrane, the subendothelial layer, and smooth myocytes in
longitudinal disposition. The tunica media contains several circular layers of smooth muscle cells,
the ground substance, collagen and elastic fibers. The tunica externa contains loose connective
tissue and bundles of smooth myocytes oriented longitudinally.
For example, the vena cava inferior is muscular vein with a large content of smooth muscle
cells; it contains myocytes in all tunics. Its tunica adventitia is approximately five times thicker
than the tunica intima and tunica media together. The adventitia contains bundles of longitudinally
arranged myocytes surrounded by collagen fibers.
There are some structural differences between the arteries and veins. Veins have a very thin
subendothelial layer. About 50% of veins have valves that prevent the backflow of the blood (the
vena cava inferior is devoid of valves). Valves consist of semilunar projections of the venous

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tunica intima; the projections are composed of loose conncective tissue lined on both sides by the
endothelium.
Veins have a poorly developed framework of elastic fibers and lack internal and external
elastic membranes (except for the vena cava inferior, wich has the internal elastic membrane).
Note that the adventitia of veins is the thickest tunic. In veins, the vasa vasorum supply three wall
tunics: the intima, the media, and the adventitia.

Microcirculatory bed
Microcirculation is concerned with the exchange of gases, fluid, nutrients and metabolic
waste products. Most of this exchange between blood and tissues occurs in the capillaries. The
blood flow within the capillaries is controlled by arterioles and muscle sphincters in the arteriolo-
capillary junctions called the precapillary sphincters. Blood from the capillaries enters the system
of venules.
Arterioles vary in diameter ranging from 30 to 400 nm (0.4 mm). The arteriolar wall is
composed of three layers: the intima, the media, and the adventitia. The intima includes the
endothelial cells lying on a basement membrane and a fine internal elastic membrane, usually not
continuous. The media consists of one or two layers of smooth muscle cells. Note that endothelial
cells have basal processes, which pierce the basement membrane and make junctional contact with
the smooth muscle cells. The latter forms precapillary sphincters. The adventitia is a very thin
layer of loose connective tissue.
Arterioles are very responsive to vasoactive stimuli and make a major contribution to
vascular resistance. I.M. Sechenov termed them the taps of the circulatory system.
Blood capillaries are the smallest vessels of the blood circulatory system (from 5 to 10 nm
in diameter) and form a complex interlinking network. Their function is the site of interchange of
different substances between blood and tissues, less often (in the lung, the intestine) between blood
and environment. That is why their wall is very thin. It consists of three layers: (1) endothelial
cells; (2) endothelial basement membrane; (3) and adventitional layer. Endothelial cells contain
many special transfer vesicles – pinocytotic vesicles. The second layer includes the pericytes
enclosed by the basement membrane. The basement membrane and pericytes support endothelial
cells. Moreover, the basement membrane takes part in capillary permeability. Pericytes can
produce proteoglycans, collagen, and elastic fibers. They contain actin and myosin filaments
suggesting a contractile function. Pericytes can give rise to smooth muscle cells during vascular
growth and after tissue injury. They can pass information from the intercellular space (interstitia)

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to endothelial cells due to the presence of junctions between endothelial cells and pericytes. The
third layer (the adventitional layer) consists of adventional cells of loose connective tissue.
Capillaries may be of three types: continuous, fenestrated, and discontinuous. In continuous
capillary, continuous endothelial cells are held together with the zonula occludens, gap junctions,
and desmosomes. Continuous basement membrane is thick (from 20 to 50 nm). This type of
capillaries is found in the muscle tissues, testis, ovary, brain, lung, and connective tissues.
In fenestrated capillary, very thin endothelial cells with fenestrations are held together with
the zonula occludens, gap junctions, and desmosomes. Fenestrations are formed of two cell
membranes, which are situated so near each other that it is not possible to observe even a short
distance between them. Basement membrane is continuous and encloses pericytes. Fenestrated
capillaries are found in the endocrine glands, kidney, and the small intestine.
In discontinuous capillary, endothelial cells are with large pores. These cells are held
together with a zonula occludens and gap junctions. The basement membrane is scanty,
discontinuous or absent at all. This type of capillaries is found in the spleen, lymphatic nodes, bone
marrow, and the liver.
Fenestrated and discontinuous capillaries are usually very large (from 20 to 35 nm in
diameter) and are characterized as sinusoidal capillaries or sinusoids. These capillaries are present
in organs, which functions and metabolism requier extremely intensive exchange (the liver,
endocrine glands, and bone marrow).
Venules. The capillaries drain blood into postcapillary venules (from10 to 15 nm in
diameter). Their wall is similar in structure to that of the capillaries, but they have more pericytes.
The blood flow in this venule is sluggish, and this venule appears to be the main point at which
white blood cells enter and leave the circulation.
Postcapillary venules drain blood into collecting venules. They are larger in diameter (from
20 to 50 nm) with a continuous layer of pericytes. Collecting venules drain blood into muscular
venules. They contain one or two layers of smooth muscle cells in tunica media and a well-
developed tunica adventitia. Muscular venules drain blood into small veins.
Shunts (anastomoses). The blood can be also shunted from arterioles bypassing the
capillary bed directly to venules via anastomoses. These vessels have a thick wall with an average
diameter of 12 to 15 nm, which may vary from 100 to 300 nm in length. Such shunts are frequent
in the skin of the finger-tips and toes, the nail beds, lips, nose, intestinal tract, thyroid, and erectile
tissue. The shunts are classified into three types. The first type of anastomoses is called simple
with supplementary smooth muscle cells within the media. These cells are rather short and thick,
forming a sphincter that on section resembles a stratified cuboidal epithelium. These cells have
been termed epitheliod cells. The second type of anastomoses is called the glomerular type with

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supplementary smooth muscle cells within the media. There are two or three branches, which have
a structure similar to that of the first type. But all of these branches have common adventitia and
this complex resembles a glomerulus on histological sections. The third type of anastomoses
contains smooth muscle cells within the intima. These muscle cells are arranged in bundles and
oriented longitudinally. Besides, some muscle cells occur within the media. Note that these
anastomoses contain a large number of both myelinated and nonmyelinated nerve fibers.
The anastomoses take part in the regulation of the blood flow to the organs and hence in the
regulation of the organ activity. The skin anastomoses paticipate in termoregulation. They dilate
in cold weather to shunt the blood to the venules to reduce the heat loss; they constrict in hot
weather allowing blood to pass through the skin capillaries to increase the heat loss.

Lymph vascular system

The lymph vascular system drains excess fluid (lymph) from the extracellular space and
returns it to the blood vascular system. Lymph is formed in the following way. Water and
electrolytes pass out of capillaries into the extracellular space; some plasma proteins also leak out
through the endothelial wall. The excess fluid is drained by a system of lymph capillaries. Lymph
sluggishly flows from the capillary network into the larger lymphatic vessels. On the way to larger
veins, the lymph passes through one or more lymph nodes. During their passage any antigen can
be processed by the components of the immune system. Lymph enters the venous system by a
single vessel on each side of the body, namely, the thoracic duct and the right lymphatic duct.
Lymphatic vessels are found in all organs, except the central nervous system, cartilage, bones, red
bone marrow, thymus, placenta, cornea, and teeth.
The structure of lymphatic vessels is similar to that of veins. But lymphatic vessels have
numerous valves that prevent the backflow of lymph. Lymphatic capillaries differ from blood
capillaries in several aspects. Lymphatic capillaries are blind-ending tubules. Their endothelial
cells are very thin and held together with the zonula occludens. In the lacteals (blind sac-like
lymphatic capillaries) of the intestinal villi, there are apertures between endothelial cells. The
basement membrane is rudimentary or absent; there are no pericytes. Note that the fine collagen
filaments known as anchoring filaments link to the endothelium and to the surrounding thick
collagen fibers, preventing the collapse of the lymphatic capillaries.

Heart
The heart is a muscle organ that pumps blood in the circulatory system. The wall of the heart
is composed of three tunics: the endocardium, myocardium, and epicardium.

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 Endocardium forms a complete lining for the atria and ventricles and covers all the
structures projectng into them such as valves, chordae tendineae, and papillary muscles.
Endocardium consists of four layers: (1) endothelium resting on the basement membrane; (2)
subendothelial layer of loose connective tissue; (3) muscular-elastic layer consisting of smooth
muscle cells, elastic and collagen fibers; (4) external or deep layer of loose connective tissue also
called the subendocardial layer. This layer contains blood vessels and branches of the impulse-
conducting system (Purkinje’s fibers).
It should be noted that there are no blood vessels in the endocardium, except the external
layer. The endocardium is supplied by diffusion from blood in the heart chambers (mainly in the
left heart part) or from the myocardium (mainly in the right heart part). In embryosenesis, the
endocardium arises from mesenchyme like blood vessels.
Myocardium mainly consists of the striated cardiac muscle tissue. A thin layer of loose
connective tissue with many blood capillaries surrounds cardiac muscle cells. The myocardium
contains numerous blood and lymphatic vessels as well as a large number of unmyelinated
parasympathetic and sympathetic nerve fibers.
Cardiac muscle cells are cylindrical in shape, have one to two centrally located nuclei. Some
cells are connected by anastomoses. Cardiomyocytes are joined end-to-end by cell junctions called
intercalated discs to form functional fibers.
At the end of the 19th century the German scientist Ebner, using special staining, described
some dark strips on the fibers of the myocardium. He called these strips intercalated discs. He was
the first to suppose that intercalated discs are the borders between two adjacent cells, and the
myocardium has cellular structure.
The amount of the myocardium and the diameter of cardiomyocytes vary according to the
workload of the chamber. The left and right atria have a thin wall composed of cells of small
diameter. The right ventricular myocardium is composed of cells intermediate in diameter between
atrial and left ventricular muscle cells. The left ventricle has the thickest myocardium and muscle
cells with the largest diameter.
Ultrastructure of cardiomyocytes resembles that of skeletal muscle fibers. Cardial muscle
cells contain many striated myofibrils and numerous longitudinally arranged mitochondria, which
reflect the extreme dependence of myocardium on aerobic metabolism. The intracellular
membrane network surrounding the myofilaments known as L-system (sER) is well-developed.
The T-tubular network is simpler and wider in cardiac myocytes than in skeletal muscle fibers. As
a rule, one T-tubule and one cistern of the L-system form a diad (in skeletal muscle fibers, two L-
tubules and one T-tubule form a triad). The sarcoplasm of cardiac muscle cells is characterized by
numerous lipid droplets and glycogen particles, reflecting nutrient reserves.

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 The intercalated disk is the means by which cardiomyocytes are electrically and
mechanically linked. It allows cardiomyocytes to function in an integrated fashion. The
intercalated disk includes intercellular junctions, i.e., specialized membrane regions that provide
electrical coupling and mechanical adhesion between adjacent cells. These junctions are as
follows: fascia adherens junctions, gap junctions, and desmosomes.
The fascia adherens junction anchors intracellular actin filaments to the plasma membrane.
Each fascia adherens consists of a submembranous dense attachment plaque containing
placoglobin, a network of actin filaments attached to the plasma membrane by alpha-actinin and
vinculin, and a very thin space filled with adhesive glycoprotein.
The gap junction (nexus) provides a low-resistance passway across the membranes of
adjoining cells. These junctions are the sites where small molecules and ions readily pass as well
as excitation spreads from one cell to another.
Desmosomes serve to anchor the plasma membranes to the intermediate cytoskeletal
filaments of cardiac muscle cells.
There are some structural differences between atrial and ventricular cardiomyocytes. Atrial
myocytes are smaller in diameter. They lack T-tubules but contain a lot of micropinocytic vesicles
associated with the plasmalemma. The intercalated discs between atrial myocytes include more
nexuses then discs between ventricular cells.
Some atrial cells contain special atrial electron-dense granules, a well-developed rER, and
Golgi complex. The granules are the site of storage of polypeptide hormone called atrial natriuretic
factor (ANF). This hormone causes a fall in arterial pressure as well as a significant diuresis and
natriuresis. Additionally, ANF inhibits the secretion of several hormones involved in the
regulation of water–salt balance (aldosterone, renin, and ADH).
Epicardium is the internal sheet of the pericardium. It consists of thin connective tissue
layer covered with flat mesothelial cells to produce a smooth outer surface. The epicardium
contains nerves and blood vessels that supply the heart wall. The coronary arteries and veins are
surrounded by adipose tissue, which expands the epicardium. In embryogenesis, the epicardium
and myocardium arise from the visceral layer of mesoderm (myoepicardial plate).

Impuls-conducting system
It is known that the heart contracts involuntarily. Atrial and ventriclar contractions do not
depend on nerve stimulation. They depend on the impulses generated within the heart itself in the
impuls-conducting system consisting of modified cardiac muscle cells (atypical cardiomyocytes).
The pace of this beating action is initiated at the sinoatrial node (SA-node) located where
the vena cava superior enters the right atrium. This node is composed of special cells with unusual

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electrophysical characteristics called pacemaker cells. These cells are small, contain only few
myofibrils and lack an organized striation pattern. There are no intercalated disks between them;
the cells connect with each other by only desmosomes. SA-node has many nerve endings.
The SA-node conducts impulses to the atrioventricular (AV) node located beneath the
endocardium of the medial wall of the right atrium (above the tricuspid valve ring). The AV-node
is also composed of the pacemaker cells. The pacemaker cells of the SA- and AV-nodes are
embedded in connective tissue with numerous blood vessels and nerve fibers.
Some small cells form a distinct bundle extending from the anterior end of the AV-node. It
is called the bundle of His. The bundle of His conducts impulses from the AV-node to Purkinje
fibers (cells). Purkinje fibers lie in clusters of up to about six cells. They are larger than the
ventricular cardiomyocytes, have few myofibrils and mitochondria, lack T-tubules, and contain a
large amount of glycogen. Conducting cardiomyocytes are anaerobic cells. Purkinje fibers transmit
impulses to transitional cells, which conduct impulses to the contractile ventricular cells.
Transitional cells are smaller than Purkinje’s cells. They look like typical cardiomyocytes but
without T-tubules. It is impossible to identify them under LM.

Central fibrous skeleton of the heart

The central fibrous skeleton of the heart anchors the heart valves and chambers together.
The skeleton is composed of dense connective tissue. Dense connective tissue forms the fibrous
ring of the aorta, the pulmonary artery, and the left and right atrioventricular rings. Besides, a
downward extension of dense connective tissue of the aortic valve ring forms a fibrous septum
between the right and left ventricles.

CONTROL PROBLEMS

1. There are two arteries in the slide. One of the arteries contains the internal elastic
membrane between the tunica intima and the tunica media as well as the external elastic membrane
between the tunica media and the tunica adventitia. The second artery contains numerous elastic
membranes in its tunica media. Identify the types of the arteries.
2. The electron micrograph shows the transverse section of a blood capillary. Its endothelial
cells possess sites of thinned cytoplasm; its basal membrane is continuous. Specify the type of the
blood capillary. What organs contain this type of capillaries?
3. There are two cells in the blood capillary wall. One of them rests on the basal membrane;
the other cell is enclosed by the basal membrane. What do we call these cells?

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 4. The electron micrograph shows a capillary. Its endothelial cells lack the basal membrane
but are attached to the surrounding collagen fibrils by the anchoring filaments. Specify the
capillary.
5. There are two veins in the slide. One of them contains smooth muscle cells only in its
tunica media. The other vein contains muscle cells in all the tunics, predominantly in the tunica
adventitia. Identify the types of the veins. Which one belongs to the lower part of the body?
6. Hypoxia (low oxygen content) results in functional myocardial disorder. Why are
contractile cardiomyocytes more vulnerable to hypoxia than conducting cardiomyocytes?

CONTROL TESTS

Directions: each of the following statements contains five suggested completions. Choose
the one that is best in each case.
1. Each of the following statements concerning the elastic type arteries is true, EXCEPT: A
– their tunica intima is relatively thick, contains smooth muscle cells and elastic fibres; B – they
are the largest-diameter arteries; C – blood pressure in these arteries is the least; D – their internal
and external membranes are not conspicuous; E – elastic fenestrated membranes are predominate
in their tunica media.
2. Each of the following statements concerning the arterioles is true, EXCEPT: A – the
internal elastic membrane may or may not be present in their tunica intima; B – blood pressure in
them is the highest in the arterial bed; C – their tunica media has one or two smooth muscle layers;
D – their smooth muscles form precapillary sphincters; E – they control blood flow to the capillary
bed.
3. The microcirculatory bed includes the following vessels, EXCEPT: A – arterioles; B –
venules; C – capillaries; D – arteriovenous anastomoses (shunts); E – lymphatic ducts.
4. Each of the following statements concerning the capillaries is true, EXCEPT: A – contain
smooth muscle cells; B – consist of endothelial cells on the basal lamina; C – their diameter is
often smaller than that of erythrocytes; D – possess selective permeability; E – histamine increases
capillary permeability.
5. Each of the following statements concerning the continuous capillaries is true, EXCEPT:
A – are endothelial tubules; B – typically found in endocrine glands; C – their endothelial cells are
joined by tight junctions; D – their endothelial cells abound in pinocytotic vesicles; E – pericytes
enclosed by the endothelial basal membrane may be found.
6. Each of the following statements concerning the postcapillary venules is true, EXCEPT:
A – consist of endothelium on the basal lamina; B – contain pericytes; C – contain smooth muscle

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cells; D – are the sites of histamine action; E – leukocytes emigrate through their wall into tissues
(especially in inflammation and allergic reactions).
7. Each of the following statements concerning the vein structure is true, EXCEPT: A – is
devoid of the internal and external elastic membranes; B – contains few elastic elements; C – blood
vessels supply all its layers; D – its tunica media is thicker than the tunica adventitia; E – its tunica
intima may possess valves.
8. Each of the following statements concerning the endocardium is true, EXCEPT: A –
includes endothelium and subendothelial layer; B – contains middle layer of elastic fibres and
smooth muscle cells; C – is supplied by diffusion; D – possesses blood vessels; E – has a deeper
layer of connective tissue.
9. The myocardium consists of the following structures, EXCEPT: A – typical cardiac
muscle cells; B – atypical cardiac muscle cells of the impulse-conducting system; C – abundance
of adipose tissue; D – blood vessels; E – connective tissue.
10. Each of the following statements concerning the epicardium is true, EXCEPT: A – it is
the internal sheet of the pericardium; B – consists of mesothelial cells and underlying connective
tissue; C – contains blood vessels and nerves; D – is supplied by diffusion; E – contains adipose
tissue.
11. Each of the following statements concerning the heart valves is true, EXCEPT: A – have
the central core of fibrous tissue; B – their surfaces are covered with endothelium; C – fibrous
cords extend from the valve free edge to papillary muscles; D – prevent blood backflow; E –
possess their own blood vessels.
12. Each of the following statements concerning the impulse-conducting system is true,
EXCEPT: A – consists of atypical cardiac muscle cells; B – contains neurons; C – includes the
sinoatrial and atrioventricular nodes; D – includes the bundle of His and Purkinje fibres; E –
generates and conducts impulses for cardiac muscle.
13. Each of the following statements concerning the lymphatic capillaries is true, EXCEPT:
A – have a continuous basal lamina; B – are formed by endothelial cells; C – drain most tissues;
D – are blind-ending tubules; E – anchoring filaments extend between the lymphatic endothelium
and the perivascular collagen.
14. Each of the following statements concerning large lymphatic vessels is true, EXCEPT:
A – are similar to venules in structure but have a larger lumen; B – lack valves; C – return lymph
to the venous system; D – their thin walls make it difficult to distinguish tunics; E – lymph moves
due to compression of lymph vessels by adjacent skeletal muscles.

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 Directions: one or more of the given statements or completions is/are correct. Choose the
answer: A – if only 1,2, and 3 are correct; B – if only 1 and 3 are correct; C – if only 2 and 4 are
correct; D – if only 4 is correct; E – if all are correct.
15. The vascular tunica intima consists of: (1) endothelium on the basal lamina (2)
subendothelial connective tissue layer (3) internal elastic membrane (mainly in arteries) (4)
circular layer of smooth muscle cells
16. The following statements regarding the vascular tunica media are true: (1) consists of
circular layers of smooth muscle cells (2) contains a variable amount of elastin (mainly in arteries)
(3) contains reticular fibres and proteoglycans secreted by smooth muscle cells (4) is relatively
thick in arteries and relatively thin in veins
17. The following statements regarding the vascular tunica adventitia are true: (1) consists
of loose connective tissue (2) contains blood vessels and nerves (3) is separated from the tunica
media by the external elastic membrane (mainly in arteries) (4) is relatively thin in arteries and
relatively thick in veins
18. The following statements regarding the artery structure are true: (1) the tunica media is
its thickest layer (2) possesses the internal and external elastic membranes (except elastic type
arteries) (3) its tunica media abounds in elastic elements (fibres or membranes) (4) blood vessels
supply only its outer portion, the inner portion is supplied by diffusion
19. The arteries are classified into the following types: (1) muscular (2) muscular-elastic (3)
elastic (4) without muscles
20. The following statements regarding the muscular-elastic arteries are true: (1) are
branches of elastic arteries (2) blood pressure is higher in these arteries than in aorta (3) their tunica
media contains approximately an equal amount of smooth muscle cells and elastic elements (4)
blood vessels supply three layers of their wall
21. The following statements regarding the muscular arteries are true: (1) blood pressure is
the highest in these arteries (2) they are small-calibre arteries (3) they lack the internal and external
elastic membranes (4) smooth muscle cells are predominant in their tunica media
22. In embryogenesis the blood vessels are derived from: (1) endoderm (2) ectoderm (3)
mesoderm (4) mesenchyme
23. The capillaries are divided into the following types: (1) continuous (2) fenestrated (3)
discontinuous (4) mixed
24. The following statements regarding the fenestrated type capillaries are true: (1) are
characterized by fenestrations (2) their fenestrations provide channels in the capillary wall (3) have
pinocytotic vesicles (4) typically found in muscles

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 25. The following statements regarding the discontinuous type capillaries are true: (1)
typically found in the liver, spleen, and bone marrow (2) are characterized by multiple pores in
endothelial cells and between them (3) are characterized by the absence of the basal lamina under
pores (4) pericytes may be found in their wall
26. The veins are classified into the following types: (1) elastic (2) muscular (3) muscular-
elastic (4) unmuscular or fibrous type
27. The muscular veins are subdivided into the following groups: (1) with a small muscle
content (2) with a moderate muscle content (3) with a large muscle content (4) muscular-elastic
28. The following statements regarding the fibre type veins are true: (1) they usually convey
blood towards gravity (2) their wall consists of the tunica intima and the tunica adventitia (3) their
wall is devoid of the tunica media (4) they contain muscles in the tunica adventitia
29. The smooth muscle cells are located in the veins with a large muscle content: (1)
circularly in the tunica media (2) longitudinally in the tunica intima (separate cells) (3)
longitudinally in the tunica adventitia (bundles of cells) (4) longitudinally in the tunica media
30. The heart embryonic origins are as follows: (1) endoderm (2) mesoderm (3) ectoderm
(4) mesenchyme
31. The following statements regarding the arteriovenous anastomoses are true: (1) may be
simple and complex (2) convey blood to venules bypassing the capillary bed (3) regulate organ
blood filling (4) serve in termoregulation at body surface
32. The following statements regarding the Purkinje fibres are true: (1) contain few
myofibrils (2) are rich in glycogen (3) are glycolytic (anaerobic) cells (4) transmit excitation to
typical cardiac muscle cells

FIGURES

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 Fig. 12.1. Arteriole
1 – endothelial cell; 2 – basement membrane; 3 – internal elastic membrane; 4 – smooth muscle
cell; 5 – endothelium–myocyte junction; 6 – adventitial cell; 7 – connective tissue fibers.

Fig. 12.2. Blood capillary types

A – continuous capillary; B – fenestrated capillary; C – discontinuous capillary; 1 – adventitial
cell; 2 – endothelial cell; 3 – basement membrane; 4 – pericytes; 5 - endothelium–pericytes
junction; 6 – fenestrations; 7 – nerve endings; pores in endothelial cells and basement
membrane.

Fig. 12.3. Lymphatic capillary

1 – capillary luman; 2 – anchoring filaments; 3 – collagen fibers; 4 – endothelial cells.

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 Fig. 12.4. Cardiomyocytes and intercalated disk
1 – basal membrane; 2 – myofibrils; 3- mitochondria; 4 – T-tubules; 5 – L-tubules (sER); 6 –
lysosomes; 7 – intercalated disk; 8 – nexus; 9 – zona of myofibril attachment; 10 – desmosome;
11 – glycogen; 12 – M-line; 13 – Z-line.

14. CENTRAL ORGANS of HEMOPOIESIS: RED BONE MARROW and

THYMUS
Blood formed element development or hemopoiesis
Hemopoiesis takes place in the embryonic period (prenatal) and in the postnatal life. Prenatal
hemopoiesis is subdivided into three stages (see below). Postnatal hemopoiesis occurs in the red
bone marrow where erythrocytes, granulocytes, monocytes, platelets, and B lymphocytes are
formed. The development of T lymphocytes starts in the bone marrow and concludes in the
thymus. The bone marrow and thymus are called the central organs of hemopoiesis where antigen-
independent proliferation and differentiation of lymphocytes occur. As for T and B lymphocytes,
contact with antigens is needed for their final differentiation (antigen-dependent proliferation and
differentiation). For this, lymphocytes migrate to the peripheral organs of hemopoiesis, such as
the spleen, lymph nodes, tonsils and lymphatic nodules (follicles) scattered in the mucosa of the
alimentary canal, the conducting portion of the respiratory system, and the urethral and urinary
bladder mucosa.

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 Prenatal hemopoiesis
The organs of blood cell formation change several times during the fetal development; the
earliest site is the wall of the yolk sac.
The first phase of prenatal hemopoiesis is called the yolk sac phase. There, hemopoiesis
begins in the 3rd week of development and continues to the 9th week. Hemopoiesis occurs in the
“blood islands” in the wall of the yolk sac. The “blood islands” are groups of mesenchyme cells.
The peripheral island cells change their shape (get flattened) and differentiate into endothelial
cells. The central island cells become round in shape and turn to the stem hemopoietic cells of the
first generation. Stem cells differentiate into megaloblasts, which give rise to megalocytes,
primitive erythrocytes that are large and have nuclei. It should be noted that in this embryonic
period, angiogenesis and hemopoiesis occur concurrently; since magalocyte formation takes place
inside the vessels this is termed intravascular hemopoiesis. On the contrary, the development of
primitive leukocytes (only granulocytes) is extravascular process.
The second phase of prenatal hemopoiesis is called hepatic phase. The first generation of
stem cells migrates to the embryo liver. Hemopoiesis in the liver begins in the 6th week of
development. The liver becomes the major organ of hemopoiesis. The formation of all blood cells
takes place extravascularly. Erythrocytes have their usual shape, lack nuclei, and contain specific
fetal form of hemoglobin (HbF). HbF is the principal hemoglobin in the fetus.
The third phase of prenatal hemopoiesis is called medullar phase. The stem cells of the
second generation initially migrate to the red bone marrow, then gradually to the spleen and lymph
nodes. Hemopoiesis stops in the 5th month in the spleen and in the 15th week in the lymph nodes.
The red bone marrow becomes the dominant hemopoietic organ in the latter half of gestation;
hemopoiesis in the liver ceases. All blood cells, except T lymphocytes, are produced in the
marrow, and hemopoiesis continues throughout postnatal life. T cell precursors originate in the
marrow and migrate to the thymus where they undergo subsequent differentiation. From the
second month of gestation, the thymus is engaged in T cell production only.
Although the liver is hemopoietically inactive after birth, it retains potential for blood formed
element production. In the cases of bone marrow failure or chronic anemia, hemopoiesis may be
resumed in the liver or in the spleen. This phenomenon is termed extramedullary hemopoiesis.
Postnatal hemopoiesis
At birth, almost all bones are involved in hemopoiesis. Over the next few years, only the
marrow of the vertebrae, ribs, skull, pelvis, and proximal femurs is hemopoietic. In the rest bones,
the red marrow having been replaced by adipose tissue and turns to the yellow bone marrow.
Hemopoietic cells of the postnatal blood development can be subdivided into six classes.

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 The first class is represented by stem cells, from which all blood cells originate. Although
there is no direct evidence of the structure of stem cells, they were supposed to look like small
lymphocytes. The stem cells are pluripotential cells, meaning that they are able to differentiate
into any type of blood formed elements. Hemapoietic stem cells divide infrequently. They are held
in reserve and are not even in the cell cycle, being in G0 period. These cells can form differentiating
colonies termed colony-forming units (CFU).
The second class includes multipotential cells arised from the stem cells. Two main types
of progenitor cells derive: (1) lymphoid progenitor cells, which give rise to T and B lymphocytes;
(2) myeloid CFU, progenitor cell, which give rise to erythrocytes, granulocytes, monocytes and
megakaryocytes (CFU-GEMM) *. Although no direct evidence of the structure of these cells,
indirect evidence indicates that they are morphologically similar to the stem cells and look like
small lymphocytes.
The third class contains unipotential cells derived from the multipotential CFU-GEMM
cells. They are committed but still look like small lymphocytes. Unipotentinal cells are as follows:
erythroid (CFU-E), which gives rise only to erythrocytes; monocyte (CFU-M), which gives rise
only to monocytes; neutrophil (CFU-N), which gives rise only to neutrophils; eosinophil (CFU-
Eo), which gives rise only to eosinophils; basophil (CFU-Bas), which gives rise only to basophils;
megakaryocyte (CFU-Meg), which gives rise only to platelets; T lymphocyte precursor (CFU-T),
which gives rise only to T lymphocytes; B lymphocyte precursor (CFU-B), which gives rise only
to B-lymphocytes.
The fourth class contains precursor cells termed blast cells. Under the LM, it is impossible
to differentiate them from each other but they can be distinguished from the cells mentioned above.
Blast cells are larger in diamiter than small lymphocytes; they have large euchromatic nuclei and
light blue cytoplasm.
The fifth class includes differentiating maturing cells. The sixth class includes mature
blood formed elements.
Erythropoiesis
The first recognizable erythrocyte precursor is known as the proerythroblast, a large cell
with a lot of ribosomes and no hemoglobin. The next stage (basophilic erythroblast) is
characterized by numerous ribosomes and little hemoglobin. The cytoplasm of these cells stains
deeply with basic dyes. The intermediate stage (polychromatophilic erythroblast) is characterized
by the loss of ribosomes and the accumulation of hemoglobin. The late stage of erythroblasts
(acidophilic erythroblasts or normoblasts) is characterized by the progressive loss of ribosomes

*
CFU – colony-forming unit; G – granulocyte, E – erythrocyte, M – monocyte, Meg – megakaryocyte.

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and progressive accumulation of hemoglobin. Due to the presence of hemoglobin, the cell
cytoplasm is acidophilic.
With maturation (beginning with erythroblasts), the cell size decreases; the nucleus becomes
smaller, markedly heterochromatic, and without nucleoli. The nucleus is lost at the stage of
acidophilic erythroblasts.
The erythroblast pool is maintained by the proliferation of basophilic and
polychromatophilic erythroblasts. Acidophilic erythroblasts are postmitotic, i.e., they lack the
ability to divide.
After nucleus extrusion, young erythrocytes called reticulocytes contain a relatively small
number of ribosomes that are aggregated with RNA in reticular clusters. Reticulocytes may be
revealed in blood smears stained with special dyes (toluidine blue). They constitute about 1% of
circulating erythrocytes in normal human blood.
The mature erythrocytes (VI class) there are no nuclei and organelles; their cytoplasm is full
of hemoglobin. Spectrin and actin filaments associated with the internal aspect of the
plasmalemma maintain biconcave erythrocyte morphology and play a role in reversible
deformation of these postcellular structures.
Note that erythropoiesis is controlled by hormons erythropoetins produced by the kidneys.
Erythropoetins stimulate the last 3 to 5 divisions in erythroid maturation.
Granulopoiesis
The first cells of the fifth class are promyelocytes arised from myeloblasts (derived from the
Greek myelos meaning “marrow”). These cells are characterized by the development of the
primary azurophilic granules.The primary granules are merely large lysosomes. The next stage of
differentiation is represented by myelocytes. The myelocytes are marked by the appearance of
specific secondary granules.
Neutrophil secondary granules are small and barely resolvable under the LM. Secondary
basophilic and eosinophilic granules can usually be recognized soon after their appearance. The
myelocyte shows early flattening or invagination of one face of the nucleus. The metamyelocytes
or juvenile cells show more advanced invagination of the nucleus to a reniform shape.
The immediate precursors of mature granulocytes, the band cells, have an irregular
horseshoe or sometimes S-shaped nucleus. Mature granulocytes (V class) have multilobulated
nuclei; their cytoplasm contain both primary (nonspecific) and secondary (specific) granules. The
myeloblasts, promyelocytes, and myelocytes are mitotic forms, whereas metamyelocytes, bands,
and mature granulocytes are postmitotic cells. A few metamyelocytes may normally circulate.

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 Some substances stimulate the formation of granulocytes *. Among them are: granulocyte–
macrophage colony-stimulating factor (GM-CSF) produced by endothelium, macrophages, and T
lymphocytes; granulocyte colony-simulating factors (G-CSF) produced by endothelium,
macrophages, and fibroblasts; stem cell factor produced by bone marrow stromal cells, endothelial
cells, and fibroblasts; interleukin-5 produced by T lymphocytes.
Monocyte formation
The fifth class includes only promonocytes developed from monoblasts. Monocytopoiesis is
characterized by the cell size reduction and progressive indentation of the nucleus. At least three
cell divisions occur before the mature monocyte stage is reached. Mature monocytes leave the red
bone marrow soon after their formation and there is no reserve pool. The monocytes remainin the
circulationfor only about several hours before migrating to the tissues, where they differentiate
into macrophages.
The monocytes formation is controlled by GM-CSF, the macrophage colony-stimulating
factor (M-CSF) produced by endothelium, monocytes, and fibroblasts; interleukin-2 produced by
T cells.
Platelet formation
Platelets originate as fragments of the megakaryocyte cytoplasm. Megakariocytes are giant
cells; their diameter measures more than 50 nm. The megakaryocyte precursors are
promegakaryocytes arised from megakaryoblasts (IV class). Promegakaryocytes undergo as many
as seven DNA reduplications without cell divisions (endomitosis). As a result, the cells contain
large polyploid nuclei with chromosome number from 2n to 64n. Nuclear lobulation occurs in
these cells. Cytoplasmic maturation involves the elaboration of granules, vesicles, and cytoplasmic
membranes. These membranes outline platelet zones as the demarcation system of membrane.
They are continuous with the plasma membrane. When platelets separate from the megakaryocyte,
the demarcation membranes fuse and become the plasmalemma of platelets. The megakaryocyte
cytoplasm is divided into three zones: the perinuclear zone contains the Golgi apparatus, rER and
sER granules, centrioles, and microtubules; the intermediate zone contains vesicles and the
demarcation membrane system; the outer marginal zone is filled with microfilaments, granules
and is traversed by membranes connecting with the demarcation membrane system.
Megakaryocytes lie nearby the bone marrow sinuses delivering platelets directly into the
vascular lumen. The humoral substance (thrombopoetin) stimulates the maturation of
megakaryocytes and the rate of platelet formation.

*
Many of these substances can now be synthesized and are being used in the treatment of the blood diseases.

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 Lymphopoiesis
The precursors of lymphocyte (both T and B) develop in the red bone marrow. Oligopotential
cells destined to become Tcells (III class) leave the marrow and migrate to the thymus where they
undergo proliferation and differentiation. B cells begin and complet maturation in the red bone
marrow. The proliferation and differentiation of T cells in the thymus and B cells in the red bone
marrow is termed antigen-independent. The formation of receptors to antigens and clusters of
differentiation (CD) molecules occurs during the process.

Red bone marrow

Bone marrow can be red because of the presence of erythrocytes and their precursors, which
is indicative of active hemopoiesis; or yellow owing to fat indicating reduced hemopoiesis. All
marrow in newborn humans is red. Fat appears in long bones from the fifth to the seventh year; by
the age of 18 years, almost all limb marrow is yellow. Hemopoietic marrow in adults is largely
restricted to the skull, clavicles, vertebrae, ribs, sternum, and pelvis.
The red bone marrow is located in the bone spaces. It is composed of stromal elements,
blood vessels, and developing hemopoietic cells at various stages of formation and maturation.
Boe marrow stroma is of reticular tissue. Reticular cells are branched; contain pale nuclei
and many rER cisternae in cytoplasm. They manufacture the ground substance and reticular fibers.
Reticular fibers consist of Type III collagen and are argyrophilic (are revealed by silver
impregnation method). The reticular cells and reticular fibers form meshwork holding the
hemopoietic cells. Additionally, reticular tissue takes part in hemopoiesis creationing
microenvironment for developing blood cells. Thus, the reticular cells produce of special
hemopoietic growth factors, which control hemopoiesis; the ground substance hyaluronic acid,
chondroitin and heparan sulfates may bind growth factors. Moreover, the ground substance
contains laminin and fibronectin, which facilitate adhesion of hemopoietic cells to the marrow
stroma.
Several bone marrow cells take part in creation of microenvironment for hemopoiesis.
Osteogenic cells, osteoblasts and osteoclasts situated in the endosteum of bone trabeculae,
adipocytes, vascular cells release some growth and regulating factors. Macrophages represented
by fixed cell population remove aged and defective erythrocytes, are involved in the production
of some growth factors, and, perhaps, facilitate the delivery of reticulocytes to the circulation.
There is the second type of macrophages in the bone marrow called nurse cells. The latter seize
iron from circulation and convey it to erythroblasts. As a rule, a macrophage often lies in the center
of the erythroblastic islet; its cytoplasm extends out and encloses the surrounding erythroblasts.

155
 Veins and arteries constitute the vascular compartment of the marrow. The marrow lacks
lymphatic vessels. The bone marrow is supplied with medullary branches from the nutrient artery
of the bone. A capillary network opens into a well-developed series of thin-walled sinusoids, which
empty into a large central sinus. The bone marrow sinusoids are postcapillary venules whose
structure resembles discontinuous capillaries. The sinusoids are lined with flat endothelial cells on
a discontinuous basement membrane. In some places the cytoplasm of endothelial cells is so thin
that forms “pores” (or “apertures”). Mature blood cells adhere to these pores before being realized
into the circulation. Sometimes mature blood cells squeeze through endothelial junctions. Blood
cells press to the junction, and the aperture appears. Apertures normally develop only in
relationship to the cell passage; they are either occupied by a cell in transit or absent.
Hemopoietic compartment
Erythroblasts are produced near sinuses, forming erythroblastic islets. Megakaryocytes lie
close against the adventitial surface of the sinusoids. They deliver platelets to the vascular lumen.
Since megakaryocytes are large cells, they resist being swept into circulation and prevent vascular
leakage. Granulocytes are produced in nests or as dispersed sheets of the cells somewhat away
from the vascular sinuses. Lymphocyte precursors occur throughout the marrow.

Thymus
The thymus is the central organ of hemopoiesis. Its main function is antigen-independent
proliferation and differentiation of T lymphocytes. The thymus produces hormons thymosins and
thymopoetin that stimulate T cell maturation.
The thymus is divided into lobes and lobules by connective tissue septa. They extend into
the organ from the connective tissue capsule. Each lobule is divided into the peripheral zone called
the cortex and the central zone called the medulla. The lobular cortex is rich in lymphocytes; the
medulla contains less number of lymphocytes and looks lighter than the cortex in histological
slides.
The stroma of the thymic lobules consists of branched epithelial cells joined together by
desmosomes. These cells are called reticulo-epithelial cells because they form a reticulum in
lobules. Reticular-epithelial stroma supports developing T lymphocytes.
Macrophages are present in the lobules too. Macrophages phagocytose degenerating T
lymphocytes and produce the factors stimulating division and differentiation of T lymphocytes.
Large multinucleated cells are present in the outer part of the cortex. As a rule, from 20 to
100 T lymphocytes surround one of these cells. They are modified reticulo-epitheliocytes and
called nurse cells. Nurse cells are supposed to secrete some factors for differentiation of T
lymphocytes.

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 The reticulo-epithelial cells of the thymic lobule medulla are less fully branched. They form
thymic or Hassall’s corpuscles. These corpuscles consist of desquamated epithelial cells tightly
wound upon one another in a concentric pattern. The central cells become swollen, calcified, and
necrotic. The corpuscle may become keratinized, resembling the epidermis. With age the
corpuscles become larger and more prominent. The functions of thymus corpuscles are not known.
Some granulocytes, plasma cells, mast cells, and fat cells are present in the thymus.
T lymphocyte development in the thymic lobules
T lymphocyte precursors migrate to the thymus during embryonic development and some
months after birth. At first, these cells appear under the capsule where proliferation and
differentiation of T lymphocytes initially occur. In adults, only lymphoblasts (the 4th class) are
present under the capsule. Lymphoblasts then gradually turn into T lymphocytes that lie only in
the lobular cortex.
This differentiation results in the subclasses of T lymphocytes: T killer and T helper cells.
Each of tham has specific membrane-binding receptors: CD8 is typical for T killers, CD4 is typical
for T helpers.
T lymphocyte development in the thymus was termed antigen-independent proliferation and
differentiation. In the lobular cortex, T lymphocytes cannot contact with an antigens due to the
presence of the blood–thymic barrier. The barrier consists of the capillary endothelial cells on their
basement membrane, perivascular connective tissue sheath containing many macrophages, and the
reticulo-epithelial cells on their basement membrane.
As T cells mature and move deeper into the cortex, more than 90% of them die. Macrophages
phagocytose only T lymphocytes that are confused about self and nonself. If this population of T
cells remains in the thymus, it would cause an autoimmune disease. Thus, only 5 to 10% of T
lymphocytes leave the thymus; they are mature but innocent. T cells migrate to the peripheral
organs of the immune system (the spleen, lymph nodes, appendix, etc.) where lymphocytes
encounter antigens and underdo antigen-dependent proliferation and differentiation.
The thymus reaches its greatest weight at puberty followed by its slow atrophy or age
involution. The lobules become irregular and smaller in size; T lymphocyte decrease in number;
thymic corpuscles are numerous; connective tissue develops and contains abound adipose cells.
Although there is considerable age involution, the thymus remains a weighty functional organ.
This normal process of slow thymic involution associated with ageing should be distinguished
from acute or accidental thymic involution. This involution may occur in response to severe
disease or stress. In stress, corticosteroid blood levels increase to induce the death of immature T
cells in the thymus.

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 CONTROL PROBLEMS

1. The erythrocytes developing in the red bone marrow cluster around macrophages. What
function do macrophages perform in the erythropoietic islets?
2. Megakaryocytes are revealed in an adult hemopoietic organ. Specify the organ. What
blood formed elements do megakaryocytes give rise to?
3. The red bone marrow from the diaphysis of a tubular bone abounds in white adipose cells.
Explain the phenomenon.
4. A student describes the structure of the hemopoietic organs and considers that the
reticular tissue forms the stroma of both the bone marrow and the thymus. Is the student right?
5. The thymus of an adult animal reveals small-sized irregular lobules, scarce lymphocytes,
numerous thymic corpuscles, and a well-developed connective tissue abounding in adipose cells.
Comment on the disordered thymic structure.
6. Experimental newborn animals were subjected to thymectomy (excision of the thymus)
followed by kidney homotransplantation. Why was the graft not rejected?

CONTROL TESTS

Directions: each of the following statements contains five suggested completions. Choose
the one that is best in each case.
1. The first phase of hemopoiesis in fetal life occurs in: A – liver; B – spleen; C – bone
marrow; D – “blood islands” in the wall of the yolk sac; E - lymph nodes.
2. Each of the following statements concerning proerythroblasts is true, EXCEPT: A – are
derived from CFU-Er; B – give rise to basophilic erythroblasts; C – contain small heterochromatic
nuclei; D – their cytoplasm is slightly basophilic due to free ribosomes; E – are able to divide.
3. Each of the following statements concerning basophilic erythroblasts is true, EXCEPT: A
– are derived from normoblasts; B – give rise to polychromatophilic erythroblasts; C – their
cytoplasm reveals strong basophilia due to numerous ribosomes; D – are able to divide; E – their
nuclei are smaller and more heterochromatic compared to the previous form.
4. Each of the following statements concerning polychromatophilic erythroblasts is true,
EXCEPT: A – are derived from basophilic erythroblasts; B – give rise to normoblasts; C – their
nuclei are smaller and heterochromatic compared to the previous form; D – their cytoplasm
displays both eosinophilia and basophilia; E – are not able to divide.
5. Each of the following statements concerning normoblasts is true, EXCEPT: A – are
derived from polychromatophilic erythroblasts; B – give rise to basophilic erythroblasts; C – their

158
cytoplasm stains eosinophilic due to a large amount of hemoglobin; D – lose nuclei by extruding
them from the cells; E – are not able to divide.
6. The following events take place in erythropoiesis, EXCEPT: A – changing of cell shape
for biconcave; B – reducing of cell dimensions; C – accumulating of hemoglobin; D – changing
of cytoplasm eosinophilia for basophilia; E – reducing and extruding of nuclei.
7. Each of the following statements concerning promyelocytes is true, EXCEPT: A – are
derived from myeloblasts; B – give rise to myelocytes; C – their cytoplasm is light blue and
contains primary granules; D – have large spherical nuclei; E – are not able to divide
8. Each of the following statements concerning myelocytes is true, EXCEPT: A – are derived
from promyelocytes; B – give rise to metamyelocytes; C – begin to form specific (secondary)
granules; D – recognition of neutrophil, eosinophil, and basophil series is not possible at this stage;
E – are able to divide.
9. Each of the following statements concerning metamyelocytes is true, EXCEPT: A – are
derived from myelocytes; B – give rise to promyelocytes; C – their nuclei are heterochromatic and
kidney-shaped; D – specific granules outnumber primary granules in their cytoplasm; E – are not
able to divide.
10. Each of the following statements concerning megakaryocytes is true, EXCEPT: A – are
derived from promegakaryocytes; B – give rise to platelets; C – are giant cells; D – have complex
multilobulated polyploid nuclei; E – are located far from the marrow blood sinuses.
11. Each of the following statements concerning the thymus is true, EXCEPT: A – consists
of lobules; B – its lobule stroma is composed of epithelial tissue; C – contains lymphatic nodules;
D – provides antigen-independent development of T lymphocytes; E – undergoes age-related
involution and is replaced by adipose tissue.
12. Each of the following statements concerning the thymic lobule is true, EXCEPT: A – its
stromal epithelioreticular cells produce thymosins; B – its cortex contains numerous small
lymphocytes; C – its medulla contains fewer lymphocytes; D – Hassall’s corpuscles are located in
its medulla; E – contains pluripotentional stem hemopoietic cells.

Directions: one or more of the given statements or completions is/are correct. Choose the
answer: A – if only 1,2, and 3 are correct; B – if only 1 and 3 are correct; C – if only 2 and 4 are
correct; D – if only 4 is correct; E – if all are correct.
13. The following statements regarding the hemopoietic stem cells are true: (1) are
pluripotential colony-forming units (2) in adults are located and function in the red bone marrow
(3) presumably look similar to small lymphocytes (4) are morphologically indistinguishable from
oligopotential and unipotential stem cells

159
 14. The following statements regarding the reticulocytes are true: (1) their cytoplasm
contains some ribosomes that look like a reticular network (2) constitute about 1% of red blood
cells in circulation (3) increase in number in cases of bleeding and hemolysis (4) possess small
heterochromatic nuclei
15. The stages of the monocyte development are as follows: (1) monoblasts (2)
promonocytes (3) monocytes (4) tissue macrophages
16. The stages of the platelet development are as follows: (1) CFU-Mg (2)
promegakaryocytes (3) megakaryocyte (4) megakaryoblasts
17. The stages of lymphopoiesis in the central organs are as follows: (1) CFU-Ly (2)
lymphoblasts (3) prolymphocytes (4) immunocompetent lymphocytes
18. Antigen-independent proliferation and differentiation of T lymphocytes proceed in the
following organs: (1) liver (2) red bone marrow (3) spleen (4) thymus
19. Antigen-independent proliferation and differentiation of B lymphocytes take place in the
following organs: (1) spleen (2) appendix (3) liver (4) red bone marrow
20. The following statements regarding the red bone marrow are true: (1) is the central organ
of hemopoiesis (2) contains blood sinuses (3) contains adipose cells (4) its stroma consists of
epithelial tissue
21. The following statements regarding the red marrow stroma are true: (1) consists of
reticular cells and reticular fibres (2) contains hemopoietic cells (3) provides support to
hemopoietic cells (4) produces substances controlling differentiation of hemopoietic cells
22. The following statements regarding the yellow bone marrow are true: (1) mostly consists
of adipose cells (2) does not retain hemopoietic potentials (3) replaces red bone marrow (4) is not
capable of transformation to the red marrow
23. The following statements regarding the thymus are true: (1) its blood-thymus barrier is
impermeable to macromolecules (2) contains numerous macrophages for phagocytosis of
degenerating lymphocytes (3) their T lymphocytes programmed against “self” antigens are
destroyed (4) provides antigen-dependent differentiation of T lymphocytes
24. The blood-thymus barrier is made up of the following components: (1) capillary
endothelium on the basal lamina (2) perivascular connective tissue spaces with numerous
macrophages (3) epithelioreticular cells on their basal membrane (4) adipose cells

FIGURES

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 Fig. 13.1. (см. папку рисунки)

15. PERIPHERAL ORGANS of HEMOPOIESIS and IMMUNOGENESIS

The peripheral organs of hemopoiesis and immunogenesis are as follows: the lymph nodes,
spleen, tonsils, appendix and lymphoid tissue located in the wall of the alimentary canal,
respiratory passages, urinary passages, and the reproductive tracts. The main function of these
organs is antigen-dependent proliferastion and differentiation of lymphocytes.
T lymphocytes and B lymphocytes leave the central organs of hemopoiesis and migrate to
the peripheral organs of hemopoiesis and immunogenesis to differentiate finally. Lymphocytes
circulate through these organs so that they can come into contact with antigens.
B lymphocytes after encounter with the antigen transform into immunoblasts. The latter
proliferate and differentiate into plasma cells, the effector cells of humaral immunity. They contain
well-developed rER to synthesize antibodies or immunoglobulins (Ig’s). Some activated cells
become dormant and remain as the so-called memory cells. Memory cells are not involved in the
primary response; they are able to react more quickly to the next encounter with the same antigen
(secondary response). The reaction of B lymphocytes to the antigens is termed antibody-mediated
or humoral immunity.
T lymphocytes that have been activated by the interaction with antigens transform into
lymphoblasts that proliferate and differentiate to effector T lymphocytes and memory cells. The
response of T lymphocytes to the antigens is known as cell-mediated immunity. It should be noted
that T lymphocytes have cell surface receptors, which recognize specific antigens. The T cell
receptors have variable regions, which can bind to different antigens. There are two types of

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resulting T cell receptors (TCR) termed TCR-1 and TCR-2. TCR-2+ cells comprise about 90% of
lymphocytes in the blood and subdivide (owing to the presense of specific markers) into three
groups: (1) T helper cells, (2) T killer or cytotoxic cells, and (3) T suppressor cells. T helper cells
are responsible for the transformation of immunoblasts into plasma cells. T killer cells are able to
kill target cells. T suppressor cells inhibit the response to T helper cells. TCR-1+ cells are abundant
in mucosa-associated lymphoid tissue (MALT) and perform cytotoxic function. Activated T cells
also secrete cytokines (lymphokines) mediated interactions between cells.
These processes leading to antibody-mediated and cell-mediated immunity reactions and
occurring after an encounter of lymphocytes with antigens are called antigen-dependent
proliferation and differentiation of T and B cells; they take place in the peripheral organs of
hemopoiesis and immunogenesis.

Lymph nodes
A lymph node is a bean-shaped encapsulated organ. It has a hilum where blood vessels,
nerves, and efferent lymphatic vessels pass. Afferent lymphatic vessels enter the node by
penetrating the capsule. The capsule is composed of dense connective tissue and may include a
few smooth muscle cells. Connective tissue trabeculae extend from the capsule into the node
interior and bring the blood vessels.
The lymph node stroma consists of the reticular tissue. It includes reticular cells and
reticular fibers. Reticular cells are branched, contain well-developed rER, and produce the ground
substance and the reticular fibers. Reticular fibers consist of Type III collagen and are argyrophilic
(are revealed by silver impregnation method). The reticular tissue stroma supports T and B
lymphocytes, macrophages, and plasma cells. Several types of macrophages are present in lymph
nodes. Usual macrophages eliminate the antigen-antibody complexs and secrete lymphokines.
Special macrophages are antigen-presenting cells. They are of two types: follicular dendrytic cells
(FDC) that present information to B lymphocytes and interdigitating cells (IDC) that present
information to T-lymphocytes, especially to T-helper cells. The complex of reticular stroma,
developing lymphocytes, macrophages, and plasma cells make up the lymphoid tissue. Antigen-
dependent proliferation and differentiation of T and B cells occur here.
The lymph node substance is subdivided divided into the cortex, paracortex, and medulla.
In the node cortex, lymphoid tissue forms the lymphoid follicles or nodules. The primary lymphoid
nodules consist of uniform tightly packed small lymphocytes, mainly naive B cells and some
memory cells. Primary nodules are not involved in immune reactions. Secondary nodules
demostrate central light zones of proliferating lymphoblasts termed the germinal centers. The
secondary nodule contains small naive B cells peripherally and activated B cells and macrophages

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in the germinal center. Secondary nodules are involved in immune reactions. The lymphatic
nodules are B-depended zones of the node.
The deep cortex or paracortex is T-dependent zone of the lymph node. It is filled with T
lymphocytes, macrophages, and interdigitating cells, which present information about antigens to
T lymphocytes. After antigen stimulation, T cells enlarge to form lymphoblasts. The latter
proliferate, differentiate, and give rise to activated T killers, T helpers, and T suppressor cells.
Additionally, memory T cells appear as well.
In the node medulla, the lymphoid tissue forms medullary cords. They are composed of
reticular cells, plasma cells, and T helper cells. Medullary cords are B-depended zone of the lymph
node because plasma transformation of B lymphocytes occurs here.
The lymph node sinuses are regions between connective tissue, on the one hand, and
lymphoid tissue, on the other hand. Lymph flows through the limph node and undergoes filtration
in subcapsular, peritrabecular, medullary, and hilum sinuses. The sinuses are filled with reticular
cells, macrophages, plasma cells, and lymphocytes. They are lined with endothelial cells.
Lymph nodes constitute extensive filtration beds. The reticular meshwork crisscrossing the
sinuses acts as a mechanical filter. The flow in the lymphatic sinuses is quite slow. Lymph readily
escapes from the sinuses. Macrophages lie in the sinuses; they can rapidly increase in number and
become activated. The efficiency of filtration is very high (about 99%) and makes lymph nodes
vulnerable. If they fail to destroy the infectious agents or malignant cells, the nodes become new
foci and facilitate the spread of disease throughout the body.
Interestingly enough, not only lymph but also lymphocytes constantly circulate through the
lymph nodes. Some lymphocytes enter the node through the afferent lymphatic vessels as a
component of lymph, but some of them enter the node through the wall of postcapillary venules
that lie in the deep cortex. These venules have unusual high endothelium that allows lymphocytes
to pass through the vessel wall.

Spleen
The spleen is surrounded by a capsule covered with the mesothelium. The trabeculae extend
from the capsule into the substance of the organ. The capsule and trabeculae consist of connective
tissue and contain a lot of smooth muscle cells. Blood vessels pass in trabeculae. Trabecular veins
are unmuscular in type and serve for blood storage. The splenic stroma is from the reticular tissue.
The lymphoid tissue forms the splenic white pulp; the rest of the spleen is termed the red pulp.
The white pulp looks light gray in a fresh section of the spleen because it contains
lymphocytes. In histolocical slides, the white pulp is blue-purple as a result of hematoxylin

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staining. The main function of the white pulp is antigen-depended proliferation and differentiation
of lymphocytes.
The white pulp includes two components consisting of lymphocytes packed tightly in the
reticular stroma. The first of them is periarterial lymphatic sheath (PALS); it is a cylinder-like
structure surrounding the central artery. The other component is lymphatic nodules (LN) bulging
outwards from the PALS. Splenic LN may be primary or secondary nodules with germinal centers.
T lymphocytes, macrophages, and interdigitating cells concentrate in the PALS, while B
lymphocytes, macrophages, and dendrytic cells lie in the lymphatic nodules. Hence, PALS may
be considered to be a T-dependent zone. The lymphatic nodule germinal center is B-depended
zone. The periphery of PALS and LN is called the marginal zone. It separates the white pulp from
the red pulp. The marginal zone reticular cells and fibers make up the circumferential network
including less densely packed T and B lymphocytes. The marginal zone contains marginal sinuses
(venules).
The red pulp looks red in colour in a fresh section of the spleen due to the presence of blood.
The red pulp consists of reticular cells and fibers, macrophages, plasma cells, all blood formed
elements, and vessels of the microcirculatory bed. It should be noted that the red pulp, except for
the blood vessels, is termed splenic cords. Splenic cords form a filtration bed receiving blood from
capillaries and conveying it to the venous sinuses. Splenic cords are populated by numerous
macrophages: they are believed to perform the function of blood filtration and elimination of aged
or abnormal erythrocytes as well as platelets. The blood formed elements are broken down by the
lysosomes of macrophages. The hemoglobin iron is retrieved and stored as ferritin. Blood plasma
protein transferrin transfers ferritin to the red bone marrow. The nurse cells of the red bone marrow
seize this ferritin for new erythrocytes.
The red pulp contains a lot of plasma cells. The final step of B lymphocyte transformation
occurs here. Thus, the red pulp is B-depended zone.
Splenic circulation
The splenic artery branches and gives rise to trabecular arteries, which leave the trabeculae
and enter the red pulp (the pulp arteries). The pulp arteries become surrounded by the periarterial
lymphatic sheath (the central arteries). Their branches supply the lymphatic nodules. The central
artery gives rise to several (from 2 to 6) arterioles that, in turn, give rise to capillaries. Most of
capillaries directly open into the splenic cords where blood is exposed to the macrophages. The
blood returns to the circulation by entering the venous sinuses (splenic postcapillary venules). This
circulation is called open circulation. It provides blood filtration and antigen removal, erythrocyte
and platelet elimination. Some capillaries are closed and continue into venous sinuses. They
represent the splenic closed circulation that provides a system for blood to pass rapidly through

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the spleen without filtration. Several venous sinuses join to form pulp veins that drain blood into
trabecular veins and then to the splenic vein.

Mucosa-associated lymphoid tissue (MALT)

In addition to lymph nodes and the spleen, the body contains lymphatic nodules, which are
located in the walls of the gastrointestinal, respiratory, urinary, and reproductive tracts. These
nodules are known as a mucosa-associated lymphoid tissue (MALT). MALT provides
immunological protection against antigens entering from the environment. Lymphocytes after an
encounter with antigens migrate to regional lymph nodes where they undergo proliferation and
differentiation. Effector lymphocytes return to the mucosal lamina propria.
The gut-associated lymphoid tissue (GALT) includes the palatine, lingual and pharyngeal
tonsils (adenoids), mucosal nodules in the esophagus, Peyer’s patches in the small intestine, and
lymphoid nodules in the large intestine and appendix. The bronchus-associated lymphoid tissue
(BALT) is located in the bronchial wall.

CONTROL PROBLEMS

1. A series of microphotographs demonstrate lymphatic nodules from different hemopoietic

organs. It is necessary to select the splenic nodules. What structural features may be employed for
selection?
2. The investigator has been set the task to look into interactions between lymphocytes and
epithelial cells in the peripheral hemopoietic organs. What organs can be used for this purpose?
3. Local inflammation causes the regional lymph nodes to enlarge. The enlarged lymph
nodes reveal abundant plasma cells in the medullary cords and sinuses. Explain the changes in the
lymph nodes.
4. A vital dye was injected into the afferent lymphatic vessel of the lymph node of an
experimental animal. What are the lymph node cells where the dye droplets are found? What
lymph node structures carry out lymph filtration and removal of foreign particles?
5. An investigator revealed that the mesenteric lymph nodes of experimental animals
increased in size in the period of active digestion. How can you explain this fact?

CONTROL TESTS

Directions: each of the following statements contains five suggested completions. Choose
the one that is best in each case.

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 1. Each of the following statements concerning the lymph node cortex is true, EXCEPT: A
– contains lymphatic nodules, each of which is a B-dependent zone; B – its deep part, paracortex,
is a T-dependent zone; C – lacks lymphatic sinuses; D – its lymphatic nodules are primary, if they
contain small lymphocytes; E – its lymphatic nodules are secondary, if they possess the germinal
centres.
2. Each of the following statements concerning the lymph node sinuses is true, EXCEPT: A
– are narrow spaces between connective tissue (capsule, trabeculae) and lymphatic tissue (nodules,
cords); B – are subcapsular, peritrabecular, and medullary; C – lack their own lining; D – contain
reticular cells, fibres, and macrophages; E – drain and filter lymph.
3. Each of the following statements concerning the spleen white pulp is true, EXCEPT: A –
consists of periarterial lymphatic sheathes and lymphatic nodules; B – contains the central artery;
C – its lymphatic nodules are a B-dependent zone; D – its periarterial sheathes are a T-dependent
zone; E – contains splenic sinuses.
4. Each of the following statements concerning the spleen red pulp is true, EXCEPT: A – its
stroma consists of reticular tissue; B – contains the central artery; C – includes red blood cells,
granulocytes, lymphocytes, numerous plasma cells, and macrophages; D – contains splenic
sinuses; E – erythrocytes are destroyed and phagocytosed by macrophages here.
5. Each of the following statements concerning the mucosa-associated lymphoid tissue is
true, EXCEPT: A – are located in the tunica mucosa of the alimentary canal, respiratory passages,
urinary passages, and genital tract; B – are unencapsulated concentrations of lymphocytes; C –
filter lymph and extract antigens from it; D – their lymphocytes after an encounter with antigen
migrate to regional lymph nodes where they undergo proliferation and differentiation; E – cells
returning to the lamina propria are effector lymphocytes.
6. Each of the following statements concerning the palatine tonsil is true, EXCEPT: A – has
crypts containing cellular debris; B – its stratified squamous epithelium is not infiltrated by
lymphocytes; C – its connective tissue is infiltrated by lymphocytes; D – contains lymphatic
nodules distributed along the crypts; E – possesses thin connective tissue capsule.
7. Each of the following statements concerning the germinal centre of lymphatic nodules is
true, EXCEPT: A – is a morphological indication of the lymphoid tissue response to antigens; B
– contains large lymphocytes (lymphoblasts); C – reveals blast mitotic divisions; D – contains
differentiating plasma cells; E – includes macrophages.
8. Each of the following statements concerning humoral immunity is true, EXCEPT: A – B
lymphocytes are responsible for this type of immunity; B – macrophages and T lymphocytes do
not take part in humoral immunity; C – activated B lymphocytes are transformed into

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immunoblasts; D – immunoblasts differentiate into plasma cells; E – plasma cells synthesize
specific antibodies.
9. Each of the following statements concerning cell-mediated immunity is true, EXCEPT:
A – T lymphocytes are responsible for this type of immunity; B – activated T lymphocytes are
transformed into lymphoblasts; C – lymphoblasts proliferate and differentiate into effector cells;
D – memory cells are not produced in the differentiation of T lymphoblasts; E – cytotoxic T
lymphocytes direct their killer activity against virus-effected cells, cancer cells, cells with
mutations, and graft cells.
10. Antigen-dependent differentiation of T lymphocytes results in the formation of the
following cell types, EXCEPT: A – plasma cells producing specific antibodies; B – T killer cells,
primary effectors of cell-mediated immunity; C – T helper cells aiding in B cell differentiation; D
–T suppressor cells suppressing B cell differentiation; E – T memory cells able to respond more
quickly to the next encounter with the same antigen.
11. Each of the following statements concerning T helper cells is true, EXCEPT: A – arise
from T lymphoblasts; B – are able to recognize foreign antigens presented by macrophages; C –
secrete interleukins; D – secrete antibodies; E – stimulate B cell differentiation.

Directions: one or more of the given statements or completions is/are correct. Choose the
answer: A – if only 1,2, and 3 are correct; B – if only 1 and 3 are correct; C – if only 2 and 4 are
correct; D – if only 4 is correct; E – if all are correct.
12. Antigen-dependent differentiation of lymphocytes takes place in the following organs:
(1) spleen (2) tonsils (3) lymph nodes (4) appendix
13. The following statements regarding the lymph nodes are true: (1) are located along the
lymphatic vessel pathway (2) their stroma consists of epithelioreticular cells (3) filtrate lymph (4)
provide antigen-independent development of lymphocytes
14. The following statements regarding the lymph node medulla are true: (1) contains
medullary sinuses (2) contains medullary cords (3) its cords possess numerous plasma cells,
macrophages, and lymphocytes (4) is a T-dependent zone
15. In the nasal and oropharyngeal infections, the cervical lymph nodes undergo enlargement
due to: (1) edema (2) lymph volume increase (3) inflammation of lymph nodes (4) lymphocyte
proliferation in response to antigens
16. The following statements regarding the spleen are true: (1) its capsule and trabeculae
contain smooth muscle cells (2) is able to accumulate large volumes of red blood cells (3)
contraction of its capsule and trabeculae returns stored red blood cells into circulation (4) has the
cortex and the medulla

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 17. The following statements regarding the marginal zone of the spleen are true: (1) is a
region between the red pulp and the white pulp (2) contains T and B lymphocytes (3) contains
small sinuses located in the periphery of lymph nodules (4) contains the central artery
18. The following statements regarding the splenic circulation are true: (1) splenic arterioles
continue into capillaries of two types: open and closed (2) closed capillaries continue into venous
sinuses (3) open capillaries empty directly into the red pulp (4) the red pulp filtrates blood and
extracts antigens from it
19. The Immune functions of the spleen are as follows: (1) antigen removal from blood (2)
antigen-dependent differentiation of lymphocytes (3) antibody production (4) blood storage
20. The hematopoietic functions of the spleen are as follows: (1) blood cell formation during
fetal life (2) destruction of aged, abnormal erythrocytes and platelets (3) blood storage (4) antibody
production
21. The macrophage participation in the immune response consists in: (1) secretion of
lymphokins stimulating lymphocyte proliferation (2) presentation of antigens to lymphocytes (3)
elimination of the antigen-antibody complex (4) antibody production
22. The immediate performers in the graft rejection reaction are the following cells: (1) T
suppressor cells (2) T helper cells (3) T memory cells (4) T killer cells

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 16. ENDOCRINE SYSTEM

The endocrine system is made up essentially of endocrine organs and discrete endocrine
cells that produce secretions directly into blood. It follows that endocrine cells must lie in close
apposition to blood capillaries that usually are fenestrated sinusoidal. The secretions of endocrine
cells are called hormones. Hormones travel in blood to target cells whose function they may
regulate. Some hormones act only on one organ or on one type of cell, while other hormones may
have a wider range of effects. Along with the autonomic nervous system the endocrine organs
coordinate and control the metabolic activities and the internal environment of the body.
Endocrine cells are distributed in three different ways. Some organs are entirely endocrine
in function. They are known as endocrine glands and traditionally include the hypophysis cerebri
(or pituitary), the thyroid gland, the parathyroid glands, the suprarenal (or adrenal) glands, and the
pineal gland.
Groups of endocrine cells may be present in organs that have other functions. They include
the islets of the pancreas, the interstitial cells of the testes, the cells of ovarian follicles and corpus
luteum. Hormones are also produced by some cells in the heart, kidney, thymus, and the placenta.
Individual endocrine cells may be distributed in the epithelial lining of an organ. Such cells
are seen most typically in the gut. Similar cells are also present in the epithelium of the respiratory
passages. Recent studies have shown that cells in many other locations in the body produce amines
that have endocrine functions. Many of these amines also act as neurotransmitters or as
neuromodulators. These widely distributed cells are grouped together as the neuroendocrine
system or the APUD (amine precursor uptake and decarboxylation) cell system.

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 Hypophysis cerebri
The hypophysis cerebri is also called the pituitary gland. It is suspended from the floor of
the third brain ventricle by the so-called infundibulum and lies in a depression on the upper surface
of the sphenoid bone.
The hypophysis cerebri is one of the most important and complex endocrine glands. It
produces several hormones some of which profoundly influence the activities of other endocrine
organs. Its own activity is influenced by the hypothalamus and by the pineal body.
The hypophysis cerebri is usually divided into an epithelial part, the adenohypophysis, and
a nervous posterior part, the pars nervosa. Adenohypophysis consists of an anterior part or the pars
distalis, an intermediate part or the pars intermedia, and the pars tubularis. The posterior part is
directly continuous with the central core of the infundibular stalk, which is made up of nervous
tissue. The posterior part and the infundibular stalk are together known as the neurohypophysis.
The area in the anterior part of the infundibulum is called the median eminence.
Adenohypophysis
Pars distalis consists of cords of cells separated by fenestrated sinusoids. Several types of
cells, responsible for the production of different hormones, are present.
Using routine staining procedures, the cells can be divided into chromophil cells, which have
brightly staining granules in their cytoplasm, and chromophobe cells, in which no granules are
present. Chromophil cells are further classified as acidophils when their granules stain with acid
dyes or basophils when the granules stain with basic dyes. Basophil granules are also PAS-
positive. The acidophil cells are often called alpha cells, and the basophils are called beta cells.
EM have shown that both acidophils and basophils can be divided into subtypes on the basis
of the size and shape of their granules. These findings have been correlated with those obtained
by immunofluorescence methods.
The following functional types of cells have been described.
Types of acidophil cells are as follows: (1) somatotrophs (somatotropes) producing the
somatotropic hormone (somatotropin, growth hormone or STH), which controls body growth,
especially before puberty; (2) mammotrophs (mammotropes) producing the mammotropic
hormone (mammotropin, prolactin, lactogenic hormone, or LTH), which stimulates the female
mammary gland activity during pregnancy and lactation.
Types of basophil cells are as follows: (1) thyrotrophs (thyrotropes) producing the
thyrotropic hormone (thyrotropin or TSH), which stimulates the activity of the thyroid gland; (2)
gonadotrophs (gonadotropes) producing the follicle-stimulating hormone (FSH) and the
luteinizing hormone (LH), which regulate functions of the male and female gonads; (3)

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adrenocorticotrophs (adrenocorticotropes) producing the adrenocortocotropic hormone
(adrenocorticotropin or ACTH), which stimulates the secretion of the adrenal cortex.
Chromophobes are probably degranulated chromophil cells. Some of them are stem cells,
which give rise to new endocinocytes.
Pars intermedia is poorly developed in the human hypophysis. In ordinary preparations,
the pars intermedia most common feature is the presence of colloid-filled vesicles. The endocrine
cells of the pars intermedia produce the melanocyte-stimulutiug hormone (MSH), which causes
increased pigmentation of the skin, and lipotropins, which regulate lipid metabolism in the white
adipose cells.
The activity of the adenohypophysis is under control of the hypothalamic neurosecretory
cells producing adenohypophysotropic factors.
Neurohypophysis (pars nervosa)
It consists of numerous unmyelinated nerve fibers, which are the axons of neurosecretory
cells located in the supraoptic and paraventricular nuclei of the hypothalamus. Special glial cells
called pituicytes are situated between the nerve fibers. These cells have long dendritic processes,
many of which lie parallel to the nerve fibers. The axons descending into the pars posterior from
the hypothalamus form axovassel synapses with sinusoidal fenestrated capillaries.
The pars posterior of the hypophysis is associated with the release into the blood of two
hormones. One of these is called the antidiuretic hormone (ADH), which controls reabsorption of
water by the kidney tubules. The second hormone is oxytocin, which stimulates contractions of
the uterine smooth muscle cells and the mammary gland myoepitheliocytes.
It is now known that these two hormones are not produced in the hypophysis cerebri at all.
They are synthesized in neurons located mainly in the supraoptic and paraventricular nuclei of the
hypothalamus. ADH is produced mainly in the supraoptic nuclei, whereas oxytocin is secreted in
the paraventricular nuclei. The hormons are transported by the neurosecretory cell axons through
the infundibular stalck into the pars nervosa. Here they are released into the capillaries and enter
the general circulation. The dilated terminal portions of the hypothalamic neuron axons
accumulating granules of hormons and contacting with fenestrated capillaries are called Herring
bodies.
Blood supply of the hypophysis cerebri
The hypophysis cerebrl is supplied with superior and inferior branches arising from the
internal carotid arteries. Some branches also arise from the anterior and posterior cerebral arteries.
The inferior hypophyseal arteries are distributed mainly in the pars posterior. Branches of the
superior hypophyseal arteries supply the median eminence. Here they end in capillaries, from
which portal veins arise. These portal vessels descend through the infundibular stalk and end in

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the sinusoids of the pars distalis. The sinusoids are drained by hypophyseal veins that end in
neighbouring venous sinuses.
There are two sets of capillaries intervened between the arteries and veins. One of them is
in the median eminence and called primary capillary plexus. The second set of capillaries is
represented by the sinusoids of the pars distalis and called secondary capillary plexus. This
arrangement is referred to as the hypothalamo-hypophyseal portal system. The functional
significance of this system is control of the secretion of the adenohypophysis hormones.
The secretion of hormones by the adenohypophysis is under higher control of the
hypothalamus neurosecretory cells that are situated near the median eminence. The axons of these
neurons end on the capillaries in the median eminence. Different neurons produce special releasing
and inhibitory factors (adenohypophysotropic factors, liberins and statins) for each hormone of the
adenohypophysis. These factors are released into the capillaries of the primary plexus. The portal
veins arising from the capillaries carry these factors to the pars anterior of the hypophysis. Here
they are released from the capillaries of the secondary plexus and stimulate or inhibit the
appropriate endocrine cells. The synthesis and discharge of the factors is under nervous control.

Pineal gland
The pineal gland (pineal body, the epiphysis cerebri) is a small piriform organ located in
relation to the posterior wall of the brain third ventricle. The organ is covered by connective tissue
representing the pia mater, from which septa pass into its interior. The epiphysis has a mass of
cells, blood capillaries, and unnlyelinated nerve fibers. A distinctive feature of the pineal gland is
the presence of irregular masses of calcium salts called the brain sand.
The main organ cells are pinealocytes. They have polyhedral bodies and spherical or oval
nuclei. The cells give off long processes with expanded terminal buds that end on the wall of
capillaries or on the ependyma of the brain third ventricle. The pinealocytes cytoplasm is rich in
Golgi complex, rER, sER, and mitochondria. The terminal buds contain vesicles with monoamines
and polypeptide hormones as well as the neurotransmitter gamma-aminobutyric acid (GABA).
The pinealocytes are separated from one another by neuroglial cells that resemble the astrocytes
in structure.
The pineal nerve fibers are sympathetic (adrenergic). The release of pineal secretions
appears to require sympathetic stimulation.
The pinealocytes produce a number of hormones that affect (chiefly inhibitory) on many
other endocrine organs such as the adenohypophysis, neurohypophysis, thyroid, parathyroids,
adrenal glands, and gonads. The pineal body hormones reach the hypophysis both through the

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blood and through the CSF. They may also influence the adenohypophysis by inhibiting the
adenohypophysotropic factors production.
The best known hormone of the pineal gland is the amino acid melatonin. It is so called
because it causes changes in the skin colour in amphibians. Considerable amounts of melatonin
and its precursor serotonin are present in the pineal gland. The pineal gland being most active in
darkness; synthesis and discharge of melatonin are remarkably influenced by exposure of animals
to light. Because of this light-mediated response, the pineal gland may act as a kind of biological
clock, which may produce circadian rhythms (variations following a 24-hour cycle) in various
parameters.
It has been postulated that polypeptide hormones first exist in the form of complexes with a
carrier protein called neuroepiphysin. When hormones are released from the complex, the carrier
protein combines with calcium ions and is deposited as the brain sand.
It has often been stated that the pineal gland degenerates with age but recent studies show
that age-related involution fails to occur.

Thyroid gland
The thyroid gland is covered by a fibrous capsule. Septa, extending into the gland from the
capsule, divide it into lobules. In microscopic examination, each lobule is seen as aggregation of
follicles. Each follicle is lined by folliclilar cells that rest on a basement membrane. The follicle
has a cavity with a homogeneous material called colloid (which appears bright pink in sections
stained with hematoxylin and eosin). Apart from follicular cells, the thyroid gland has
parafolliclilar cells, which are situated between the follicular cells and the basement membrane.
They may also lie in the intervals between the follicles. The spaces between the follicles are filled
by a stroma made up of delicate connective tissue in which there are numerous blood and
lymphatic capillaries as well as sympathetic nerves. Blood capillaries are sinusoidal fenestrated;
they lie in close contact with the walls of the follicles.
The follicular cells vary in shape, depending on the level of their activity. Normally (at an
average level of activity) the cells are cuboidal; colloid in the follicles is moderate in amount.
When the functional activity is low, the cells are flat (squamous) and the follicles are distended
with abundant colloid. Lastly, when the cells are highly active, they become columnar and colloid
is scanty. Different follicles may show differing levels of activity. The activity of follicular cells
is influenced by the thyroid-stimulating hormone (TSH or thyrotropin) produced by the
adenohypophysis basophils.
The follicular cells secrete two hormones that influence the rate of metabolism. Iodine is an
essential constituent of these hormones. One hormone containing three atoms of iodine in each

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molecule is called triiodothyronine (T3). The second hormone containing four atoms of iodine in
each molecule is called tetraiodothyronine (T4) or thyroxine.
The synthesis and release of the thyroid hormones take place in two phases. In the first phase,
thyroglobulin is synthesized by granular endoplasmic reticulum and is packed into secretory
granules in the Golgi complex. The granules travel to the luminal surface where they release
thyroglobulin into the follicular cavity by exocytosis. Here the thyroglobulin combines with iodine
to form colloid. Colloid is iodinated thyroglobulin.
In the second phase, particles of colloid are taken back into the cell by endocytosis. In the
cell cytoplasm, the iodinated thyroglobulin is acted upon by lysosomal enzymes releasing the
hormones T3 and T4, which pass through the cell and are released into blood.
The parafollicular cells are also called C-cells, clear cells, or light cells. They are polyhedral
in shape and have oval eccentric nuclei. Typically, they lie between the follicular cells and their
basement membrane. They may, however, lie between follicular cells, but they do not reach the
lumen. In some species many parafollicular cells may lie in the connective tissue between the
follicles and may be arranged in groups. Under the EM, the cells show well-developed rER, Golgi
complexes, numerous mitochondria, and membrane-bounded secretory granules. Parafollicular
cells secrete the hormone calcitonin. This hormone has an action opposite to that of the parathyroid
hormone on calcium metabolism. This hormone comes into play when the serum calcium level is
high. It tends to lower the calcium level by suppressing the release of calcium ions from bones.
This is achieved by suppressing bone resorption by osteoclasts.

Parathyroid glands
The parathyroid glands lie in close relationship to the thyroid gland. Normally, there are two
parathyroid glands, one superior and one inferior, on either side; there being four glands in all.
Each gland has a connective tissue capsule from which some septa extend into the gland substance.
Within the gland a network of reticular fibers supports the cells.The parenchyma of the gland is
made up of cells that are arranged in cords. Numerous sinusoids lie in close relationship to the
cells.
The cells of the parathyroid glands are of two main types: chief cells (principal cells) and
oxyphil cells (eosinophil cells). The chief cells are much more numerous than the oxyphil cells.
Under the LM, the chief cells are seen to be small cells with vesicular nuclei. Their cytoplasm is
either mildly eosinophilic or basophilic. Three types of chief cells (light, dark, and clear) have
been described. Under the EM, active chief cells are seen to have abundant rER and well-
developed Golgi complex. Small secretory granules are seen in parts of the cytoplasm near the
blood sinusoids. These features become much less prominent in inactive cells. Both active and

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inactive cells contain glycogen, which is much more abundant in the latter. In the normal
parathyroid gland the number of inactive cells is greater than that of active cells.
The chief cells produce the parathyroid hormone (or parathormone). This hormone tends to
increase the level of serum calcium mainly by increasing bone resorption through the stimulation
of osteoclastic activity and increasing calcium resorption from the renal tubules.
The oxyphil cells are much larger and contain granules that stain strongly with acid dyes.
Their nuclei are smaller and stain more intensely than those of chief cells. Under the EM, it is seen
that the granules of oxyphil cells are really mitochondria, large numbers of which are present in
the cytoplasm. True secretory granules are not present. The functions of oxyphil cells are
unknown.

Adrenal glands
The adrenal (suprarenal) glands lie near the upper poles of the kidneys. In many animals
they do not occupy a “supra” renal position, but lie near the kidneys.
Each adrenal gland is covered by a connective tissue capsule from which septa extend into
the gland substance. The gland is made up of two functionally distinct parts: a superficial part
called the cortex and a central part called the medulla. The volume of the cortex is about ten times
that of the medulla.
The adrenal cortex is made up of epithelial cells arranged in cords. Sinusoids lie between
the cords. The cortex is divided into three layers or zones. The outermost layer is the zona
glomerulosa where cells are arranged in oval or U-shaped structures. The zona glomerulosa
constitutes the outer one-fifth of the cortex thickness. The next layer is the zona fasciculata where
the cells are arranged in straight columns. Sinusoids lie between the columns. This layer forms the
middle three-fifths of the cortex thickness. The innermost layer of the cortex (the inner one-fifth)
is the zona reticularis. It is made up of cellular cords that branch and anastomose with each other
to form a kind of reticulum.
Under the LM, the cells of the zona glomerulosa are seen to be small, polyhedral or columnar
in shape, with deeply stained nuclei. The cells of the zona fasciculata are large, polyhedral, with
vesicular nuclei. Their cytoplasm is very rich in liplds, which can be demonstrated by suitable
staining. With routine methods the lipids are dissolved out during the processing of tissue,
imparting the cells vacuolated appearance. These cells also contain considerable amounts of
vitamin C. The cells of the zona reticularis are similar to those of the zona fasciculata but the lipid
content is less.

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 Under the EM, the cells in all layers of the cortex are characterized by the presence of sER,
well-developed Golgi apparatus, mitochondria with tubular or vesicular cristae, and numerous
lipid droplets.
The cortical cells are steroid-secreting. The cells of the zona glomerulosa produce the
mineralocorticoid hormones; the main of them is aldosterone. These hormones influence the
electrolyte and water balance of the body. The secretion of aldosterone is influenced by renin,
hormone secreted by juxtaglomerular cells of the kidney. The cells of the zona fasciculata produce
the glucocorticoids (for example, cortisone and cortisol). These hormones have widespread
effects, including those on carbohydrate metabolism and protein metabolism. They decrease
antibody responses and have an anti-inflammatory effect. The cells of the zona reticularis produce
some weak androgens possessing strong anabolic effects.
All zones of the adrenal cortex are dependent on adenohypophysis and controlled by ACTH.
The adrenal medulla is both functionally and embryologically distinct from the cortex. This
part of gland arises from the neural crest, consists of modified nervous endocrine cells, produces
catecholamine hormons, and is independant on adenohypophysis. Using the special chromaffin
reaction, the medullary cells give a positive reaction and are called chromaffin cells. The medulla
is made up of cell groups that are separated by wide sinusoids. The cells are polyhedral and have
a basophilic cytoplasm. Functionally, the cells of the suprarenal medulla are considered to be
modified postganglionic sympathetic neurons. Like typical postganglionic sympathetic neurons,
they secrete noradrenaline (norepinephrine) and adrenaline (epinephrine) into the blood. This
secretion takes place mainly at times of stress and results in widespread effects similar to those of
stimulation of the sympathetic nervous system (e.g., an increase in the heart rate and blood
pressure).
Under the EM, the cells of the medulla are seen to contain abundant rER (in contrast to the
sER of cortical cells) and a prominent Golgi apparetus. The cell cytoplasm is rich in secretory
vesicles containing noradrenaline and adrenaline.

APUD system (diffuse endocrine system)

Apart from the endocrine organs, there are groups of endocrine cells located in various parts
of the body. These cells have some common characteristics with each other and also with the cells
of some endocrine organs. All these cells take up precursor substances from the circulation and
process them by decarboxylation to amines or peptides. They are, therefore, included in what is
called the amine precursor uptake and decarboxylation (APUD) cell system. These peptides or
amines serve as hormones. Hence, the APUD cell system is also called the diffuse endocrine
system.

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 The diffuse endocrine system is regarded as the one representing a link between the
autonomic nervous system, on the one hand, and the organs classically recognized as endocrine,
on the other hand. The effects of the amines or peptides produced by the cells of the system are
sometimes local (paracrine) and sometimes widespread (endocrine).
The list of cell types included in the APUD cell system, as well as of their secretions, is long.
The most studied of them are cells of the gastro-entero-pancreatic endocrine system. This system
includes the cells of the pancreatic islets, cells of the gastric and intestinal epithelia. They produce
one or more of the following substances: 5-hydroxytryptamine, glucagon, dopamine, somatostatin,
substance P, motilin, gastrin, cholecystokinin, secretin, vasoactive intestinal polypeptide (VIP),
and some other peptides.

CONTROL PROBLEMS

1. Two histological slides demonstrate glands. One of them has secretory portions and ducts.
The second gland consists of secretory cells surrounded by a dense network of capillaries. Which
of the glands is endocrine? What capillary type is typical of the endocrine glands?
2. Three groups of experimental animals were injected somatostatin, gonadoliberin, and
thyroliberin, respectively. What endocrine gland is supposed to have an altered function in each
of the cases? What endocrine cells are the targets for these hormones?
3. A histologist is analyzing two fields of view in the hypophysis section. One of them
consists of numerous nerve fibers arranged in different directions and small cells among them. The
second field of view demonstrates cords of epithelial cells with different tinctorial properties.
Identify the portions of the hypophysis in each field of view.
4. The migration of the neural crest cells in an animal was experimentally arrested in
embryogenesis. Which endocrine gland was affected by the intervention?
5. There are two slides of the thyroid gland. One of them was treated by silver impregnation.
The second slide was prepared after an injection of radioactive iodine into an experimental animal.
What thyroid gland cells are revealed in each of the slides? What hormones do these cells secrete?
Are the cells adenohypophysis-dependent?
6. The histological examination of the thyroid gland reveals small follicles, columnar
thyrocytes, and vacuolated colloid. What functional state of the organ does such a structure
correspond to?
7. The histological examination of the thyroid gland reveals large follicles, flat thyrocytes,
and dense colloid. What functional state of the organ does such a structure correspond to?

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 CONTROL TESTS

Directions: each of the following statements contains five suggested completions. Choose
the one that is best in each case.
1. The specific hormone interaction with target cells is provided by: A – hormone chemical
compound; B – tissue belonging of target cells; C – target cell origination; D – existence of
receptors for hormone on the target cell plasma membrane; E – origination of endocrine gland
producing hormone.
2. Each of the following statements concerning the adenohypophysis is true, EXCEPT: A –
consists of glandular epithelial tissue; B – originates from the neural crest; C – its endocrine cells
respond to signals from the hypothalamus; D – contains fenestrated secondary plexus capillaries;
E – is composed of the pars distalis, pars intermedia, and pars tubularis.
3. Each of the following statements concerning the hypophyseal portal system is true,
EXCEPT: A – its capillaries are narrow and continuous; B – its secondary capillary plexus arises
from the portal veins and supplies the adenohypophysis; C – the portal veins run from the median
eminence along the pars tubularis into the pars distalis; D – its primary capillary plexus is located
in the median eminence; E – its primary capillary plexus arises from the superior hypophyseal
arteries and drains into the portal veins.
4. The pars distalis of the adenohypophysis contains the following endocrine cells, EXCEPT:
A – acidophils: somatotropes and lactotropes; B – chromophobes; C – basophils: thyrotropes and
gonadotropes; D – oxytocin-secreting; E – basophils: adrenocorticotropes.
5. Each of the following statements concerning the physiological effect of adenohypophysial
hormones is true, EXCEPT: A – GH stimulates long bone growth; B – LTH initiates and maintains
milk secretion; C – ACTH controls adrenal medulla secretion; D – TSH regulates thyroid hormone
secretion; E – FSH and LH regulate gonadal functions.
6. Each of the following statements concerning the neurons of the hypothalamic supraoptic
and paraventricular nuclei is true, EXCEPT: A – their cell bodies reside in the hypothalamus; B –
their axons convey neurosecretory products to the secondary plexus of the hypophyseal portal
system; C – their axons pass via the infundibular stalk to the neurohypophysis; D – their axons
terminate on fenestrated capillaries of the pars nervosa; E – they secrete oxytocin and ADH.
7. Each of the following statements concerning the pineal gland is true, EXCEPT: A –
consists of pinealocytes and glial cells; B – produces serotonin (usually during the day) and
melatonin (usually at night); C – contains calcified concretions called the brain sand; D – is an
epithelial endocrine gland; E – modulates reproductive functions depending on the day length.

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 8. Each of the following statements concerning the thyroid gland follicles is true, EXCEPT:
A – are surrounded by continuous capillaries; B – are filled with gel-like mass called the colloid;
C – their wall is made up of follicular and parafollicular cells; D – the colloid contains
thyroglobulin, the inactive storage form of thyroid hormones; E – are the thyroid gland functional
units.
9. Each of the following statements concerning the thyroid gland follicular cells is true,
EXCEPT: A – their basal portions rest on the basal membrane, their apical portions are in contact
with the colloid; B – their cytoplasm contains colloid-resorbing droplets; C – transport iodide from
blood into their cytoplasm and into the colloid; D – arise from the neural crest; E – secrete
thyroxine (T4) and triiodothyronine (T3).
10. Each of the following statements concerning the process of T4 and T3 secretion is true,
EXCEPT: A – follicular cells synthesize and secrete thyroglobulin into the follicular lumen; B –
thyroglobulin is an active form of the thyroid hormones; C – iodination of thyroglobulin occurs in
the colloid near the apical cell surfaces; D – hormones are liberated from the storage form by
resorption; E – hormones are released into fenestrated capillaries.
11. Each of the following statements concerning the thyroid parafollicular cells is true,
EXCEPT: A – arise from the neural crest; B – occur in the follicular wall or in the interfollicular
spaces; C – their basal portions rest on the basal lamina; D – their apical portions are in contact
with the colloid; E – their cytoplasm contains numerous granules with calcitonin.
12. Each of the following statements concerning calcitonin is true, EXCEPT: A – is a
physiological antagonist to parathyroid; B – lowers the blood calcium level; C – suppresses bone
resorption and increases bone calcification; D – its secretion is regulated directly by the blood
calcium level; E – its release is controlled by the pituitary gland.
13. Each of the following statements concerning the adrenal medulla is true, EXCEPT: A –
its secretion is modulated by ACTH; B – originates from the neural crest; C – secretes
norepinephrine and epinephrine; D – its chromaffin cells are modified neurons; E – contains
sinusoidal blood capillaries and large veins.
14. Each of the following statements concerning the adrenal cortex is true, EXCEPT: A –
secretes steroid hormones; B – consists of epithelial cells; C – arises from the mesoderm; D –
secretes catecholamines; E – is divided into three zones: glomerulosa, fasciculata, and reticularis.
15. Each of the following statements concerning the adrenal cortex zona glomerulosa is true,
EXCEPT: A – lies beneath the capsule; B – its cells are arranged in the ovoid clusters surrounded
by fenestrated capillaries; C – its cells secrete mineralocorticoids, primarily aldosterone; D – is
not controlled by ACTH; E – is under feedback control of the renin-angiotensin system.

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 16. Each of the following statements concerning the adrenal cortex zona fasciculata is true,
EXCEPT: A – its cells are arranged in the straight cords; B – contains narrow continuous
capillaries; C – its cell cytoplasm is rich in lipid droplets containing steroid hormone precursors;
D – secretes glucocorticoids, primarily cortisol; E – is controlled by ACTH.

Directions: one or more of the given statements or completions is/are correct. Choose the
answer: A – if only 1,2, and 3 are correct; B – if only 1 and 3 are correct; C – if only 2 and 4 are
correct; D – if only 4 is correct; E – if all are correct.
17. The following statements regarding the adenohypophysial hormones are true: (1) are
small proteins or glycoproteins (2) are tropic hormones modulating other endocrine gland activity
(3) their secretion is controlled by releasing and inhibitory factors from the hypothalamus (4) are
accumulated in the Herring bodies
18. The following statements regarding the functional significance of the hypophyseal portal
system are true: (1) hypothalamic regulating factors are released into the primary capillary plexus
(2) hypophyseal portal veins carry these factors to the adenohypophysis (3) releasing factors leave
the blood and enter the adenohypophysis through the secondary capillary plexus (4)
adenohypophysotropic factors are released into the secondary capillary plexus
19. The following statements regarding the pars intermedia of the adenohypophysis are true:
(1) contains acidophils: somatotropes and lactotropes (2) its endocrine cells surround the colloid-
filled cysts (3) hypophyseal portal veins run through it to the pars distalis (4) its endocrine cells
presumably secrete lipotropins and the melanocyte-stimulating hormone
20. The following statements regarding the adenohypophysotropic factors are true: (1) are
synthesized by the neurons of the hypothalamic arcuate, ventromedial, and dorsomedial nuclei (2)
are releasing and inhibitory factors (3) their synthesis and discharge are controlled by negative
feedback (4) are accumulated and released into the bloodstream in the pars nervosa
21. The following statements regarding the neurohypophysis are true: (1) originates from
nervous tissue (2) contains unmyelinated axons, pituicytes, fenestrated capillaries, and the Herring
bodies (3) stores and releases into the blood secretory product from the hypothalamus (4) is a
typical endocrine gland
22. The following statements regarding the Herring bodies are true: (1) are dilated terminal
portions of hypothalamic neuron axons (2) accumulate granules of oxytocin and ADH (3) are in
contact with fenestrated capillaries (4) are located in the pars distalis of the adenohypophysis
23. The following statements regarding the functional effect of the neurohypophysial
hormones are true: (1) oxytocin promotes contraction of the uterine muscle cells (2) physiological
ADH doses increase blood pressure by contraction of the arteriolar muscle cells (3) oxytocin

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stimulates contraction of the breast myoepithelial cells providing milk ejection (4)
nonphysiological ADH doses are responsible for water resorption by the kidney nephron tubular
cells
24. The following statements regarding the pituicytes are true: (1) are principal cells of the
neurohypophysis (2) store and release the hypothalamic hormones (3) are glia-like cells similar to
astrocytes (4) are endocrine cells
25. The morphological features of the thyroid gland hyperfunction are as follows: (1)
follicular cells become columnar (2) follicles enlarge in diameter (3) the colloid is more vacuolated
and resorbed rapidly (4) the colloid amount increases
26. The morphological features of the thyroid gland hypofunction are as follows: (1)
follicular cells become flat (2) follicles enlarge in diameter (3) the colloid is less vacuolated due
to the inhibition of its resorption (4) the colloid amount is reduced
27. The following statements regarding the thyroid follicular cell hormones are true: (1) are
thyroxine and triiodothyronine (2) regulate cell and tissue metabolism (3) their release is controlled
by the feedback system (4) their secretion is stimulated by TSH
28. The following statements regarding the parathyroid glands are true: (1) contain principal
and oxyphil endocrine cells (2) their endocrine cell cords are surrounded by fenestrated blood
capillaries (3) produce parathyroid hormone (4) are adenohypophysis-dependent glands
29. The following statements regarding the parathyroid hormone (PTH) are true: (1)
increases the blood calcium level (2) its secretion is regulated by serum calcium levels (3)
stimulates bone resorption by osteoclasts (4) reduces the kidney exretion and increases the
intestinal absorption of calcium
30. The following statements regarding the adrenal medulla chromaffin cells are true: (1) are
equivalent to postganglionic neurons (2) sympathetic nerve fibres are in contact with them (3)
release their hormones in response to nerve impulses (4) glucocorticoids induce them to convert
norepinephrine to epinephrine
31. The catecholamines produce the following effects: (1) increase in blood pressure (2)
dilation of the coronary blood vessels (3) increase in the heart rate (4) increase in the rate and
depth of breathing
32. The following statements regarding the adrenal cortex zona reticularis are true: (1) its
cells are arranged in anastomosing cords (2) its secretion is modulated by ACTH (3) secretes weak
androgens (4) arises from the neural crest
33. The morphological features of steroid-secreting cells are the presence in their cytoplasm
of: (1) well-developed sER (2) scantily-developed Golgi complex (3) numerous mitochondria with
tubular cristae (4) few lipid droplets

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 34. The following statements regarding the physiological effects of the adrenal cortex
hormones are true: (1) aldosterone acts on nephron tubules and stimulates sodium resorption (2)
glucocorticoids regulate gluconeogenesis and glycogenesis (3) glucocorticoids depress the
immune response and inflammatory reactions (4) mineralocorticoids regulate sodium and
potassium homeostasis and water balance

FIGURES

Fig. 15.1. Hypothalamohypophyseal complex

1 – supraoptic nucleus of the hypothalamus; 2 – paraventricular nucleus of the hypothalamus; 3
– adenohypophysis tropic nuclei of the hypothalamus; 4 – primary capillary network in the
median eminence; 5 – portal veins; 6 – secondary capillary network; 7 – capillaries of the
neurohypophysis; 8 – axovasal synapses; 9 – the pars distalis.

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 Fig. 15.2. Thyroid follicles in different functional states
A – hyperfunction; B – normofunction; C – hypofunction; 1 – follicular cells; 2 – colloid; 3 –
resorption vacuoles; 4 – fenestrated capillaries.
17.DIGESTIVE SYSTEM : ORAL CAVITY and ESOPHAGUS

The digestive system is primarily involved in breaking down food for absorption into the
body. This process has five main phases: ingestion, fragmentation, digestion, absorption, and
elimination of waste products.
Ingestion and initial fragmentation of food products occur in the oral cavity, resulting in the
formation of a food bolus; this is then conveyed to the esophagus by the action of the tongue and
pharyngeal muscles during swallowing. Fragmentation and swallowing are facilitated by the
secretion of saliva from three pairs of major salivary glands and numerous small accessory glands.
The esophagus conducts food from the oral cavity to the stomach where fragmentation is
completed and digestion is initiated. Digestion is the process by which food is enzymatically
broken down into molecules, which are small enough to be absorbed into the circulation. In the
stomach, ingested proteins are first reduced to peptons (small peptides). They are further degraded
to amino acids, which can then be absorbed.
The small intestine receives chyme from the stomach; digestion occurs here under action of
intestinal and pancreatic enzymes. Bile enters the duodenum and takes part in degradation of
chyme lipids. Formed small molecules underdo absorption.
In the large intestine, water is absorbed from the liquid residue, which becomes
progressively more solid as it passes towards the anus.
Food is passed along the gastrointestinal tract by two main mechanisms: voluntary muscular
action (in the oral cavity, pharynx, and upper third of the esophagus) and involuntary waves of
smooth muscle contractions called peristalsis. Peristalsis and the secretory activity of the entire
gastrointestinal system are modulated by the autonomic nervous system and a variety of hormones,

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some of which are secreted by the endocrine cells located in the gastrointestinal tract itself. These
cells constitute a diffuse endocrine system called here the gastrointestinal endocrine system.

Alimentary canal structure

The structure of the alimentary canal, from the esophagus up to the anal canal, shows several
features that are common to all these parts. From the upper end of the esophagus up to the lower
end of the anal canal the alimentary canal has the form of a fibromuscular tube. The wall of the
tube is made up of four tunics. The innermost tunic is the mucosa, which is made up of a lining
epithelium; a layer of connective tissue, the lamina propria that supports the epithelium, and a
layer of smooth muscle cells called the muscularis mucosae. The second tunic is the submucosa
formed by connective tissue. The next tunic is the muscularis externa consisting of either skeletal
or smooth muscle tissues. The external tunic may be a serosa or an adventitia

Oral cavity
The wall of the oral cavity is made up partly of bone and partly of muscles and connective
tissue (lips, cheeks, the soft palate, and the floor of the mouth). These structures are lined by
mucosa. The mucosa is lined by stratified nonkeratinized squamous epithelium, which rests on
connective tissue. Over the alveolar processes (where the mucosa forms the gums) and over the
hard palate, the mucosa is closely adjoins to the underlying periosteum. Elsewhere it is connected
to the underlying structures by loose connective tissue. In the cheeks, this connective tissue
contains many elastic fibers and much fat (especially in children).
Each lip has an “external” surface lined by skin and an “internal” surface lined by mucosa.
The “external” surface of the lip is lined by true skin in which hair follicles and sebaceous glands
are located. The internal substance of the upper or lower lips is predominantly muscular and
contains skeletal muscle fibers.

Tooth
A tooth consists of an “upper” part, the crown, which is seen in the mouth; and one or more
roots, which are embedded in sockets in the bone (mandible or maxilla). The greater part of the
tooth is formed by a bone-like material called dentin. In the region of the crown, the dentin is
covered by a much harder material called the enamel. Over the root the dentin is covered by a thin
layer of cementum. The cementum is attached to the wall of the bony socket by bundles of collagen
fibers called the periodontal ligaments. The tooth core is a pulp chamber containing the pulp. The
dental pulp is made up of loose connective tissue. Delicate collagen fibers, connective tissue cells,
numerous blood vessels, lymphatics and nerve fibers are present. The nerve fibers are partly

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sensory and partly sympathetic. The vessels and nerve fibers enter and leave the pulp chamber
through the pulp canal.
The enamel is the hardest material in the body. It is made up almost entirely (96%) of
inorganic salts. These salts are mainly in the form of complex crystals of hydroxyapatite (as in
bone). The crystals contain calcium phosphate and calcium carbonate. The crystals of
hydroxyapatite are arranged in the form of rod-shaped prisms, which run from the deep surface of
the enamel to its superficial surface.
Dentin is a hard material that is made up basically of calcified ground substance in which
there are numerous collagen fibers. The calcium salts are mainly in the form of hydroxyapatite.
The inorganic salts account for 70% of the weight of dentin. Dentin is permeated by numerous
fine canaliculi that pass radially from the pulp cavity towards the enamel (or towards cementum).
These are the dentinal tubules. Each dentinal tubule contains a protoplasmic process arising from
the cells called odontoblasts that line the pulp cavity.
The cementum may be regarded as a layer of true bone that covers the tooth root, more
precisely, the entire dentin that is not covered by enamel. In some parts (especially towards the
tooth apex) the cementum contains lacunae and canaliculi as in bone. The lacunae are occupied by
cementocytes, the cells similar to osteocytes.
Cementum is covered by a fibrous membrane called the periodontal ligament. The
periodontal ligament fixes the tooth in its socket. It contains numerous nerve endings that provide
sensory information.
Tooth development
Each tooth may be regarded as a highly modified form of the stratified squamous epithelium
covering the alveolar process. The thickening of epithelium grows downwards into the underlying
connective tissue and enlarges to form an enamel organ. The enamel organ is invaginated (from
below) by a mass of mesenchymal cells: these mesenchymal cells form the dental papilla.
As a result of this invagination the enamel organ becomes cup-shaped. The cells that line the
inner wall of its cup-shaped lower end differentiate into columnar cells that are called ameloblasts,
the enamel-forming cells. Ameloblasts cover the external aspect of the enamel and are removed
by surface friction after the tooth erupts. Mesenchymal cells of the papilla become cuboidal and
form an epithelium-like layer. The cells of this layer are odontoblasts, the dentine-forming cells.
The odontoblasts persist as a lining for the pulp cavity.

Tongue

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 The tongue lies on the floor of the oral cavity. The substance of the tongue is made up chiefly
of skeletal muscle tissue supported by connective tissue. The muscle fibers are arranged in bundles
that run in vertical, transverse, and longitudinal directions.
The surface of the tongue is covered by the mucosa lined by stratified squamous epithelium.
The epithelium is supported on a layer of connective tissue (lamina propria). The mucosa covering
the anterior part of the dorsum of the tongue forms numerous projections or papillae. Each papilla
consists of epithelium and a core of connective tissue. The epithelium over the papillae is partly
keratinized.
The papillae are of various types. The most numerous papillae are small and conical in shape.
They are called filiform papillae. The epithelium over the top of these papillae is keratinized. At
the apex of the tongue, and along its lateral margins, there are larger papillae with rounded summits
and narrower bases. These are called fungiform papillae. The foliate papillae occur on the lateral
edges of the tongue. The largest papillae of the tongue are called circumvallate papillae. In contrast
to the filiform papillae, the epithelium of fungiform, foliate, and circumvallate papillae is not
keratinized. The taste buds are present on the lateral surfaces of these papillae.
The mucous membrane of the posterior (pharyngeal) part of the tongue dorsum has
numerous rounded elevations that are quite different from the papillae described above. These
elevations are produced by collections of lymphoid tissue forming the lingual tonsil. Numerous
mucous and serous salivary glands are present in the thick of the tongue between the muscle
bundles.

Salivary glands
There are the parotid, submandibular, and sublingual glands and numerous small glands in
the the lips (labial glands), cheeks (buccal glands), tongue (lingual glands) and palate (palatine
glands). The secretion of these glands keeps the mouth moist and provides a protective and
lubricant coat of mucus. Saliva enzymes (amylase, maltase) digest carbohydrates, primarily starch.
Its bactericidal substences (lysozyme, lactoferrin) take part in controlling the bacterial flora in the
oral cavity. Saliva contains antibodies, immunoglobulins A, implementing immune protection.
Salivary glands are compound tubulo-alveolar glands. The secretory elements of the glands
are supported by connective tissue, which divides the glands into lobules and forms capsules
around them. The secretory elements lead into a series of ducts, through which their secretions are
released into the oral cavity. Intralobular ducts (intercalated and striated ducts) take part in saliva
production, regulating its water-salt balance.
Their secretory portions may be rounded or pear-shaped (acini or alveoli), tubular or
tubuloalveolar.The cells of secretory portions are usually described either as serous or mucous. In

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sections stained with hematoxylin and eosin, serous cells stain darkly basophilic. In contrast,
mucous cells stain very lightly and, therefore, appear empty. The cells are in fact almost
completely filled in by a mucoid material that stains very poorly.
An alveolus is typically made up entirely of serous cells or of mucous cells. However, in
some cases mucous alveoli are covered by groups of serous cells that are arranged in the form of
demilunes. These secretory portions are called mixed acini.
In the parotid glands, the alveoli are only serous. In the submandibular glands, some alveoli
are serous and some of them are mixed. The sublingual glands are made up predominantly of
mucous alveoli; serous and mixed acini are present in less number.
Myoepithelial cells are located in relation to the alveoli and the intercalated ducts of salivary
glands. These cells lie between the epithelial cells and their basement membrane. The
myoepithelial cells located on alveoli are often stellate and may form “baskets” around the alveoli.
Myoepithelial cells are contractile, their contraction aiding in squeezing out secretion from alveoli.

Esophagus
The esophagus is a tube, whose wall has the usual four tunics: mucosa, submucosa,
musclularis externa, and adventitia. The esophagus does not have a serous covering, except over
a short length near its lower end.
The mucous membrane of the esophagus shows several longitudinal folds that disappear
when the tube is distended. The mucosa is lined by stratified squamous epithelium, which is
normally not keratinized. At the upper and lower ends of the esophagus, some tubuloalveolar
glands (eosophageal cardiac glands) are present in the lamina propria.
The submucosa consists of moderately dence connective tissue, contains large blood vessels
and the submucosal nerve plexus. In the submucosa, the compound tubuloalveolar glands
(eosophageal glands proper) are located.
The muscularis externa consists of the usual circular and longitudinal layers. The tunic
consists of both skeletal muscle fibers and smooth muscle cells. In the upper one-third of the
esophagus, there is skeletal tissue, while the lower one-third demonstrates only smooth myocytes.
Both types of tissues are present in the middle one- third of the esophagus. The thick circular
muscle layers present at the lower end of the esophagus could possibly act as a sphincter guarding
the cardio-esophageal junction.
The muscle tunic of the esophagus is surrounded by a layer of connective tissue that forms
an adventitial coat for the esophagus. The lowest part of the esophagus is intra-abdominal and
covered by the peritoneum or serosa. In contrast to the adventitia, the serosa is covered with
mesothelium.

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 CONTROL PROBLEMS

1. The microphotograph demonstrates the cross section of the tongue but its dorsal and
lower surfaces are not designated. What structural features are indicative of the dorsal and lower
surfaces of the tongue?
2. The oral cavity contains a lot of various microorganisms; therefore, lymphocytes undergo
antigen-dependent proliferation and differentiation here. Where in the oral cavity do these immune
processes occur?
3. Carbohydrates acted upon by the enzymes are broken down in the mouth where the first
step of digestion takes place. What glands in the oral cavity secrete these enzymes?
4. The histological slides of three major salivary glands were treated with the method
staining mucous cells bright crimson. Is it possible to differentiate between the parotid,
submandibular, and sublingual salivary glands in the slides?
5. A student suggests that dentin is the hardest tooth component composed of collagen
fibrils, the amorphous substance, and odontoblasts. What mistakes did the student make?
6. A student is examining two slides of the esophagus. In one of them, he has found skeletal
muscle fibers in the muscularis externa and smooth muscle cells in the other slide. The student has
explained the distinctions revealed by some pathologic changes. Is the explanation correct?
7. Gastric-like ulcers may sometimes appear in the esophagus. What features of the
esophageal mucosa are linked to ulcer development? What parts of the esophagus may be
vulnerable to ulceration?

CONTROL TESTS

Directions: each of the following statements contains five suggested completions. Choose
the one that is best in each case.
1. Each of the following statements concerning the alimentary canal mucosa is true,
EXCEPT: A – is a barrier separating the tract lumen from the body; B – secretes digestive
enzymes, hormones, mucus, and antibodies into the lumen; C – selectively absorbs digested
products; D – lacks diffuse lymphoid tissue and lymphatic nodules; E – may contain glands.
2. Each of the following statements concerning the muscularis externa of the alimentary
canal is true, EXCEPT: A – usually consists of three layers; B – its muscle contractions produce
peristalsis; C – the myenteric nerve plexus is present between muscle layers; D – circular muscles
form sphincters along the tract; E – its contraction moves the contents along the tract.

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 3. Each of the following statements concerning the structure of the oral cavity organs is true,
EXCEPT: A – mucosa is covered with stratified epithelium; B – epithelium is partially keratinized;
C – mucosa possesses the muscularis mucosae; D – submucosa is absent at many sites; E – the
organs contain striated muscles.
4. Each of the following statements concerning the tooth is true, EXCEPT: A – consists of
three parts: the crown, neck, and root; B – enamel covers all the tooth parts; C – dentin is the
principal tooth substance; D – the root is covered with cementum; E – contains the pulp chamber.
5. Each of the following statements concerning the tooth pulp is true, EXCEPT: A – is filled
with connective tissue; B – contains blood vessels and nerves; C – the narrow canal extends from
the pulp outside; D – the blood vessels and nerves enter and leave the pulp through the tooth canal;
E – is lined with cementum.
6. Each of the following statements concerning the tooth development is true, EXCEPT: A
– the enamel organ cells induce odontoblast formation; B – odontoblasts arise from the outer
enamel epithelium; C – odontoblasts produce dentin; D – ameloblasts arise from the inner enamel
epithelium; E – ameloblasts deposit enamel on the dentinal surface.
7. Each of the following statements concerning the tooth development is true, EXCEPT: A
– odontoblasts produce predentin; B – predentin calcifies to become dentin; C – dentin appears
first, enamel and cementum are secreted later; D – the dental pulp arises from the enamel organ
pulp; E – cementum is secreted by cementocytes.
8. Each of the following statements concerning the myoepithelial cells is true, EXCEPT: A
– are contractile cells; B – are located only in the salivary gland acini; C – possess numerous
processes; D – lie between the basal lamina and epithelial cells; E – provide secretion discharge
towards ducts.
9. Each of the following statements concerning the intercalated ducts of the salivary glands
is true, EXCEPT: A – are lined with columnar cells possessing basal striations; B – secrete
bicarbonate ions into the acinar product; C – absorb chloride ions from the acinar product; D – are
most prominent in serous salivary glands; E – are short and difficult to identify in mucous salivary
glands.
10. Each of the following statements concerning the esophageal glands is true, EXCEPT: A
– esophageal glands proper occur in the submucosa; B – esophageal glands proper are compound
tubuloalveolar ones; C – produce serous secretion; D – esophageal cardiac glands occur in the
mucosal lamina propria; E – esophageal cardiac glands are present in the proximal and terminal
portions of the organ.
11. Each of the following statements concerning the esophageal muscularis externa is true,
EXCEPT: A – consists of two muscle layers; B – contains striated muscles in the upper third; C –

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contains striated and smooth muscles in the middle third; D – contains only smooth muscles in the
distal third; E – lacks myenteric plexus.

Directions: one or more of the given statements or completions is/are correct. Choose the
answer: A – if only 1,2, and 3 are correct; B – if only 1 and 3 are correct; C – if only 2 and 4 are
correct; D – if only 4 is correct; E – if all are correct.
12. The mucosa of the alimentary canal consists of: (1) lining epithelium (2) lamina propria
from connective tissue (3) muscularis mucosae from smooth muscles (4) muscularis mucosae from
striated muscles
13. The following statements regarding the submucosa of the alimentary canal are true: (1)
consists of connective tissue (2) contains blood vessels (3) contains nerve plexus (4) may contain
glands
14. The submucosa of the alimentary canal contains glands in the following organs: (1) large
intestine (2) esophagus (3) stomach (4) duodenum
15. The adventitia of the alimentary canal is composed of: (1) connective tissue (2)
mesothelium (3) blood vessels and nerves (4) striated muscles
16. The following statements regarding the serosa of the alimentary canal are true: (1) is
equivalent to the visceral peritoneum (2) includes connective tissue (3) is covered with
mesothelium (4) contains blood vessels and nerves
17. The following statements regarding the dorsal surface of the tongue are true: (1) its
mucosa forms papillae (2) its papillary epithelium contains taste buds (3) its epithelium covering
filiform papillae is keratinized (4) possesses the submucosa
18. The following statements regarding the lower surface of the tongue are true: (1) its
mucosa forms papillae (2) its epithelium is keratinized (3) its epithelium contains taste buds (4)
possesses the submucosa
19. The following statements regarding the serous acini of the salivary glands are true: (1)
are spherical (2) serous cells are high (3) cell cytoplasm is basophilic due to numerous ribosomes
(4) their lumen is narrow and not conspicuous
20. The following statements regarding the mucous acini of the salivary glands are true: (1)
are large and oval (2) mucous cells are deep basophilic due to numerous ribosomes (3) mucous
cells are light due to mucinogen granules (4) mucous cells are characterized by basal striations
21. The distinctive feature of the mixed acini of the salivary gland is the presence of: (1)
myoepithelial cells (2) striated epithelial cells (3) stratified cuboidal epithelium (4) serous
demilunes

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 22. The following statements regarding the striated ducts of the salivary glands are true: (1)
are lined with simple cuboidal or columnar epithelium (2) their cells have basal striations (3) may
be surrounded by small amount of connective tissue (4) are intralobular ducts
23. The following statements regarding the basal striations of the striated duct epithelial cells
of the salivary glands are true: (1) consists of numerous infoldings of the basal plasmalemma (2)
contains longitudinally oriented mitochondria (3) reabsorbs sodium from the secretion (4) adds
potassium to the secretion

FIGURES

Fig. 16.1. Tooth morphology

I – crown; II – neck; III – root; 1 – enamel; 2 – dentin; 3 – pulp chamber; 4 – cementum; 5 –
blood vessels; 6 – gingiva; 7 – bone; 8 – periodontal ligament.

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 Fig. 16.2. Dentin and pulp
I – dentin; II – predentin; III – pulp periphery zone; IV – pulp cell-free zone; V – pulp cell-rich
zone; 1 – odontoblast processes in dentinal tubules; 2 – odontoblast cell bodies.

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 18. DIGESTIVE SYSTEM: STOMACH and SMALL INTESTINE

Stomach
The wall of the stomach has the four basic tunics: a mucosa, a submucosa, a muscularis
externa, and a serosa.
The mucosa shows numerous folds that disappear when the stomach is distended. The lining
epithelium is simple columnar and mucus-secreting. The apical parts of the lining cells are filled
with mucin. It is usually removed during tissue processing so that the cells look empty (or
vacuolated). The mucus secreted by the cells of the lining epithelium protects the gastric mucosa
against acid and enzymes of the gastric juice. The lining epithelium dips into the lamina propria
to form the depressions called gastric pits. The pits extend for a variable distance into the thickness
of the mucosa. The gastric pits occupy the superficial one-fourth or less of the mucosa. Deep to
the gastric pits, the mucous membrane is packed with numerous gastric glands. The glands open
into gastric pits; each pit receives the openings of one or several glands.
The gastric glands are of three types: the main, cardiac, and pyloric glands. The main gastric
glands are present in the body of the stomach and in the fundus. The main gastric glands are simple
slightly branched tubular glands that lie at right angles to the mucosal surface. The gastric glands
consist of five types of cells, three of which secrete components of the gastric juice. The most
numerous cells in gastric glands are called chief cells (peptic or zymogen cells). They are
particularly numerous in the basal parts of the glands. The cells are cuboidal or low columnar.
Their cytoplasm is basophilic. They secrete the digestive enzymes of the stomach including pepsin.
With special methods the cells are seen to contain prominent secretory granules in the apical parts
of their cytoplasm. The granules contain pepsinogen, which is a precursor of pepsin.
The parietal (oxyntic) cells are large, ovoid or polyhedral in shape, with large nuclei. They
are present singly among the chief cells. They are more numerous in the upper half of the gland
than in its lower half. They are called oxyntic cells, because they stain strongly with eosin. They
are called parietal cells as they lie against the basement membrane. Under the LM, they appear to
be situated under buried chief cells. The EM shows, however, that each parietal cell has a narrow
apical part that reaches the lumen of the gland. The cell membrane of this apical region shows
several invaginations into the cytoplasm, producing intracellular canaliculi that communicate with
the glandular lumen. The canaliculi have microvilli that project inwards. The cytoplasm is packed
with mitochondria. Secretory granules are not present. Parietal cells are responsible for the
secretion of hydrochloric acid, which converts pepsinogen to pepsin. They also produce an
intrinsic factor, which combines with food vitamin B12 and provides its further absorption in the

193
small intestine. Vitamin B12 is necessary for normal formation of erythrocytes in the red bone
marrow.
The mucus-secreting cells occupy the upper end of the gland (“neck”) that is why they are
called mucous neck cells. These are large cells with a clear cytoplasm. The nucleus is flattened
and is pushed to the base of the cell by accumulated mucus. The chemical structure of the mucus
secreted by these cells is different from that secreted by the mucous cells lining the surface of the
gastric mucosa.
The argentaffin (endocrine) cells occupi the gastric gland bottoms. These cells contain
basaly located granules that blacken when treated with appropriate solutions of silver salts. They
do not reach the lumen but lie between the chief cells and the basement membrane. These cells
belong to the gastro-entero-pancreatic endocrine system. They secrete hormones (gastrin,
serotonin, secretin, etc.), which serve as local regulaters of various gastric functions.
The cambial (undifferentiated) cells reside in the gland necks and take part in renewing of
both covering and glandular gastric epithelia.
The cardiac glands are situated in a small area near the opening of the esophagus called the
cardiac region of the stomach. The mucosa of cardiac region is relatively thin; gastric pits are
shallow; the cardiac glands are simple brunched tubular or tubular-alveolar and mucus-secreting.
In the pyloric region of the stomach, the gastric pits are deep and occupy two-thirds of the
depth of the mucosa. The pyloric glands are short and occupy the deeper one-third of the mucosa.
They are simple branched tubular coiled and mucus-secreting glands.
The mucous membrane of the stomach is packed with glands. The connective tissue of the
lamina propria is, therefore, scanty. It contains the usual connective tissue cells. Occasional
aggregations of lymphoid tissue are present in it. The muscularis mucosae is composed of three
layers, facilitating the gastric glands to release their secretion.
The submucosa consists of moderately dence connective tissue, contains large blood vessels
and the submucosal nerve plexus.
The muscularis externa of the stomach is well-developed. Three types of layers – oblique,
circular, and longitudinal (from inside out) – are usually described. The appearance of the layers
in sections is, however, highly variable, depending upon the part of the stomach sectioned. The
circular layer is greatly thickened at the pylorus where they form the pyloric sphincter. There is
the myenteric nerve plexus between muscular layers.
The serosa is represented by connective tissue covered by methothelium. The subserosal
nerve plexus and blood vessels are located here.

Small intestine

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 The small intestine is a tube about five meters long. It is divided into three parts. These are
(in craniocaudal sequence) the duodenum (about 25 cm long), the jejunum (about 2 m long), and
the ileum (about 3 m long). The wall of the small intestine is made up of the four tunics: a mucosa,
a submucosa, a muscularis externa, and a serosa.
The mucosa surface area of the small interstine is extensive to allow adequate absorption of
digested products. This is achieved by the length of the small intestine, the mucosal villi, and
microvilli of the epithelial cells lining the mucosa.
The intestinal villi are finger-like processes of the mucosa that project to the lumen of the
small intestine. They consist of a core of connective tissue covered by a surface epithelium. The
connective tissue core contains numerous blood sinusoidal capillaries forming a plexus. The
endothelium of capillaries is fenestrated, thus allowing rapid absorption of nutrients into the blood.
Each villus contains a central lymphatic vessel called a lacteal. Smooth muscle cells arising from
the muscularis mucosae accompany the villus lacteals to help lymph outflow since the intestinal
lymph is dense (chyle) due to absorped lipids. The villi are the greatest and the most numerous in
the duodenum; they progressively decrease in size and in number in proceeding caudally along the
small intestine.
The crypts are deep tubular invaginations of the intestinal epithelium into the lamina propria.
They invade the mucosa lower rigion just under the villi.
The epithelium of the small intestine mucosa is smple columnar striated arising from the
endoderm. It covers the villi and forms the crypts. The epithelial layer mainly consists of columnar
absorptive cells (enterocytes) that are specialized for absorption. The enterocyte apical portions
possess microvilli forming the brush border that provides major surface amplification for
membrane digestion and absorption.
There are goblet cells in the intestinal epithelium among the columnar cells. These cells look
like a drinking glass, which is broad above, and has a narrow stem attached to a base. Goblet cells
are so named because of a similar shape. Each goblet cell has an expanded upper part that is
distended with mucin granules. The nucleus is flattened and situated near the base of the cell.
Goblet cells are mucus-secreting cells.
The epithelium of villi and crypts contains the enteroendocrine cells also called argentaffin
cells because their basally located granules blacken when treated with a silver solution. Some of
these cells give a positive chromaffin reaction and are, therefore, called enterochromaffin cells.
With the introduction of immunofluorescence techniques, it has been demonstrated that these cells
are of various functional types and contain many amines performing the endocrine function. Apart
from the small intestine, these cells are also present in the stomach, the large intestine, the
pancreas, and the duodenal glands. All these cells are now grouped together under the term gastro-

195
entero-pancreatic endocrine system and belong to APUD (Amine Precursor Uptake and
Decarboxylation) cell system.
In contrast to villi, crypts possess Paneth cells and intermediate (undifferentiated) cells.
Paneth cells (zymogen cells) are found only in the deeper parts of intestinal crypts. They
contain prominent eosinophilic secretory granules. The function of zymogen cells is not clear.
They are known to produce lysozyme and other bactericidal substances as well as some digestive
enzymes (dipeptidases).
Uundifferentiated intermediate cells are cambial cells that give rise to absorptive columnar
cells, goblet cells, enteroendocrine cells, and Paneth cells. Undifferentiated cells actively
proliferate by mitosis. The newly formed cells migrate upwards from the crypt to reach the villus
epithelium. The lifespan of each cell is only a few days. The cells are shed off (desquamated) from
the villus tips. In this way, the epithelial lining is being constantly replaced,
The submucosa of the small intestine is composed of moderately dence connective tissue,
large blood vessels and the submucosal nerve plexus. In the duodenum, submucosa contains
compound branched tubular-alveolar glands called the duodenal glands (Brunner glands). They
are most numerous in the proximal part of the duodenum and few in its distal part. The mucous
secretion of the Brunner glands is rich in bicarbonate ions to neutralize acidic gastric chyme
entering the duodenum.
The muscularis extertna is represented by two layers of smooth muscle cells. Their
contractions produce peristaltic movements of the small intestine transporting chyme towards the
colon. There is the myantaric nerve plexus between muscular layers.
The serosa is the peritoneal visceral layer and corresponds exactly to the description of the
wall of the gastro-interstinal tract.

CONTROL PROBLEMS

1. There are two slides of different parts of the stomach. One of them reveals branched
glands mainly consisting of mucous cells. In the second slide, the gastric glands look like tubules
and contain the chief and parietal cells. What divisions of the stomach are seen in the slides? What
components of gastric juice do the cells revealed secrete? What gastric tunic are the glands found
in?
2. The histological slides of different digestive organs were treated with the method staining
mucous cells bright crimson. What cells were revealed in the stomach and in the small intestine?
Name the tunics where the cells are found.

196
 3. The patient was diagnosed as having poor gastric digestion of proteins. His gastric juice
had low acidity. What cells of the gastric glands were functionally incompetent?
4. The stomach biopsy revealed numerous gastrin-secreting cells (G-cells) and their
increased activity. What gastric cells are the targets for gastrin? What physiological changes are
caused by the increase in gastrin production?
5. The epithelium of the small intestine villi is completely renewed every 5 days. What cells
in the small intestine epithelium are cambial and where are they located?
6. The electron micrographs of the small intestine crypts show cells with secretory granules.
Some of the cells contain large dense granules at the apical cytoplasmic pole. The other cells
contain smaller granules concentrated at the basal cytoplasmic pole. Identify the secretory cells
and their functions.
7. Among the microphotographs of different parts of the small intestine, it is necessary to
select the duodenum. What structural features are indicative of the duodenum?

CONTROL TESTS

Directions: each of the following statements contains five suggested completions. Choose
the one that is best in each case.
1. Each of the following statements concerning the gastric mucosa is true, EXCEPT: A –
gastric pits form its microrelief; B – is covered with simple columnar mucous epithelium; C –
possesses its own nerve plexus; D – its lamina propria contains simple tubular glands; E – its
muscularis mucosae consists of three muscle layers.
2. Each of the following statements concerning the gastric fundic glands is true, EXCEPT:
A – occur in the submucosa; B – are simple tubular and slightly branched; C – secrete gastric juice;
D – consist of five cell types; E – open into gastric pits.
3. The gastric fundic glands consist of the following cells, EXCEPT: A – chief cells; B –
parietal cells; C – mucous neck cells; D – enteroendocrine cells; E – goblet cells.
4. Each of the following statements concerning the parietal cells of the gastric glands is true,
EXCEPT: A – secrete hydrochloric acid; B – secrete pepsinogen; C – their activity is stimulated
by gastrin, histamine, and acetylcholine; D – secrete an intrinsic factor; E – their intrinsic factor is
essential for vitamin B12 absorption.
5. Each of the following statements concerning the pyloric region of the stomach is true,
EXCEPT: A – pyloric gastric pits are deep and occupy about half of the mucosa thickness; B –
pyloric glands are tubular branched; C – mucous cells are predominant in pyloric glands; D –
pyloric glands contain parietal cells; E – its muscularis externa is very thick.

197
 6. Each of the following statements concerning the undifferentiated cells of the gastric glands
is true, EXCEPT: A – are located mainly in the neck region of the glands; B – are absent in the
pyloric glands; C – give rise to all glandular cell types; D – serve for renewal of gastric surface
epithelium; E – their descendants migrate upwards along the pit and are shed at the luminal surface.
7. Each of the following statements concerning the intestinal villus is true, EXCEPT: A – its
core consists of connective tissue; B – contains fenestrated sinusoidal blood capillaries; C –
contains a blind-ending lymphatic capillary called the lacteal; D – smooth muscle cells derived
from muscularis mucosae extend to the villus and accompany the lacteal; E – lacks the covering
epithelium.
8. Each of the following statements concerning the enterocytes of the small intestine
epithelium is true, EXCEPT: A – are tall columnar; B – lack microvilli; C – are specialized for
absorption and transport of substances from the gut lumen to circulation; D – enterocyte junctions
establish a barrier between the lumen and the intercellular compartment; E – produce enzymes
needed for terminal digestion and absorption.
9. Each of the following statements concerning the lipid absorption in the small intestine is
true, EXCEPT: A – enterocytes absorb fatty acids and glycerol from the lumen; B – enterocytes
resynthesize neutral fat; C – neutral fat is transported into the lacteal; D – neutral fat is transported
into the blood capillaries; E – contractions of the villus muscle cells drive away chyle from the
lacteal.
10. Each of the following statements concerning the Paneth cells of the small intestine
mucosa is true, EXCEPT: A – are located in villus epithelium; B – have large acidophilic apical
granules; C – their granules contain the antibacterial enzyme lysozyme; D – their lysozyme digests
cell walls of certain bacteria; E – take part in regulation of normal intestinal bacterial flora.
11. Each of the following statements concerning the renewal of the intestinal epithelium is
true, EXCEPT: A – all mature cells arise from the common stem (intermediate) cells; B –
intermediate cells are located in the lower half of crypts; C – epithelial cells, except Paneth cells,
migrate from crypts onto villi; D – Paneth cells are stem cells for intestinal epithelium; E – mature
cells are shed at tops of villi.
12. The distinctive feature of the duodenum is the presence of: A – lymphatic nodules; B –
Pejer’s patches; C – mucosal villi; D – mucosal crypts; E – submucosal glands.

Directions: one or more of the given statements or completions is/are correct. Choose the
answer: A – if only 1,2, and 3 are correct; B – if only 1 and 3 are correct; C – if only 2 and 4 are
correct; D – if only 4 is correct; E – if all are correct.

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 13. The gastric surface epithelium is called mucous, because: (1) it is covered with thick
mucus layer (2) gastric mucosa contains glands (3) gastric glands possess mucous cells (4) each
cell of this epithelium produces mucus
14. The following statements regarding the chief cells of the gastric glands are true: (1) are
located in the deepest parts of the fundic glands (2) are typical protein-secreting cells (3) secrete
pepsinogen, an inactive pepsin precursor (4) pepsinogen is converted to pepsin after contact with
the acid gastric juice
15. The following statements regarding the parietal cells of the gastric glands are true: (1)
are located both in the neck and in the deeper gland parts (2) secrete hydrochloric acid and the
intrinsic factor (3) their cytoplasm stains intensely with eosin and other acid dyes (4) have an
extensive intracellular canalicular system
16. The gastric pits are: (1) glands (2) crypts (3) villi (4) invaginations of the epithelium into
the mucosal lamina propria
17. The stomach functions are: (1) chyme formation from the food bolus (2) passage of
chyme into the duodenum (3) protein digestion by pepsin (4) neutral fat absorption
18. The following statements regarding the enteroendocrine cells of the gastric glands are
true: (1) they are more prevalent at the base of the glands (2) any cells do not reach the gland
lumen (3) some cells are in contact with the gland lumen (4) secrete hormones: gastrin, secretin,
etc.
19. The three smooth muscle layers of the gastric muscularis mucosae provide: (1) gastric
peristalsis (2) chyme passing into the duodenum (3) plication of the gastric mucosa (4) outflow of
gland secretion
20. The amplification of the small intestine mucosa surface for digestion and absorption is
provided by: (1) plicae circulares (2) intestinal villi (3) microvilli of enterocytes (4) goblet cells
21. The following statements regarding the microvilli of the small intestine epithelium are
true: (1) are small finger-like projections of the enterocyte apical plasma membrane (2) microvilli
appear as a “brush border” (3) provide major surface amplification for digestion and absorption
(4) the brush border is broken off over goblet cells
22. The following statements regarding the crypts of the small intestine mucosa are true: (1)
are epithelial invaginations into the lamina propria (2) extend through the lamina propria thickness
up to the muscularis mucosae (3) are tubular structures (4) open onto the luminal surface at villus
bases
23. The following statements regarding the intestinal goblet cells are true: (1) contain
mucinogen granules in the apical distended portion (2) contain organelles and nuclei in the narrow
basal portion (3) produce mucus (4) are located only in intestinal villi

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 24. The epithelium of the small intestine villi contains the following cells: (1) absorptive
cells (2) goblet cells (3) endocrine cells (4) Paneth cells
25. The epithelium of the small intestine crypts contains the following cells: (1) goblet cells
(2) intermediate cells (3) Paneth cells (4) endocrine cells
26. The following statements regarding the gut-associated lymphoid tissue are true: (1)
lymphocytes infiltrate the mucosal epithelium and the lamina propria (2) lamina propria contains
lymphatic nodules and Pejer’s patches (3) epithelial M cells transport antigens from the gut lumen
to lymphocytes (4) antigens stimulate lymphocytes for immune response
27. The following statements regarding the gut-associated lymphoid tissue are true: (1) after
antigen stimulation, lymphocytes migrate to lymphatic nodes and differentiate into plasma cells
(2) plasma cells secrete IgA (3) enterocytes produce secretory glycoprotein (4) the IgA-secretory
glycoprotein complex passes into the lumen to inactivate antigens

FIGURES

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 Fig. 17.1. Gastric mucosa and gastric main glands
I – gastric pit; II – gland neck; III – gland corpus; IV – gland bottom; 1 – gastric mucosa
epithelium; 2 – mucous cells; 3 – chief cells; 4 – parietal cell; 5 – intracellular canalicular
system; 6 – endocrine cell; 7 – blood capillary; 8 – mucosa lamina propria; 9 – muscularis
mucosae.

Fig. 17.2. Small intestine mucosa

I – villi; II – crypts; 1 – lamina propria; 2 – smooth muscle cells; 3 – absorptive cells; 4 – goblet
cells; 5 – endocrine cells; 6 – dividing cells; 7 – intermediate cells; 8 – Paneth cells; 9 – blood
capillary; 10 – lymphatic capillary; 11 – muscularis mucosae.

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 19. DIGESTIVE SYSTEM: LARGE INTESTINE, LIVER, and PANCREAS

Large intestine (colon)

The large intestine structure conforms to the general description of the gastro-interstinal tract
structure. Its wall consists of fore tunics: a mucosa, a submucosa, a muscularis externa, and a
serosa.
The mucosa of the colon shows numerous folds. There are no villi but numerous closely
arranged tubular crypts similar to those in the small intestine are present. Crypts occupy the entire
thickness of the mucosal lamina propria The mucosa is lined with a simple columnar striated
epithelium consisting of absorptive cells with the brush border that absorb water and electrolytes
from the intestinal contents, goblet cells, enteroendocrine cells, and intermediate cambial cells. In
the epithelium of the large intestine, goblet cells are prevalent, their number increases caudally.
The mucus secreted by them serves as a lubricant that facilitates the passage of semisolid contents
through the colon. The mucus is rich in antibodies (lgA) providing immune protection against
pathogenic organisms. The muscularis mucosae is present and represented by two layers.
The colon limphoid tissue is well-developed, reflecting the diversity of microflora in the
lumen. Lymphocytes infiltrate the mucosa and, often, submucosa, forming large lymphatic
nodules.
The submucosa consists of moderately dence connective tissue, large blood vessels and the
submucosal nerve plexus. It often contains fat cells.
The muscularis externa includes two layers (inner circular and outer longitudinal) of
smooth muscle tissue. Muscle cells of the outer longitudinal layer are collected to form three thick
bands, the teniae coli. A thin layer of longitudinally arraged cells is present in the intervals between
the teniae. The teniae are shorter in length than the other layers of the large intestine wall. This
results in the production of sacculations (also called haustrations) on the wall of the colon.
The serosa is composed of connective tissue and mesothelium. The peritoneum is missing
over the posterior part of the ascending and descending colon. The serosa contains blood vessels
and nerve plexus. The peritoneum forms small pouch-like processes that are filled with fat. These
yellow masses are called the appendices epiploicae.

Vermiform appendix
The appendix is finger-like projection from the cecum. It is the narrowest part of the large
intestine. The structure of the vermiform appendix is similar to that of the colon, but has some
differences. The mucosal crypts are poorly formed. Both the mucosa and submucosa are occupied
by a great number of lymphoid follicles forming a structure that looks like the tonsil (intestinal

202
tonsil). The teniae coli are not present. The longitudinal muscle layer is complete and equally thick
all around.

Rectum and anal canal

The structure of the rectum is similar to that of the colon but there are no teniae, a continuous
longitudinal muscle layer is present. The anal canal is a part of the rectum. The mucosa shows six
to twelve longitudinal folds that are called the anal columns. The lower ends of the anal columns
are united to each other by short transverse folds called the anal valves. The mucosa of the upper
15 mm of the canal is lined with columnar epithelium.The mucosa of the next 15 mm of the rectum
is lined with stratified squamous nonkeratinized epithelium. This region has no anal columns. The
lowest 8 to 10 mm of the anal canal are lined with true skin in which hair follicles, sebaceous
glands, and sweat glands are present. Above each anal valve there is a depression called the anal
sinus. The anal glands, atypical sweat glands, open into each sinus. The anal canal is surrounded
by circular and longitudinal layers of smooth muscle cells. The circular muscles are thickened to
form the internal anal sphincter. Outside the layer of smooth myocytes, there is the external anal
sphincter, which is made up of striated muscle fibers.

Liver
The liver may be regarded as a modified exocrine gland that also has other functions. It is
made up of liver cells or hepatocytes. Each hepatocyte is a large polygonal cell with a round
nucleus. The liver substance is divisible into large lobes (right, left, and caudal), each of which
consists of numerous lobules. The exocrine secretion of the liver cells is called bile. Bile passes
from the liver cells into very delicate bile canaliculi that are present in intimate relationship to the
cells. From the canaliculi, bile enters into progressively larger ducts, which end in the bile duct.
This duct conveys bile into the duodenum where it plays a role in the digestion of fat.
The blood draining from the stomach and intestines and containing absorbed food materials
reaches the liver through the portal vein and its branches. Within the liver, this blood passes
through sinusoids and comes into very intimate relationship with liver cells. The liver is thus able
to “screen” all substances entering the body through the gut. Some of them (e.g., amino acids) are
used for the synthesis of new proteins needed by the body. Others (e.g., glucose, lipids) are stored
in liver cells for subsequent use; while harmful substances (e.g., drugs, alcohol) are detoxified.
The portal vein also delivers blood rich in hormones (e. g., insulin, glucagon) from the pancreas
and blood from the spleen. This blood contains high concentrations of products formed by the
breakdown of erythrocytes in the spleen. Some of these products (e.g., bilirubin) are used by the

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liver for producing bile, while some (e.g., iron) are stored for re-use in new erythrocytes. This very
active exchange between blood and hepatocytes is so-called “endocrine function” of the liver.
In addition to deoxygenated blood reaching the liver through the portal vein, the organ also
receives oxygenated blood through the hepatic artery and its branches. The blood entering the liver
from both these sources mixes and passes through the hepatic sinusoids; then it is collected by the
different types of the hepatic veins. One such type runs through the centre of each lobule of the
liver where it is called the central vein. The central veins drain into the sublobular veins, which in
turn drain into the hepatic veins; the hepatic veins leave the liver to end in the inferior vena cava.
The vessels in a portal triad usually give branches to parts of three lobules. The area of liver
tissue (comprising parts of three hepatic lobules) supplied by one branch of the portal vein is
regarded as the true functional unit of liver tissue and is referred to as a portal lobule (in distinction
to the hepatic lobule described above).
The liver is covered with a connective tissue capsule (Glisson’s capsule). This connective
tissue extends into the liver substance through the portal canals where it surrounds the portal triads.
The sinusoids are surrounded by reticular fibers. Connective tissue does not intervene between the
adjoining liver cells.
Bile is secreted by the liver cells into bile canaliculi. These canaliculi have no walls of their
own. They are spaces between the plasma membranes of two liver cells. The canaliculi form
hexagonal networks around the liver cells. On the periphery of a lobule, the canaliculi become
continuous with delicate intralobular ductules, which then become continuous with larger
interlobular ducts of the portal triads. The interlobular ducts are lined with cuboidal epithelium.
Some smooth muscle cells are present in the walls of larger ducts.
The liver performs numerous functions. The liver acts as an exocrine gland for the secretion
of bile. Liver cells take up numerous substances from the blood and also pour many substances
back into the blood (so-called “endocrine function”). The liver plays a prominent role in the
metabolism of carbohydrates, proteins, and fats. Metabolic functions include the synthesis of the
plasma proteins (e. g., fibrinogen, prothrombin) and the regulation of the blood glucose and lipid
levels. The liver acts as a store for various substances including glucose, such as glycogen, lipids,
vitamins, and iron.
The liver plays a protective role by detoxifying substances, including drugs and alcohol.
Removal of bile pigments from the blood and their excretion in the bile is a part of this process.
The macrophages (Kupffer cells) lining the sinusoids of the liver have a role similar to that of other
cells of the mononuclear phagocyte system. They are of particular importance, as they are the first
cells of this system that come in contact with materials absorbed in the gut. They also remove
damaged erythrocytes from the blood. During fetal life the liver is the centre for hemopoiesis.

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 Gallbladder
The gallbladder stores and concentrates bile. This bile is discharged into the duodenum when
required. The wall of the gallbladder is made up of a mucous membrane, a fibromuscular coat, and
a serosa that partially covers the organ. The mucosa of the gallbladder is lined with a simple
columnar epithelium with a brush border that absorbs water to concentrate bile. The mucosa is
highly folded. The folds are called rugae. The fibromuscular coat is made up mainly of connective
tissue containing the usual elements. Smooth muscle cells are present and run in various directions.
The serosa has a lining of mesothelium resting on connective tissue.

Pancreas
The pancreas is covered with connective tissue that forms its capsule. The septa arising from
the capsule extend into the gland, dividing it into lobules.
The pancreas is an exocrine and endocrine gland. The exocrine pancreas secretes enzymes
that play a very important role in the digestion of carbohydrates, proteins, and lipids. The endocrine
part of the pancreas produces two very important hormones, insulin and glucagon.
The exocrine component of the pancreas is in the form of a serous, compound tubulo-
alveolar gland. Its general structure is very similar to that of the parotid gland, but the two are
easily distinguished due to the presence of endocrine elements in the pancreas.
The secretory elements of the exocrine pancreas are long and tubular, but they are usually
described as alveoli as they appear rounded or oval in sections. Their lumen is small. The lining
cells appear triangular in section and have spherical nuclei located basally. In sections stained with
hematoxylin and eosin, the cytoplasm is highly basophilic in the basal part and acidophilic in the
apical cell part.
Under the EM, the cells lining the aiveoli show features that are typical of secretory cells.
Their basal cytoplasm is packed with rER. A well-developed Golgi complex is present in the
supranuclear part of the cell. Numerous secretory granules occupy the greater part of the cytoplasm
(except the most basal part). The secretory cells produce a secretion that contains numerous
enzymes, including trypsinogen, chymotrypsinogen, amylase, etc.
In addition to secretory cells, the alveoli contain centroacinar cells that are located near the
centre of the acinus (or alveolus). These cells really belong to the intercalated ducts, which are
invaginated into the secretory elements.
From the intercalated ducts the secretions pass into larger intralobular and then interlobular
ducts. They finally pass into the duodenum through the main pancreatic duct and the accessory
pancreatic duct.

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 The endocrine component of the pancreas produces two very important hormones, insulin
and glucagon. These two hormones are also carried through the portal vein to the liver, where they
have a profound influence on the metabolism of carbohydrates, proteins, and fats.
The endocrine part of the pancreas is in the form of numerous rounded collections of cells
that are embedded within the exocrine part. These collections of cells are called the pancreatic
islets (the islets of Langerhans). The human pancreas has about one million islets. They are most
numerous in the tail of the pancreas. Each islet is separated from the surrounding alveoli by a thin
layer of connective tissue. The islets are very richly supplied with blood through a dense capillary
plexus. The intervals between the capillaries are occupied by cells arranged in groups or cords. In
ordinary preparations stained with hematoxylin and eosin, all the cells appear similar, but with the
use of special procedures two main types of cells can be distinguished. A cells secrete the hormone
glucagon. They comprise about 20% of the islet cells. B cells secrete the hormone insulin. They
comprise about 70% of the islet cells. D cells secrete somatostatin. They comprise about 10% of
the islet cells.
Apart from the main types of cells described above, there is minor population of the
pancreatic islet endocrinocytes that includes D-1 cells producing vasoactive intestinal polypeptide
(VIP), PP cells producing pancreatic polypeptide, and EC cells producing secretin, motilin, and
substance P.
The cells of the pancreatic islets belong to the gastro-entero-pancreatic endocrine system.
They are independent on the adenohypophysis. A-cells and B-cells are mainly regulated by the
blood glucose levels. Pancreatic islets are richly innervated by autonomic nerves. Noradrenaline
and acetylcholine released at nerve endings influence secretion of the islet cells.

CONTROL PROBLEMS

1. If necessary, patients are administered medicines using enemas. What large intestine cells
provide absorption of the medications?
2. There are two microphotographs of the lymphoid organs. They are supposed to be the
tonsil and the appendix. What histological structures may be used to differentiate between the
organs?
3. It was stated in a scientific article that the triad (portal area) is the hepatic lobule center.
A student considers that this statement is erroneous, because the hepatic lobule center contains the
central vein. Is the student right?
4. Bacterial food poisoning induces sER development in hepatocytes. What liver function
is associated with sER development?

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 5. Some diseases cause venous blood congestion, which impairs tissue oxygenation and
metabolism. Which part of the hepatic lobule (the center or periphery) is primarily affected in this
case?
6. Some toxins may be absorbed in the small intestine and reach the liver in the portal blood.
Which part of the hepatic lobule (the center or periphery) is primarily affected in this case?
7. Experimental ligation of the main pancreatic duct causes the death of some secretory
cells. Which pancreatic cells die and which of them survive after this operation?
8. Some people like sweets and eat a lot of sugar. What pancreatic cells function with
overstrain in this case?

CONTROL TESTS

Directions: each of the following statements contains five suggested completions. Choose
the one that is best in each case.
1. Each of the following statements concerning the large intestine mucosa is true, EXCEPT:
A – contains numerous crypts; B – forms villi; C – its surface epithelium is the same as that of the
small intestine; D – goblet cells are more numerous in its epithelium than in the small intestine; E
– Paneth cells are normally absent in its crypts.
2. Each of the following statements concerning the liver circulation is true, EXCEPT: A –
the liver receives blood from the portal vein and the hepatic artery; B – blood is mixed in sinusoidal
capillaries; C – capillaries empty into central veins; D – central veins lead to sublobular veins; E
– sublobular veins carry blood into the portal vein.
3. Each of the following statements concerning the classic hepatic lobule is true, EXCEPT:
A – is a hexagonal block of tissue; B – triads are at its angles; C – the sublobular vein is its centre;
D – cell plates radiate from its centre to the periphery; E – sinusoids carry blood from the periphery
to the centre.
4. Each of the following statements concerning the hepatic sinusoids is true, EXCEPT: A –
arise from roundlobular arteries and roundlobular veins; B – perfuse cells with mixed portal and
arterial blood; C – carry blood into the central veins; D – are the parts of hepatic plates; E – are
surrounded by the space of Disse.
5. Each of the following statements concerning the portal area (the triad) is true, EXCEPT:
A – includes the central vein from the hepatic vein system; B – includes the interlobular bile duct;
C – includes the interlobular vein from the portal vein system; D – includes the interlobular artery
from the hepatic artery system; E – is surrounded by a small amount of loose connective tissue.

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 6. The central vein and the sublobular vein of the liver have common features, EXCEPT: A
– belong to the hepatic vein system; B – have equal diameters and wall thickness; C – are fibre
type veins; D – are solitary veins (travel alone); E – carry blood away from the liver.
7. Each of the following statements concerning the hepatocytes is true, EXCEPT: A – are
large polygonal cells; B – have one or two nuclei with well-developed nucleoli; C – many of them
are tetraploid; D – are not capable of regeneration when the liver substance is lost; E – are arranged
in plates.
8. Each of the following statements concerning the hepatocyte organelles is true, EXCEPT:
A – Golgi apparatus and lysosomes are absent; B – sER is involved in the degradation of toxins
and drugs, the synthesis of cholesterol and lipids; C – peroxisomes are involved in the breakdown
of hydrogen peroxide and in alcohol metabolism; D – rER is involved in protein synthesis; E –
numerous mitochondria reflect the high energy requirement.
9. Each of the following statements concerning the bile canaliculi is true, EXCEPT: A – are
intercellular gaps between the hepatocytes within the plates; B – drain bile into the roundlobular
and interlobular ducts; C – have walls of their own; D – hepatocyte microvilli project into their
lumen; E – are isolated from the intercellular compartment by tight junctions.
10. Each of the following statements concerning the perisinusoidal space of Disse is true,
EXCEPT: A – lies between the hepatocyte basal surfaces and the endothelial cell basal surfaces;
B – contains few reticular fibres; C – hepatocyte microvilli project into this space; D – fetal
hemopoiesis occurs here; E – is the site of exchange between bile and hepatocytes.
11. Each of the following statements concerning the exocrine part of pancreas is true,
EXCEPT: A – is a compound branched acinar gland; B – produces pancreatic juice; C – its acini
secrete digestive enzymes: trypsin, amylase, and lipase; D – its intercalated ducts secrete fluid rich
in sodium and bicarbonate; E – its secretion enters the stomach.
12. Each of the following statements concerning the pancreatic acini is true, EXCEPT: A –
consist of pyramidal serous cells; B – basal portions of cells are acidophilic; C – the cell basal
cytoplasm abounds in rER; D – apical portions of cells are acidophilic; E – the cell apical
cytoplasm contains zymogen (secretory) granules.
13. Each of the following statements concerning the pancreatic islets is true, EXCEPT: A –
are scattered throughout the organ; B – are more numerous in the pancreas tail; C – contain five
types of endocrine cells; D – lack blood capillaries; E – autonomic nerves are in contact with
endocrine cells and influence the hormone secretion.

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 Directions: one or more of the given statements or completions is/are correct. Choose the
answer: A – if only 1,2, and 3 are correct; B – if only 1 and 3 are correct; C – if only 2 and 4 are
correct; D – if only 4 is correct; E – if all are correct.
14. The extensive development of GALT in the large intestine reflects the presence in its
lumen of: (1) mucus (2) a large number and a variety of microorganisms (3) chyle (4) noxious and
metabolic products
15. The principal functions of the large intestine are as follows: (1) absorption of electrolytes
and water (2) digestion of proteins and lipids (3) formation of feces (4) absorption of amino acids,
glycerol, and fatty acids
16. The following statements regarding the liver portal system are true: (1) the portal vein
carries venous blood from the digestive tube, the pancreas, and the spleen (2) portal blood contains
nutrients and noxious materials from the intestine (3) portal blood contains products of the blood
cell breakdown from the spleen (4) hepatocytes convert toxic substances to harmless ones
17. The liver blood capillaries are: (1) continuous (2) discontinuous (3) fenestrated (4)
sinusoids
18. The hepatic sinusoid wall contains the following cells: (1) endothelium (2) hepatocytes
(3) stellate macrophages (4) centroacinar
19. The following statements regarding the portal hepatic lobule are true: (1) is a triangular
block of tissue (2) the triad is its centre (3) three central veins are at its angles (4) is a diamond-
shaped block of tissue
20. The following statements regarding the hepatic acinus are true: (1) is a diamond-shaped
block of tissue (2) its short axis is between two triads (3) its long axis is between two central veins
(4) the sublobular vein is its centre
21. The following statements regarding the Kupffer cells of the liver are true: (1) are stellate
macrophages (2) are located in the hepatic sinusoid wall (3) belong to the mononuclear phagocytic
system (4) arise from blood monocytes
22. The following statements regarding the hepatic plates are true: (1) consist of two
hepatocyte rows (2) bile canaliculi (capillaries) are between two cell rows (3) are separated by the
blood sinusoids (4) hepatocyte junctions isolate the bile canaliculi
23. The following statements regarding the lipocytes of the liver are true: (1) are the storage
site for vitamin A (2) resemble fibroblasts and secrete reticular fibres (3) their broad basal portion
faces the space of Disse (4) their narrow apical portion takes part in bile production
24. The following statements regarding the hepatocyte polarization are true: (1) the vascular
hepatocyte pole faces the perisinusoidal space (2) the vascular pole is involved in the exocrine

209
function (3) the biliar hepatocyte pole faces the bile canaliculi (4) the biliar pole is involved in the
endocrine function
25. The endocrine hepatocyte function includes the secretion into the blood the following
substances: (1) albumins and nonimmune globulins (2) prothrombin and fibrinogen (3) cholesterol
(4) glucose released by hydrolysis of glycogen
26. The centroacinar cells from the pancreas belong to: (1) acinus (2) interlobular duct (3)
intralobular duct (4) intercalated duct
27. The following statements regarding the pancreatic duct system are true: (1) is short (2)
includes intercalated, intralobular, and interlobular ducts (3) the ducts are lined with the cuboidal
or columnar epithelium (4) the duct cells are not involved in the pancreatic juice production
28. The following statements regarding the pancreatic endocrine cells are true: (1) A cells
secrete glucagon (2) B cells secrete insulin (3) D cells secrete somatostatin (4) are
adenohypophysis-dependent cells
29. The following statements regarding the pancreatic hormones are true: (1) insulin
influences the liver, skeletal muscles, and the adipose tissue (2) insulin decreases the blood glucose
level (3) glucagon raises the blood glucose level (4) the blood glucose level regulates the release
of both insulin and glucagon

FIGURES

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 Fig. 18.1. Liver lobules and plates
A – hepatic lobules: 1 – classic lobule; 2 – portal lobule; 3 – hepatic acinus; 4 – portal area
(triad); 5 – central veins. B – hepatic plates: 1 – hepatic plate; 2 – hepatocyte; 3 – blood capillary
(hepatic sinusoid); 4 – perisinusoidal space of Disse; 5 – Ito cell (lipocyte); 6 – bile canaliculus;
7 – triad: 7a – interlobular vein; 7b – interlobular artery; 7c – interlobular bile duct; 8 – central
vein.

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 Fig. 18.2. Hepatocyte and hepatic sinusoid
1 – hepatic sinusoid lumen; 2 – erythrocyte; 3 – endothelial cells; 4 – stellate macrophage
(Kupffer cell); 5 – reticular fibers; 6 – perisinusoidal space of Disse; 7 – lipocyte (Ito cell); 8 –
pinocytic vesicles; 9 – microvilli; 10 – desmosomes and tight junctions; 11 – bile canaliculi; 12 –
sER; 13 – Golgi apparatus; 14 – mitochondria; 15 – rER; 16 – lysosomes; 17 – nucleus; 18 –
glycogen clumps.

Fig. 18.3. Pancreas exocrine and endocrine parts

1 – epithelium of the duodenum mucosa; 2 – main pancreas duct; 3a – simple acinus; 3b –
compound acinus; 4 – serous acinar cells; 5 – intercalated duct; 6 – centroacinar cells; 7 –
pancreatic islet; 8 – endocrine cells; 9 – fenestrated blood capillaries.

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 20. RESPIRATORY SYSTEM

The respiratory system consists of a conducting portion and a respiratory portion. The
conducting portion includes: the nasal cavities, nasopharynx, larynx, trachea, and bronchi. The
latter undergo extensive branching. The terminal parts of branching are called terminal
bronchioles. The respiratory portion includes respiratory bronchioles, alveolar ducts, and alveolar
sacs. Collectively they constitute an acinus. All parts of the acinus contain alveoli.

The lung conducting portion

The conducting portion structure conforms to a general plan. The respiratory tract organs
consist of four tunics: a mucosa, a submucosa, a fibrocartilaginous tunic, and an adventitia.
Mucosa includes a pseudostratified ciliated columnar epithelium, mucosal lamina propria,
and the lamina muscularis mucosae.
The ciliated columnar epithelium is composed of the following cell types: (1) ciliated cells,
(2) goblet cells, (3) basal or stem cells, (4) intermediate cells, young differentiating cells, (5)
endocrine cells, (6) brush cells, (7) Langerhans cells. Cilliated cells contain cilia on their luminal
surface (about 200 cilia on each cell). The cilia beat in the direction of the larynx, moving mucus
and inspired dust particles up. This air cleaning process is called the mucociliary transport. Goblet
cells produce mucus. Basal and intermediate cells are cambial cells; they rest on the basement
membrane, but no reach the lumen. Endocrine cells are small basally granulated cells; they belong
to the diffuse endocrine system and produce verious hormones. Brush cells contain short microvilli
on the apical cell portion and nerve fiber synaptic contact on the cell basis. These cells are
supposed to serve as chemoreceptors. Langerhans cells are antigen-presenting cells.
The mucosa lamina propria located beneath the epithelium consists of loose connective
tissue rich in elastic fibers and plasma cells. The lamina muscularis mucosae is composed of
circularly arranged smooth muscle cells. This layer is absent in the upper organs of respiratory
tract, including the trachea.
Submucosa (tela submucosa) is of loose connective tissue; it contains mixed glands, whose
secretory portions include both mucous and serous cells. The latter are of two types: (a) cells with
basophilic granules producing amylase and (b) cells with eosinophilic granules producing
lysozyme.

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 Fibrocartilaginous tunic consists of hyaline or elastic (in the larynx and middle bronchi)
the cartilaginous structures. In the trachea and the main bronchi, there are C-shaped hyaline
cartilages. Large and middle bronchi have cartilage plates. Small bronchi have no cartilage at all.
The adventitia of trachea and extrapulmonary bronchi is composed of loose connective
tissue; that of intrapulmonary bronchi, of dense irregular connective tissue.

Nasal cavity
The main functions of the nasal cavity are to filter, warm, and moisten inhaled air. Mucosa-
associated- lymphoid- tissue (MALT) is present in the nasopharyngeal tonsils called adenoids. The
root of the nasal cavity is the site of olfactory mucosa including bipolar olfactory neurons.
The external aspect of the nostrils is covered by epidermis, which extends for a short
distance. The stratified squamous keratinized epithelium then becomes a nonkeratinized squamous
and, eventually, a pseudostratified columnar epithelium. The nasal cavity and the paranasal sinus
cavities are lined with a pseudostratified columnar ciliated epithelium. The lamina propria contains
numerous glands and vessels.
Inspired air is moistened by secretion of the glands and goblet cells. The mucus picks up the
dust and is moved through the nasopharynx by the action of the cilia. The mucous will then be
swallowed or expectorated.
The lamina propria of the nasal cavity mucosa contains a large number of thin-walled veins.
Under normal conditions these veins are collapsed. However, under certain circumstances they
can become distended with blood. This increases the thickness of the nasal mucosa and renders
breathing more difficult; it is commonly encountered in “stuffed up” nose.

Larynx
The larynx conducts air, guards against entry of anything but air, and is involved in
phonation. The mucosa is lined with pseudostratified columnar epithelium, except the true vocal
cords. The latter are covered with stratified squamous nonkeratinized epithelium. The lamina
propria contains many mixed glands. The lamina muscularis mucosa is absent. The cartilage layer
is formed by irregularly shaped plates of hyaline and elastic cartilage. The vocal folds contain the
vocal ligament to which the skeletal muscle fibers are attached.

Trachea
The mucosa of the trachea is lined by the pseudostratified columnar ciliated epithelium on
the distinct basement membrane. The lamina propria contains numerous longitudinally arranged
elastic fibers, plasma cells, lymphocytes, and lymphatic nodules. The muscularis mucosae is

214
absent, but some smooth muscle cells can be found. The submucosa contains mixed tracheal
glands. The fibrocartilagenous tunic is formed by an incomplete cartilage ring. There is a gap
between the ends of the cartilage ring. This gap is filled with connective tissue ligament that is
rich in elastic fibers and bundles of smooth muscle cells. This ligament bridges the two cartilage
ends to prevent dilatation. The adventitia is composed of loose connective tissue and binds the
trachea to adjacent structures.

Bronchi
Extrapulmonary bronchi have the same structure as the trachea. Intrapulmonary bronchi
differ from the extrapulmonary ones. Intrapulmonary bronchi are subdivided into large, middle,
and small bronchi.
Large bronchi are lined with a ciliated epithelium. It is similar in structure to the epithelium
of the other parts of the conducting airways. The lamina propria is composed of loose connective
tissue with many elastic fibers. The muscularis mucosae is well-developed and composed of a
circular layer of smooth muscle cells. The longitudinal mucosal folds characteristic of
intrapulmonary bronchi seen in histological sections are provoked by postmortem contraction of
smooth muscle cells. The submucosa contains mixed bronchial glands. The fibrocartilagenous
tunic is formed by large plates of hyaline cartilage. The adventitia is formed by dense irregular
connective tissue containing bronchial arteties and veins, lymphatics, and nerve fibers.
Middle bronchi are lined with a ciliated epithelium with a decreasing number of goblet
cells. The submucosa contains bronchial glands. The fibrocartilagenous tunic consists of small
elastic cartilage plates that become reduced in size as the bronchial diameter diminishes. The
adventitia consists of dense irregular connective tissue.
Small bronchi are lined with ciliated columnar epithelium, in which goblet cells decrease
in number and gradually disappear. The muscularis mucosae is well-developed. The submucosa,
bronchial glands, and cartilages are absent. The adventitia consists of dense irregular connective
tissue.
Terminal bronchioles are lined with a simple cuboidal ciliated epithelium consisting of
ciliated cells, brush cells, endocrine cells, and Clara cells. There are no goblet cells at all. Clara
cells increase in number as ciliated cells decrease along the length of the bronchiole. Clara cells
have many large mitochondria, abundant sER, and secretory granules. Clara cells take part in
detoxification and secretion; they produce lipoproteins, which prevent adhesion of bronchioles
during expiration. Moreover, Clara cells release some special proteins that inhibit the chemotaxis
of fibroblasts. In some cases, when Clara cells cannot produce these specific proteins, the

215
fibroblasts increase in number and secrete collagen fibers that may result in interstitial fibrosis of
the lung.
The muscularis mucosae of the terminal bronchiole is formed by discontinuous layer of
smooth muscle cells. The adventitia is of loose connective tissue containing small branches of
bronchial arteries, veins, lymphatic vessels, and autonomic nerve fibers.

The lung respiratory portion

The functional unit of the respiratory portion of the lungs is the acinus. It consists of
respiratory bronchioles, alveolar ducts, and alveolar sacs. All parts of the acinus contain alveoli
where blood-air gas exchange occurs.
Respiratory bronchioles are lined by cuboidal epithelium including ciliated cells, Clara
cells, occasional brush cells, and endocrine cells. Lamina propria of loose connective tissue and
some smooth muscle cells are present. The wall of the respiratory bronchioles has many openings
(or apertures) that lead to the alveoli.
Alveolar ducts are elongated airways that have almost no walls becouse the distance
between the openings is very short. Numerous alveoli open into an alveolar duct. Smooth muscle
cells form a ring at the peripheral border of the alveoli. Owing to these myocytes, there are knob-
like structures that are distinctive features of the alveolar ducts in histological slides.
The alveolar sac is a cluster of alveoli at the end of an alveolar duct.
Alveoli are air-filled vesicles, which are the main site of gas exchange. Alveoli are connected
by apertures to alveolar ducts, alveolar sacs, and respiratory bronchioles. Most alveoli open into
the alveolar sac. The alveolus is lined with epitheliual cells called pneumocytes (alveolar cells,
alveolocytes) of two types.
Type I alveolar cells are very thin squamous cells that are joined together by tight junctions.
They contain scanty mitochondria and organelles. These cells take part in the formation of the air–
blood barrier. This barrier consists of the following structures: (a) type I alveolar cells, (b) the
basement membrane of epithelial cells, (c) the basement membrane of capillary endothelial cells,
and (d) endothelial cells.
Type II alveolar cells occupy only from 5 to 10 % of the alveolar surface area. These cells
are cuboidal in shape containing numerous mitochondria, well-developed sER and rER, and large
lamellar bodies. The latter include phospholipids, proteins, and glycosaminoglycans. The contents
of lamellar bodies are released into the alveolar space by exocytosis and form a special layer
known as surfactant. The surfactant reduces alveolar surface tension and prevents collapse of the
alveoli. There is some water and lipids between the surfactant and pneumocytes (type I

216
alveolocytes). This layer is termed “hypophase” or “fluid phase.” Both the surfactant and
hypophase compose the alveolar–surfactant complex.
Type II alveolocytes may act as stem cells for type I cells. If extensive destruction of type I
cells occurs, type II cells increase in number and then turn into type I cells.
The alveoli are surrounded and separated from one another by thin loose connective tissue
called the alveolar septa containing numerous blood capillaries. The elastic fibers are an important
component of the alveolar septa. The elastic fibers allow the lung to stretch in breath and allow air
to be expelled from the alveoli in exalation. Fibroblasts, mast cells, plasma cells, leukocytes, and
macrophages are found in the interalveolar septa.
Alveolar macrophages are an important component of the lung defense system. As a rule,
alveolar macrophages lie on interalveolar septa, but they can also be observed free in the alveolar
spaces. They phagocytose inhaled bacteria and particulate matter (dust, carbon, nicotine gums).
They also remove superfluous surfactant and secrete lysozyme, collagenase, elastase, and acid
hydralase. After phagocytosis, macrophages may pass into lymphatic vessels are transported with
lymph to the regional lymph nodes. In other cases, macrophages may enter the lumen of the
respiratory and terminal bronchioles where they adhere to ciliated epithelium that is the first step
on the mucociliary transport or escalator. This escalator carries them up to the main bronchi and
trachea, from which they are removed by coughing.

CONTROL PROBLEMS

1. Inspired air contains dust and some foreign particles. What is the mechanism whereby air
is filtered out in the respiratory passages? What cells take part in the removal of foreign particles?
How do they end up in the lung interalveolar connective tissue?
2. There is a slide of the lung that shows large blood vessels next to the bronchi. Which of
the circulations (systemic or pulmonary) do the blood vessels belong to?
3. The microphotograph of the lung alveolus shows an alveolar cell (pneumocyte) bulging
into the air space and containing numerous cytoplasmic lamellar bodies. Specify the pneumocyte
and its function.
4. On expiration, the lung alveoli become smaller, and deoxygenated air is expelled from
the lungs. What structures of the interalveolar septa actively reduce the volume of pulmonary
alveoli? What disease is associated with lysis and destruction of these interalveolar structures?
5. In bronchial asthma, paroxysmal dyspnea (spasm) is due to constriction of small bronchi.
What structural elements of the bronchial wall cause a sudden spasm? Why constriction of the
small bronchi is markedly pronounced?

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 CONTROL TESTS

Directions: each of the following statements contains five suggested completions. Choose
the one that is best in each case.
1. The functions of the respiratory conducting passages are as follows, EXCEPT: A – air
filtration (removal of particles); B – air conduction; C – warming of inspired air; D – gas exchange;
E – moistening of inspired air.
2. The tracheal epithelium consists of the following cells, EXCEPT: A – goblet cells (mucus
secreting); B – chief cells (enzyme-secreting); C – brush cells (receptor cells); D – small granule
cells (endocrine cells); E – basal cells (stem cells).
3. Each of the following statements concerning the tracheal cartilages is true, EXCEPT: A –
are C-shaped structures; B – consist of hyaline cartilaginous tissue; C – are stacked on one another
to form supporting structure; D – tracheal muscles bridge the free ends of each cartilage; E – lack
perichondrium.
4. The structure of the large bronchi and the middle bronchi are similar, EXCEPT: A – the
epithelium is simple pseudostratified ciliated; B – the submucosa contains glands; C – the
cartilaginous layer consists of large hyaline plates; D – the mucosa possesses the muscularis
mucosae; E – the adventitia is composed of connective tissue.
5. Each of the following statements concerning the small bronchus is true, EXCEPT: A –
contains small plates of elastic cartilage; B – lacks the submucosa and glands; C – consists of the
mucosa and adventitia; D – the mucosa forms large folds; E – possesses the well-developed
muscularis mucosae.
6. Each of the following statements concerning the terminal bronchiolar epithelium is true,
EXCEPT: A – transforms into simple cuboidal; B – ciliated cells decrease in number; C – goblet
cells are absent; D – brush cells and granule cells are prevalent; E – Clara cells increase in number.
7. Each of the following statements concerning type II alveolar cells is true, EXCEPT: A –
are cuboidal cells bulging into the air space; B – cover about 95% of the alveolar surface; C – are
surfactant-secreting cells; D – their apical cytoplasm is filled with lamellar bodies; E – their
lamellar bodies are rich in phospholipids.
8. Each of the following statements concerning the surfactant is true, EXCEPT: A – forms
the phospholipid layer over the alveolar epithelium; B – reduces surface tension at the air-
epithelium interface; C – appears from lamellar bodies of alveolar cells by exocytosis; D – its
adequate secretion prevents alveolar collapse on exhalation; E – is produced by type I
pneumocytes.

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 9. On exhalation the alveoli diminish in size due to the presence in the alveolar septum of:
A – smooth muscle cells; B – collagen fibres; C – elastic fibres; D – fibroblasts; E – pericytes.
10. Each of the following statements concerning the air-blood barrier is true, EXCEPT: A –
includes cells and cell products, across which gases diffuse between the alveolar air and blood; B
– type II alveolar cells are the principal barrier cells; C – contains thick and thin portions; D – most
gas exchange occurs across the thin barrier portion; E – connective tissue cells and fibres widen
the barrier and form its thick portion.

Directions: one or more of the given statements or completions is/are correct. Choose the
answer: A – if only 1,2, and 3 are correct; B – if only 1 and 3 are correct; C – if only 2 and 4 are
correct; D – if only 4 is correct; E – if all are correct.
11. The pulmonary acinus consists of: (1) respiratory bronchioles (2) alveolar ducts (3)
alveolar sacs (4) terminal bronchioles
12. The pulmonary internal bronchial tree consists of: (1) large bronchi (2) middle bronchi
(3) small bronchi (4) terminal bronchioles
13. The epithelium covering the mucosa of the air passages is: (1) simple (2) pseudostratified
(3) ciliated (4) striated
14. The following statements regarding the tracheal glands are true: (1) are located in
submucosa (2) contain mucus-secreting acini with serous demilunes (3) deliver their product on
the epithelial surface (4) contain parietal cells
15. As the bronchi become reduced in size their cartilages change in the following way: (1)
cartilaginous rings are replaced by plates (2) cartilaginous plates become smaller and fewer in
number (3) hyaline cartilage is replaced by elastic cartilage (4) cartilages disappear in small
bronchi
16. The following statements regarding the Clara cells of the bronchiolar epithelium are true:
(1) are nonciliated cells (2) have dome-shaped apical surface projection (3) display the
characteristics of protein-secreting cells (4) produce lipoproteins
17. In comparison with the terminal bronchiole wall, the respiratory bronchiole wall
contains: (1) knob-like septa (2) the well-developed muscularis mucosae (3) submucosal glands
(4) alveoli
18. The distinctive feature of the alveolar ducts is the presence in their wall of: (1) blood
capillaries (2) alveoli (3) Clara cells (4) knob-like interalveolar septa
19. The following statements regarding type I alveolar cells (pneumocytes) are true: (1) are
extremely thin squamous cells (2) line most of the alveolar surface (3) gas exchange occurs
through these cells (4) are secretory cells

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 20. The components of the alveolar septum are as follows: (1) blood capillaries (2)
fibroblasts (3) macrophages (4) collagen and elastic fibres
21. The air-blood barrier includes: (1) surfactant (2) type I alveolar cell and its basal lamina
(3) capillary endothelial cell and its basal lamina (4) connective tissue cells and fibres may be
between two basal laminae
22. The following statements regarding the alveolar macrophages are true: (1) remove
particles from the air alveolar spaces (2) pass through the alveolar septum and may then return
into septal connective tissue (3) filled with accumulated material, they remain in septal connective
tissue (4) phagocytose infectious organisms such as tubercle bacilli

FIGURES

Fig. 19.1. Lung morphology

A – intrapulmonary bronchi and acini; B – alveoli and interalveolar connective tissue; 1 – large
bronchus; 2 – middle bronchus; 3 – small bronchus; 4 – terminal bronchiole; 5 – respiratory
bronchiole; 6 – alveolar duct; 7 – alveolar sacs; 8 – ciliated epithelium; 9 – muscularis mucosae;
10 – glands in submucosa; 11 – cartilaginous tunic; 12 – adventitia; 13 – alveolar macrophage;
14 – cytoplasm of type I alveolar cell; 15 – alveolar basal membrane; 16 – blood capillary basal
membrane; 17 – endothelial cell cytoplasm; 18 – air-blood barrier; 19 – nucleus of type I
alveolar cell; 20 – nucleus of endothelial cell; 21 – fibroblast; 22 – type II alveolar cell; 23 –
erythrocyte; 24 – elastic fibers.
21. INTEGUMENTARY SYSTEM: SKIN and APPENDAGES

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 The skin is the largest organ of the body, constituting almost one-sixth of the total body
weight. The skin consists of epidermis, dermis, and hypodermis. The epidermis is a stratified
squamous keratinized epithelium. The dermis is composed two layers: (1) the papillary layer
consisting of loose connective tissue and (2) the reticular layer consisting of dense irregular
connective tissue. The hypodermis contains a variable amount of white adipose tissue.
The skin epidermal derivatives (appendages) are as follows: hairs, sweat glands, sebaceous
glands, mammary glands, and nails.
The skin performs multiple functions. It provides protection against ultraviolet light,
mechanical, chemical, and thermal damages, and dessication. The skin performs sensory function
due to a variety of receptors of touch, pressure, pain, and temperature.The skin takes part in
thermoregulation. This function is associated with termoreceptors, sweat glands, and a rich
vascular network. Hairs and subcutaneous adipose tissue prevent heat loss. The skin participates
in the metabolism of some hormones and vitamins. Vitamin D is formed in the epidermis. The
skin is the site of blood storage thanks to rich network of blood vessels. The skin performs immune
function. Keratinocytes have been shown to secrete some factors that stimulate pre-T lymphocytes
to migrate from the red bone marrow to the epidermis. Moreover, the keratinocytes secrete a
thymus-like factor stimulating antigen-independent proliferation and differentiation of T
lymphocytes.

Epidermis
The epidermis consists of five layers: (1) stratum basale, (2) stratum spinosum, (3) stratum
granulosum, (4) stratum lucidum, and (5) stratum corneum.
The stratum basale is a germinal layer resting on the basement membrane. It consists of
cuboidal cells riched in mitochondria, ribosomes and keratin filaments. The filaments are
aggregated in intracellular fibrils known as tonofibrils. They are firmly attached to the basal aspect
of a cell by hemidesmosomes and to to the lateral aspect of a cell by desmosomes. Numerous cell
devisions occur in this layer. Formed daughter cell may remain in the basal layer (in G0 phase) or
move outward for differentiation.
The stratum spinosum consists of large cells that are polyhedral in shape. The cells are
jointed by numerous desmosomes that look like prickles when observed under the LM. That is
why this layer was termed the prickle cell layer. Tonofibrils increase in number; they are arranged
in bundles oriented in different directions. Many of them are associated with desmosomes. In some
disease (e.g., Hayley-Hayley disease), the associations between tonofibrils and desmosomes are
disturbed; desmosomes break down. These disorders lead to the appearance of many blisters on
the surface of the skin. Beginning with the upper spinous layer, keratinocytes accumulate specific

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granules termed keratinosomes (Odland bodies, lamellar granules) containing glycolipids and
lysosomal enzymes. The cells of this layer proliferate; cell divisions are followed by
differentiation.
The stratum granulosum consists of 3 to 5 rows of oval cells. Keratinosomes increases in
number; they are situated in the cytoplasm and under the cell membrane. The content of the
keratinosomes is then secreted by exocytosis into the intercellular spaces of the upper portion of
the stratum granulosum. The glycolipid coating of the membrane, containing
acylglucosylceramide, forms the water barrier of the epidermis. The tonofibrils are arranged in
parallel bundles due to protein filaggrin secreted by keratinocytes. Under the LM, granules termed
keratohyaline granules can be seen. Under the EM, these granules include tonofibrils, filaggrin,
and ribosomes.
Keratinocytes produce specific proteins keratolinin and loricrin. These proteins line the inner
surface of the cell membrane, making it thicker. In the uppermost granular layer, keratinocytes
undergo a sudden and dramatic transition: the lysosomes and keratinososmes release their enzymes
that destroy nuclei and organelles, except the keratin. Keratolinin and other proteins prevent the
destruction of the cell membrane. Thus, after such transition, the cell is surrouded by thick
envelope and filled only with keratin tonofibrils.
The stratum lucidum consists of anucleated cells that are devoid of organelles and filled
with keratin.
The stratum corneum consists of anucleated cells. The cells look like flattened
tetrakaidecahedrons (14-sided polygons) and are packed in interlocking columns. They adhere to
each other firmly due to the presence of lipids (ceramids) in the intercellular space. These lipids
arise from cells of the uppermost granular layer where keratinosomes situated near the cell
membranes release their contents into the intercellular spaces by exocytosis. Thank to these lipids,
the stratum corneum prevents the penetration of exogenous water and microorganisms as well as
the evaporation of endogenous water.
The final step in epidermal maturation is desquamation (removal of corneocytes or scales).
The epidermal cells leave the superficial layer of the stratum corneum by alteration of the lipids
deposited between the cells. It was shown that lipids (ceramids) turn into cholesterol, indusing cell
desquamation. In medical practice, it is known disease called ichthyosis. The skin of a patient
looks like fish scales; desquamation fails to occur. It is difficult to treat this disease, because these
patients have no special enzyme for converting ceramids to cholesterol.
The process of keratinization described above is termed orthokeratosis. There is
parakeratosis is which the stratum corneum cells contain nuclei. Parakeratosis is inherent in the

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oral cavity epithelium (at some regions) but may be a pathological process symptom (e.g., in
psoriasis).
The five-layered epidermis exists in the thick skin covering the palms of the hands and the
soles of the feet. The epidermis of the thin skin covering the rest body surface is thinner and
includes only four layers. The stratum basale is similar to that of the thick skin; the stratum
spinosum is thinner; the stratum granulosum is poor-developed; the stratum lucidum is absent; the
stratum corneum is very thin
In addition to keratinocytes, the epidermis contains melanocytes, Langerhans cells, and
Merkel cells.
Melanocytes arise from the neural crest and migrate to the epidermis to be situated in the
stratum basale. Melanocytes have numerous dendritic processes. They lack desmosomal
attachment to the adjacent keratinocytes, but adhere to the basal membrane by junctions similar to
hemidesmosomes. The main function of melanocytes is to produce melanin and to distribute it to
keratinocytes. It is known that melanin is the pigment that protects the skin from ultraviolet light
and the ionizing effect of electromagnetic radiation. Note that the formation and deposition of
melanin occur within melanosomes. The melanosomes are membrane-bounded granules that carry
the enzyme tyrosinase responsible for melanin synthesis. Melanosomes are transferred to
keratinocytes by phagocytosis.
Cutaneous pigmentation is controlled by hereditary, hormonal, and environmental factors.
For example, melanocyte-stimulating hormone (MSH) stimulates the melanocyte branching and
the melanosome transfer to keratinocytes, causing hyperpigmentation. In pregnancy, estrogens and
progesterone stimulate increased pigmentation of facial, abdominal, and genital skin, as well the
areola and nipple of the breast.
Langerhans cells are intraepidermal macrophages. They were described in 1868 by the
medical student Paul Langerhans. For about 100 years, the scientists supposed that these cells
belonged to nervous tissue. Approximately 30 to 40 years ago, it was established that these cells
are macrophages. Monocytes leave the blood stream and migrate to the epidermis, where the
monocytes are converted to macrophages. Langerhans cells have an irregularly indented nucleus
and characteristic racket-shaped granules (the Birbeck granules). These cells have no desmosomes,
tonofilaments, and melanosomes. Langerhans cells carry receptors for immunoglobulins (Fc) and
complement proteins (C3). Due to these receptors, Langerhans cells can present antigens directly
to T lymphocytes. The inportant function of these cells is to organize the epidermal proliferative
unit (EPU) or epidermal pillar. One Langerhans cell is associated with 10 to 15 basal keratinocytes,
10 to 15 spinous keratinocytes, and some cells of the stratum granulosum. Langerhans cells control
the proliferation and differentiation of keratinocytes due to secretion and accumulation of some

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special factors (e.g., one of them is epinephrine, an inhibitor of proliferation). The Langerhans
cells are supposed to stimulate keratinization: they release some factors for the disruption of
lysosome and keratinosome membranes. It was shown under experimental conditions that the
destruction of Langerhans cells leads to parakeratosis, i.e., the appearance of nuclei the in the
stratum corneum cells.
Merkel cells are located in the stratum basale. Since these cells have intermediate keratin
filaments in the cytoplasm, it was concluded that Merkel cells are epithelial cells. Merkel cells are
bound to keratinocytes by desmosomes. The main feature of these cells is the presence of
neurosecretory granules that are morphologically identical to the chromaffin granules found in the
adrenal medulla. Merkel cells are associated with the terminal bulb of unmyelinated nerve fiber
(Merkel corpuscle) to form a very sensitive mechanoreceptor.

Dermal–epidermal junction
The epidermis is attached to the dermis by the dermo-epidermal junctions including the basal
cells with hemidesmosomes; the epidermis basement membrane, and underlying connective tissue
fibers (anchoring fibrils, microfibril bundles, and collagen fibers). The epidermis basement
membrane consists of the lamina lucida and the lamina densa The former contains laminin
(adhering glycoprotein); the latter contains collagen fibers (type IV) and heparan sulfate. In some
skin diseases, basal keratinocytes cannot produce laminin, and the epidermis separates from the
dermis; as a result, many blisters appear on the surface of the skin.
The dermo-epidermal junction functions to bind the epidermis and dermis, to support the
epidermis, and to prevent the transfer of the material and cells across the junction.

Dermis
The dermis is subdivided in the papillary layer and the reticular layer.
The papillary layer consists of loose connective tissue extending into the epidermis with
papillae. The papillae are complemental by what appears to be similar to epidermal protrusions
called epidermal ridges or rete ridges. The epidermal ridges can be seen with the naked eye. The
ridges form a distinctive pattern that is determined by hereditary factors. The surface of the thin
skin, unlike that of the thick skin, is not thrown into ridges. The papillary layer has a rich blood
supply. Some capillaries extend into the papillae and provide the epidermis nourishment and are
also involved in heat regulation. Other capillaries form a flat bed below the basis of papillae.
The reticular layer consists of dense irregular connective tissue; its bundles of collagen and
elastic fibers form a network, which varies in character and thickness with a body region. The
mechanical properties of this layer depend on the extensible elastic fibers interwoven in the mesh

224
of rather rigid collagen fibers. The orientation of collagen and elastic fibers varies from area to
area. The pattern of their orientation gives rise to certain lines of extensibility namede Langer’s
lines. The direction of these tension lines can be demonstrated by removing a round piece of skin
and observing the resultant elliptical hole. The reticular layer contains two vascular plexuses: (1)
a deep vascular plexus in the lower reticular dermis close to its border with the hypodermis and
(2) a superficial vascular plexus in the upper reticular dermis close to its border with the papillary
layer. Located in the reticular layer skin appendages (hair, sweat and sebaceous glands) are
supplied with branches connecting the deep and superficial vascular plexuses.

Skin appendages
Skin appendages are derived from the downgrowth of the skin epithelium during the
embryonic development. Thick skin contains only sweat glands. The thin skin contains sweat
glands, hair follicles, sebaceous glands, smooth muscle cells (the arrector pili muscle), and nails..
The sweat glands are merocrine (eccrine) and apocrine glands. In humans, the major source
of evaporative heat loss is through merocrine sweat glands. Sweat is a hypotonic watery solution
containing various sodium, potassium, and chloride ions. These glands are found over the body;
they are particularly numerous on the forehead, scalp, axillae, palms and soles, but absent on the
glans penis, clitoris, and labia minora. The merocrine gland is a simple unbranched tubular coiled.
Its tubular structure consists of ductal and secretory segments. The coiled secretory portion resides
in the deep dermis. It consists of secretory cells forming the inner layer of the secretory segment
and myoepithelial contractile cells forming its outer layer. The duct is subdivided into dermal and
epidermal portions. The dermal duct consists of two layers of dark-staining cuboidal cells. The
epidermal duct is coiled and lined with flattened cells.
The apocrine sweat glands are located in the axillae and anogenital areas. Modified apocrine
glands are found in the eyelids (Moll’s gland), in the areolar skin around the nipple, and in the
external auditory canal. Here, they form the seruminous glands responsible for the production of
ear wax.
The apocrine gland is a simple branched tubular gland consisting of a secretory coil and
more or less straight ducts. Its duct system opens into the pilosebaceous unit usually above the
entrance of the sebaceous gland. The secretory segment is composed of cuboidal single-layer
epithelium and myoepithelial cells. The duct consists of a double layer of cuboidal cells. The
apocrine secretion contains proteins, carbohydrates, ammonia, lipids, ferric ions, and fatty acids.
The apocrine sweat glands develop at puberty; their secretory activity is under controlling of sex
hormones. Some symbiotic bacteria live in the apocrine gland ducts. The bacteria metabolise cell

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debris contained in secretion to produce odorant substances. The function of these glands has not
been exactly established.
The sebaceous glands are simple branched alveolar glands with holocrine mode of
secretion. Their secretory portions are sac-like; their short duct empties into the upper hair follicle.
The secretory portion consists of secretory cells, sebocytes. They are basal cells, secretory
sebocytes, and broken cells. Basal (cambial) cells rest on the basement membrane and serve as the
source of secretory cells. Secretory cells accumulate sebum vesicles until the cytoplasm is filled;
at this point the cell breaks down and releases its contents into the duct (holocrine secretion).
Sebum consists of glycerides, fatty acids, wax esters, and squalene. Sebum is believed to be
secreted continuously. The sebaceous glands are devoid of myoepithelial cells. The gland activity
is stimulated by androgens and inhibited by estrogens.
The number, size, and activity of sebaceous glands vary from site to site. They are
particularly abundant on the face, scalp, ears, nostrils, vulva, and around the anus, but are absent
on the soles and palms. In certain areas of the body, these glands do not empty into hair follicles,
but open directly onto the epidermal surface: the labia minora, the areolar skin around the nipple,
the eyelids where they are known as Meibomian glands, the lips, and buccal mucosa (Fordyce
spots).
The pilosebaceous apparatus is made up of a hair follicle, its attached smooth muscle, a
sebaceous gland, and, in specific regions, an apocrine gland.
The hair follicle is composed of the hair, external and internal root sheathes, a follicular
bulb with the germinal matrix (it gives rise to hair), and a dermal papilla consisting of loose
connective tissue. The hair consists of a medulla, cortex, and cuticle. The outermost part of the
hair follicle or the external root sheath represents a downward continuation of the epidermis. The
internal root sheath arises from the cells of the bulb germinal matrix. The follicle is surrounded by
a connective tissue sheath to which the arrector pili muscle is attached.
There are differences in the growth period and the growth rate of a hair follicle that is why
the hair length varies from region to region. The hair growth is cyclical. Three phases of the hair
growth cycle are known: anagen, the growth phase; catagen, the regressing phase; and telogen, the
resting phase. In the human scalp, the anagen phase varies from 2 to 6 years; the catagen phase,
from 2 to 3 weeks; the telogen phase, from 3 to 4 months. After telogen, the old hair shaft sheds,
and a new hair shaft appears.

Skin afferent innervation

The skin is rich in both free and encapsulated receptors. The most numerous of them are free
nerve endings. They are located in the epidermis and the papillary layer of dermis. They serve as

226
thermoreceptors and nociceptors (painful receptors). Basket-like arrangements of free nerve
endings surround hair follicles. They serve as mechanoreceptors.
Encapsulated nerve endings include Pacinian corpuscles, Meissner’s corpuscles, and Ruffini
endings. Pacinian corpuscles respond to pressure and vibrations; Meissner’s corpuscles are touch
receptors; Ruffini endings are mechanoreceptors.

CONTROL PROBLEMS

1. A student asserts that the epidermis contains macrophages and lymphocytes. Another
student considers that it is not true because the epidermis lacks blood vessels. What student opinion
is correct?
2. The skin biopsy microscopic examination revealed the five-layer epidermis and simple
tubular glands in the dermis. What the skin area was analyzed? What the skin glands were
distinguished in the biopsy?
3. A cold weather provokes so-called “goose-skin” appearance. What is a mechanism of the
symptom development? What the skin structures take part in the reaction?
4. The skin of Europeans becomes brown in color under ultra-violet ray action. What the
skin cells take part in the reaction? What is the reaction significance?
5. The thick skin was proposed to study glands with merocrine and holocrine modes of
secretion. Is the choice true?
6. The finger skin is characterized by the papillary picture as well as the face skin lacks it.
What the skin peculiarities may explain the difference?

CONTROL TESTS

Directions: each of the following statements contains five suggested completions. Choose
the one that is best in each case.
1. Each of the following statements concerning the thick skin is true, EXCEPT: A – covers
the palms and the soles; B – undergoes considerable abrasion; C – is hairless; D – possesses
sebaceous glands; E – has the thickest epidermis.
2. The epidermis of the thin skin contains the following layers, EXCEPT: A – stratum
spinosum; B – stratum basale; C – stratum lucidum; D – stratum corneum; E – stratum granulosum.
3. Each of the following statements concerning the epidermis stratum basale is true,
EXCEPT: A – is represented by a single layer of stem cells; B – its cells are not capable of division;
C – rests on the basal lamina; D – new keratinocytes arise from its cells; E – is basophilic.

227
 4. The distinctive feature of the cells of the epidermis stratum granulosum is: A – they exhibit
numerous cytoplasmic processes; B – they are capable of division; C –they are anucleate squamous
cells; D – they rest on the basal lamina; E – their cytoplasm contains keratohyalin granules.
5. Each of the following statements concerning the epidermis stratum lucidum is true,
EXCEPT: A – has a refractile appearance; B – contains eosinophilic cells; C – is present both in
the thick and in thin skin; D – the nuclei and the cytoplasmic organelles of its cells become
disrupted; E – its cells gradually fill with keratin.
6. Each of the following statements concerning the cells of the epidermis stratum corneum
is true, EXCEPT: A – are capable of division; B – are anucleate squamous cells; C – are filled
with keratin; D – their plasma membrane is thickened and coated with glycolipids; E – are
sloughed off at the epidermis surface.
7. Each of the following statements concerning the process of keratinization is true,
EXCEPT: A – keratinocytes produce tonofilaments that are grouped into tonofibrils; B –
keratinocytes synthesize keratohyalin granules; C – the substance of keratohyalin granules
combines with tonofibrils converting them to keratin; D – keratinocyte plasma membrane
gradually disappears; E – the nuclei and the organelles of keratinocytes break down.
8. Each of the following statements concerning the epidermis Merkel’s cells is true,
EXCEPT: A – are macrophage-like cells; B – are located in the stratum basale; C – contain
granules with a neurosecretion; D – are associated with the ending of afferent nerve fibres; E – the
combination of Merkel’s cell and a nerve fibre is a mechanoreceptor.
9. Each of the following statements concerning the hair is true, EXCEPT: A – consists of the
medulla, cortex, and cuticle; B – its keratinized cells are filled with soft keratin; C – a hair follicle
is surrounded by the connective tissue sheath, external and internal root epithelial sheathes; D –
the hair bulb contains the matrix and is invaginated by the connective tissue papilla; E – hair cells
and cells of the internal root sheath arise from the matrix.
10. Each of the following statements concerning the sebaceous glands is true, EXCEPT: A
– are simple branched alveolar glands; B – are characterized by the holocrine mode of secretion;
C – empty onto the epidermis surface; D – secrete sebum coating hair and the skin surface; E –
their new secretory cells arise from basal cells at the secretory portion periphery.

Directions: one or more of the given statements or completions is/are correct. Choose the
answer: A – if only 1,2, and 3 are correct; B – if only 1 and 3 are correct; C – if only 2 and 4 are
correct; D – if only 4 is correct; E – if all are correct.

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 11. The skin functions are as follows: (1) protection against environmental physical,
chemical, and biologic agents (2) regulation of body temperature and water loss (3) reception of
external stimuli (4) excretion of some products via sweat glands
12. The following statements regarding the thin skin are true: (1) has hair follicles (2)
possesses sebaceous glands (3) its epidermis is thin (4) contains arrector pili muscles
13. The following statements regarding the cells of the epidermis stratum spinosum are true:
(1) exhibit numerous spines, short cytoplasmic processes (2) spines of adjacent cells are attached
to each other by desmosomes (3) their cytoplasmic tonofilaments become grouped in tonofibrils
(4) are stem cells
14. The following statements regarding the keratinocyte lamellar bodies are true: (1)
keratinocytes produce lamellar bodies containing glycolipids (2) the body content is secreted by
exocytosis into intercellular spaces (3) glycolipids coat and thicken keratinocyte plasma
membranes (4) glycolipids form the epidermis water barrier
15. The following statements regarding the skin melanocytes are true: (1) originate from the
neural crest (2) are pigment-producing cells (3) are dendritic cells (4) reside both in the epidermis
and in the dermis, especially in the sites of pigmentation
16. The following statements regarding the epidermis Langerhans cells are true: (1) play a
role in the immune response by presenting antigens to T cells (2) reside in the stratum spinosum
(3) belong to the mononuclear phagocytic system (4) arise from the neural crest
17. The following statements regarding the skin dermis are true: (1) its papillary layer
consists of loose connective tissue (2) lacks blood vessels and nerve fibres (3) its reticular layer
consists of dense irregular connective tissue (4) does not possess receptors
18. The following statements regarding the merocrine sweat glands are true: (1) are simple
tubular coiled glands (2) their secretory portions include secretory cells and myoepithelial cells
(3) take part in body temperature regulation (4) are associated with hair follicles
19. The following statements regarding the functions of the merocrine sweat glands are true:
(1) regulate body temperature due to evaporation of water from the sweat on the body surface (2)
produce “goose flesh” (3) participate in excretion of urea, uric acid, and ammonia (4) provide
bacteriostatic protection of the skin
20. The following statements regarding the appocrine sweat glands are true: are limited to
the skin of the axilla, areola, nipple, and external genitalia (2) are associated with hair follicles (3)
become functional only at puberty and are dependent on sex hormones (4) its odourless secretion
undergoes bacterial action on the skin surface and becomes odorant

FIGURES

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 Fig. 20.1. Hair follicle
1 – connective tissue sheath; 2 – external root sheath; 3 – internal root sheath; 4 – hair cuticle; 5
– hair cortex; 6 – hair medulla; 7 – hair infundibulum; 8 – stratum basale and stratum spinosum
of the epidermis; 9 – stratum corneum of the epidermis; 10 – sebaceous gland; 11 – arrector pili
muscle; 12 – hair matrix; 13 – connective tissue papilla.

22. URINARY SYSTEM

The urinary system consists of the kidneys, the ureters, the urinary bladder, and the urethra.

230
 Kidney
Each kidney has a convex lateral margin and a concavity on the medial side, which is called
the hilum. The hilum leads into a space called the renal sinus. The renal sinus is occupied by the
upper expanded part of the ureter, which is called the renal pelvis. Within the renal sinus the pelvis
divides into two or three parts called major calices. Each major calyx divides into a number of
minor calices. The end of each minor calyx is shaped like a cup. A projection of kidney tissue,
called a papilla, fits into the cup. Kidney tissue consists of an inner part called the medulla and an
outer part called the cortex.
The renal medulla is made up of triangular areas of renal tissue that are called renal
pyramids. Each pyramid has a base directed towards the cortex; and an apex (or papilla), which is
directed towards the renal pelvis and opens into a minor calyx. Pyramids show striations that pass
radially towards the apex.
The renal cortex consists of two parts. The tissue lying between the bases of the pyramids
and the surface of the kidney forms the cortical lobules. This part of the cortex shows light and
dark striations. The light lines are called medullary rays; the tissue lying between the pyramids
constitutes the renal columns.
From the functional point of view the kidney may be regarded as a collection of numerous
tubules that are specialized for the excretion of urine. Each tubule consists of an excretory part
called the nephron and of a collecting tubule. The collecting tubules, draining different nephrons,
join to form larger tubules called the papillary ducts (ducts of Bellini), each of which opens into a
minor calyx at the apex of a renal papilla. Urinary tubules are held together by connective tissue
containing blood vessels, lymphatics, and nerves.
The nephron is epithelial morphofunctional unit of the kidney. Each kidney contains one to
two million nephrons. The nephron consists of a Bowman’s capsule and a long complicated tubule.
Bowman’s capsule is a two-layered cup surrounding the glomerulus of blood capillaries. The
glomerulus enclosed by Bowman’s capsule forms a rounded structure called the renal corpuscle
(Malpighian corpuscle). Between the two layers of the capsule there is a urinary space, which is
continuous with the lumen of the renal tubule.
The renal tubule is divisible into several parts. Starting from Bowman’s capsule, there are
the proximal convoluted tubule, the loop of Henle consisting of a descending limb, a loop, and an
ascending limb, and the distal convoluted tubule, which ends by joining a collecting tubule.
Renal corpuscles, the proximal and distal convoluted tubules are located in the cortex of the
kidney. The loops of Henle and the collecting ducts lie either in the medullary rays or in the
pyramid substance.

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 The glomerulus is a rounded tuft of anastomosing capillaries. Blood enters the tuft through
an afferent arteriole and leaves it through an efferent arteriole. The afferent and efferent arterioles
lie close together at a point that is called the vascular pole of the renal corpuscle.
The Bowman’s capsule outer (parietal) layer is lined by squamous epithelial cells. Under the
LM, the inner (visceral) layer also appears to be lined by squamous cells, but the EM shows that
these cells, called podocytes, have a highly specialized structure. The urinary space becomes
continuous with the lumen of the renal tubule at the urinary pole of the renal corpuscle. This pole
lies diametrically opposite the vascular pole.
Along its entire length, the renal tubule is lined by a single layer of epithelial cells on a
basment membrane. The proximal convoluted tubules have a relatively small lumen. They are
lined by cuboidal cells having a prominent brush border. The nuclei are central and euchromatic.
The cytoplasm stains pink with eosin. The basal part of the cell shows a basal striation.
The descending limb, the loop itself, and part of the ascending limb of the loop of Henle are
narrow and thin-walled. They constitute the thin segment of the loop. The upper part of the
ascending limb has a larger diameter and a thicker wall and is called the thick segment. The thin
segment of the loop of Henle is lined by low cuboidal or squamous cells. The thick segment is
lined by cuboidal cells.
The distal convoluted tubule has a short straight part continuous with the ascending limb of
the loop of Henle and a convoluted part lying in the cortex. At the junction between the two parts,
the distal tubule lies very close to the renal corpuscle of the nephron to which it belongs. The distal
convoluted tubules can be distinguished from the proximal tubules as they have a much larger
lumen, the cuboidal cells lining them do not have a brush border, and they stain less intensely pink
with eosin.
The smallest collecting tubules are lined by a simple cuboidal or columnar epithelium.
Collecting tubules can be easily distinguished from convoluted tubules. Collecting tubules have
larger lumina. In transverse sections, their profiles are circular in contrast to the irregular shapes
of convoluted tubules.
In the renal corpuscle, water and various small molecules pass by filtration from the blood
of the glomerular capillaries to the urinary space of Bowman’s capsule. Theoretically, the barrier,
across which the filtration occurs, is constituted by the capillary endothelium, by the cells –
podocytes, forming the capsular visceral layer, and by the glomerular basement membrane, which
intervenes between the two layers of the cells named above.
The endothelial cells show numerous pores that are larger than pores in many other
capillaries. The pores are not closed by membrane. As a result, filtrate passes easily through the
pores, and the endothelial cells do not form an effective barrier.

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 The podocytes are so called, because they possess foot-like processes. Each podocyte has a
few primary processes that give the cell a star-shaped appearance. Each primary process terminates
in numerous pedicels or end feet, which rest on the basal lamina. The cell body of the podocyte
comes in contact with the basal lamina only through the pedicels. Between the areas of attachment
of individual pedicels there are gaps in which the basal lamina is not covered by podocyte
cytoplasm. Filtration takes place through the basal lamina at these gaps, which are, therefore,
called filtration slits. These slits are covered by a layer of fine filaments that constitute the
glomerular slit diaphragm. From what has been said above it will be clear that the filtrate does not
have to pass through the podocyte cytoplasm. The cytoplasm of podocytes contains numerous
mitochondria, vesicles, and filaments.
In addition to the endothelial cells and podocytes, the renal corpuscle contains mesangial
cells that are present around capillaries. These cells are believed to be phagocytic.
Under the EM, the lining cells of the proximal convoluted tubules show microvilli on their
luminal surfaces. The basal striation seen under the LM near the base of each cell are shown by
the EM to be produced by infoldings of the basal plasma membrane and by numerous mitochondria
that lie longitudinally in the cytoplasm intervening between the folds. The presence of microvilli
and the basal infoldings greatly increases the surface area available for transport.
The loop of Henle is also called the ansa nephroni. Under the EM, the flat cells lining the
thin segment of the loop of Henle show very few organelles, indicating that the cells play only a
passive role in ionic movements across them. The thick segment of the loop of Henle is lined by
cuboidal cells with short microvilli, numerous mitochondria, and deep folds of the basal plasma
membrane.
The cells of the distal convoluted tubules have no microvilli. The basal infoldings of plasma
membrane are very prominent and reach almost to the luminal surface of the cell. This feature is
characteristic of cells involved in the active transport of ions.
The cells of the collecting ducts do not have microvilli, or lateral infoldings of the plasma
membrane. Very few organalles are present in their cytoplasm.
The ultimate composition of urine leaving the kidneys depends upon these three processes
of filtration, reabsorption, and secretion.
Water and various other molecules pass from blood into the urinary space of the glomerular
capsule by the process of filtration. Selective reabsorption takes place mainly in the proximal
convoluted tubules. The substances reabsorbed include water, glucose, amino acids, proteins of
small molecular size, and various ions including sodium, chloride, phosphate, bicarbonate, and
calcium. Reabsorption is facilitated by the presence of microvilli and foldings of the lateral and

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basal plasma membranes. Energy for the process is provided by the numerous mitochondria.
Reabsorption in the proximal convoluted tubules is independent on any hormones.
Considerable quantities of sodium and chloride are reabsorbed through the distal convoluted
tubules. When first formed, the glomerular filtrate is isotonic with blood. With the selective
reabsorption of ions it tends to become hypotonic so that an osmotic gradient is created, which
forces water out of the tubules. Reabsorption in the distal convoluted tubules depends on hormone
aldosterone produced by the adrenal cortex and ADH released by the neurohypophisis.
A very large proportion of water in the renal filtrate is reabsorbed through the loops of Henle.
This is possible because of the following factors. The spaces, surrounding the descending and
ascending limbs of the loops of Henle, are surrounded by a tissue fluid, which is hypertonic. The
hypertonicity is achieved by the active transport of chloride and sodium ions out of the ascending
loop limbs into the surrounding space, but the flow of water is not allowed. On the contrary, the
walls of the descending loop limbs are highly permeable to water. Because of this permeability,
water passively diffuses out of the loops into the surrounding space due to the osmotic gradient.
The absorption of water from the filtrate would be expected to make the filtrate hypertonic.
However, this does not happen as the absorption of water is accompanied by the selective
absorption of sodium and chloride by the cells of the ascending limb of the loop of Henle and the
distal convoluted tubule. As a result, the filtrate entering the collecting ducts is in fact hypotonic.
As the filtrate passes through the collecting ducts, it once more enters the hypertonic environment
of the medulla. This hypertonic environment, combined with the high permeability of the
collecting ducts to water, renders the urine hypertonic by the time it is poured into the renal pelvis.
This is the so-called countercurrent multiplier mechanism.
The cells of the proximal and distal convoluted tubules, as well as the collecting ducts, take
part in secretion being that they add various substances to the glomerular filtrate. These include
hydrogen ions, ammonia, creatinine and paraaminohippuric acid. Various drugs or their
breakdown products are also excreted in this way.
Juxtaglomerular apparatus
A part of the distal convoluted tubule lies close to the vascular pole of the renal corpuscle,
between the afferent and efferent arterioles. In this region, the muscle cells in the wall of the
arterioles (primary afferent) are modified. They become large rounded with spherical nuclei. Their
cytoplasm exhibits granules that can be stained with special methods. These are juxtaglomerular
cells. The wall of the distal convoluted tubule is also modified at the site of contact with the
arteriole. Its columnar cells are densely packed together to form the macula densa. The cells of the
macula densa lie in close contact with the juxtaglomerular cells. The region between arterioles is

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occupied by the juxtavascular cells. The juxtaglomerular cells, the macula densa, and the
juxtavascular cells together make up the juxtaglomerular apparatus or complex.
The granules of the juxtaglomerular cells contain the enzyme renin. Renin acts on
angiotensin, a substance present in blood, and converts it to angiotensin I. Another enzyme
converts angiotensin I to angiotensin II. Angiotensin II increases blood pressure. The
juxtaglomerular apparatus is a mechanism that controls the blood pressure by release of renin. The
macula densa cells are osmorecepters registering blood sodium levels. The juxtavascular cells
serve as reserve.
The kidney interstitial cells are present in the renal medulla. They lie in the connective tissue
between collecting ducts. The long axis of each cell is placed at right angles to that of the ducts
and to neaby blood capillary, bridging them. These cells are endocrine and produce prostaglandins.

Ureters
The wall of the ureter has three tunics: mucosa, muscularis externa, and adventitia. The
mucosa has a lining of transitional epithelium and lamina propria of loose connective tissue
containing many elastic fibers.
The muscle layer has an inner layer and an outer spiral layer of smooth muscle tissue. In the
low ureter portion, there are three muscle layers. The layers are not distinctly marked off from
each other. Some workers have reported that the musculature of the ureter is really in the form of
a meshwork formed by branching and anastomosing muscle bundles.
The adventitia consists of loose connective tissue and contains numerous blood vessels,
nerves, lymphatics, and some fat cells.

Urinary bladder
The wall of the urinary bladder consists of three tunics: mucosa, muscularis externa, and
serosa.
The mucosa is lined by transitional epithelium. The epithelium rests on lamina propria of
loose connective tissue. There is no muscularis mucosae.
The muscularis externa is thick and consists of three layers of smooth muscle cells forming
a meshwork. Internally and externally the cell bundles tend to be longitudinal. In between them,
there is a thicker layer of oblique bundles. Contraction of this muscle coat is responsible for
emptying of the bladder. That is why it is called the detrusor muscle. Just above the junction of
the bladder with the urethra, the circular smooth muscle cells thicken to form the sphincter vesicae.
The serosa covers most of the bladder and has the usual structure. It includes a layer of loose
connective tissue and mesothelium.

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 Urethra
The structure of the male and female urethra is the same. The wall of the urethra is composed
of the mucosa, submucosa, and muscles. The mucosa is lined by transitional epithelium, which is
typical for all parts of the excretory passages. In males, the prostatic urethra is surrounded by
prostatic tissue; the penile urethra is enclosed by erectile tissue of the corpus spongiosum.

CONTROL PROBLEMS

1. The microphotograph shows the renal substance with renal corpuscles and tubules.
Specify the renal substance (the cortex or the medulla) and the type of visible tubules.
2. Some diseases are characterized by stimulation and proliferation of mesangial cells. What
are the renal structures where the mesangial cells are found? What functional changes occur as a
result of mesangium activation?
3. The urinalysis revealed the presence of numerous erythrocytes. Examination of the
patient’s excretory passages did not reveal any bleeding. What nephron divisions are affected,
which results in the appearance of erythrocytes in the urine?
4. The urinalysis revealed the presence of sugar. The urine was sampled in the morning on
an empty stomach. What nephron divisions are affected? What epithelial cell structures are
damaged?
5. The microphotograph demonstrates two renal corpuscles. The afferent and efferent
arterioles of one of them are equal in diameter. The afferent arteriole of the other renal corpuscle
is larger compared to the efferent one. Which nephron types do the corpuscles belong to?
6. The patient was diagnosed as having renal hypertension, i.e., his renal disease caused his
blood pressure to increase. What renal structural disorder is responsible for this complication?
7. Two students explain the localization of the renal macula densa. One of them thinks it is
found in the distal convoluted tubule. The other student considers that the macula densa is part of
the renal juxtaglomerular apparatus. Who is right?

CONTROL TESTS

Directions: each of the following statements contains five suggested completions. Choose
the one that is best in each case.
1. Each of the following statements concerning the kidney functions is true, EXCEPT: A –
produce the urine; B – conserve water, essential electrolytes, and metabolites; C – secrete

236
angiotensin; D – remove waste products of metabolism from body; E – secrete erythropoietin and
renin.
2. The following structures are located in, and make up, the kidney cortex, EXCEPT: A –
renal corpuscles; B – transitional epithelium; C – proximal convoluted tubules; D – distal
convoluted tubules; E – medullary rays.
3. Each of the following statements concerning the nephrons is true, EXCEPT: A – are
functional units of the kidney; B – have Bowman’s capsules; C – include the proximal and distal
convoluted tubules; D – include the descending and ascending limbs of the loop of Henle; E –
empty into the minor calyx.
4. Each of the following statements concerning the renal corpuscles is true, EXCEPT: A –
include the double-layered capsule; B – the capsular parietal layer consists of flat cells and
surrounds the capsular space; C – the capsular visceral layer consists of podocytes and surrounds
the capillary glomerulus; D – the glomerulus contains continuous- type capillaries; E – the site
where afferent and efferent arterioles penetrate the capsule is the corpuscle vascular pole.
5. Each of the following statements concerning the renal filtration barrier is true, EXCEPT:
A – includes the capsular parietal layer; B – includes the endothelium of glomerular capillaries; C
– the glomerular basement membrane is the principal barrier component; D – the glomerular
basement membrane consists of three layers; E – the lamina densa of the glomerular basement
membrane contains collagen network and acts as a physical filter.
6. Each of the following statements concerning the renal proximal convoluted tubules is true,
EXCEPT: A – are more tortuous and longer than the distal convoluted tubules; B – possess
cuboidal cells specialized for absorption and fluid transport; C – lack the brush border and basal
striations; D – reabsorb 80% of primary filtrate; E – reabsorb amino acids, sugars, and other
organic substances.
7. Each of the following statements concerning the renal distal convoluted tubules is true,
EXCEPT: A – have cuboidal cells with basal striation; B – their epithelial cells possess the brush
border; C – reabsorb Na+ under aldosterone control; D – reabsorb water under ADH regulation; E
– are less tortuous and shorter than the proximal convoluted tubules.
8. Each of the following statements concerning the renal collecting tubules is true, EXCEPT:
A – are lined with the cuboidal or low columnar epithelium; B – their epithelium includes dark
and light cells; C – water permeability of their epithelium is regulated by ADH; D – their cells
possess the brush border; E – their dark cells secrete hydrogen ions into the urine creating its acid
reaction.
9. Each of the following statements concerning the renal macula densa is true, EXCEPT: A
– is formed in the distal convoluted tubule at the site of tubule contact with the vascular pole of its

237
parent renal corpuscle; B – is located between afferent and efferent arterioles; C – its epithelial
cells become higher and narrower, their nuclei appear crowded; D – its cells control sodium
concentration in the urine and regulate renin release; E – its cells produce renin.
10. Each of the following statements concerning the renal juxtaglomerular cells is true,
EXCEPT: A – are modified smooth muscle cells; B – are located in afferent and sometimes in
efferent arterioles; C – contain secretory granules; D – are sodium osmoreceptors; E – synthesize,
store, and release renin.
11. Each of the following statements concerning the transitional epithelium is true,
EXCEPT: A – lines the mucosa of all excretory passages; B – its surface cells are dome-shaped
and bulge into the lumen; C – is highly permeable for salts and water; D – consists of 5 or 6 layers
in unstretched condition; E – consists of 2 or 3 layers in stretched condition.
12. Each of the following statements concerning the juxtamedullary nephrons is true,
EXCEPT: A – are the principal nephrons producing the urine; B – the diameters of their afferent
and efferent arterioles are equal; C – their vasa recta have arteriovenous anastomosis; D – their
corpuscles are in proximity to the base of medullary pyramids; E – serve for the blood passage
during exercise.

Directions: one or more of the given statements or completions is/are correct. Choose the
answer: A – if only 1,2, and 3 are correct; B – if only 1 and 3 are correct; C – if only 2 and 4 are
correct; D – if only 4 is correct; E – if all are correct.
13. The following structures are located in, and make up, the kidney medulla: (1) descending
limbs of the loops of Henle (2) ascending limbs of the loops of Henle (3) collecting tubules and
ducts (4) vasa recta
14. The following statements regarding the kidney medullary rays are true: (1) are parts of
the kidney cortex (2) radiate from the medulla to the cortex periphery (3) contain the collecting
tubules (4) include the straight tubule components of nephrons
15. The following statements regarding the kidney lobule are true: (1) consists of the
collecting duct and all the nephrons it drains (2) the medullary ray is the lobular centre (3) the
interlobular blood vessels mark the boundaries between the adjacent lobules (4) it is a renal
secretory unit
16. The following statements regarding the kidney arterial portal system are true: (1) the
afferent arteriole branches and forms the glomerular capillaries (2) the glomerular capillaries drain
into the efferent arteriole (3) the efferent arteriole branches and forms the peritubular capillary
network (4) the diameter of the efferent arteriole is larger than that of the afferent arteriole

238
 17. The following statements regarding the renal podocytes are true: (1) are the cells of the
capsular parietal layer (2) have processes subdivided into pedicels (3) lack their own basement
membrane (4) the processes of neighboring podocytes interdigitate to form filtration slits
18. The following statements regarding filtration in the renal corpuscle are true: (1) filtration
is caused by high blood pressure in the glomerular capillaries (2) the blood formed elements and
large proteins do not pass through the filtration barrier (3) filtration results in the primary urine
formation (4) contraction of afferent arterioles reduces filtration, contraction of efferent arterioles
increases it
19. The following statements regarding the renal mesangial cells are true: (1) these cells and
their extracellular matrix constitute the mesangium (2) are positioned among the loops of
glomerular capillaries (3) are enclosed by the capillary basal lamina (4) are parts of the filtration
barrier
20. The following statements regarding the functions of the renal mesangial cells are true:
(1) are phagocytic and remove proteins, residues, and debris from the glomerular basement
membrane (2) provide structural support for podocytes where the basement membrane is absent
or incomplete (3) are contractile and play a certain role in regulating the glomerular blood flow
(4) take part in filtration
21. The structures taking part in the countercurrent exchange are as follows: (1) loops of
Henle (2) collecting ducts (3) vasa recta (4) convoluted tubules
22. The following statements regarding the renal loop of Henle are true: (1) water diffuses
into the hypertonic interstitium from its descending limb (2) its ascending limb is largely
impermeable for water (3) its ascending limb actively transports ions from the lumen to the
interstitium (4) the interstitium becomes hypertonic due to the action of its ascending limb
23. The following statements regarding the renal collecting ducts are true: (1) are lined with
columnar epithelial cells (2) pass through the hypertonic medullary interstitium (3) water leaves
their lumen passively, without energy (4) take part in countercurrent exchange

FIGURES

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 Fig. 21.1 Nephron part structure
A – renal corpuscle: 1 – glomerular capillaries; 2 – mesangial cell; 3 – endothelial cell; 4 –
glomerular basal membrane; 5 – podocyte; 6 – renal filtration barrier; 7 – capsule cavity; 8 –
capsule parietal layer; 9 – proximal convoluted tubule. B – renal convoluted tubules: 1 –
proximal convoluted tubule; 2 – peritubular blood capillary; 3 – distal convoluted tubule; 4 –
brush border; 5 – basal striations.

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 Fig. 21.2. Kidney endocrine apparatus
A – juxtaglomerular apparatus: 1 – afferent arteriole; 2 – efferent arteriole; 3 – juxtaglomerular
cells; 4 – macula densa of the distal convoluted tubule; 5 – juxtavascular cells. B – prostaglandin
apparatus: 1 – nephron loop tubule; 2 – medulla capillary; 3 – interstitial (prostaglandin
secreting) cells.

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 23. MALE REPRODUCTIVE SYSTEM

The male reproductive system consists of the testes, the epididymes, the genital ducts
(excurrent duct system), the accessory reproductive glands, and the external genitalia. The
accessory glands include the seminal vesicles, the prostate, and the bulbourethral glands.

Testis (male sex gland, male gonad)

The testis functions to produce spermatozoa and to secrete the male sex hormones
androgens, mainly testosterone.
The testis is an egg-shaped organ housed inside the scrotum. A thick connective tissue
capsule – the tunica albuginea – covers each testis. On the testicular posterior surface, the capsule
thickens to form the mediastinum. Blood vessels, lymphatics, and the genital ducts pass through
the mediastinum as they either enter or leave the testis.
Connective tissue septa project from the capsule inward the testis and divide it into
approximately 250 lobules. Each lobule contains seminiferous tubules and intertubular connective
tissue (interstitial tissue). The seminiferous tubules are responsible for spermatogenesis, whereas
the interstitial tissue contains steroid–secreting cells and represents the endocrine part of the male
gonad. Each seminiferous tubule within the lobule forms a loop and, because of its considerable
length, is highly convoluted. Two free ends of the loop open into short straight tubules (the tubuli
recti), which are the origin of the genital ducts. The straight tubules continue into anastomosing
channels within the mediastinum called the rete testis. Only the seminiferous tubules are the sites
of sperm production, the tubuli recti and the rete testis are intratesticular genital ducts. The
extratesticular excurrent duct system is composed of the ductuli efferentes (about 12 to 15) that
make up the epididymal head, the ductus epididymidis that constitutes the epididymal body and
tail, the ductus deferens that fuses with the seminal vesicle ductus excretorius to form the ductus
ejaculatorius. The latter enters the prostate to empty into the prostatic urethra.
Spermatogenesis
The spermatogenesis is a process of the sperm development. It includes four stages or
phases: the stage of proliferation, stage of growth, stage of maturation, and stage of formation.
The stage of proliferation (spermatogonial phase) is represented by population of
spermatogonia that mitotically divide and undergo determination. Human spermatogonia are
typical diploid cells, which are classified into three types: Type A dark (Ad) spermatogonia are
thought to be the stem cells, type A pale (Ap) spermatogonia and type B spermatogonia are
committed spermatogonia. The stem cell divides to give rise to two daughter cells: one remains as
a stem cell (Ad), while the other (Ap) is committed to the differentiation process that produces the

242
sperm. Type Ap spermatogonia undergo several successive mitotic divisions increasing their
progeny number. An unusual feature of committed spermatogonium division is that the daughter
cells remain connected by a thin cytoplasmic bridge as a result of incomplete cytokinesis. The
same phenomenon is characteristic of each subsequent mitotic and meiotic division, and eventually
all offspring of a stem spermatogonium becomes connected with bridges to form a syncytium.
These connections remain intact up to the last stages of spermatid maturation. It is believed that
the syncytium is essential for synchronous development of each clone from an original Ap cell.
The stage of growth is represented by primary spermatocytes. They enter the meiosis,
replicate their DNA (2n, 4c), and pass through the prophase of the first meiotic division, complex
phase with conjugation, tetrad formation, and exchange of genetic material known as crossing-
over. In fact, cell growth is not pronounced.
The stage of maturation includes the meiosis: secondary spermatocytes (n, 2c) appear after
the first division and early spermatids (n, c) result from the second meiotic division. In some
textbooks, the stage of growth and the stage of maturation are united and called the spermatocyte
phase.
The stage of formation (spermatid phase, spermiogenesis) is represented by spermatids that
differentiate into spermatozoa. Spermatids are haploid in DNA content and in chromosome
number, but morphologically they are trivial cells containing a cytoplasm with the usual set of
organelles. The spermatids undergo the transformation process known as spermiogenesis that
produces mature spermatozoa. The spermiogenesis includes four phases: the Golgi phase, the cap
phase, the acrosome phase, and the maturation phase.
In the Golgi phase, the acrosomal granule appears in the Golgi apparatus. This granule is
positioned above the nucleus and determines the anterior sperm pole. The centrioles migrate in the
opposite direction to determine the posterior sperm pole. The proximal centriole remains near the
nucleus, forming connecting piece of the sperm, and the distal centriole initiates the assembling of
microtubules that constitute the sperm axonemal complex (nine peripheral doublets and a central
doublet of microtubules).
In the cap phase, the acrosomal vesicle covers the anterior half of the nucleus and becomes
condensed to form an acrosomal cap or acrosome. The acrosome contains enzymes
(hyaluronidase, acid phosphatase, and acrosin) necessary for the penetration of the membranes
covering the ovum. The nucleus also becomes more condensed.
In the acrosome phase, the nucleus becomes most condensed and elongated. The
mitochondria migrate to arrange helically around the axonemal complex in the middle piece of the
sperm tail. The mitochondria provide sperm movements by energy. The principal piece of the

243
sperm tail includes the axonemal complex surrounded by the fibrous sheath; the end piece consists
of microtubules only.
In the maturation phase, the spermatids lose the excess of cytoplasm (a residual cytoplasm
or residual body). The residual bodies are phagocytosed by the Sertoli cells; the intercellular
bridges remain with the residual cytoplasm. Spermatozoa become individual cells; they are no
longer attached to one another. Individualization completes spermatogenesis.
The spermiogenesis produces a structurally unique cell. The mature human spermatozoon is
about 60 µm long. Its head includes the nucleus and the acrosomal cap surrounded with a narrow
cytoplasmic rim. Its tail is subdivided into the connecting piece, the middle piece, the principal
piece, and the end piece. The short connecting piece contains a centriole and the origin of the
coarse fibers. The middle piece contains the mitochondria helically wrapped around the coarse
fibers and the axonemal complex. The principal piece contains the fibrous sheath external to the
coarse fibers and the axonemal complex. The end piece contains only the axonemal complex.
Morphologically mature testicular spermatozoa are functionally immature, because they are
not motile. They acquire capacity for motion after longer incubation in the epididymal channels.
Nonmotile spermatozoa are carried from the testis with the testicular fluid by contractions of the
seminiferous tubules.
There are specific associations of differentiating spermatogenic cell types. These
associations occur, because intercellular bridges are present between the progeny of each stem
spermatogonium; they undergo synchronous mitosis, meiotic divisions and differentiation. These
cell associations are known as stages of the seminiferous epithelium cycle (there are 6 stages in
the human cycle). The seminiferous epithelium cycle is the stage series that appears between two
same stages at any tubule site. The seminiferous epithelium wave is the stage distribution along
the tubule length. There are no waves in the human seminiferous epithelium.
Certain physiological conditions are essential for normal proceeding of spermatogenesis.
Testosterone is necessary as the only hormone directly regulating almost all the stages of the sperm
production; the androgen-binding proteins (ABP) from the testicular fluid provide a high
testosterone concentration inside the seminiferous tubules.
Spermatogenesis requires the optimal temperature. The scrotum temperature is 2 to 3oC
below the body temperature; this low temperature is essential for sperm production. Shortly before
birth, the fetus testes descend from the abdominal cavity into the scrotum. If the testes fail to
descend into the scrotum (cryptorchidism), spermatogenesis does not begin.
Spermatogenic cells are in need of isolation from the immunocompetent cells.
Spermatogenic cells (except spermatogonia) are recognized as antigenic (not self, foreign) by the
immune system. Spermatogenic cells first appear at puberty long after the individual has become

244
immunocompetent. The blood–testis barrier plays an essential role in isolating of spermatogenic
cells from the immune system.
Spermatogenesis includes two unique processes: meiosis and spermiogenesis. Due to their
complexity these processes may give rise to mistakes and produce abnormal cells. Meiosis results
in the formation of approximately 5% of abnormal cells; spermiogenesis gives rise to about 25%
of pathological sperms. Both the male and female reproductive systems possess cell populations
to eliminate these abnormal cells.
Spermatogenic cells are very sensitive to noxious agents, such as dietary deficiencies,
general or local infections, elevated testicular temperature, steroid hormones, pesticides, and
radiation. Proliferating cells are particularly sensitive to these agents. Stem cells, which
demonstrate low mitotic activity, are much less vulnerable than actively dividing and
differentiating spermatogenic cells.
Seminiferous tubules
Seminiferous tubules consist of the seminiferous epithelium surrounded by the tunica
propria. The central tubular cavity (lumen) is filled with the testicular fluid. The seminiferous
epithelium is a cellular complex with stratified appearance including two populations of cells:
spermatogenic cells, which regularly replicate and differentiate into mature sperm, and Sertoli
cells (supporting or sustentacular cells) that do not undergo proliferation. In this complex, only
Sertoli cells are true epithelial components, mesodermal by nature. The spermatogenic cells arising
from the extragonadal embryonic origin – primordial germ cells (gonoblasts) – are not epithelial.
Sertoli cells are tree-shaped cells, their broad basal portions (trunks) rest on the basement
membrane; their multiple apical and lateral processes (branches) extend through the full thickness
of the seminiferous epithelium towards the lumen. The lower processes of the adjacent cells are
bound to one another by an unusual junctional complex. The latter includes tight junctions,
flattened sER cisternae parallel to the plasma membrane of each cell, and hexagonally packed
actin filament bundles interposed between sER cisternae and the plasma membrane. The Sertoli–
Sertoli junctions give structural organization to the tubules, because they establish two
compartments in the seminiferous epithelium: a basal compartment, between the junctions and the
basement membrane, and a luminal compartment, above the junctions. The basal compartment is
easy to reach for substances entering the tubule from blood or lymph. The tight junctions block
free access to the luminal compartment, and only selective transport of Sertoli cells creates its
unique chemical composition, rich in androgens, but free from cholesterol, LH, and
immunoglobulins. Thus, the luminal compartment manufactures the specific microenvironment
for spermatogenic cell development.

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 The Sertoli cell cytoplasm contains an extensive sER and rER, numerous mitochondria, a
well-developed Golgi complex, and varying numbers of microtubules, lysosomes, lipid droplets,
vesicles, glycogen granules, and filaments. The Sertoli cell nucleus is light, euchromatic, ovoid or
triangular in shape, and with deep folds of karyolemma. Its shape and location vary. The nucleolus
is present and may be complex in shape.
The appearance of the Sertoli cell nucleus and the organelle richness of its cytoplasm reflect
the variety of cell functions. Sertoli cells support spermatogenic cells, provide tubular
compartmentalization, and exchange metabolites between the tubular lumen and the circulatory
system. They phagocytose and break down the residual bodies, eliminate abnormal spermatogenic
cells, secrete the tubule fluid, and produce the ABP necessary for the high testosterone
concentration to be attained in the seminiferous tubules. It is believed that Sertoli cells are involved
in local regulation of spermatogenesis and, notably, of spermiogenesis. In addition, they possess
endocrine capacity: Sertoli cells secrete inhibin, a protein hormone involved in the feedback loop
that regulates FSH production by the adenohypophysis. These cells can metabolize all the steroids
reaching the seminiferous tubules to testosterone and, partially, to estrogens. Sertoli cells
themselves are under hormonal control: receptors for FSH and testosterone are found on their
plasma membrane. Both FSH and testosterone stimulate Sertoli cell functions, FSH is believed to
be essential for their secretory activity, notably, the ABP production.
Spermatogenic elements occupy both the basal and luminal compartments. Spermatogonia
and early primary spermatocytes reside in the basal compartment. More mature and antigenic
spermatocytes and spermatids are housed in the luminal compartment; meiosis and spermiogenesis
take place here. In development, primary spermatocytes must pass through the junctional complex
to gain the luminal compartment from the basal one. This displacement occurs through the
formation of a transitional compartment: a new junctional complex between Sertoli cell processes
appears beneath the newly formed spermatocytes, and then the junction above them breaks down
to allow spermatocytes to enter the luminal compartment. This phenomenon maintains chemical
and immunological homeostasis necessary for spermatogenesis.
The tunica propria (lamina propria) of the seminiferous tubules is a multilayered connective
tissue structure disposed externally to the Sertoli cell basal lamina and including the amorphous
ground substance, fibers, and cells. The tunica propria lacks typical fibroblasts; it contains the so-
called myoid cells (peritubular contractile cells) that are true highly modified myofibroblasts.
These elongated cells are concentrically arranged in three or five layers with interposed collagen
fibrils. Ultrastructurally, the myoid cells demonstrate features associated with smooth muscle
cells: they are surrounded by their own basal lamina, their plasma membrane is bound to numerous
pinocytotic vesicles, and their cytoplasm contains large numbers of actin filaments. They also

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exhibit a significant amount of rER, a feature indicative of their role in collagen synthesis in the
absence of typical fibroblasts. Rhythmic contractions of the myoid cells create peristaltic waves
that help spermatozoa and the testicular fluid to move through the seminiferous tubules towards
the duct system. Due to their border position, the myoid cells are involved in the selective transport
of metabolites both into and out of the seminiferous tubules, which allows the peritubular cells, as
well as the whole tunica propria, to be assigned to the essential components of the blood–testis
barrier.
Leydig cells
Leydig cells (glandulocytes) are endocrine testicular cells located in the intertubular
connective tissue. They are large, polygonal, and acidophilic cells arising from the mesenchyme.
Their ultrastructure corresponds to the morphology of other steroid-secreting cells: their cytoplasm
is rich in sER, Golgi apparatus, mitochondria with tubulovesicular cristae, and lipid droplets. The
lipochrome pigment is frequently seen in these cells. They typically contain the crystals of Reinke,
whose function is unknown.
In embryogenesis, Leydig cells differentiate early and secrete testosterone during the fetal
life. Androgens take part in the normal development of a male fetus; they influence the formation
of the male reproductive organs and hypothalamic sex differentiation. At puberty, Leydig cells
again differentiate into androgen-secreting cells and resume hormone production. In this period,
androgens are responsible for sexual maturation, the initiation of spermatogenesis, secretion of the
accessory sex glands, and development of the secondary sex characteristics. In the adult, the
secretion of testosterone is essential for sperm production, the functional activity of the genital
ducts and the male accessory glands, and the maintenance of secondary sex characteristics.
Like typical endocrine cells, Leydig cells are in contact with capillaries, but the testicular
blood capillaries are narrow and of continuous type. Testosterone is primarily released into the
testicular lymph. The testicular lymphatic capillaries are extraordinary: they are sinusoidal and
surround seminiferous tubules like sheaths.
Blood–testis barrier
The blood–testis barrier is a structural complex disposed on the pathway of substances
between the testicular blood and spermatogenic cells. It includes the capillary wall, the interstitial
connective tissue, the lymphatic sinusoid, the tunica propria of the seminiferous tubules, Sertoli
cells, and the Sertoli–Sertoli junctional complex. The blood–testis barrier provides the selective
transport of metabolites and creates a specific microenvironment for sperm maturation. The ionic,
amino acid, carbohydrate, and protein content of the testicular fluid considerably differs from the
composition of the blood plasma and testicular lymph.

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 The blood–testis barrier maintains the hormonal balance and homeostasis in the
seminiferous tubules: it blocks the access of cholesterol and LH, but provides the free transport of
androgens and FSH. The levels of exocrine secretary products of the Sertoli cells, particularly the
ABP, are high in the lumen. As testosterone is essential for normal maturation of the developing
sperm, the ABP contributes to the testosterone concentration in the seminiferous tubule lumen.
The blood–testis barrier plays an essential role in isolating the spermatogenic cells from the
immune system of an adult male. Spermatogenic cells (except spermatogonia) are recognized as
antigenic by the immune system. That is the reason why, on the one hand, plasma
immunoglobulins are excluded from the lumen of the tubules; on the other hand, the sperm
antigens are prevented from reaching the systemic circulation. The damage to the blood–testis
barrier (e.g., posttraumatic alteration) increases the barrier permeability and results in the
development of the autoimmune reaction, causing the destruction of spermatogenic cells.
Regulation of the testis functions
The testes are adenohypophysis-dependent glands. Two gonadotropins – FSH and LH –
possess target cells in the male gonads. FSH interacts with Sertoli cells and stimulates their
functions, in particular, the secretory activity and ABP production. The protein hormone inhibin
secreted by Sertoli cells provides a feedback loop with the adenohypophysis and inhibits FSH
release. The testicular Leydig cells possess plasma receptors to LH that stimulate androgen
synthesis by these endocrinocytes. The blood testosterone level takes part in negative feedback
interaction with the pituitary gland and inhibits LH production. Estrogens inhibit secretory activity
of the testicilar Leydig cells.
Testosterone is the only hormone that directly regulates spermatogenesis. The testosterone
transport through the blood–testis barrier and its sufficient concentration in the tubular lumen are
provided by the high ABP level in the testicular fluid.

Prostate gland
The prostate is the largest accessory sex gland. It surrounds the proximal urethra. It is
enclosed with a connective tissue capsule and consists of the prostatic glands, interglandular loose
connective tissue, and smooth muscle bundles disposed in the stroma. The prostate contains 30 to
50 tubuloalveolar glands that are arranged in three concentric layers around the urethra: a mucosal
layer, a submucosal layer, and the most peripheral layer containing the main prostatic glands. The
glands empty into the urethra at the time of ejaculation by contraction of the prostatic smooth
muscle cells. The muscles also serve as an additional urethral sphincter. The prostatic juice
abounds in zinc ions, acid phosphatase, fibrinolysin, citric acid, and prostaglandins. The
epithelium of the prostate is dependent on testosterone for normal morphology and function. The

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prostatic alveoli, especially in older men, often contain prostatic concretions. They are believed to
be formed by precipitation of secretory material around cell fragments. They may become partially
calcified.
Nodular hyperplasia occurs in the mucosal and submucosal glands and can lead to partial or
total urethra obstruction. Prostate cancer usually develops peripherally, in the main glands.

CONTROL PROBLEMS

1. Medical examination revealed retention of one of the testes in the abdominal cavity
(cryptorchism). Which of the testicular functions will be affected if surgical operation (bringing
the testis down into the scrotum) is not performed?
2. The mechanical trauma of the testis results in the cessation of spermatogenesis and
desolation of seminiferous tubules. What testicular structures are damaged to cause this
disturbance? What process is pathogenetic for the post-traumatic testicular changes?
3. The chromosomes of a spermatogenic cell become visible and conjugate forming
bivalents. Determine the seminiferous epithelium cell and the spermatogenetic stage.
4. The nucleus of a spermatogenic cell becomes more condensed and elongated. The Golgi
apparatus forms the acrosomal granule, and the distal centriole gives rise to the axonemal complex.
Determine the seminiferous epithelium cell and the spermatogenetic stage.
5. Two male rats were experimentally made to lower their FSH and LH production,
respectively. What cells of the male gonads respond to the intervention in each case?
6. The histological examination of the prostate gland revealed thickened connective tissue
trabeculae and dilated alveoli containing dense, partially calcified secretions. What age period is
typical of such a prostate structure?

CONTROL TESTS

Directions: each of the following statements contains five suggested completions. Choose
the one that is best in each case.
1. Spermatogenesis takes place in the following tubules: A – straight tubules; B – rete testis;
C – seminiferous tubules; D – ductuli efferentes; E – ductus deferens.
2. Each of the following statements concerning the spermatogenetic stage of proliferation is
true, EXCEPT: A – stem cells divide to give rise to two daughter cells: one remains as a stem cell,
the other is committed spermatogonium; B – stem cells undergo meiotic divisions; C – committed
spermatogonia undergo several successive divisions to increase their number; D – the daughter

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cells of committed spermatogonium remain connected by cytoplasmic bridges; E – offspring of a
stem cell is united to form the syncytium.
3. The following events take place at the spermatogenetic stage of growth: A – mitotic
division of primary spermatocytes; B – meiotic division of secondary spermatocytes; C – mitotic
division of spermatogonia; D – meiotic division of spermatogonia; E – prophase of the first meiotic
division.
4. The following transformations of the spermatid take place in spermiogenesis (stage of
formation), EXCEPT: A – the nucleus becomes decondensed; B – Golgi complex produces an
acrosomal granule that is converted to an acrosome; C – mitochondria form the helical sheath
round the axonemal complex; D – the distal centriole initiates formation of the axonemal complex,
the proximal centriole remains near the nucleus; E – residual cytoplasm is lost.
5. Each of the following statements concerning the testicular myoid cells is true, EXCEPT:
A – their cytoplasm is rich in myofilaments; B – are surrounded by the basal laminae; C – their
rhythmic contractions create peristaltic waves of the seminiferous tubules; D – are not capable of
collagen synthesis; E – are involved in selective transport into and out of the seminiferous tubules.
6. Each of the following statements concerning the testicular Sertoli cells is true, EXCEPT:
A – their basal portions rest on the basal lamina; B – their apical portions have processes extending
into the tubule lumen; C – possess centrioles and are capable of division; D – their plasma
membranes have receptors for FSH and testosterone; E – their cytoplasm is rich in organelles and
inclusions.
7. Each of the following statements concerning the testicular Sertoli cell functions is true,
EXCEPT: A – support spermatogenic cells; B – provide the exchange of substances between
spermatogenic cells and blood; C – eliminate residual bodies and abnormal sperms; D – secrete
testicular fluid, ABP, and inhibin; E – provide peristaltic contractions of the seminiferous tubules.
8. Each of the following statements concerning the compartmentalization of the seminiferous
tubules is true, EXCEPT: A – Sertoli-Sertoli tight junctions establish basal and luminal
compartments; B – spermatogonia are in the basal compartment; C – spermatocytes and spermatids
are in the luminal compartment; D – meiosis and spermiogenesis occur in the basal compartment;
E – primary spermatocytes pass from the basal compartment to the lumenal one due to the
formation of a new transitional compartment.
9. Each of the following statements concerning the testicular Leydig cells is true, EXCEPT:
A – are parts of the seminiferous epithelium; B – their cytoplasm is rich in sER, Golgi complex,
vesicular mitochondria, and lipid droplets; C – produce androgens, mainly testosterone; D – their
plasma membranes possess receptors for LH and estrogens; E – primarily release the hormone into
testicular lymph.

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 10. The following structures constitute the blood-testis barrier. Choose the firmest structures
providing the immune isolation: A – capillary wall; B – connective tissue; C – lymphatic sinusoid;
D – Sertoli-Sertoli tight junctions; E – the tunica propria of seminiferous tubules.
11. Each of the following statements concerning the hormonal regulation of the testis is true,
EXCEPT: A – FSH effects on the Sertoli cells and they produce ABP in testicular fluid; B – LH
effects on the Leydig cells and they secrete testosterone; C – ABP concentrates testosterone within
the tubules to regulate sperm maturation; D – inhibin from Sertoli cells provides feedback with
LH; E – testosterone is involved in feedback loop regulating LH production.
12. Each of the following statements concerning the epididymis is true, EXCEPT: A – has
the head, body, and tail; B – sperm maturation in it is not androgen-dependent; C – sperms acquire
motility passing through it; D – its epithelial cells secrete glycoproteins that are added to the sperm
glycocalyx preventing from premature acrosomal reaction; E – smooth muscle coat of the ductus
epididymis increases in thickness and becomes three- layered in the tail.
13. Each of the following statements concerning the prostate gland is true, EXCEPT: A –
surrounds the ejaculatory duct; B – its glands are mucosal, submucosal, and peripheral; C – the
glandular epithelium depends on testosterone; D – the glands are surrounded by connective tissue
with bundles of smooth muscle cells; E – its alveoli often contain concretions, especially in elderly
males.

Directions: one or more of the given statements or completions is/are correct. Choose the
answer: A – if only 1,2, and 3 are correct; B – if only 1 and 3 are correct; C – if only 2 and 4 are
correct; D – if only 4 is correct; E – if all are correct.
14. The intratesticular part of the male genital ducts includes: (1) seminiferous tubules (2)
rete testis (3) ductuli efferentes (4) straight tubules
15. The extratesticular part of the male genital duct system consists of: (1) ductuli efferentes
(2) ductus epididymidis (3) ductus deferens (4) ductus ejaculatorius
16. The following statements regarding the spermatogenic syncytium are true: (1) is a
specific association of differentiating cells (2) occurs because intercellular bridges are present
between the progeny of each stem spermatogonium (3) intercellular connections remain intact
until the last stages of spermatid maturation (4) all its cells undergo synchronous divisions and
differentiation
17. The spermatogenetic stage of maturation includes: (1) first meiotic division (2) mitotic
division (3) second meiotic division (4) sperm maturation

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 18. The spermatogenetic stage of formation includes: (1) mitotic division (2) meiotic
division of primary spermatocytes (3) meiotic division of secondary spermatocytes (4)
differentiation of spermatids into spermatosoa
19. The physiological conditions that are necessary for spermatogenesis are as follows: (1)
the presence of testosterone (2) temperature that is equal to body temperature (3) isolation of
spermatogenic cells from the immune system (4) the absence of any hormones
20. The following statements regarding the vulnerability of spermatogenic cells are true: (1)
spermatogenic cells are not sensitive to noxious agents (2) spermatogenic cells are very sensitive
to noxious agents (3) proliferating cells are not sensitive to injury (4) stem spermatogonia are much
less vulnerable then actively dividing and differentiating cells
21. The tunica propria of the seminiferous tubules consists of: (1) Sertoli cell basement
membrane (2) collagen and elastic fibres (3) several layers of myoid cells (4) amorphous ground
substance
22. The following statements regarding the seminiferous epithelium are true: (1) is complex
stratified epithelium (2) is composed of two cell populations (3) the Sertoli cells are its true
epithelial parts (4) spermatogenic cells are its principal parts
23. The androgens are responsible for: (1) normal development of the male fetus (2)
development and maintenance of secondary male sex characteristics (3) initiation and maintenance
of sperm production (4) initiation and maintenance of the male accessory gland functions
24. The following statements regarding the testicular interstitial connective tissue are true:
(1) is testicular endocrine part due to the presence of Leydig cells (2) its blood capillaries are
continuous (3) contains lymphatic sinusoids surrounding the seminiferous tubules like sheathes
(4) its blood capillaries are sinusoidal fenestrated
25. The following statements regarding the blood-testis barrier functions are true: (1) creates
specific chemical composition for spermatogenic cell development (2) provides hormonal
homeostasis in the seminiferous tubules (3) isolates antigenic spermatocytes and spermatids from
the immune system (4) prevents sperm antigen entering the systemic circulation
26. The ductus deferens wall consists of the following tunics: (1) mucosa (2) adventitia (3)
three-layered muscularis externa (4) submucosa

FIGURES

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 Fig. 22.1. Spermatozoon structure
A – microscopic spermatozoon appearance in two planes; B – spermatozoon ultrastructure; C –
fragment of tail proximal region; D – fragment of tail distal region; I – sperm head; II – sperm
tail: a – connecting piece; b – middle piece; c – principal piece; d – end piece; 1 – plasmalemma;
2 – acrosome; 3 – nucleus; 4 – proximal centriole; 5 – distal centriole; 6 – mitochondria; 7 –
axonemal complex; 8 – coarse fibers; 9 – peripheral microtubules; 10 – central microtubules.

Fig. 22.2. Spermatogenesis

I – phase of proliferation (mitotic divisions); II – phase of growth (prophase of the first meiotic
division); III – phase of maturation (meiotic division); IV – phase of formation (spermiogenesis)

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 Fig. 22. 3. Seminiferous tubule and intertubular connective tissue
1 – late spermatid; 2 – early spermatid; 3 – secondary spermatocytes; 4 – primary spermatocytes;
5 – Sertoli-Sertoli tight junction; 6 – spermatogonium; 7 – Sertoli cell; 8 – tubule basement
membrane; 9 – collagen fibrils; 10 – myoid cells; 11 – lymphatic sinusoid; 12 – intertubular
connective tissue; 13 – endothelial cell of blood capillary; 14 – Leydig cell; 5, 7-13 – make up
the blood-testis barrier.

24. FEMALE REPRODUCTIVE SYSTEM: OVARIES

The female reproductive system consists of the following organs: the ovaries, the oviducts,
the uterus, the vagina, and the external genitalia. The mammary glands are also included in this
system, because their development and functional state are directly related to the hormonal activity
of the female reproductive organs. The organs of this system perform numerous important
functions: they produce the ova, secrete female sex hormones, create a suitable environment for
the early stages of embryogenesis, provide implantation and development of the fetus during
pregnancy, participate in parturition, and ensure nutrition of the newborn.

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 Ovogenesis
Ovogenesis is a process of the ovum maturation, the entire sequence of events, by which
oogonia are transformed into ova. Ovogenesis possesses some peculiarities in comparison with
spermatogenesis.
The phase of reproduction begins in early fetal life, when the oogonia proliferate by mitotic
division and are converted to the primary oocytes before birth that is why the ovaries of a newborn
female infant lack the oogonia and possess only the primary oocytes.
The phase of growth is pronounced and subdivided into two steps: the small growth and the
large growth. The small growth begins in the embryogenesis, since the oogonia have been
transformed into the primary oocytes. The primary oocytes enter the prophase of the first meiotic
division, but the completion of the prophase does not occur until puberty. The primary oocytes
remain in suspended prophase called the dictyotene for several years, until sexual maturity is
reached and the reproductive cycles start at puberty.
The large growth begins at puberty. Monthly, several primary oocytes enter the large growth
and considerably enlarge in size, because they accumulate organelles, synthesize yolk granules,
and manufacture specialized secretory vesicles known as the cortical granules. The yolk granules
provide embryo nutrition during the first days of development. The cortical granules are located
just beneath the oocyte plasma membrane and contain enzymes that are released by exocytosis
during fertilization to form the fertilization envelope preventing polyspermy. The large growth
lasts for about two weeks until just before ovulation. This time the completion of the first meiotic
prophase occurs. Thus, primary oocytes remain arrested in the dictyotene stage of the first meiotic
division for 12 to 50 years. This long period of meiotic arrest makes the primary oocytes more
sensitive to environmental influences and probably contributes to errors such as nondisjunction of
chromosomes. This results in chromosomal anomalies such as trisomy of chromosome 21 –
Down’s syndrome.
The phase of maturation includes two meiotic divisions. Shortly before ovulation, the
primary oocyte completes the first meiotic division; however, the division of cytoplasm is unequal.
The secondary oocyte receives almost all the cytoplasm, and the first polar body receives a
minimal amount of the cytoplasm. The polar body is a small nonfunctional cell that does not divide
(in humans) and soon degenerates. At ovulation, the nucleus of the secondary oocyte begins the
second meiotic division, but progresses only to metaphase, when division is arrested. If
fertilization occurs, the second meiotic division is completed (if the secondary oocyte is penetrated
by a spermatozoon) and most cytoplasm is again retained by one cell, the zygot. The other cell –
the second polar body – is small and soon degenerates.

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 In contrast to spermatogenesis, female gametogenesis proceeds in three phases; the phase of
formation is absent. After ovulation, the secondary oocyte remains viable for a period of
approximately 24 hours. If fertilization does not occur during this period, the secondary oocyte
degenerates as it passes through the oviduct.

Ovary (female sex gland, female gonad)

The ovary is a small, almond-shaped organ. It has the dense connective tissue capsule (the
tunica albuginea) that is invested by the germinal epithelium (a simple squamous or cuboidal
epithelium). The term germinal epithelium is a carryover from earlier days when it was incorrectly
thought to be the site of germ cell formation in development. It is now known that the primordial
germ cells (of both the male and female) are of extragonadal origin and they migrate from the yolk
sac to the embryonic gonad where they induce differentiation of the ovary. The ovary is subdivided
into the cortex and the medulla, the central portion of the ovary. The boundary between the medulla
and cortex is indistinct. The cortex contains ovarian follicles at various stages of development,
atretic follicles and atretic bodies, and the corpus luteum at various stages of development up to
the corpus albicans. The medulla contains loose connective tissue rich in blood vessels,
lymphatics, and nerves.
The ovaries have two interrelated functions: production of female gametes (oogenesis) and
secretion of female sex hormones – estrogens and progesterone.
Ovarian follicles and folliculogenesis
The ovarian follicle is the oocyte surrounded by envelopes. The ovarian follicles provide the
microenvironment for developing oocytes, their sizes and structure correlate with the
developmental state of the oocyte. The stages of the ovarian folliculogenesis are as follows:
primordial follicles, primary follicles, secondary (growing) follicles, and mature follicles
(Graafian vesicles).
The primordial follicle is the earliest stage of the follicular development. The primordial
follicles predominate in the ovary; they are located in the periphery of the cortex, just beneath the
tunica albuginea. These follicles are the smallest and the simplest in structure. They are composed
of a primary oocyte arrested at the meiotic dictyotene and a single layer of squamous follicular
cells. The follicular cells are separated by a basal lamina from the surrounding stroma and are
attached to each other by desmosomes. The oocyte measures about 30 µm in diameter and has an
acentric nucleus with a single nucleolus.
The primary follicle is the first stage of follicle growth. The primary oocyte enters the large
growth and considerably enlarges in size: its diameter becomes about 50 to 80 µm. As the oocyte
grows, a homogeneous acidophilic layer called the zona pellucida appears around the oocyte,

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between it and the adjacent follicular cells. The growing oocyte and follicular cells secrete this
gel-like layer that is rich in glycosaminoglycans and glycoproteins. The follicular cells proliferate
and become cuboidal in shape; they are arranged in one or two layers round the oocyte. The
follicular cells are separated from the stroma by their own basal membrane.
The secondary (growing) follicle is larger than the primary follicle. Secondary follicles
contain a primary oocyte surrounded by the zona pellucida. The oocyte has reached its final size
– about 125 to 150 µm in diameter. Through rapid mitotic proliferation, the single layer of
follicular cells gives rise to a stratified epithelium now named the membrana granulosa or stratum
granulosum; the follicular cells are identified as the granulosa cells. The basal lamina retains its
position. The follicular cells of the outermost layer become columnar, the rest of them have narrow
processes and communicate with each other via gap junctions. The narrow processes of the
granulosa cells and the oocyte microvilli extend into and contact each other within the zona
pellucida. When the stratum granulosum reaches a thickness of 6- to 12-cell layers, fluid-filled
cavities appear among the granulosa cells. This fluid is called the liquor folliculi; it continues to
accumulate among the granulosa cells; the cavities begin to coalesce, eventually forming a single
cavity called the antrum. The follicle is now identified as a secondary antral follicle. The liquor
folliculi is secreted by the granulosa cells.
The granulosa cells possess a number of FSH receptors. FSH stimulates the follicular growth
and secretion of the liquor folliculi. In response to FSH influence, the granulosa cells convert
androgens to estrogens and release them. Estrogens, in turn, activate proliferation of the granulosa
cells.
As the granulosa cells proliferate, the stroma immediately surrounding the follicle forms a
sheath of connective tissue, known as the theca folliculi, just external to the basal lamina. The
theca folliculi further differentiates into two layers: the theca interna and the theca externa.
The theca interna is the inner layer. It contains loose connective tissue, a rich network of
small vessels, and secretory cells called the theca cells. These are cuboidal cells possessing
ultrastructural features characteristic of steroid-producing cells: they are rich in sER profiles, Golgi
apparatus, vesicular mitochondria, and lipid droplets. They synthesize and secrete the androgens
that are the precursors of estrogens. These cells possess a large number of LH receptors; in
response to LH stimulation, the theca cells produce the androgens.
The theca externa is the outer layer of connective tissue; it mainly contains bundles of
collagen fibers and numerous myofibroblasts. The boundaries between the thecal layers, as well
as between the theca externa and the surrounding stroma are not distinct.
The growing follicles are hormone-producing structures of the ovary, they produce
estrogens. As the follicles grow, the estrogen blood level increases and attains the maximal size

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by approximately the 14th day of the menstrual cycle, just before ovulation. Estrogen production
is adenohypophysis-dependent. Gonadotropin-releasing hormone (GnRH) from the hypothalamus
causes the release of FSH and LH by the pars anterior of the pituitary gland. LH stimulates the
theca cells to produce androgens. FSH stimulates the granulosa cells to convert androgens to
estrogens and release them into the liquor folliculi and then into the blood. Estrogens inhibit FSH
release (by suppressing the release of GnRH), but stimulate LH production to facilitate an increase
in the LH blood content by the time of ovulation called the peak (surge) of LH.
The mature follicle or Graafian vesicle represents the final stage of the follicular
development, just prior to ovulation. It measures 10 mm and more in diameter. Because of its very
large size, it extends through the full thickness of the cortex as a bulge on the ovarian surface. The
oocyte is acentrically positioned, and its final size is about 150 µm in diameter. Before ovulation,
the first meiotic division of the primary oocyte resumes forming the secondary oocyte and the first
polar body. The oocyte is surrounded by the zona pellucida and the corona radiata, i.e., the
granulosa cells located immediately around the zona pellucida. The microvilli of the oocyte and
processes of the corona radiata cells contact with each other via gap junctions. The antrum
increases in size and is surrounded by several layers of follicular cells. The stratum granulosum
has relatively uniform thickness except for the region associated with the oocyte. Here, the
granulosa cells form a thickened mound – the cumulus oophorum – that projects into the antrum.
The thecal layers become more prominent.
Ovulation
The ovulation is a hormone–mediated process resulting in the release of the secondary
oocyte with the zona pellucida and the corona radiata from the Graafian follicle. The primary
oocyte completes its first meiotic division just prior to ovulation. The secondary oocyte begins the
second meiotic division, but progresses only to the metaphase, when division is arrested. Thus,
metaphase II secondary oocyte leaves the ovary in ovulation to become the ovum.
Just before ovulation, the blood flow stops in a small area of the ovarian surface overlying
the bulging follicle called the stigma. The stigma ruptures, forming a small gap in the capsule,
germinal epithelium, and the wall of the Graafian follicle. Via this gap, the secondary oocyte with
its surroundings leaves the ovary. Combinations of hormonal changes and enzymatic effects are
responsible for this rupture and exit of the oocyte. They are as follows: increase in volume and
pressure of the follicular fluid, enzymatic proteolysis of the follicular wall, enzymatic separation
of the oocyte–cumulus complex from the stratum granulosum, and contractions of the
myofibroblasts in the theca externa. The hormonal control of ovulation is primarily realized by
LH, whose blood level reaches the maximum at ovulation. This maximum is called the surge or
peak of LH. The lack of the LH surge in women results in the lack of ovulation (anovulation) and

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the impossibility of pregnancy. The block of the LH surge and, as a result, the inhibition of
ovulation is the basis of female hormonal contraception. FSH also reaches high concentrations by
the time of ovulation, forming the FSH peak.
The oocyte is then transported into the oviduct infundibulum. At the time of ovulation, the
fimbriae of the oviduct envelop the ovary, normally directing the oocyte into the oviduct and not
allowing it to pass into the peritoneal cavity. Normally, only one follicle completes maturation in
each cycle and ruptures to release its secondary oocyte. Rarely, oocytes are released from other
follicles that have reached full maturity during the same cycle, leading to the possibility of multiple
zygotes and fetuses.
Corpus luteum
After ovulation, the collapsed follicle undergoes reorganization into the corpus luteum or
yellow body. At first, bleeding from the capillaries in the theca interna into the follicular lumen
leads to the formation of the corpus hemorrhagicum with a central clot. The stromal connective
tissue invades the former follicular cavity. The cells of the granulosa and the theca interna
proliferate, the blood vessels from the theca interna rapidly grow into the granulosa layer, and a
rich vascular network is established. The the granulosa cells and the theca cells undergo
morphological changes: they increase in size, become filled with lipid droplets, accumulate sER
and mitochondria with tubulovesicular cristae. At the ultrastructural level, the cells demonstrate
features associated with steroid-secreting cells. The lipid-soluble pigment lipochrome in the cell
cytoplasm imparts to them a yellow appearance in fresh preparations. Two types of luteal cells are
identified: granulosa lutein cells, large (about 30 µm in diameter), pale, centrally located cells
derived from the granulosa cells; and theca lutein cells, smaller (about 15 µm), more deeply
staining, peripherally located cells derived from the theca interna cells. The formation of the corpus
luteum is controlled by LH, a pituitary gland hormone.
The mature corpus luteum secretes progesterone that stimulates the growth and secretory
activity of the endometrium to prepare it for the implantation of the developing embryo, but blocks
the cyclic development of the ovarian follicles. If implantation occurs, the corpus luteum increases
in size to form the corpus luteum of pregnancy. In early pregnancy, the corpus luteum attains a
size of 2 to 3 cm, thereby filling most of the ovary. The corpus luteum retains its full functional
capacity about half a year, and then its activity decreases. If implantation fails to occur, the corpus
luteum remains active only for 12 days; in this case, it is called the corpus luteum of menstruation.
The active secretion of the corpus luteum is stimulated by prolactin (LTH) from the pituitary gland.
The corpus luteum degenerates and undergoes slow involution after pregnancy or
menstruation. The cells undergo apoptosis, and their remnants are phagocytosed by macrophages.
A white scar – the corpus albicans – is formed in place of the former corpus luteum. The corpus

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albicans sinks deeper into the ovarian cortex as it slowly disappears over a period of several
months.
Atresia
A few of the ovarian follicles that begin their differentiation in the embryonic ovary reach
maturation and ovulate. Most of the follicles degenerate and disappear through the process called
the follicular atresia. A large number of follicles undergo atresia during fetal development, early
postnatal life, and puberty. About 2 million primary oocytes are usually present in the ovaries of
the newborn female infant, but many regress during childhood so that by puberty only 30 to 40
thousand remain. Only about 400 become secondary oocytes and are expelled at ovulation during
the reproductive period.
A follicle may undergo atresia at any stage of its maturation. In atresia of primordial and
primary follicles, the oocyte becomes smaller and degenerates; similar changes occur in the
follicular cells. As the cells disappear, the surrounding stromal cells migrate into the space
previously occupied by the follicle, leaving no trace of its existence.
In atresia of large growing follicles, the oocyte degeneration appears to occur secondarily to
degenerative changes in the follicular wall. The following events take place: invasion of the
granulosa layer by neutrophils, macrophages, and vascularized connective tissue; sloughing of the
granulosa cells into the antrum; invasion of connective tissue into the cavity of the follicle;
hypertrophy of the theca interna cells; collapse of the follicle.
The oocyte undergoes typical changes associated with apoptosis; its remnants are
phagocytozed by invading macrophages. The zona pellucida becomes folded and collapses as it is
slowly broken down within the cavity of the follicle. Macrophages are involved in the
phagocytosis of the zona pellucida. The basement membrane of the follicular cells separates and
increases in thickness, forming a hyaline layer called the glassy membrane. This structure is
characteristic of follicles in late stages of atresia.
The enlargement of the theca interna cells occurs in the atretic follicles, and a rich capillary
network develops among them. These cells produce steroid hormones, mainly estrogens. These
cells are an important source of the estrogens that influence the growth and development of the
secondary sex organs. In the climacteric period, the process of atresia becomes more active,
resulting in serum estrogen elevations, and this, in turn, may cause malignant growth in females.

CONTROL TESTS

Directions: each of the following statements contains five suggested completions. Choose
the one that is best in each case.

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 1. Each of the following statements concerning the large growth of ovogenesis is true,
EXCEPT: A – begins at puberty; B – is represented by primary oocytes leaving the dictyotene; C
– includes accumulation of organelles, yolk granules, and cortical granules; D – lasts about two
weeks until just before ovulation; E – is hormone-independent.
2. Each of the following statements concerning the ovogenesis stage of maturation is true,
EXCEPT: A – the primary oocyte completes the first meiotic division shortly before ovulation; B
– the secondary oocyte begins the second meiotic division at ovulation; C – cytoplasm division
between daughter cells is equal; D – the second meiotic division progresses only to metaphase
when it is arrested; E – the second meiotic division is completed if the secondary oocyte is
fertilized.
3. Each of the following statements concerning the ovary is true, EXCEPT: A – is invested
by a connective tissue capsule and the germinal epithelium; B – its germinal epithelium is a source
of new oogonia; C – its cortex contains follicles, atretic bodies, and the corpus luteum; D – its
medulla contains connective tissue with blood vessels, lymphatics, and nerves; E – produces
female gametes and secretes female sex hormones.
4. Each of the following statements concerning the secondary ovarian follicles is true,
EXCEPT: A – contain the primary oocyte at large growth surrounded by the zona pellucida; B –
their follicular epithelium becomes stratified and is named the membrana granulosa; C – fluid-
filled cavities appear among their granulosa cells; D – small cavities begin to coalesce eventually
forming the antrum; E – lack the theca layer.
5. Each of the following statements concerning the ovarian theca cells is true, EXCEPT: A
– are located in the theca interna of growing and mature follicles; B – their cytoplasm is rich in
sER, Golgi apparatus, vesicular mitochondria, and lipid drops; C – secrete androgens; D – their
secretory activity is under FSH control; E – their androgens are transported to the granulosa cells
where they become estrogens.
6. Each of the following statements concerning the ovarian mature follicle is true, EXCEPT:
A – represents the earliest stage of follicular development; B – bulges on the ovary surface because
of its large size; C – its oocyte is surrounded by the zona pellucida and the corona radiata; D – its
oocyte is acentrically positioned at the cumulus oophorum; E – its antrum increases in size and is
surrounded by the granulosa cells.
7. Each of the following statements concerning the ovulation is true, EXCEPT: A – it is
controlled by the LH and FSH peaks; B – the secondary oocyte at metaphase II leaves the ovary
and enters the oviduct; C – before ovulation the stigma disappears; D – the stigma ruptures forming
a small gap in the capsule, germinal epithelium, and follicle wall; E – the oocyte with its
surrounding leaves the ovary via this gap.

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 8. Each of the following statements concerning the corpus luteum activity and its hormonal
regulation is true, EXCEPT: A – the corpus luteum formation is controlled by LH; B – mature
corpus luteum secretes progesterone; C – the corpus luteum secretion is controlled by prolactine
(LTH); D – high blood progesterone levels stimulate the cyclic development of ovarian follicles;
E – progesterone stimulates the endometrium to prepare it for future implantation.
9. Each of the following statements concerning the ovarian corpus luteum is true, EXCEPT:
A – the corpus luteum of pregnancy reaches the size of 2–3 cm and retains its functional capacity
for about half a year; B – the corpus luteum of menstruation remains active for 28 days; C – the
granulosa lutein cells are large, pale, and centrally located; D – the theca lutein cells are small,
dark, and peripherally located; E – the corpus luteum undergoes involution after pregnancy or
menstruation and is replaced by the corpus albicans.
10. Each of the following statements concerning the ovarian follicle atresia is true, EXCEPT:
A – oocyte degeneration appears later than degenerative changes in the follicular wall; B – the
oocyte undergoes degeneration and autolysis; C – oocyte remnants are removed by macrophages;
D – the zona pellucida is slowly broken down in the follicular cavity; E – results in the corpus
luteum formation.

Directions: one or more of the given statements or completions is/are correct. Choose the
answer: A – if only 1,2, and 3 are correct; B – if only 1 and 3 are correct; C – if only 2 and 4 are
correct; D – if only 4 is correct; E – if all are correct.
11. The following statements regarding the ovogenesis stage of proliferation are true: (1)
begins and ends during early fetal life (2) is represented by oogonia that divide by mitosis (3)
completes before birth when all oogonia become primary oocytes (4) includes the arrested phase
called dictyotene
12. The following statements regarding the small growth of the ovogenesis are true: (1)
begins in embryogenesis (2) its essence is the prophase of the first meiotic division (3) prophase I
completion does not occur until puberty (4) primary oocytes remain in the arrested prophase called
dictyotene for several years
13. The following statements regarding the ovarian primordial follicles are true: (1) are
composed of the primary oocyte at the dictyotene surrounding by a single layer of squamous
follicular cells (2) are the earliest stage of follicular development (3) predominate in number
among ovarian follicles (4) are located in the ovarian medulla
14. The following statements regarding the ovarian primary follicles are true: (1) their
primary oocytes begin the large growth and considerably enlarge in volume (2) oocytes and

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follicular cells produce the zona pellucida (3) follicular cells proliferate, become cuboidal in shape,
and form one layer (4) the theca layer appears
15. The following statements regarding the ovarian follicle granulosa cells are true: (1)
secrete liquor folliculi (2) are involved in selective transport between blood and the oocyte (3) can
convert androgens to estrogens (4) possess plasma membrane FSH receptors
16. The following statements regarding the ovarian follicle theca are true: (1) theca interna
contains loose connective tissue, blood vessels, and theca cells (2) is present only in mature
(Graafian) follicles (3) theca externa consists of dense irregular connective tissue (4) produces
estrogens
17. The following statements regarding the events preceding follicle rupture in ovulation are
true: (1) follicular fluid volume and pressure increase (2) myofibroblasts of the theca externa
contract (3) the follicular wall undergoes enzymatic proteolysis (4) the oocyte-cumulus complex
separates from the granulosa layer
18. The following events take place in the ovarian corpus luteum formation: (1) the basement
membrane of granulosa cells undergoes destruction (2) granulosa cells and theca cells proliferate
(3) blood vessels from the theca interna grow into the granulosa layer (4) a rich network of
sinusoidal fenestrated capillaries is established
19. The granulosa cells and theca cells undergo the following morphological changes in the
corpus luteum formation: (1) increase in size (2) become filled with lipid droplets (3) accumulate
sER and vesicular mitochondria (4) lipochrome imparts the yellow colour to them in fresh
specimens
20. The following statements regarding the ovarian follicle atresia are true: (1) numerous
follicles undergo atresia during fetal development, early postnatal life, and puberty (2) atresia of
primordial and primary follicles leaves no traces of their existence (3) atresia of growing follicles
results in their reorganisation into atretic bodies secreting estrogens (4) atresia declines in the
climacteric period
21. The following events take place in the ovarian follicle atresia: (1) blood vessels,
neutrophils, and macrophages invade the granulosa layer (2) granulosa cell slough into the follicle
antrum (3) theca cells acquire the ability to secrete estrogens (4) the basement membrane separates
from follicular cells, increases in thickness, and becomes a glassy membrane

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FIGURES

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 Fig. 23.1. Ovogenesis
I – phase of proliferation (mitotic divisions); II – phase of growth; III – phase of maturation
(meiotic division).

Fig. 23.2. Ovum structure

A – light microscopy; B – ultrastructure: 1 – nucleus: 2 – cytoplasm with yolk inclusions; 3 –
cortical granules; 4 – plasmalemma; 5 – zona pellucida; 6 – follicular cells of the corona radiata.

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 25.FEMALE REPRODUCTIVE SYSTEM: REPRODUCTIVE CYCLE,
UTERUS, OVIDUCTS, VAGINA, and MAMMARY GLANDS

The female reproductive system functions cyclically. The ovaries, oviducts, uterus, vagina,
and the mammary glands are involved in this cycle. The female or menstrual cycle averages about
28 to 30 days. The initiation of the female cycle, referred to as the menarche, occurs in females
between the ages of 9 and 14 years and marks the end of puberty and the beginning of the
reproductive lifespan. Between the ages of 45 and 55 years, the menstrual cycles become
infrequent and then cease. This change in reproductive function is referred to as the menopause or
climacterium. The cause of the female reproductive cyclic function is the cyclical secretion of the
female pituitary gland that takes place only in women and develops in early embryogenesis.

Ovarian cycle
The ovary undergoes cyclic changes constituting the ovarian cycle. It involves two phases:
the follicular phase and the luteal phase; ovulation occurs between the phases on the 14th day of a
28-day cycle.
The follicular phase lasts from the 1st to 14th day. It begins with the development of a small
number of primary follicles. During this phase, follicles grow and develop, most of them undergo
atresia and only one of them reaches the ovulation. Both growing follicles and atretic follicles
produce steroid hormones, principally estrogens; therefore, the follicular phase is named the
estrogen phase. The circulating level of estrogens rises during the follicular phase and reaches its
peak by the ovulation.
The luteal phase begins immediately after ovulation and lasts up to the 28th day of cycle.
During the first 2 or 3 days of this phase, the granulosa and theca cells of the ruptured follicle
undergo rapid morphologic transformation to form the corpus luteum. Later in the phase, the
corpus luteum actively secretes and produces a large amount of progesterone; therefore, this phase
is named the progesterone phase. Progesterone stimulates the development of the uterus and
mammary glands for possible pregnancy and blocks the development of the ovarian follicles. If
the ovulated oocyte is not fertilized, the corpus luteum regresses into a nonfunctional corpus
albicans by the 14th day after ovulation, and the progesterone level declines. This action initiates
follicular development and a new ovarian cycle.
The ovarian cycle is controlled by the adenohypophysial hormones, FSH and LH. During
the follicular phase, FSH is the principal circulating gonadotropic hormone. It influences the
growth and maturation of ovarian follicles and stimulates them to secrete estrogens. Estrogens, in
turn, produce an inhibitory effect on FSH release. The circulating FSH level rises during the

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follicular phase twice, forming two peaks of FSH: on the 7th day and shortly before ovulation; the
level then decreases and remains low up to the end of the cycle.
The circulating LH level is very low during the follicular phase up to the 12th day and then
sharply increases by the 14th day (a brief surge of LH release). This increased level of LH induces
the ovulation and formation of the corpus luteum. The LH level then declines by the 16th day and
remains low up to the end of the cycle. Estrogens stimulate LH production by the
adenohypophysis. At midcycle, estrogen secretion reaches a peak that causes a brief surge of LH
release and ovulation. In cases of anovulatory cycle, estrogens are administrated to stimulate
ovulation.
During the luteal phase, the corpus luteum dominates in the ovary and secretes progesterone.
The functional activity of the corpus luteum is controlled by prolactin. The increasing progesterone
level has an inhibitory effect on further release of LH by the adenohypophysis. Progesterone
administration at midcycle may block the LH surge and inhibit ovulation, which is used for the
female hormonal contraception. For this purpose they may also employ a mixture of estrogens and
progesterone; this mixture inhibits the release of FSH and LH, hence, ovarian folliculogenesis.

Uterus
The human uterus is a pear-shaped organ located in the pelvis between the bladder and
rectum. Anatomically, the uterus is subdivided into the fundus, corpus, and the cervix. The uterine
functions are multiple: it houses the developing embryo and fetus during pregnancy; its
endometrium participates in the formation of the placenta; as the fetus enlarges, the uterus
increases in size, forming its thick muscular coat; its myometrium contracts at parturition, aiding
in the fetus and placenta expulsion.
The uterine wall is composed of three tunics. From the lumen outward they are the
endometrium, myometrium, and perimetrium. The endometrium is the uterine mucosa. The
myometrium is a thick muscular tunic. It is composed of three layers of smooth muscle cells: the
inner layer, stratum submucosum, the middle layer, stratum vasculosum containing numerous
blood vessels and lymphatics; and the outer layer, stratum supravasculosum. During pregnancy,
the myometrium thickens due to the hypertrophy of existing smooth muscle cells and the
development of new cells through the cambial muscle cell division and differentiation. There is
also an increase in the amount of connective tissue. At parturition, the hormone oxytocin released
by the neurohypophysis stimulates powerful contractions of the myometrium. After parturition,
the uterus becomes smaller: some muscle cells degenerate, but most return to their original size;
the collagen is enzymatically degraded.

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 The perimetrium is the uterine serosa consisting of the mesothelium and a thin layer of loose
connective tissue. The serosa covers the entire posterior surface of the uterus and only a part of
the anterior surface; the remaining part has only connective tissue or adventitia.
The endometrium undergoes the most marked cyclic changes each month to prepare the
uterus for implantation. These changes constitute the uterine cycle named the menstrual cycle,
because it is accompanied by uterine discharge called the menstruation or menses. If an embryo
implants, the cycle stops.
The endometrium is subdivided into the superficial functional layer and the deeper basal
layer. The functional layer is the thick part of the endometrium that degenerates, is sloughed, and
is then reestablished during the menstrual cycle. The basal layer is the thin deeper endometrial
layer that is retained during the cycle and serves for regeneration of the functional layer. The
boundary between the two layers is indistinct.
The endometrial epithelium is simple columnar, consisting of secretory and ciliated cells.
The underlying lamina propria – the endometrial stroma – is composed of loose connective tissue.
The stroma houses uterine glands; they are simple tubular slightly branched and produce a mucous
secretion. The glandular bottoms extend into the basal layer and contain stem cells for
reepithelialization of the endometrium and for reestablishment of the uterine glands after
menstruation.
The endometrium system of blood vessels is unique. It receives arteries from the
myometrium; some branches called the straight arteries enter the basal layer and supply it; the
main branches called the spiral (helical) arteries extend into the functional layer and supply it. The
spiral arteries give rise to highly coiled spiral arterioles; the latter, in turn, give rise to a rich
capillary bed. The straight arteries and the proximal part of the spiral arteries do not change during
the cycle. The distal portion of the spiral arteries and arterioles undergo degeneration and
regeneration with each menstrual cycle.
Uterine or menstrual cycle
The menstrual cycle is a sequence of morphological and functional changes of the
endometrium, primarily of its functional layer. The cycle normally repeats every 28 days and is
controlled by the ovarian hormones, estrogens and progesterone. The menstrual cycle has three
phases: the proliferative phase, secretory phase, and menstrual phase.
The proliferative phase occurs concurrently with follicular maturation and is influenced by
estrogens. The proliferative phase starts at the end of the menstrual phase, after regular
menstruation. At this time, the endometrium consists of the basal layer only: a thin band of
connective tissue, about 1mm thick, containing the basal portions of the uterine glands and the
lower portions of the spiral arteries; the functional layer having been sloughed off in the menstrual

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discharge. Under the influence of estrogens, stromal, endothelial, and epithelial cells proliferate
rapidly. Epithelial cells of the glandular bottoms migrate to cover the denuded endometrial surface
and reconstitute the glands. Stromal cells proliferate and manufacture collagen and the ground
substance; thus, the endometrium thickens (at the end of this phase it has reached a thickness of
about 3 mm). The uterine glands are straight and narrow, because they lack secretory activity. By
the end of the proliferative phase, the glands acquire a slightly wavy appearance and their cells
begin to store glycogen. Spiral arteries and arterioles are reestablished; they are only slightly coiled
and do not extend into the upper third of the endometrium. Stromal cells undergo the decidual
reaction: they store glycogen, enlarge, and become pale-staining decidual cells. Thus, the
functional layer of the endometrium is renewed. The proliferative phase continues for 2 to 3 days
after ovulation.
The secretory phase of the menstrual cycle occurs concurrently with the corpus luteum
functional activity and is influenced by progesterone. The secretory phase starts two or three days
after ovulation. This phase is characterized by the endometrial edema and the secretion of uterine
glands. The endometrium becomes edematous and may reach a thickness of 5 to 6 mm. The glands
enlarge and acquire a corkscrew appearance; they become wide and full of secretory products.
Their mucoid fluid is rich in glycogen required to support development, if implantation occurs,
and immunoglobulins to provide endometrial sterility. The spiral arteries become longer and more
coiled, so that they reach the superficial aspect of the functional layer.
The menstrual phase starts approximately two weeks after ovulation if fertilization does not
occur, when the corpus luteum begins to regress and the circulating level of progesterone rapidly
declines. Initially, the absence of progesterone causes contractions of the spiral arterioles, lasting
for several hours, which results in ischemia and subsequent necrosis of the functional layer. After
the extended period of vascular constriction, the spiral arterioles dilate, and their walls rupture,
leading to hemorrhage into the stroma. The necrotic functional layer is then shed in the menstrual
flow. Blood, uterine fluid, stromal cells, and epithelial cells mix to form the vaginal discharge.
The desquamation continues until only the basal layer remains. The basal layer is not sloughed
and does not become necrotic, since it is supplied by short straight vessels that do not undergo
vasoconstriction. The menstrual flow normally lasts about 5 days. Blood clotting is localy inhibited
during this period. Increased estrogen level stimulates the rapid cell proliferation in the basal layer
and stops menstrual discharge; the proliferative phase of the next cycle begins.
In cases of anovulation, the corpus luteum does not develop. In the absence of progesterone,
the endometrium does not enter the secretory phase and remains in the proliferative phase until
menstruation. Prolonged proliferation of the endometrium under the influence of estrogens may
result in cancerous diseases.

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 Uterine cervix
The cervix is a region of the uterus that projects into the vagina. The cervical canal has a
constricted opening or os at each end. The internal os communicates with the uterine cavity; the
external os communicates with the vagina.
The cervical mucosa, which is about 2 to 3 mm thick, differs from the rest of the uterine
endometrium. It lacks the spiral arteries and is not sloughed in menstruation. The cervical mucosa
is lined with a simple columnar epithelium, except a portion projecting into the vagina that is
covered with a stratified squamous nonkeratinized epithelium. There is an abrupt transition just
outside the external os between this squamous epithelium and simple columnar epithelium of the
cervical canal. Metaplastic changes in this transition zone constitute precancerous lesions of the
cervix.
The cervical glands are branched and produce their secretion during the whole cycle. During
each menstrual cycle, however, the cervical glands undergo important functional changes that are
related to the transport of spermatozoa in the cervical canal. The amount and properties of the
glandular mucus vary under the influence of the ovarian hormones. During the proliferative phase,
the secretion of the cervical glands is thin and watery. This type of secretion allows an easier
passage of sperm into the uterus. At midcycle, near the ovulation, under the influence of the
maximal estrogen level, there is a 10-fold increase in the amount of mucus, which provides more
favourable environment for sperm migration. During the luteal phase, the cervical secretion
becomes highly viscous and hinders the passage of sperm or microorganisms into the uterus. In
pregnancy, the character of the cervical secretion is similar to that in the luteal phase of the
menstrual cycle.
Compared with the uterine body, the cervical myometrium has more connective tissue with
numerous elastic fibers and less smooth muscle cells. It is very important for the possibility of
parturition: prior to parturition the cervix becomes dilated and softens due to the lysis of collagen
in response to the hormone relaxin. The softening of the cervix allows the cervical canal to be
dilated and facilitates the passage of a fetus during parturition.

Oviduct (fallopian tube)

The oviducts are paired tubes about 10 to 12 cm long that extend bilaterally from the uterus
toward the ovaries. They transmit the ovum from the ovary to the uterus; provide the necessary
environment for fertilization and for the initial development of an embryo up to the morula stage.
Anatomically, the tube can be divided into four segments: the infundibulum with the
fimbriae, the ampulla, the isthmus, and the intramural part.

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 The wall of the oviduct is composed of three tunics: the mucosa, muscularis externa, and
serosa. The mucosa lacks glands and exhibits thin longitudinal folds that project into the lumen of
the oviduct throughout its length. The mucosal simple columnar epithelium is composed of ciliated
and nonciliated secretory cells producing the oviduct fluid. The wave of the cilia is directed toward
the uterus, facilitating the transport of an embryo, but muscular contractions are equally important.
The epithelial cells undergo cyclic hypertrophy during the follicular phase and atrophy during the
luteal phase in response to changes in hormonal levels, particularly estrogens. The ciliated to
nonciliated cell ratio also changes during the cycle: estrogens stimulate ciliogenesis, while
progesterone increases the number of secretory cells.
The muscularis externa is composed of smooth muscle cells and organized into an inner
circular layer and an outer longitudinal layer. The serosa consists of mesothelium and a thin layer
of connective tissue.

Vagina
The vagina is a fibromuscular tube whose wall is composed of three tunics: the mucosa,
muscularis externa, and adventitia. The mucosa is lined with stratified squamous nonkeratinized
epithelium including superficial, intermediate, parabasal, and basal cell layers. Epithelial cells
synthesize and accumulate glycogen; they are continuously desquamated into the vaginal lumen
where the bacterial flora metabolizes glycogen into lactic acid to lower the pH of the vaginal fluid.
The acid pH of the vagina limits the growth of pathogenic organisms.
The vaginal epithelium exhibits cyclic changes in the menstrual cycle. During the follicular
phase and estrogenic stimulation, the vaginal epithelium thickens. The epithelial cells synthesize
and accumulate increased amounts of glycogen, especially by the moment of ovulation. Thus, the
pH of the vaginal fluid, which is normally low (pH≈4) becomes more acid near the midcycle. Later
in the cycle, as estrogen levels decline, glycogen is less abundant and the vaginal pH increases.
Epithelial cells are continuously desquamated, but during the proliferative phase, superficial cells
are desquamated, while during progesterone stimulation, epithelial cells from deeper layers
undergo desquamation.
Stained preparations of the vaginal epithelial cells (vaginal smears) are a routine clinical
method. Vaginal cytology closely correlates with the ovarian cycle. Characteristic features of
vaginal smears permit to assess the follicular activity during normal menstrual cycle or after
estrogenic and other therapy. Vaginal smears also provide important information for detecting
pathologic or malignant conditions.
The vaginal lamina propria is composed of loose connective tissue. Neutrophils and
lymphocytes are found in the lamina propria. Many of them migrate into the epithelium. The

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number of lymphocytes and neutrophils in the mucosa and vaginal lumen increases around the
time of menstrual flow.
The muscularis externa is composed of a thin inner circular and a thicker outer longitudinal
layers of smooth muscle. The external orifice is circumscribed by skeletal muscle fibers. The
adventitia consists of connective tissue that fixes the vagina to the surrounding structures.

Mammary glands
The mammary glands are characteristic of only mammals. Phylogenetically, they are
modified apocrine sweat glands and belong to the integumentary system, but their development
and functional state are directly related to the hormonal activity of the female reproductive system.
The mammary glands produce milk that nourishes the newborn and provides an immunological
defence for the neonate.
The mammary glands are compound alveolar glands: approximately 20 glands empty at the
apex of each nipple. The mammary gland has 15 to 20 lobes separated by connective tissue and
subdivided into numerous lobules. Numerous adipose cells are present in the connective tissue.
In embryogenesis, the mammary glands arise from the epidermal thickenings called the milk
lines, in both sexes. During embryogenesis the nipple, areola, and the rudimentary duct system
develop. The duct system consists of the lactiferous ducts that open onto the nipple and the
lactiferous sinuses, i.e., dilated portions of each duct. The male and female mammary glands are
identical until puberty. Then, in the male, the glands remain rudimentary; in the female, the
mammary glands undergo further development under hormonal influence.
At puberty, influenced by estrogens, the female mammary glands enlarge due to further
formation of the duct system, mainly the terminal ductules, and the development of connective
and adipose tissues in their stroma. But the secretory portions do not develop, and prepuberal
mammary glands lack alveoli that appear only during pregnancy. That is why, the size of the
prepuberal and nonlactating mammary glands cannot be evidence of their future secretory
capacity.
During pregnancy, the mammary glands undergo dramatic proliferation and development
under the hormonal influence of the corpus luteum and the placenta. The mammary glands exhibit
a number of changes in preparation for lactation: the ducts branch, and alveoli develop due to cell
proliferation in the terminal ductules. In the later stages of pregnancy, alveolar development
becomes more prominent; the secretory cells enlarge and accumulate the secretory product. The
changes in the glandular tissue are accompanied by decreases in the amount of connective and
adipose tissues. The corpus luteum and placenta continuously produce estrogens and progesterone.

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Estrogens stimulate the proliferation of the lactiferous duct component, and progesterone
stimulates the growth of alveoli.
The alveoli are composed of secretory alveolar cells and myoepithelial cells. The alveolar
cells become columnar; they have numerous apical microvilli, abundant sER and rER, a well-
developed Golgi apparatus, numerous mitochondria, lysosomes, and many vesicles. These cells
possess abundant lipid and milk protein (casein) droplets. The protein component of the milk is
released from the cell by the merocrine mode of secretion. The lipid component of the milk forms
large droplets that pass to the apical cell region, are invested with envelope of the plasma
membrane and a thin layer of cytoplasm, and are then released from the cell by the apocrine mode
of secretion.
The myoepithelial cells lie between the secretory cells and their basal lamina. These cells,
arranged in a basket-like network, are present in the secretory portions of the gland but are more
apparent in the larger ducts. They contain numerous contractile microfilaments that help to eject
milk from alveoli and ducts.
Human milk contains proteins (casein), lipids, lactose, electrolytes, vitamins, and water; it
also contains nonspecific antibacterial substances such as lactoperoxidase and lysozyme. The milk
is rich in immunoglobulins that protect the infant from the enteric infections that can cause diarrhea
and dehydration. Immunoglobulins are produced by the plasma cells infiltrating the stroma of the
mammary glands and are secreted across the glandular cells into the alveolar lumen.
Lactation is under the neurohormonal control of the adenohypophysis and hypothalamus.
The secretory activity of the alveolar cells is regulated by the hormone prolactin. The act of
suckling initiates sensory impulses from the nipple to the hypothalamus. The impulses inhibit the
release of prolactin-inhibiting factor, and prolactin is then released from the adenohypophysis. The
sensory impulses also cause the release of oxytocin in the neurohypophysis. The oxytocin
stimulates the myoepithelial cells, causing them to contract and eject the milk from alveoli and
ducts. In the absence of suckling, secretion of milk ceases, and the mammary glands begin to
regress.
Nursing women exhibit lactational amenorrhea (lack of menstruation during lactation) and
infertility. This is due to the high level of serum prolactin, which suppresses the LH and FSH
secretion.
The mammary glands undergo involution after menopause. Whithout ovarian hormone
stimulation, the secretory cells degenerate and are replaced by adipose and connective tissues.

CONTROL PROBLEMS

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 1. There are three slides of the human ovaries. The first slide shows primordial, primary,
and atretic follicles. The ovary in the second slide contains secondary and tertiary follicles. The
third slide shows fewer growing follicles, numerous atretic follicles, and well-developed
connective tissue. What age periods are characterized by such ovary morphology?
2. The measurement of the blood levels of gonadotropins during the cycle revealed
invariably high FSH and low LH concentrations. What changes in the ovarian cycle take place in
such a case? What morphology is characteristic of the ovaries? What ovarian hormone is
produced?
3. The histological examination of the endometrium showed numerous enlarged, highly
coiled glands filled with a mucous secretion. What phase of the menstrual cycle does the
endometrium morphology correspond to? What ovarian structure is characteristic of this phase?
What female sex hormone is predominantly produced during this phase?
4. The ovary contains follicles at different stages of development, atretic follicles, and atretic
bodies on the 22nd day of the cycle. Is the ovary morphology normal? Is pregnancy possible?
5. Miscarriage occurred in the third month of gestation. What functions of the ovarian
structures were impaired inducing the termination of pregnancy?
6. The release of milk in a breast-feeding woman decreased whereas the secretion of milk
was active. What hormone is responsible for this phenomenon?

CONTROL TESTS

Directions: each of the following statements contains five suggested completions. Choose
the one that is best in each case.
1. Each of the following statements concerning the follicular phase of the ovarian cycle is
true, EXCEPT: A – lasts from the 1st to the 14th day of a cycle; B – actively secreting corpus
luteum is present in the ovary; C – follicles at various stages of development, atretic follicles, and
the corpus luteum in involution up to the corpus albicans are present in the ovary; D – the ovaries
primarily secrete estrogens; E – estrogen blood level rises and reaches the peak by ovulation.
2. Each of the following statements concerning the luteal phase of the ovarian cycle is true,
EXCEPT: A – begins after ovulation and lasts up to the 28th day of a cycle; B – at the beginning
of this phase, the corpus luteum is formed; C – the corpus luteum produces progesterone; D –
progesterone stimulates the ovarian follicle development; E – at the end of this phase, the corpus
luteum begins to regress, and progesterone level declines.
3. Each of the following statements concerning the hormonal regulation of the ovarian cycle
is true, EXCEPT: A – FSH blood level possesses two peaks: on the 7th day and on the 14th day;

274
B – LH blood level sharply increases by the 14th day; C – progesterone inhibits LH production;
D – estrogens stimulate LH secretion and inhibit FSH secretion; E – prolactin (LTH) does not take
part in the ovarian cycle regulation.
4. Each of the following statements concerning the endometrium is true, EXCEPT: A – its
epithelium is simple columnar, consisting of secretory and ciliated cells; B – its glands are simple
slightly branched tubular; C – secretion of its glands is controlled by estrogens; D – its glandular
bottoms contain stem cells for re-epithelialization; E – the endometrial stroma consists of loose
connective tissue.
5. Each of the following statements concerning the proliferative phase of the menstrual cycle
is true, EXCEPT: A – is regulated by progesterone; B – epithelial cells in glandular bottoms
proliferate and cover the endometrial surface; C – the endometrium thickens due to proliferation
of stromal cells and matrix secretion; D – uterine glands are restored; E – the helical arterioles are
re-established.
6. Each of the following statements concerning the secretory phase of the menstrual cycle is
true, EXCEPT: A – starts in 2 or 3 days after ovulation; B – the endometrium thickens by edema;
C – the uterine glands begin to secrete; D – the helical arterioles become more coiled; E – is
controlled by estrogens.
7. Each of the following statements concerning the menstrual phase of the uterine cycle is
true, EXCEPT: A – starts when the corpus luteum begins to regress, and progesterone level
declines; B – initially, contractions of the helical arteriole wall occur and last several hours; C –
arterial contractions result in ischemia and necrosis of the functional layer; D – subsequent arterial
dilation leads to vessel rupture, bleeding, and desquamation of the necrotic functional layer; E –
the rising level of progesterone stops menstrual discharge.
8. Each of the following statements concerning the oviduct epithelium is true, EXCEPT: A
– its secretory cells produce mucus providing embryo implantation; B – its secretory cells produce
mucus providing the initial embryo development till the morula stage; C – its secretory cells create
the environment for fertilization; D – its ciliated cells facilitate the transport of gametes and an
embryo; E – its cilium waves are directed towards the uterus;
9. Each of the following statements concerning the vaginal epithelium is true, EXCEPT: A
– is stratified squamous; B – undergoes keratinization during the cycle; C – its cells synthesize
and accumulate glycogen; D – its cells are continuously desquamated into the vaginal lumen where
bacteria metabolise glycogen into lactic acid; E – vaginal acid pH limits the growth of pathogenic
organisms.
10. Each of the following statements concerning the mammary gland development is true,
EXCEPT: A – the nipple, areola, and rudimentary duct system develop in embryogenesis; B – at

275
puberty, the glands increase in size due to duct formation and connective tissue development; C –
secretory portions develop at puberty under estrogen stimulation; D – progesterone stimulates
alveolus growth in pregnancy; E – alveoli begin to secrete milk after delivery.
11. Each of the following statements concerning the lactation regulation is true, EXCEPT:
A – the act of suckling initiates sensory impulses from the nipple to the hypothalamus; B –
prolactin is released from the adenohypophysis in response to the impulses; C – sensory impulses
cause oxytocin release in the neurohypophysis; D – oxytocin stimulates myoepithelial cells to
contract; E – prolactin inhibits milk secretion in the alveolar cells.

Directions: one or more of the given statements or completions is/are correct. Choose the
answer: A – if only 1,2, and 3 are correct; B – if only 1 and 3 are correct; C – if only 2 and 4 are
correct; D – if only 4 is correct; E – if all are correct.
12. The following statements regarding the ovarian cycle are true: (1) includes the follicular
phase and the luteal phase (2) ovulation occurs between two phases at midcycle (3) is controlled
by the adenohypophysial hormones (4) averages about 28 days in length
13. The following statements regarding the endometrial functional layer are true: (1) is
sloughed and then re-established during the cycle (2) includes the covering epithelium and the
lamina propria (3) is supplied by the helical arterioles (4) includes the bottoms of uterine glands
14. The following statements regarding the endometrial basal layer are true: (1) is retained
during the cycle and serves for regeneration of the functional layer (2) is supplied by the helical
arterioles (3) includes the bottoms of uterine glands (4) lacks stem and undifferentiated cells for
re-epithelialization
15. The following statements regarding the menstrual cycle are true: (1) is accompanied by
the uterine discharge called menstruation (menses) (2) is controlled by the ovarian hormones:
estrogens and progesterone (3) consists of three phases (4) if embryo implants, the cycle stops
16. The following statements regarding the uterine gland mucoid secretion are true: (1) is
rich in nutrients, particularly glycogen (2) is produced under FSH control (3) its immunoglobulins
provide endometrial sterility (4) is secreted during the whole cycle
17. The following statements regarding the uterine cervix are true: (1) its mucosa lacks the
helical arterioles and is not sloughed during the cycle (2) its branched glands secrete the whole
cycle (3) the volume and character of secreted mucus change during the cycle (4) its myometrium
contains more connective tissue and less smooth muscle cells
18. The following statements regarding the secretion of uterine cervix glands are true: (1) is
watery under estrogen influence that allows easier sperm passage (2) increases in volume at
midcycle under estrogen influence (3) is highly viscous under progesterone influence that hinders

276
the passage of sperms or microorganisms (4) its character in pregnancy is the same as that in the
luteal phase
19. The following statements regarding the oviduct mucosa are true: (1) lacks the glands (2)
forms folds that fill the oviduct lumen (3) its simple epithelium consists of ciliated and secretory
cells (4) is not sensitive to the ovarian hormones
20. The following statements regarding the vaginal epithelium cyclic changes are true: (1)
epithelium thickens and its superficial cells are desquamated under estrogen control (2) estrogens
inhibit the synthesis and accumulation of glycogen in the epithelial cells (3) cells of intermediate
and parabasal layers are desquamated under progesterone control (4) progesterone stimulates the
synthesis and accumulation of glycogen in the epithelial cells
21. The following statements regarding the mammary glands are true: (1) are the features of
only mammals (2) phylogenetically, are modified apocrine sweat glands and belong to the skin
system (3) are compound branched alveolar glands (4) produce milk that nourishes newborns and
provide their immunological defence from enteric infections
22. The following statements regarding the mammary gland alveoli are true: (1) consist of
secretory and myoepithelial cells (2) secretory cells are rich in lipid and protein droplets (3)
myoepithelial cells are arranged in basket-like network between secretory cells and their basal
lamina (4) myoepithelial cell contractions help to eject milk from the acini
23. The following statements regarding the secretion mode of the mammary gland alveolar
cells are true: (1) the protein component of milk is released via the apocrine mode (2) the lipid
component of milk is released via the apocrine mode (3) the lipid component of milk is released
via the merocrine mode (4) the protein component of milk is released via the merocrine mode

FIGURES

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 Fig. 24.1. Ovarian–menstrual cycle and its regulation
A – dynamics of gonadotrophin levels: FSH – follicle-stimulating hormone; LH – luteinizing
hormone; LTH – luteotrophic hormone (prolactin); B – ovarian cycle; C – dynamics of female sex
hormone levels; D – menstrual cycle.

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 26. HUMAN EMBRYOLOGY: INITIAL STAGES OF EMBRYONIC
DEVELOPMENT

Ontogenesis, the process of individual development, includes the prenatal (until birth) and
the postnatal (after birth) periods. Progenesis, the process of gamete formation, precedes
ontogenesis. The prenatal period or embryogenesis begins when an ovum is fertilized by a sperm
forming a zygote and lasts 280 days (40 weeks or 10 lunar months). Embryogenesis is divided into
three periods: the initial period (the first week of development), the embryonic period (from the
2nd week until the 8 to 9th weeks), and the fetal period (from the 8 to 9th weeks up to birth).
During the first two months the developing individual is called an embryo. From the third month
until birth it is called a fetus.
The embryonic development includes the following stages: fertilization and zygote
formation, cleavage and blastocyst formation, gastrulation and trilaminar embryo formation,
differentiation of germ layers and axial organ formation, and the last period (the longest and most
complex) of histogenesis and organogenesis. These processes are accompanied by the
development of the provisory organs and by the establishment of close relations between the
developing individual and the maternal organism, namely, implantation and placentation.

The initial period: the first week of development

The initial period includes following events: fertilization, cleavage, and biginning of
implantation.
Fertilization
Fertilization is the sequence of events, by which a sperm fuses with an ovum, forming a
unicellular organism called a zygote.
The mature sperm is a microscopic, free-swimming, and actively motile cell consisting of a
head and a tail (flagellum). The head, forming most of the bulk of the sperm, includes the nucleus
whose chromatin is greatly condensed. The anterior two thirds of the nucleus are covered by the
acrosome, a membrane-limited organelle containing the enzymes that facilitate sperm penetration
of the corona radiata and zona pellucida during fertilization. The sperm tail is subdivided into the
connecting piece, the middle piece, the principal piece, and the end piece. The short connecting
piece contains a centriole and the origin of the coarse fibers. The middle piece contains the
mitochondria helically wrapped around the coarse fibers and the axonemal complex. The principal
piece contains the fibrous sheath external to the coarse fibers and the axonemal complex. The end
piece contains only the axonemal complex. The tail provides the sperm motility, which assists in
its transport to the site of fertilization. The mitochondria generate the energy for sperm motility.

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With respect to the sex chromosome constitution, there are two kinds of normal spermatozoon: 22
+ X and 22 + Y.
The mature ovum is the secondary oocyte arrested at the metaphase of the second meiotic
division (female meiosis may be completed only after fertilization). The secondary oocyte released
at ovulation is surrounded by the zona pellucida and a layer of follicular cells called the corona
radiata. Compared with ordinary cells and, notably, the sperm the ovum is truly large. It has an
abundance of cytoplasm containing organelles, yolk granules, RNA, morphogenetic factors, and
cortical granules. The ovum nucleus is haploid (22 + X), euchromatic, and metabolically active.
The ovum is immotile and transported down the oviduct passively.
The usual site of fertilization is the oviduct ampulla, the longest and the widest portion of
the organ. The fertilization process requires about 24 h.
At ovulation, the secondary oocyte enters the infundibulum of the oviduct and then passes
into the tubular ampulla largely as a result of the beating action of cilia on some tubal epithelial
cells, and by muscular contractions of the tubal wall. It takes the oocyte about 25 minutes to reach
the site of fertilization. Studies indicate that the ovum is viable during 24 hours after ovulation and
is usually fertilized within 12 hours after expulsion.
The sperms pass by movements of their tails through the cervical canal; sperm passage
through the uterus and uterine tubes is assisted by muscular contractions of the organs. The
prostaglandins of the seminal plasma stimulate uterine motility. Besides, spermatozoa have ability
to move towards the flow of fluid (mucus in the oviducts and uterus) called rerotaxis. The ovum
produces chemical substances that attract the sperms; the sperm movement is directed by
chemotaxis too.
It is not known how long it takes sperms to reach the fertilization site, but the time of
transport is probably short. Only 300 to 500 sperms from 200 to 500 million sperms deposited in
the vagina reach the fertilization site. The reduction of sperms in number during the passage
through the female reproductive tract is mainly the result of selecting (eliminating) abnormal and
poorly motile sperms by the cervical mucus.
Before a mature motile sperm can penetrate the oocyte surroundings, it must undergo
capacitation. This process consists of enzymatic changes that result in the removal of the thick
glycoprotein coat from the plasma membrane over the acrosome. No morphological changes are
known to occur during the capacitation. Sperms are capacitated by substances in secretions of the
female genital tract. It takes about 7 hours to capacitate.
The acrosome reaction occurs after sperm capacitation. This reaction consists of structural
changes. The outer membrane of the acrosome fuses at many places with the overlying sperm head
membrane; the fused membranes then rupture, producing multiple perforations, through which the

280
enzymes leave the acrosome. The acrosomal enzymes facilitate the sperm passage through the
oocyte envelopes. Hyaluronidase enables the sperm to penetrate the corona radiata. Acrosin
appears to cause lysis of the zona pellucida, forming a pathway for the first sperm.
In penetration, the sperm head attaches itself to the surface of the secondary oocyte. The
plasma membranes of the oocyte and the sperm fuse and then break down at the point of contact.
The sperm nucleus and the sperm centriole enter the oocyte cytoplasm, leaving the sperm plasma
membrane and the sperm tail outside attached to the oocyte plasmalemma when they rapidly
degenerate.
Once the first sperm passes through the zona pellucida, the zona (cortical) reaction occurs.
It is produced by cortical granules containing lysosomal enzymes. At penetration, the cortical
granules release the enzymes that deprive the zona pellucida of receptors for the sperm attachment,
converting it to impermeable to other sperms and preventing polyspermy. Alterations in the
chemical characteristics of the zona pellucida are associated with the zona reaction, but no
morphological changes are visible. There is some experimental evidence that aged oocytes do not
open cortical granules. As a result, the zona reaction does not take place, and multiple penetrations
of sperms occur. Polyspermy is unlikely to produce a viable embryo.
After penetration, the secondary oocyte completes the second meiotic division and separates
the second polar body. The ovum nucleus is known as the female pronucleus. The sperm nucleus
enlarges to form the male pronucleus. The human zygote looks like a synkaryon. The male and
female pronuclei approach each other, come in contact, and lose their nuclear membranes. Then
the maternal and paternal chromosomes intermingle at the metaphase of the first mitotic division
of the zygote. Fertilization is completed.
The biological significance of fertilization consists in the restoration of the diploid number:
the fusion of two haploid germ cells produces a diploid cell with 46 chromosomes. Because half
of the chromosomes come from the mother and half from the father, the zygote contains a new
combination of chromosomes and genetic material that is different from those of the parents.
Moreover, the embryo sex is determined at fertilization by the kind of sperm that fertilizes the
ovum. Fertilization by an X-bearing sperm produces an XX zygote, which normally develops into
a female. Fertilization by a Y-bearing sperm produces an XY zygote, which normally develops
into a male.
Fertilization initiates a series of rapid mitotic cell divisions called the cleavage. Cleavage of
the secondary oocyte may occur without fertilization. This process is called parthenogenesis.
There is evidence that the human oocyte may start to undergo parthenogenetic cleavage, but this
does not result in organized development.

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 Cleavage
Cleavage is a process of successive rapid mitotic divisions without growth of the daughter
cells called blastomeres. As G1 phase is not present in these mitotic cycles, the volume of cell
cytoplasm does not increase; the blastomeres become progressively smaller until they acquire the
size of most of the somatic body cells. The normal nucleus to cytoplasm volume ratio is restored.
That is why this stage of development is termed segmentation or cleavage, but not division.
Cleavage begins with the first mitotic division of the zygote and ends with the blastocyst
formation. It proceeds in the oviduct during the first 3 or 4 days when the morula – a solid ball of
8 to 16 blastomeres that looks like a mulberry – is formed. The morula enters the uterus as it is
forming. The process then continues in the uterus for about 3 days when the blastula forms.
Human cleavage is holoblastic (total); it means that all the zygote cytoplasm is cleft. Human
cleavage is unequal; it means that blastomeres are different in size: there are small and large
blastomeres. Human cleavage is asynchronous; it means that blastomeres divide at different time;
blastomeres may be either even or odd in number.
Blastomeres do not leave the cell cycle; they never begin to differentiate. They do not use
their genome and synthesize proteins on maternal RNA. Through the first mitotic divisions
blastomeres retain totipotentiality. Occasionally, two or more blastomeres separate, and each
develops into an embryo. Thus, identical twins appear.
Initially, the embryo is under the control of maternal informational macromolecules that
have accumulated in the ovum cytoplasm during oogenesis. Later, development depends on the
activation of the embryonic genome, which encodes various growth factors and other
macromolecules required for normal progression to the blastocyst stage.
In blastocyst development, the uterine fluid passes in the morula, forming a cavity. As fluid
increases, the cavity separates blastomeres into two parts: an outer cell layer – the trophoblast,
from which the chorion and a part of the placenta develop; and an inner cell mass – the
embryoblast, from which the embryo proper arises. The human blastula looks like a cyst and is
called the blastocyst: the trophoblast forms its wall; the embryoblast is attached to the inner side
of the trophoblast and projects into the cavity. The blastocyst surrounded by the zona pellucida
lies free in the uterine secretions before implantation. The zona pellucida then degenerates and
disappears, which allows the attachment of the blastocyst to the endometrium at the beginning of
implantation. The zona pellucida prevents the blastocyst implantation at an abnormal site.
Occasionally, the embryoblast is duplicated and each develops into an embryo. This
doubling results in twinning too.

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 Implantation
It is a process of the blastocyst invasion into the endometrium. It begins on the 5th or 6th
day after fertilization. Invasion proper (nidation) lasts about 40 hours; implantation completely
ends during the second week of development.
Once the zona pellucida disappears (hatching), the trophoblast attaches itself to the uterine
epithelium. The trophoblast starts to proliferate and differentiate, forming two layers: an inner
layer – the cytotrophoblast, which maintains the cellular structure, and an outer layer – the
symplastotrophoblast (syncytiotrophoblast), consisting of a multinucleated cytoplasm mass
without cell boundaries. The cytotrophoblast is mitotically active and forms new cells that migrate
to the syncytiotrophoblast where they fuse to form a symplast.
The symplastotrophoblast never demonstrates mitoses, but displays high metabolic activity:
it produces and releases enzymes facilitating the blastocyst invasion. The finger-like processes of
symplastotrophoblast grow into the endometrium and invade the uterine mucosa: its epithelium,
stroma, capillaries, and glands. The blastocyst goes deeper and deeper in the mucosa until the
whole of it has buried itself within the thickness of the endometrium lamina propria. It is called
the interstitial type of implantation.
The blastocyst invasion stimulates the decidual reaction of the uterine mucosa: the
endometrial stromal cells (either fibroblasts or macrophages) undergo transformation into large
pale cells rich in glycogen, the so-called decidual cells. They form the cellular layer restricting the
blastocyst invasion.
By the end of the first week, the blastocyst is implanted in the superficial layer of the
endometrium; by the 10th day, the embryo is completely embedded in the endometrium. For about
two days, the defect in the endometrium (implantation crater) is closed by a closing plug consisting
of a blood clot and cellular debris. By the 12th day, regenerated uterine epithelium covers the
endometrial defect, completing implantation.
Implantation window is the period when the uterus is receptive for the blastocyst invasion.
The human implantation window begins on the 6th day and is completed by the 10th day after
ovulation.
Implantation site is an endometrial region where the blastocyst invasion occurs. The human
blastocyst usually implants in the midportion of the uterine body, more frequently on the posterior
than on the anterior wall. Implantation in the lower uterine segment near the internal os of the
cervical canal may cause the placenta previa and severe bleeding. Implantation outside the uterine
cavity is called ectopic and includes tubular, cervical, and others types. The decidual reaction never
develops in the uterine cervix or in the oviduct; the blastocyst invasion in these organs results in
severe bleeding and is dangerous for the woman’s life.

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 The embryonic period: the second week of development
The second week of development includes following events: the first stage of gastrulation,
formation of some provisory organs (amnion, yolk sac, and chorion), and the completion of
implantation described above.
Gastrulation: the first stage
Gastrulation is a process of highly integrated cell movements whereby the germ layers,
namely, the ectoderm, endoderm, and mesoderm, are formed. The gastrulation events resulting in
the formation of the germ layers are as follows: extensive cell rearrangement and segregation,
mitotic cell divisions, and cell differentiation. In mammalian species, gastrulation is a two-stage
process, and all morphological changes take place only in the embryoblast.
The first stage of gastrulation occurs on the 7th day of development. Only the inner cell mass
of the blastocyst, namely the embryoblast, participates in gastrulation; the trophoblast does not
take part in this process. The embryoblast is transformed into a bilaminar embryonic disk by the
mechanism called delamination. The upper layer of the embryonic disk called the epiblast consists
of high columnar cells; the lower layer called the hypoblast consists of cuboidal cells. The epiblast
subsequently gives rise to all three germ layers of the embryo (ectoderm, mesoderm, and
endoderm). The hypoblast does not take part in the formation of the embryo body proper and is
later displaced to extraembryonic regions.
Formation of the provisory organs
The distinctive feature of the human embryogenesis is the early development of the provi-
sory organs: the chorion, the amnion, and the yolk sac.
Concurrently with the first stage of gastrulation, two small vesicles appear. These are the
amniotic vesicle and the yolk sac. The vesicles are associated with the embryonic disk: the epiblast
forms the floor of the amniotic cavity, whereas the hypoblast represents the roof of the yolk sac.
The cells forming the amniotic wall are called the amnioblasts or amniotic epithelium. The wall
of the yolk sac is called the yolk extraembryonic endoderm. The loosely arranged cells called the
extraembryonic mesoderm migrate from the embryonic disk and surround the amnion and the yolk
sac, stabilizing their walls.
The trophoblast grows, forming processes called the primary chorionic villi that extend
toward the endometrium, penetrating it. Only the trophoblast makes up the primary villi: the
symplastotrophoblast lies superficially, and the cytotrophoblastic cells underlie it. When the
extraembryonic mesoderm grows into the primary villi, they become the secondary chorionic villi.
Each secondary villus acquires a mesodermal core enclosed by the cytotrophoblast and the
symplastotrophoblast along the surface. The latter produces the enzymes that lyse and erode the

284
endometrium, forming the cavities called the lacunae. Owing to the high enzymatic activity of the
symplastotrophoblast, the trophoblastic lacunar network is established. The lacunae are filled with
maternal blood from ruptured endometrial vessels. The chorionic villi contact with maternal blood,
providing the mother–embryo exchange.
The chorion forms the chorionic sac with the chorionic cavity (extraembryonic coelom)
within it. The embryo, its amnion, and the yolk sac are suspended in this cavity by the connecting
stalk from the extraembryonic mesoderm. The connecting stalk attaches the complex of the
embryonic disk with its vesicles to the inner surface of the chorionic sac.
The second week of the embryogenesis is often called as “the period of twos", because two
embryonic layers – the epiblast and hypoblast – make up the embryonic disk; two vesicles – the
amnion and yolk sac – develop; and two layers of the trophoblast – the cytotrophoblast and
symplastotrophoblast – differentiate.

The embryonic period: the third week of development

The third week of development includes following events: the second stage of gastrulation,
differentiation of germ layers and axial organ formation, primitive cardiovascular system
emergence, beginning of folding, and further development of provisory organs.
Gastrulation: the second stage
Human gastrulation proceeds in two stages: during the first stage two germ layers – the
epiblast and hypoblast – are formed; during the second stage three germ layers – the ectoderm,
endoderm, and mesoderm – develop. The first stage of gastrulation occurs on the 7th day, the
second stage occurs at the 14th or15th day of embryogenesis.
In the second stage of gastrulation, the morphological changes take place only in the epiblast.
The hypoblast does not take part in the embryo formation. The primitive streak, the key structure
of the gastrulation second stage, appears in the epiblast. Epiblastic cells from the cranial end of
the embryonic disk proliferate and migrate along the disk margins to its caudal end. Cellular
currents converge at the disk caudal end, turn towards the midline, and elongate back to the disk
cranial end. The anterior portion of the primitive streak thickens to form the primitive knot
(Hensen’s nodule). Concurrently, a narrow primitive groove develops in the primitive streak,
which is continuous with a depression in the primitive knot known as the primitive pit.
The primitive streak is a source of the embryonic mesoderm and embryonic endoderm:
epiblastic cells move medially towards the primitive streak and enter the primitive groove. They
lose their attachment to the rest of the epiblastic cells and migrate inwardly between the epiblast
and hypoblast. The early-migrating cells are those that replace hypoblastic cells to become the
endoderm. The later-migrating cells begin to spread laterally, ventrally, and cranially to form the

285
mesoderm. As soon as the primitive streak gives rise to the mesoderm and endoderm, the cells that
remain in the epiblast are referred to as the embryonic ectoderm. Thus, the gastrulation is
completed: the trilaminar embryo is formed.
In rare cases, the primitive streak undergos duplication that may give rise to identical
conjoint twins.
Formation of the axial organs
The complex of axial organs includes the following structures: the notochord, the neural
tube, and the mesodermal somites.
The notochord is the first to appear. The primitive pit extends into the primitive knot to form
the notochordal canal. The cells migrating through this canal give rise to the notochord. The
notochordal process looks like a cellular rod extending cranially from the primitive knot between
the ectoderm and endoderm. The wing-like mesoderm is on each side of the notochordal process.
The notochord forms a midline axis of the embryo. The notochord induces the overlying ectoderm
to form the neural plate, i.e., the embryonic induction of neurulation.
Neurulation is a process of the neural tube formation. It includes a sequence of events, by
which the neural plate, the neural groove with neural folds, and the neural tube successively
develop. As the notochord develops, the embryonic ectoderm over it, the so-called neuroectoderm,
thickens to form the neural plate. The developing notochord with the adjacent mesoderm induces
this process. On about the 18th day, the neural plate invaginates along the central axis to form the
neural groove with neural folds on each side of it. By the end of the third week, the neural folds
begin to move and close up, converting the neural plate to the neural tube. The neural tube is
separated from the surface ectoderm.
As the neural folds close, some ectodermal cells lying along and over each fold are not
incorporated in the neural tube. They look like a cell mass between the neural tube and the covering
ectoderm constituting the neural crest.
The mesoderm on each side of the appeared notochord and neural tube thickens to form the
longitudinal columns of the paraxial mesoderm. Each paraxial mesoderm is continuous laterally
with the intermediate mesoderm, which gradually thins laterally to form the lateral mesoderm. The
paraxial mesoderm begins to divide into paired cuboidal bodies called somites. This series of
mesodermal tissue blocks is located on each side of the developing neural tube.
Within the lateral mesoderm the space called the coelom appears dividing the lateral
mesoderm into two layers: the parietal layer, the somatopleure, and the visceral one, the
splanchnopleure. Some mesodermal cells migrate and are disposed among the axial organs; they
form a loose origin called the mesenchyme.

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 Differentiation of the axial organs and beginning of histo- and organogenesis.
Histogenesis is tissue development; organogenesis is organ development. Tissues and organs
arise from differentiation of the germ layers and the axial organs.
Differentiation is the development of specialized cell types from stem cells, during which
changes in the cell structure and biochemistry occur for the cell to perform distinctive functions.
The process of cell determination precedes cell differentiation.
Determination is the process of a cell’s particular fate choice, when the cell differentiation
pathway is chosen.
The differential genome activity underlies determination. Each cell contains a complete
genome established in the zygote during fertilization; the DNAs of all cells are identical. As cells
develop, the genetic material does not change but some genes are expressed (activated) and others
repressed (inactivated). Only a small percentage of the genome is expressed in each cell, so that a
portion of RNA synthesized by this cell type is specific. Because determination occurs step-wise,
the cells can exist in different states of differentiation and possess different potentialities.
Potentiality is the capability of a cell for differentiation that has not yet been realized.
According to their potentialities, cells may be distributed in some populations. Stem cells are
pluripotential; they usually give rise to several cell types. Their immature offspring is
multipotential and oligopotential; their potentialities become gradually less. Mature cells are
unipotential; they have chosen the only way of differentiation. The zygote is a totipotential cell,
because it serves as the progenitor for all the kinds of body cells (“single produces whole”).
The notochord does not give rise to any tissues. It is not the embryonic origin of the skeleton
(the skeleton arises from the sclerotome); it is the structure, around which the vertebral column
forms. The notochord degenerates and disappears where it becomes surrounded by the vertebral
bodies, but persists as the nucleus pulposus of the intervertebral disks.
The surface ectoderm differentiates into the skin epidermis, sweat and sebaceous glands,
hair, nails, tooth enamel, salivary glands, and mammary glands.
The neural tube is the primordium of the central nervous system consisting of the brain and
the spinal cord.
The neural crest gives rise to the spinal ganglia and the ganglia of the autonomic nervous
system, as well as Schwann cells, the meningeal covering of the brain and the spinal cord (the pia
mater and the arachnoid), the skin pigment cells, and the adrenal gland medulla.
Mesodermal somites are subdivided into three regions: the myotome that gives rise to
skeletal muscles; the dermotome that gives rise to the skin dermis; and the sclerotome, from which
bones and cartilages arise. The intermediate mesoderm, the so-called somite cord, differentiates
into nephrogonadotome that gives rise to the kidney and gonads.

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 The coelom is divided into the following body cavities: the pericardial, pleural, and
peritoneal ones. The cells of the parietal and visceral layers give rise to the mesothelium lining
these cavities. The splanchnopleure also takes part in the development of the myocardium,
epicardium, and the adrenal gland cortex.
The mesenchyme gives rise to the blood, all types of connective tissue, smooth muscle cells,
blood vessels, microglial cells, and the endocardium.
The embryonic endoderm develops into the epithelium of the gastrointestinal tract, the liver,
the pancreas, the gallbladder, and the epithelial parts of the lung.

CONTROL PROBLEMS

1. In the process of spermatogenesis, acrosome formation is impaired. What sperm function

is lost?
2. A student contends that the sperm acrosome is a derivative of the Golgi apparatus; another
student considers that the acrosome is a modified lysosome; the third student thinks that the
acrosome contains hydrolytic enzymes. Assess the opinions of these students.
3. A large-sized cell with two pronuclei surrounded by envelopes is found in the oviduct.
Name the cell. What embryogenesis stage does the cell correspond to?
4. The microphotograph shows an embryo in the uterus. The embryo looks like a vesicle
and consists of the embryoblast and the trophoblast. What embryogenesis stage does the embryo
correspond to?
5. The case of birth of identical twins was explained by the ovum having been fertilized by
two spermatozoa. Comment on the explanation.
6. A blastomere isolated from the murine embryo after the first or the second cleavage
divisions is known to develop into a normal animal. Any attempt to grow a murine embryo from
the blastula blastomeres is unsuccessful. Explain the experimental results.
7. A student contends that the human embryo endoderm arises from the epiblast; another
student considers that the endoderm develops from the hypoblast. Who of them is right?
8. A student answers that the mesenchyme appears during gastrulation and gives rise to
blood vessels. Correct and enlarge on the student’s answer.
9. The histological examination of an embryo revealed the body folds and the amniotic
folds. Is it possible to conclude that this is a human embryo?

CONTROL TESTS

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 Directions: each of the following statements contains five suggested completions. Choose
the one that is best in each case.
1. The results of fertilization are as follows, EXCEPT: A – sex determination; B – restoration
of the diploid number; C – blastocyst formation; D – cleavage initiation; E – creation of new
chromosome and gene combination.
2. Each of the following statements concerning the sperm passage in the female genital tract
is true, EXCEPT: A – sperm selection does not occur in passage; B – through the cervical canal
spermatozoa pass by their tail movements; C – sperm passage through the uterus and oviduct is
assisted by organ muscular contractions; D – seminal plasma prostaglandins stimulate these
muscular contractions; E – ovum produces substances attracting sperms.
3. Each of the following statements concerning the acrosome reaction is true, EXCEPT: A
– may occur only after sperm capacitation; B – the acrosomal outer membrane fuses with the
overlying sperm plasmalemma at many places; C – fused membranes rupture producing multiple
perforations; D – the enzymes leave the acrosome through perforations; E – cortical granules open
and release their enzymes.
4. Each of the following statements concerning the ovum penetration by a sperm is true,
EXCEPT: A – acrosomal enzymes facilitate the sperm passage through the oocyte envelopes; B –
when the sperm passes through the zona pellucida, cortical reaction occurs; C – the oocyte and
sperm plasma membranes fuse and break down at the point of contact; D – the sperm plasma
membrane enters the oocyte cytoplasm; E – the sperm nucleus and centriole enter the oocyte
cytoplasm.
5. Each of the following statements concerning the human cleavage is true, EXCEPT: A –
is a process of successive rapid mitotic divisions; B – blastomeres increase in volume becoming
progressively larger; C – proceeds in the oviduct during the first three days when the morula is
formed; D – continues in the uterus during 3 or 4 days when the blastula is formed; E – is
holoblastic, unequal, and asynchronous.
6. Each of the following statements concerning the blastocyst is true, EXCEPT: A – contains
the outer layer called the trophoblast, from which the chorion arises; B – is surrounded by the zona
pellucida before implantation; C – lacks its own cavity; D – contains the inner cell mass called the
embryoblast, from which the embryo proper arises; E – lies in the uterine secretions until it is
attached to the endometrium.
7. Each of the following statements concerning the first stage of gastrulation is true,
EXCEPT: A – embryoblast is transformed into the bilaminar disk; B – delamination is a
mechanism of this stage; C – epiblast will give rise to three germ layers; D – hypoblast will be
displaced to extraembryonic regions; E – occurs during the first week of development.

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 8. Each of the following statements concerning the second stage of gastrulation is true,
EXCEPT: A – occurs on the 7th day of development; B – morphological changes take place only
in epiblast; C – proliferation and migration of epiblastic cells give rise to the primitive streak with
a primitive groove; D – the primitive streak cells migrate through the primitive groove inwardly
between epiblast and hypoblast to form endoderm and mesoderm; E – the cells that remain in
epiblast after migration are referred to as ectoderm.
9. Each of the following statements concerning the notochord is true, EXCEPT: A – is
formed by cell migration through the primitive knot; B – looks like a cellular rod that grows
between ectoderm and endoderm from the primitive knot towards the cranial end; C – forms the
midline axis of the embryo; D – gives rise to the embryo skeleton; E – degenerates, but persists as
the nucleus pulposus of intervertabral disks.
10. Each of the following statements concerning the mesoderm differentiation is true,
EXCEPT: A – somites divide into the myotome, dermotome, and sclerotome; B – the somite cord
differentiates into the nephrogonadotome; C – coelom appears in the paraxial mesoderm; D – the
somatopleure and splanchnopleure surround the coelom; E – some cells leave the mesoderm and
become the mesenchyme.
11. Each of the following statements concerning the mesoderm differentiation is true,
EXCEPT: A – myotome gives rise to skeletal muscles; B – dermotome gives rise to the skin
dermis; C – sclerotome gives rise to the skeleton; D – nephrogonadotome gives rise to the kidney
and gonads; E – coelom will become the abdominal cavity.
12. Each of the following statements concerning the mesoderm and mesenchyme
differentiation is true, EXCEPT: A – somatopleure and splanchnopleure give rise to the
mesothelium lining serous cavities; B – mesenchyme develops into blood, lymph, and blood
vessels; C – endocardium is derived from mesenchyme; D – myocardium and epicardium arise
from mesenchyme; E – splanchnopleure takes part in the adrenal cortex development.
13. Each of the following statements concerning the cell determination and differential
genome activity is true, EXCEPT: A – include changes in cell structure, biochemistry, and
functions; B – they determine the pathway of cell differentiation; C – each cell nucleus contains a
complete genome established in the zygote during fertilization; D – as cells develop, some genes
are expressed and others repressed; E – only a small percentage of genome is expressed in each
cell, and RNA portion is specific for a given cell type.

Directions: one or more of the given statements or completions is/are correct. Choose the
answer: A – if only 1,2, and 3 are correct; B – if only 1 and 3 are correct; C – if only 2 and 4 are
correct; D – if only 4 is correct; E – if all are correct.

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 14. The following statements regarding the ovum transport along the uterine tube are true:
(1) the ovum passes through the oviduct by beating action of epithelial cilia (2) muscular
contractions of the tubal wall assist the ovum passage (3) it takes the oocyte 25 minutes to reach
the oviduct ampulla (4) the ovum is viable during 24 hours after ovulation
15. The following statements regarding the fertilization are true: (1) occurs in the oviduct
ampulla (2) is part of progenesis (3) requires about 24 hours (4) completes the initial period
16. The following statements regarding the sperm capacitation are true: (1) is removal of the
glycoprotein coat from the plasma membrane over the acrosome (2) spermatozoa are capacitated
by substances of the female genital tract (3) lasts for 7 hours (4) acrosome reaction occurs after
capacitation
17. The following statements regarding the cortical reaction are true: (1) cortical granules
open and release their enzymes (2) physiochemical characteristics of the zona pellucida change,
and the zona reaction is formed (3) zona reaction is impermeable to spermatozoa (4) zona reaction
facilitates oocyte penetration
18. The following statements regarding the events of fertilization after penetration are true:
(1) the second meiotic division is completed (2) the sperm head enlarges to form the male
pronucleus (3) male and female pronuclei approach, contact, and lose their membranes (4)
chromosomes intermingle at metaphase of the first zygote division
19. The following statements regarding the cleavage are true: (1) blastomeres do not
differentiate (2) through the first divisions blastomeres retain totipotentiality (3) initially, cleavage
is under control of maternal macromolecules (4) later, development depends on the embryonic
genome
20. The following statements regarding the neurulation are true: (1) includes the formation
of the neural plate, neural groove, neural tube, and neural crest (2) the neural tube is the
primordium of the central nervous system (3) the neural crest gives rise to spinal and autonomic
ganglia, Schwann cells, meningeal covering of the brain, pigment cells, and the adrenal medulla
(4) dermotome induces overlying ectoderm to form the neural plate
21. The following statements regarding the mesoderm differentiation are true: (1) paraxial
mesoderm divides into somites (2) intermediate mesoderm forms the somite cord (3) lateral
mesoderm is divided into somatopleure and splanchnopleure (4) somatopleure and
splanchnopleure surround the coelom
22. The following statements regarding the germ layer differentiation are true: (1) some
mesoderm cells migrate to form the mesenchyme (2) mesenchyme gives rise to blood, all types of
connective tissue, smooth muscle cells, blood vessels, microglia, and the endocardium (3) surface
ectoderm differentiates into the epidermis, hair, nails, skin glands, mammary glands, salivary

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glands, and tooth enamel (4) endoderm gives rise to the digestive tract epithelium, liver, pancreas,
and lung epithelium
23. The following statements regarding the folding of the human embryo are true: (1)
longitudinal and transverse folds are formed in the early embryonic period (2) folds convert the
flat embryonic disk to a C-shaped cylindrical embryo (3) folding separates the embryo body from
the yolk sac and closes the primitive gut (4) folding results in the formation of the human amnion
24. Differentiation is: (1) the choice of a cell’s particular fate (2) development of specialized
cell types from stem cells (3) cell capabilities have not yet been realized (4) changes in the cell
structure and biochemistry for the cell to perform distinctive functions
25. The following statements regarding the cell potentialities are true: (1) the zygote is
totipotential (2) stem cells are pluripotential (3) immature descendants of stem cells are usually
oligopotential (4) mature cells are unipotential

FIGURES

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 Fig. 25.1. Initial stages of embryonic development
1 – primordial follicles; 2 – growing follicles; 3 – mature follicle; 4 – ovulation; 5 – secondary
oocyte surrounded by zona pellucida and corona radiata; 6 – fertilization; 7 – zygote with two
pronuclei (synkaryon); 8 – the first cleavage division; 9-12 – embryo at different cleavage stages;
13 – morula; 14 – blastocyst; 15 – start of implantation; 16 – completion of implantation, the first
stage of gastrulation; 17 – endometrium; 18 – myometrium and perimetrium.

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 Fig. 25.2. Fertilization and cleavage
1 - cytoplasm of secondary oocyte; 2 – second meiotic division; 3 – polar bodies; 4 – zona
pellucida; 5 – tubercle of fertilization; 6 – sperms; 7 – follicular cells; 8 – female pronucleus; 9 –
formation of male pronucleus; 10 – prophase of the first cleavage division; 11 – anaphase of the
first cleavage division; 12 – two first blastomeres; 13 – multicellular embryo; 14 – zona reaction
(zona fertilization).

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 Fig. 25.3. Gastrulation and differentiation of germ layers (a bird embryo)
A –formation of the primitive streak and primitive knot; B – the primitive streak cell migration
and mesoderm formation: 1 – primitive knot; 2 – primitive pit; 3 – primitive streak; 4 – primitive
groove; 5 – ectoderm; 6 – endoderm; 7 – mesoderm; C – formation of the axial organ complex: 1
– ectoderm; 2 – neural tube; 3 – somite; 4 – somite cord; 5 – parietal mesodermal layer
(somatopleure); 6 – coelom; 7 – visceral mesodermal layer (splanchnopleure); 8 – lateral
mesoderm; 9 – notochord; 10 – endoderm; 11 – blood vessels; D – formation of body and amniotic
folds: 1 – surface ectoderm; 2 – neural tube; 3 – dermatome; 4 – sclerotome; 5 – myotome; 6 -
nephrogonadotome; 7 – notochord; 8 – aorta; 9 – coelom; 10 – amniotic fold; 11 – extraembryonic
ectoderm; 12 - parietal mesodermal layer; 13 – body fold; 14 - visceral mesodermal layer; 15 –
endoderm; 16 – blood vessels.

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 Fig. 25.4. Implantation
A – the 6th day of development; B – the 8th day of development; C – the 10th day of development;
1 – trophoblast; 2 –embryoblast; 3 – the uterine epithelium;;4 – endometrium connective tissue; 5
– hypoblast; 6 – epiblast; 7 – amniotic vesicle roof; 8 – amniotic cavity; 9 – endometrium blood
vessels; 10 – syncytiotrophoblast; 11 – cytotrophoblast; 12 – mitotic division of cytotrophoblastic
cell; 13 – extraembryonic mesoderm; 14 – closing plug; 15 – trophoblastic lacunar network; 16 –
trophoblastic cavity.

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 Fig. 25.5. Human embryo at the second week of development
A – 13th day of development; B – 15th day of development; 1 – epiblast; 2 – hypoblast; 3 – yolk
sac cavity; 4 – amniotic cavity; 5 – syncytiotrophoblast; 6 – closing plug; 7 – extraembryonic
mesoderm; 8 – cytotrophoblast; 9 – trophoblastic lacunae; 10 – primary chorionic villi; 11 –
amniotic wall; 12 – yolk sac wall; 13 – connecting stalk; 14 – chorion; 15 – chorionic cavity
(extraembryonic coelom); 16 – chorionic mesoderm; 17 – primary yolk sac remnant; 18 –
secondary chorionic villi.

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 27. HUMAN EMBRYOLOGY: EMBRYONIC PERIOD, PROVISORY
ORGANS, and PLACENTATION

The embryonic period of the prenatal development starts from the 2nd week and lasts up to
the 8th or 9th week. The events of the second week, as well as some events of the third week have
been described above.

Formation of the primitive cardiovascular system

In the third week of embryogenesis, blood vessel development, i.e. angiogenesis, begins in
the extraembryonic mesoderm of the yolk sac, the connecting stalk, and the chorion. Blood vessels
of the embryo proper begin to develop from mesenchyme about two days later. The primitive heart
also arises from mesenchymal cells. It appears as paired endothelial channels called the
endocardial heart tubes. The cardiovascular system is the first body system to attain a functional
state.
The mesenchymal cells inside the chorionic villi differentiate into blood vessels. These
vessels then become connected with the embryonic vessels via the vessels differentiating in the
connecting stalk. Here, angiogenesis and hemopoiesis occur concurrently: the primitive blood cells
differentiate from mesenchyme inside the vessels (the so-called intravascular hemopoiesis). By
the end of the third week, the embryonic blood begins to circulate through the capillaries of the
chorionic villi. The villi containing the blood vessels are called the tertiary villi. Some villi are
attached to the maternal tissue and are called the stem or anchoring villi. The villi growing from
the stem villi are called the branch villi. The villi absorb nutrients from the maternal blood in the
intervillous spaces and excrete wastes from the embryo into them.

Folding
By the end of the third week, two longitudinal folds – the cranial and caudal folds – and two
transverse folds appear. Each transverse fold comprises the surface ectoderm, the parietal layer,
the somatopleure, the visceral one, the splanchnopleure, and the endoderm. The folds move down
and converge under the embryo body. They convert the flat trilaminar embryonic disk into a C-
shaped cylindrical embryo, and the body shape is thus established. During folding, the embryo
body is separated from the yolk sac, and the primitive gut is formed.
The three germ layers differentiate into various tissues and organs, so that by the end of the
embryonic period all the main organ systems begin to develop, but the function of most organs is
minimal. That is why the period from the 4th to the 8th weeks is the most critical period of the

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embryonic development. Developmental disturbances during this period may give rise to major
congenital malformations.

Provisory organs
Human provisory organs are as follous: the chorion, the amnion, the yolk sac, the allantois,
the umbilical cord, and the placenta. All organs are formed during the embryonic period of
development. Some of them function throughout entire pregnancy; other organs exsist only short
period and soon degenerate.
The chorion develops from blastocyst trophoblast in the second week of emryogenesis. It
is the outmost embryo and fetus envelope coming in contact with maternal tissues. It forms the
chorionic sac with the chorionic cavity (extraembryonic coelom). Developing individual is
suspended in this cavity by the connecting stalk and then by the umbilical cord that attach themself
to the inner surface of the chorionic sac. The chorion has processes called the chorionic villi that
extend toward the endometrium, penetrating it. The primary villi are composed of only the
trophoblast: the symplastotrophoblast lies superficially, and the cytotrophoblastic cells underlie it.
When the extraembryonic mesoderm grows into the primary villi (in the 2nd week), they become
the secondary chorionic villi. Each secondary villus acquires a mesodermal core enclosed by the
cytotrophoblast and the symplastotrophoblast along the surface. In the third week of development,
the mesenchymal cells inside the chorionic villi differentiate into blood vessels. The villi
containing the blood vessels are called the tertiary villi. Some chorionic villi are attached to the
maternal tissue and are called the stem or anchoring villi. The villi growing from the stem villi are
called the branch villi; they are bathed with the maternal blood in the intervillous spaces and
provide the mother–embryo exchange.
By the end of the second month, the chorionic sac is subdivided into the villous chorion that
takes part in placenta formation and the smooth chorion that represents one of the membranes
forming the fetal bladder wall.
The chorion exsists and functions up to the parturition. It provides exchange between the
embryo and the maternal organism, secretes enzymes to erode the endometrium, provides defence
of the embryo, especially immune defence, and produces hormones. Human chorionic
gonadotropin (hCG) is secreted by the symplastotrophoblast, beginning from the second week.
hCG is released into maternal blood and then excreted with maternal urine. This hormone
maintains the corpus luteum and stimulates it to continue progesterone production. The detection
of hCG in the woman’s urine is a simple, rapid, and an early test to detect pregnancy. Further, the
chorion will take part in the placenta formation.

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 The amnion appears in the second week and exsists throughout entire pregnancy. It is a sac
surrounding the embryo and containing the amniotic fluid. The amnion wall consists of amniotic
epithelium and underlyning layer of extraembryonic connective tissue. The amnion grows with
the embryo and fetus development. As the amnion enlarges, it gradually obliterates the chorionic
cavity and sheathes the umbilical cord, forming its epithelial covering. Its junction with the embryo
is located on the ventral surface of the body. The amniotic fluid is derived from the maternal blood
by transport across the amnion; the amniotic cells also take part in the fluid production. Fetal
swallowing of amniotic fluid is a normal occurrence. Most of the fluid passes into the
gastrointestinal tract, but some of it passes into the lungs. In either case, the fluid is absorbed into
the fetal circulation and then passes into the maternal circulation via the placental barrier. The
amniotic fluid contains water, approximately equal portions of organic substances and inorganic
salts, and desquamated fetal epithelial cells. Because fetal urine is added to the amniotic fluid,
studies of the fetal enzyme system, amino acids, hormones, and other substances can be conducted
using the fluid removed by amniocentesis. Studies of the amniotic fluid composition allow the
fetal malformations and chromosomal abnormalities to be determined.
The amnion exists and functions up to birth as part of the fetal bladder or the amniochorionic
membranes. The amnion creates watery environment for both the embryo and fetus, provides their
mechanical defence (forms a protective buffer like a water cushion), helps to control the embryo
body temperature, and enables the fetus to move freely, thus aiding in musculo-skeletal
development.
At the beginning of the parturition, the fetal bladder ruptures, and the amniotic fluid flows
out into the vagina.
The yolk sac appears in the second week of development concurrently with the amnion.
They both look like vesicles associated with the embryonic disk; the hypoblast represents the roof
of the yolk sac. The wall of the yolk sac consists of the yolk endoderm and extraembryonic
connective tissue.
The yolk sac exists only for two months and then undergoes regression. By the 8th week,
the yolk sac shrinks, forming a small pear-shaped remnant that exists as part of the umbilical cord.
The yolk sac lacks yolk and does not take part in the embryo nourishment. The yolk sac
functions to produce the first blood cells and blood vessels. Moreover, from the end of the first
week to the beginning of the third week, the primordial germ cells, known as gonoblasts, are
located in the yolk sac endoderm. Subsequently, gonoblasts migrate back to the embryo
developing gonads, where they become either spermatogonia or oogonia.
The allantois appears on about the15th day as a relatively thin finger-like projection from
the embryo into the connecting stalk. It remains very small in the human embryo. During the

300
second month, the extraembryonic portion of the allantois degenerates, but its remnant may be
seen in the umbilical cord. It is involved in blood formation and angiogenesis. Its intraembryonic
portion is associated with the development of the urinary bladder.
The umbilical cord develops from the connecting stalk: as the amniotic sac enlarges, the
amnion sheathes the stalk, forming its covering. The umbilical cord usually contains two arteries
and one vein surrounded by mucoid connective tissue arising from the extraembryonic mesoderm
of the connecting stalk. Because the umbilical vessels are longer than the cord, the vessels
frequently form loops. The umbilical cord also includes the remnants of the yolk sac and allantois.
The umbilical cord attaches the embryo and fetus to the inner surface of the chorionic sac.
The umbilical cord connects the fetal circulation with blood vessels branched in the chorionic villi
of the fetal part of placenta.

Placenta
Placenta is provisory organ the main function of which is the exchange between the maternal
and fetal blood. Placenta formation (placentation) starts after implantain and finishes by the end
of the second month of development. Placenta exists and functions up to birth. In parturition, the
placenta, a part of the umbilical cord, and the remnants of ruptured amniochorionic membranes
are delivered after the child birth.
Both the fetus and the maternal body take part in placenta formation. The fetal portion is
represented by chorion whereas the maternal portion consists of the endometrium.
During pregnancy, the endometrium is called the decidua graviditas, because it will be shed
with the placenta at parturition. Three different regions of the decidua are identified by their
relationship to the site of implantation:(1) the decidua basalis is the portion of the endometrium
that underlies the implantation site;(2) the decidua capsularis is a thin portion of the endometrium
that lies between the implantation site and the uterine lumen;(3) the decidua parietalis includes
the remaining endometrium.
As the fetus grows to the point, at which the overlying decidua capsularis fuses with the
decidua parietalis of the opposite wall, the uterine cavity obliterates. Concurrently with the fetus
development, the amnion enlarges so that the amniotic wall becomes fused with the chorionic wall
and underlies it. The developing fetus is disposed inside the amnion. The amniotic fluid surrounds
and bathes the fetus body. The fetus and its amnion completely fill the chorionic cavity.
Up to about the 8th week, the chorionic villi cover the entire surface of the chorionic sac. As
the sac grows, the villi associated with the decidua capsularis become compressed, their blood
supply is reduced. Subsequently, these villi begin to degenerate, producing a relatively avascular
area known as the smooth chorion or the chorion laeve. The villi associated with the decidua

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basalis rapidly increase in number, branch, and enlarge. This portion of the chorionic sac is known
as the villous chorion or the chorion frondosum. Thus, the chorion is divided into two parts: the
villous chorion that faces the decidua basalis and takes part in placenta formation and the smooth
chorion that faces the decidua capsularis and represents one of the membranes enveloping the
fetus. The fetal membranes make up the fetal bladder and are as follows from inside outwards: the
amniotic wall, the smooth chorion, and the thinnest layer of the decidua capsularis.
Thus, the placenta is a combined organ: the fetal portion of the placenta is formed by the
villous chorion; the maternal portion is represented by the decidua basalis of the endometrium.
These two parts are involved in the physiological exchange of substances between the maternal
and fetal circulation. The shape of the placenta is determined by the form of the villous chorion:
the latter is circular, imparting to the placenta a discoid shape.
The fetal part of the placenta includes the chorionic plate, a layer of extraembryonic
connective tissue containing large blood vessels coming from the fetus body through the umbilical
cord. The tertiary villi arise from the chorionic plate and project into the intervillous spaces or
lacunae containing the maternal blood. The tertiary villi are formed by the end of the third week,
when the blood vessels have been developed in the cores of the secondary villi. Some villi are
attached to the maternal tissues and called the stem or anchoring villi. At the sites of attachment,
the cytotrophoblastic cells penetrate the symplastotrophoblastic layer to form the cytotrophoblastic
shell, by which the villi are attached to the endometrium. The villi that grow from the stem villi
are called the branch or the floating villi; they float in the lacunae and are bathed by the maternal
blood. The main fetoplacental exchange occurs here, through the branch villi. The
symplastotrophoblast is highly invasive; as a result, there is considerable necrosis of the decidua
basalis and deposition of the fibrinoid material. A more or less continuos layer of the fibrinoid
material separates the fetal and maternal parts of the placenta, preventing immune conflict between
genetically different tissues. The amnion underlies the chorionic plate and continues as a covering
of the umbilical cord that is attached to the fetal surface. The umbilical cord vessels are subdivided
on the fetal surface to form the chorionic vessels, which supply the tertiary villi.
The maternal part of the placenta is represented by the decidua basalis, which comprises all
the endometrium beneath the fetal component of the placenta, except the deepest part called the
decidual plate. This layer remains after parturition and is involved in the subsequent regeneration
of the endometrium. A characteristic feature of the decidua is the decidual cells. They are large,
pale, and rich in glycogen and lipids. They begin to appear just after implantation, which stimulates
the decidual reaction of the endometrium, when stromal cells undergo transformation into decidual
cells. The full significance of the decidual reaction is not understood at present. It is suggested that
the decidual cells may provide some nourishment for the embryo, protect the maternal tissues

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against uncontrolled invasion by the trophoblast, and create a specialized layer facilitating the
placenta separation from the uterine wall at the termination of pregnancy. These cells secrete the
peptide hormone relaxin involved in the softening of the cervix and the pelvic ligaments in
preparation for parturition.
As the villi invade the decidua basalis, they leave several wedge-like areas of the
endometrium called the placental septa. They arise from the decidua basalis and divide the placenta
into 15 to 25 irregular lobules called the cotyledons. Each cotyledon consists of two or more main
stem villi and their many branches.
Placentation results in the establishment of the uteroplacental circulatory system. Fetal blood
enters the placenta through paired umbilical arteries. As the arteries pass into the placenta, they
branch into several vessels in the chorionic plate and then in the villi, forming an extensive
capillary network in close association with maternal blood-filled lacunae. Fetal blood returns
through a system of veins that converge on a single umbilical vein.
The maternal blood reaches the placenta through the spiral endometrial arteries penetrating
the basal plate and flows into the base of the intervillous spaces. The lacunae are divided into
compartments by the placental septa, but because the septa do not reach the chorionic plate, there
is a communication between the compartments. The differential pressure between the arterial and
venous vessels that communicate with the lacunae establishes directional flow from the maternal
arteries into the maternal veins, thereby establishing a primitive uteroplacental circulation.
Maternal blood circulates through the intervillous spaces, delivering nutritive and other substances
necessary for fetus development, and carries away the waste products of fetal metabolism.
Fetal blood never mixes with maternal blood. This separation of the fetal and maternal blood,
refered to as the placental barrier, is maintained primarily by the layers of the fetal tissues. The
placental barrier consists of the symplastotrophoblast, cytotrophoblast, the trophoblastic basal
lamina, villous connective tissue, the endothelial basal lamina, and the endothelium of the
capillaries in the tertiary villi. By the last trimester of pregnancy, the barrier becomes very thin:
the inner cytotrophoblastic layer degenerates, connective tissue disappears, and capillaries become
disposed just below the symplastotrophoblast. This thinning serves to facilitate the exchange of
products through the placental barrier.
The selective exchange between fetal and maternal blood is the main placental function.
Oxygen and carbon dioxide pass through the placental barrier by simple diffusion. Fetal hypoxia
primarily results from the factors that diminish either the uterine blood flow or the fetal blood
flow. Nutrients, water, free fatty acids, vitamins, and glucose are transported through the barrier.
There is little or no transfer of maternal cholesterol, triglycerides, and phospholipids. Electrolytes
are freely exchanged across the placenta. When a mother receives intravenous fluid, they also pass

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to the fetus and affect its water and electrolyte status. Urea and uric acid pass through the placental
barrier by simple diffusion.
Hormones of protein nature do not reach the fetus in significant amounts, except thyroxine
and triiodothyronine. Steroid hormones cross the placental barrier freely. Testosterone passes
through the placenta and may cause musculinization of the female fetus.
Antibodies can pass through the barrier and enter the fetal circulation to provide passive
immunity against such diseases as diphtheria, smallpox, and measles, but no immunity is acquired
to pertussis (whooping cough) and chickenpox.
Erythrocytes may pass in either direction through breaks in the placental barrier. If the fetus
is Rh-positive and the mother Rh-negative, the fetal cells may stimulate the formation of anti-Rh
antibodies by the mother. These pass into the fetal bloodstream and cause hemolysis of the fetal
Rh-positive blood cells and anaemia in the fetus.
Most drugs freely cross the placenta by simple diffusion; many of them cause congenital
malformations. Fetal drug addiction may occur after maternal use of drugs such as heroin.
Infectious agents, such as viruses of measles and poliomyelitis, may pass through the barrier
and cause fetal infection. In some cases (rubella virus), congenital malformations may be
produced. The etiological agent of syphilis may cross the placenta, causing congenital syphilis of
the fetus.
The placental barrier does not exclude many potentially dangerous agents (alcohol, nicotine,
and heavy metals). Therefore, during pregnancy there is need to avoid the use of these agents to
reduce the risk of damage to the embryo or fetus.
The placenta, particularly during early pregnancy, synthesizes glycogen, cholesterol, and
fatty acids, serving as a source of nutrients and energy for the embryo. Placental
symplastotrophoblast releases the enzymes to erode the maternal endometrium.
The placenta is a major endocrine gland producing steroid and protein hormones:
progesterone, estrogens, human chorionic gonadotropin (hCG), human placental lactogen (hPL)
or human chorionic somatomammotropin (hCS), and several growth factors.
Immunocytochemical studies show the symplastotrophoblast to be the main site of hormone
synthesis.

CONTROL PROBLEMS

1. The student analyzing the section of a human embryo reveals the bilaminar embryonic
disk associated with two vesicles. What is the embryo gestation age? What stage of embryonic
development does the embryo correspond to? What vesicles are associated with the embryo?

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 2. An experimental female rat was subjected to ovariectomy (excision of the ovaries) in the
early period of pregnancy. Is implantation possible in such a case?
3. The injection of the urine of a pregnant woman into immature female mice stimulates the
development of their ovarian follicles. Identify the substance in the urine that causes this effect.
Where is this substance produced?
4. A microphotograph shows the chorionic villi floating in the blood-filled lacunae. A
student assumes that the lacunae contain fetal blood. Is he right?
5. It is known that fetal blood never mixes with maternal blood in the placenta. But if a
pregnant woman takes some medicine, it may be found in the fetal body. Explain the phenomenon.
6. The picture shows a human embryo in the third trimester of pregnancy developing in the
uterus. The embryo has the amnion, the chorion, the placenta, and the umbilical cord, but the yolk
sac and the allantois are absent. Is the picture correct?

CONTROL TESTS

Directions: each of the following statements contains five suggested completions. Choose
the one that is best in each case.
1. Each of the following statements concerning implantation is true, EXCEPT: A – is a
process of blastocyst invasion into the endometrium; B – begins on the 5th or the 6th day when
the blastocyst loses the zona pellucida and is attached to the endometrium; C – invasion proper
lasts about 40 h; D – is hormone-independent; E – finishes when regenerated epithelium covers
the endometrial defect.
2. The events of the second week of embryonic development are as follows, EXCEPT: A –
blastocyst formation; B – the first stage of gastrulation; C – amniotic vesicle formation; D –
chorion development; E – yolk sac formation.
3. Each of the following statements concerning the yolk sac is true, EXCEPT: A – exists
only two months and then regresses; B – its remnant will be a part of the umbilical cord; C –
contains yolk and provides embryo nourishment; D – first blood cells develop in its endoderm; E
– gonoblasts are located in its endoderm before they return into the embryo.
4. Each of the following statements concerning the chorion functions is true, EXCEPT: A –
provides selective exchange between the embryo and maternal organism; B – secretes enzymes to
erode the endometrium; C – provides immune defence of the embryo; D – creates watery
environment for the fetus; E – produces human chorionic gonadotropin (hCG).
5. Each of the following statements concerning the decidual reaction is true, EXCEPT: A –
trophoblastic cells undergo transformation and become decidual cells; B – implantation is a

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stimulus for this reaction; C – decidual cells are large, pale, and rich in glycogen; D – decidual
cells take part in the embryo nourishment; E – decidual cells create a specialized layer facilitating
placenta separation from the uterus at the end of pregnancy.
6. Each of the following statements concerning the endometrium in pregnancy is true,
EXCEPT: A – is called the decidua because it is shed in parturition; B – its decidua basalis
underlies the implantation site; C – its decidua capsularis separates the embryo from the uterine
lumen; D – its decidua parietalis includes the remaining part of the endometrium; E – lacks
decidual cells.
7. Each of the following statements concerning the chorion is true, EXCEPT: A – its
secondary villi become tertiary villi when they acquire blood vessels; B – its portion associated
with the decidua basalis is a villous chorion; C – its portion associated with the decidua capsularis
is a smooth chorion; D – its villi are never attached to maternal tissues; E – stem villi project from
the chorionic plate and are divided into branch villi.
8. Each of the following statements concerning the fetal part of the placenta is true,
EXCEPT: A – the umbilical cord is not attached to the fetal surface; B – includes the chorionic
plate and tertiary villi arising from it; C – the villi project into lacunae and are bathed by maternal
blood; D – anchoring villi are attached to maternal tissues by the cytotrophoblastic shell; E – the
amnion underlies the chorionic plate and continues as the umbilical cord covering.
9. Each of the following statements concerning the maternal part of the placenta is true,
EXCEPT: A – includes the decidua basalis; B – the decidua basalis lacks decidual cells; C –
placental septa project from the decidua basalis towards the chorionic plate; D – the septa divide
the placenta into lobules (cotyledons); E – the deepest layer of the decidua basalis called the
decidual plate remains after parturition and provides endometrial regeneration.
10. Each of the following statements concerning the uteroplacental circulatory system is
true, EXCEPT: A – fetal blood enters the placenta through the umbilical arteries; B – umbilical
vessels branch in the chorionic plate and supply the villi; C – fetal blood returns through villous
veins that converge to form the umbilical vein; D – fetal and maternal blood mix; E – maternal
blood circulates through intervillous spaces and returns into the venous system through veins that
communicate with the lacunae.
11. The placental barrier includes the following structures, EXCEPT: A –
syncytiotrophoblast of chorionic villi; B – connective tissue of the decidua basalis; C – chorionic
cytotrophoblast with its basal lamina; D – connective tissue of tertiary villi; E –endothelium of
chorionic capillaries and its basal lamina.
12. The placental barrier undergoes the following changes in pregnancy, EXCEPT: A –
gradually disappears; B – the cytotrophoblast degenerates; C – villous connective tissue lying

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between the capillaries and trophoblast thins out and disappears; D – villous capillaries become
disposed just below the trophoblast; E – the barrier gets thin to facilitate product exchange.

Directions: one or more of the given statements or completions is/are correct. Choose the
answer: A – if only 1,2, and 3 are correct; B – if only 1 and 3 are correct; C – if only 2 and 4 are
correct; D – if only 4 is correct; E – if all are correct.
13. The human embryonic development is divided into the following periods: (1) initial (2)
embryonic (3) fetal (4) postnatal
14. The events of the first week of the human embryonic development are as follows: (1)
fertilization (2) cleavage (3) blastula formation (4) gastrulation
15. The following statements regarding the trophoblast in implantation are true: (1)
trophoblast differentiates into cytotrophoblast and syncytiotrophoblast (2) cytotrophoblastic cells
divide, migrate outwards, fuse, and form a syncytiotrophoblast (3) syncytiotrophoblast produces
enzymes to erode the endometrium (4) syncytiotrophoblast forms processes that invade the
endometrium
16. The following statements regarding the implantation sites are true: (1) blastocyst usually
implants in the upper portion of the uterus (2) implantation in the lower uterine portion may cause
severe bleeding (3) blastocyst usually implants on the posterior wall or rarely on the anterior wall
of the uterus (4) implantation outside the uterine cavity is called ectopic
17. The following statements regarding the amnion are true: (1) is filled with the amniotic
fluid that creates watery environment for the fetus (2) provides mechanical defence of the fetus
(3) exists and functions up to birth (4) appears in the first week of development
18. The following statements regarding the chorion are true: (1) its primary villi consist of
the trophoblast and blood vessels (2) its secondary villi include the trophoblast and extraembryonic
mesoderm (3) its villi never contact with maternal blood (4) intervillous spaces form the
trophoblastic lacunar network
19. The following statements regarding the embryo in the second week of development are
true: (1) the embryo appears like a bilaminar disk (2) the embryo is associated with the amniotic
vesicle and the yolk sac (3) the chorion forms the chorionic sac with a cavity (4) the embryo is
attached to the inner side of the chorion by a connecting stalk
20. The following statements regarding the human chorionic gonadotropin (hCG) are true:
(1) is produced by the embryonic disk cells (2) is excreted in the maternal urine (3) inhibits
progesterone production (4) maintains the corpus luteum of the maternal ovary
21. The events of the third week of the human embryonic development are as follows: (1)
the second stage of gastrulation and trilaminar embryo formation (2) development of axial organs

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and their initial differentiation (3) formation of the primitive cardiovascular system (4) further
development of chorionic villi
22. The following statements regarding the primitive cardiovascular system formation are
true: (1) angiogenesis begins in the yolk sac, the connecting stalk, and the chorion (2) development
of embryonic vessels begins later (3) the primitive heart arises from the mesenchyme and appears
like paired endothelial channels (4) the cardiovascular system is the last system to attain a
functional state
23. The following statements regarding the selective exchange through the placental barrier
are true: (1) antibodies cannot cross the barrier (2) gases, electrolytes, some nutrients, and wastes
freely pass the barrier by simple diffusion (3) erythrocytes never pass the barrier (4) protein
hormones do not reach the fetus in significant amounts, steroid hormones freely pass the barrier
24. The following statements regarding the placental barrier permeability for dangerous
agents are true: (1) most drugs freely cross the placenta by simple diffusion (2) measles,
poliomyelitis, and rubella viruses may pass through the barrier (3) alcohol and nicotine cross the
placental barrier (4) most of dangerous agents may cause congenital malformations
25. The following statements regarding the placenta metabolism are true: (1) placenta
synthesizes glycogen, cholesterol, and fatty acids (2) syncytiotrophoblast is the site of placental
metabolic activity (3) placenta serves as a source of nutrients and energy for the embryo (4)
placenta cannot synthesize hormones
26. The placenta is the major endocrine gland producing the following hormones: (1) human
chorionic gonadotropin (hCG) (2) human chorionic somatomammotropin (hCS) (3) relaxin (4)
estrogens and progesterone
27. The following statements regarding the umbilical cord are true: (1) is covered with the
amniotic epithelium (2) includes one artery and two veins (3) contains mucoid connective tissue
(4) lacks the allantois and yolk sac remnants
28. The following statements regarding the critical periods of the embryonic development
are true: (1) developmental disturbances may cause congenital malformations in these periods (2)
implantation is not a critical period (3) the time from the 4th to the 8th weeks is the most critical
period (4) placentation is not a critical period
29. The following statements regarding the allantois are true: (1) appears on the 15th day as
a finger-like projection elongating from the embryo into the connecting stalk (2) degenerates
during the second month, its remnant is found in the umbilical cord (3) directs blood vessel growth
from the embryo towards the chorion (4) its intraembryonic portion is associated with development
of the urinary bladder

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FIGURES

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 Fig. 26.1. Human embryo and provisory organs in development
1 – amniotic vesicle; 1a – amniotic cavity; 2 – embryo body; 3 – yolk sac; 4 – chorionic cavity
(extraembryonic coelom); 5 – primary chorionic villi; 6 – secondary chorionic villi; 7 – connecting
stalk; 8 – tertiary chorionic villi; 9 – allantois; 10 – umbilical cord.

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 Fig. 26.2. Human placenta
A – placenta structure (arrows indicate blood circulation in lacunae); B, C, D – primary, secondary,
and tertiary chorionic villi respectively; E, F – placenta barrier structure at the 3rd and the 9th month
of development respectively (dotted line indicates the barrier thickness); 1 – amniotic epithelium;
2 – chorionic plate; 3 – stem chorionic villus; 4 –fibrinoid material; 5 – reduced yolk sac; 6 –
umbilical cord; 7 – placental septa between cotyledons; 8 – lacunae; 9 – spiral endometrial arteries;
10 – decidua basalis; 11 – myometrium; 12 – syncytiotrophoblast; 13 – cytotrophoblast; 14 –
cytotrophoblastic basement membrane; 15 – chorionic villus blood capillary; 16 – fibroblast; 17 –
mesoderm of the secondary chorionic villus; 18 – blood vessel of the tertiary chorionic villus.

CONTROL PROBLEMS: ANSWERS AND EXPLANATIONS

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 Cytology
1. The ions can pass through the plasmalemma into the cell against the concentration
gradient by active transport that requires energy.
2. The cells are attached to the substratum and to each other by their plasma membranes.
3. The cells do not respond to the influence of the hormone, because they lack membrane
receptors specific to this hormone.
4. Cells appear in the healing wound by migration and cell divisions. Fibers result from
active fiber production by fibroblasts.
5. It is not true. The cells producing fibers are rich in the rough endoplasmic reticulum and
Golgi apparatus. The cells revealed in the healing wound and containing numerous lysosomes
perform the phagocytic function.
6. Young growing cells are characterized by diffuse basophilia of their cytoplasm due to
plentiful free ribosomes. Free ribosomes synthesize cytosol proteins as well as proteins for cell
growth and cell differentiation.
7. The cell autolysosomes utilize the organelle residues.
8. In this case, the cells with a large amount of the rough endoplasmic reticulum increase
in number, because antibodies are secretory proteins produced on the rough endoplasmic
reticulum.
9. Intermediate keratin filaments are inherent in epitheliocytes; therefore, the malignant
cells arise from epithelial cells.
10. The neurons are characterized by intense protein synthesis. The nuclei appear light,
because they contain euchromatin that takes part in transcription. The marked nucleoli synthesize
rRNA and assemble ribosome subunits.
11. Protein synthesis fails to occur in the dividing cells, because DNA is condensed in
chromosomes and transcription is impossible.
12. One-nucleated tetraploid cells result from either endomitosis (reduplication without
subsequent mitosis) or abortive mitotic division arrested at the metaphase. Binucleated tetraploid
cells result from abortive mitosis arrested at the telophase (mitosis without cytokinesis).
13. The forensic experts came to this conclusion, because the neutrophils from the blood
smear they examined demonstrate the so-called “drumstick” in their nuclei. The “drumstick” is a
variant of “sex chromatin” that inheres in female cells only. One of two X chromosomes is strongly
condensed and looks like a drumstick-appearing appendage on a neutrophil nuclear lobe.
14. The first type of cell death is necrosis; the second type is apoptosis.

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 Epithelial Tissues
1. Epithelium of the small intestine is simple columnar striated and specialized for
absorption. It consists of tall columnar cells (absorptive cells) resting on the basement membrane.
Apical portions of the epitheliocytes have numerous microvilli that form the brush border.
2. The brush border of the intestinal epithelium enlarges the cell surface area for absorption
and membrane digestion. If the brush border is destroyed, these functions are impaired.
3. The epithelium that covers the surface of the organ is the covering epithelium. Its main
functions are protection and external exchange. The epithelium located in the wall depth of the
organ is glandular epithelium that forms exocrine and some endocrine glands. Its main function is
secretion.
4. Proliferating epithelial cells may be found in the flask with the stratum basale cells,
because this layer is cambial and contains stem cells. The stratum lucidum consists of
differentiating cells that lack mitotic capacity.
5. The epithelium covering the thick skin consists of five distinct layers: the stratum basale,
the stratum spinosum, the stratum granulosum, the stratum lucidum, and the stratum corneum. The
epithelium covering the thin skin consists of only four layers, because it lacks the stratum lucidum.
Its stratum granulosum is poor-developed; its stratum corneum is thin.

Blood and Lymph

1. The deficiency of circulating erythrocytes clinically manifests itself as anemia.
Reticulocytes account for about 1% of all blood erythrocytes. The abundance of reticulocytes
results from hemolytic diseases or bleeding.
2. A highland is characterized by low partial oxygen pressure; therefore, the blood of the
highlander contains more erythrocytes than the blood of the patient living in lowlands.
3. These are lymphocytes. In accordance with the leukocytic formula, lymphocytes account
for 19 to 39%.
4. The clinical blood test reveals an increase in the eosinophil count. Allergic reactions or
parasite invasions may be the causes of the formula alteration.
5. The leukocytic formula shows 30% of neutrophils and 60% of lymphocytes if the child
age varies between 4 days and 4 years.

Connective Tissues
1. The first tissue visible in the slide is the loose connective tissue; the second tissue is the
dense regular connective tissue.

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 2. Eosin stains collagen fibers pink; reticular fibers are revealed by silver impregnation (they
become black); elastic fibers stain brown by orcein.
3. The enzyme hyaluronidase acts upon hyaluronic acid separating water from it. The
permeability of loose connective tissue and capillaries increases with the resultant swelling.
4. Vitamin C (ascorbic acid) functions as a cofactor in collagen fiber formation. Vitamin C
deficiency is characterized by poorer development of collagen fibers in connective tissues, bones,
blood vessels, and periodontal ligaments, which causes the symptoms of scurvy.
5. The first type of cells is the white (unilocular) adipocyte; the second type of cells is the
brown (multilocular) adipocyte. The functions of white adipose cells include storage of energy,
insulation, cushioning of vital organs, and secretion of hormones. Brown adipose cells metabolize
lipids to generate heat, mainly in newborns and infants.
6. Immunoglobulins (antibodies) are produced by plasma cells. They arise from B
lymphocytes and function as the effectors of humoral immunity.
7. White adipose cells are the targets of the hormone insulin that promotes lipid synthesis
and inhibits lipid degradation. Type I diabetes is characterized by low insulin levels that stimulate
lipid utilization and a quick loss of weight by the patients.
8. Melanocytes (pigment cells) arise from the neural crest; therefore, melanoma is classified
as a nervous tissue tumor.

Skeletogenic Tissues: Cartilage and Bone Tissues

1. The perichondrium is described. It consists of two layers: the outer fibrous layer
composed of dense connective tissue and the inner cellular layer composed of loose connective
tissue. The cellular layer contains chondrogenic cells and chondroblasts.
2. Eosin stains collagen fibers in histologic sections. In hyaline cartilage, the collagen fibers
are not discernible, because they are fine and have the same refractive index as the amorphous
substance. In fibrocartilage, the collagen fibers are visible, because they are more in number and
arranged in thick bundles. Orcein reveals elastic fibers abundant in the elastic cartilage matrix.
3. The first slide shows the coarsely bundled bone tissue (primary, immature). It mainly
occurs in embryogenesis. Later, it is replaced by the secondary bone tissue, except for the tooth
sockets, the skull suture lines, and the insertion sites of tendons. The second slide shows the
lamellar bone tissue (secondary, mature) that replaces the primary bone tissue and makes up the
human skeleton.
4. The first cell is an osteoblast; its function is to secrete the organic portion of the bone
matrix. The second cell is an osteocyte; it maintains bone homeostasis but lacks secretory activity.

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 5. The electron micrograph reveals an osteoclast; its function is bone resorption. Osteoclasts
arise from the blood monocytes and belong to the mononuclear phagocytic system.
6. The slide shows the perichondral bone and the endochondral bone. The perichondral
bone matrix stains strongly eosinophilic due to abundant collagen fibers. The endochondral bone
matrix includes the basophilic areas of calcified cartilage.

Muscle Tissues
1. The slide, in which the cells are surrounded by the basement membrane, shows either the
smooth muscle tissue or the cardiac muscle tissue. The second slide, in which the cells rest on the
basement membrane, shows any simple epithelium.
2. The cells tightly adjacent to each other and joined together by numerous desmosomes are
epitheliocytes. The cells enclosed by the basement membrane and joined together by numerous
gap junctions are smooth muscle cells.
3. Both the skeletal muscle tissue and the cardiac muscle tissue reveal crossbanding
striations due to striated myofibrils. The skeletal muscle tissue lacks cellular structure and consists
of the symplasts called muscle fibers. The cardiac muscle tissue consists of cardiomyocytes; their
intercellular junctions are termed intercalated disks. The intercalated disks, which can be seen in
slides stained with Iron hematoxylin, enable us to identify the cardiac muscle tissue.
4. This cell is a satellite cell. It is a stem cell of the skeletal muscle tissue which takes part
in muscle reparative regeneration.
5. The skeletal muscle fiber, in which thin myofilaments deeply penetrate into the A bands
so that the I bands considerably decrease, is in a contracted state. The second muscle fiber, in
which the I bands are wide, is in a resting state.
6. The electron micrograph shows a cross section of skeletal muscle fibers in the peripheral
regions of the sarcomere A bands.
7. Both of them. The first slide with the fibroblast-like cells represents the stage of
myoblasts arising from satellite cells. The second slide with tube-like structures containing several
nuclei represents the stage of myotubes resulting from myoblast fusion.

Nervous Tissue
1. The blue clumps revealed in the neuron with Toluidine blue staining are called Nissl
bodies. They are characterized by strong basophilia, because they contain the rough endoplasmic
reticulum. Nissl bodies are located in the neuron soma and the neuron axon; they are absent in the
neuron dendrites, because dendrites lack rER.

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 2. “Neurofibrils” are invisible in slides stained with Hematoxylin and Eosin; they are
revealed using Silver impregnation method. The term “neurofibrils” is in inverted commas,
because they are fixation artifacts and represent aggregated microtubules and microfilaments.
3. The glial cells surrounding the neuron soma are satellites; the cells surrounding the
neuron processes are called lemmocytes. They both belong to oligodendrocytes.
4. Both slides show the myelinated fibers cut across. The myelinated fiber contains a single
axis cylinder surrounded by a myelinated sheath. The myelinated sheath includes several layers of
the lemmocyte plasma membrane and is predominantly made up of lipids. In the first slide, Osmic
acid stains lipids black; therefore, the myelinated sheath appears black. In the second slide, the
myelinated sheath looks white, because myelin lipids are removed by alcohol in Silver nitrate
staining; the axis cylinder appears black due to “neurofibrils.”
5. The right synaptic part including synaptic vesicles with neurotransmitters is the
presynapse. The left synaptic part is the postsynapse containing the membrane receptors for
neurotransmitters. The synapse conducts nerve impulses from right to left.
6. In such a case, either the reflex arch motor or associative neuron may be damaged.
7. If the patient feels pain but cannot jerk his hand away, his damaged neurons are motor or
associative. If the patient does not feel pain on pricking, his damaged neurons are sensitive or
associative.

Nervous System: Peripheral Nervous System and Spinal Cord

1. The sensory (afferent) neurons are found in the PNS. They occupy the sensory ganglia
(the dorsal root ganglia and the ganglia associated with some cranial nerves) and the primary
sentient sense organs (the retina and the olfactory epithelium). Sensory neurons belong to either
pseudounipolar or bipolar morphological types.
2. The neurons innervating the skeletal muscles are called the somatic motor neurons and
found in the CNS. They occupy the spinal cord anterior horns and the brain stem efferent nuclei.
The neurons innervating the smooth muscle cells are called the autonomic motor neurons and
found in the autonomic ganglia. Both the somatic and autonomic motor neurons belong to the
multipolar morphological type.
3. The spinal cord dorsal roots contain myelinated axons of the sensory pseudounipolar
neurons of the spinal ganglia. These fibers send sensory impulses to the CNS; therefore, the spinal
cord dorsal roots are called sensory roots.
4. The spinal cord ventral roots contain myelinated axons of the spinal cord somatic motor
and autonomic associative neurons. These fibers conduct impulses away from the CNS; therefore,
the spinal cord ventral roots are called efferent roots.

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 5. The spinal cord dorsal root contains the myelinated axons of the sensory neurons of the
spinal ganglion. After the operation, the cut fibers in the root portion connected with the spinal
ganglion may regenerate, because they retain structural integrity with the neuron bodies. The cut
fibers in the portion connected with the spinal cord have no connection with the neuron bodies and
degenerate. Their remnants are phagocytosed by glial cells.
6. The spinal ventral root contains the myelinated axons of the somatic motor neurons. The
axons innervate the skeletal muscle fibers and terminate to form effectors – the motor end plates.
After being cut, these effectors stop functioning.
7. Both ganglia are autonomic, contain the autonomic motor neurons, and perform the
motor function. Their efferent neurons innervate smooth muscle cells, cardiac muscle cells, and
glands. The extramural ganglion may be either sympathetic or parasympathetic; the intramural
ganglion belongs to the parasympathetic system. The intramural ganglia located in the wall of
hollow tubular organs are called metasympathetic ganglia. These ganglia contain motor, sensory,
and associative neurons forming the local reflex arch. The metasympathetic ganglia provide
peristalsis of the tubular organs.
8. The postganglionic nerve fibers are unmyelinated. Their axis cylinders are the motor
neuron axons located in the autonomic ganglia.
9. The nerve fibers of the spinal cord posterior columns include the sensory neuron axons
located in the spinal ganglia. Damage to these neurons causes degeneration of the posterior column
nerve fibers forming the ascending tracts of the spinal cord.

Nervous System: Brain

1. The mossy fibers terminate in the granular layer of the cerebellar cortex and synapse with
the dendrites of the granular neurons (the postsynaptic component).
2. The climbing fibers terminate in the molecular layer of the cerebellar cortex and synapse
with the dendrites of the Purkinje cells (the postsynaptic component).
3. The neuron belongs to the cerebellar cortex and is called Purkinje cell. The axons of the
basket cells form the basket-like synapses on the Purkinje cell soma. These synapses inhibit the
activity of Purkinje cells.
4. The pyramidal neurons belong to the cerebral cortex. The axons of the pyramidal neurons
extend away from the cortex to form descending pyramidal tracts. The latter terminate in the
anterior horns of the spinal cord and synapse on the motor somatic neurons.
5. The 2nd and the 4th layers of the cerebral cortex are called the external granular layer and
the internal granular layer, respectively. These layers are well-developed in the granular type of

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the cerebral cortex. This cortex is sensory and responsible for the analysis of impulses coming
from the sense organs.
6. The 3rd and the 5th layers of the cerebral cortex are called the external pyramidal layer
and the internal pyramidal layer, respectively. These layers are well-developed in the agranular
type of the cerebral cortex. This cortex is motor and sends impulses to the motor neurons of the
spinal cord.
7. The neurons with damaged axons are the pyramidal cells located in the 3rd and the 5th
layers of the cerebral cortex. The pyramidal cell axons make up the pyramidal tracts conducting
impulses to the motor neurons of the spinal cord. These tracts fail to conduct impulses as a result
of the traumatic injury.
8.
Primary Sentient Sense Organs: Organ of Vision and Organ of Smell
1. This photoreceptor cell is a rod. Its flat membranous disks contain the photosensitive
pigment rhodopsin. The rods are sensitive to low-intensity light and responsible for black-white
vision (twilight and night vision).
2. This photoreceptor cell is a cone. Its membranous invaginations contain the
photosensitive pigment iodopsin. The cones are sensitive to bright light and are responsible for
colour vision (day vision).
3. The phenomenon is called accommodation; it is a function of the ciliary muscles. The
contraction and relaxation of the ciliary muscles change tension on the suspensory ligaments
attached to the lens, which becomes more or less convex. Accommodation allows the lens to focus
images of nearby or distant objects on the retina.
4. The vitamin A aldehyde form called retinal is part of rhodopsin, a photosensitive pigment
of the rods. Hypovitaminosis A causes rhodopsin deficiency and an impairment of the rod function
(night blindness).
5. The vascular tunic of the eye and the retina contain numerous pigment cells with melanin
that absorbs light. Lack of pigmentation activates iodopsin dissociation and inhibits its resynthesis,
which impairs the cone function (day blindness).
6. The first slide corresponds to darkness. The melanin granules are concentrated in the
pigment cell bodies, thus enabling the rods to function. The second slide corresponds to bright
light. The melanin granules migrate to the pigment cell processes and protect rhodopsin against
the unnecessary dissociation.
7. On mountain tops, sparkling Alpine snow activates iodopsin dissociation and inhibits its
resynthesis blinding mountaineers.

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 8. Profuse discharge from the mucous membrane of the nose carries away the dissolved
odoriferous molecules and prevents their interactions with the olfactory receptors.

Secondary Sentient Sense Organs: Organ of Hearing, Organ of Equilibrium,

and Organ of Taste
1. The organ of hearing develops from the optic vesicle, but it belongs to secondary sentient
organs, because its receptors (hair cells) are epitheliocytes, i.e., neuroepithelial cells.
2. The first auditory neurons are located in the spiral ganglion housed inside the spiral
lamina. They are afferent bipolar neurons. Their axons pass through the modiolus to form the nerve
fibers of the eighth cranial nerve. Their dendrites pass through the tunnel and form afferent
synapses on the hair cells.
3. Afferent and efferent nerve fibers innervate the neuroepithelial cells. The afferent fibers
are the dendrites of the sensory neurons; they form light contacts on the neuroepithelial cells. The
efferent fibers are the axons of the brain neurons; they form dark contacts on the neuroepithelial
cells.
4. The student is not right. The neuroepithelial cell with numerous stereocilia and a single
kinocilium on its apical surface belongs to the vestibular apparatus.
5. The use of a hearing-aid is effective in cases of ankylosis of the auditory ossicles and the
tympanic membrane trauma.
6. In such a case, the function of the hair cells located in the vestibular maculae is lost.
7. The “furred tongue” symptom results from active epithelium keratinization on the dorsal
surface of the tongue. Thick keratinous masses close the interpapillary clefts and prevent the taste
molecules from interacting with the taste bud receptors.

Cardiovascular System
1. The first artery belongs to the muscular type of arteries; the second artery belongs to the
elastic type of arteries.
2. This is the fenestrated type of capillaries. These capillaries are typical of the endocrine
glands, the small intestine, and the kidney.
3. The cell resting on the basal membrane is an endothelial cell. The cell enclosed by the
basal membrane is a pericyte.
4. This is a lymphatic capillary.
5. Both veins are muscular veins. The first of them is a vein with small muscle content. The
second vein is a vein with large muscle content and belongs to the lower part of the body.

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 6. The contractile cardiomyocytes are aerobic cells susceptible to hypoxia. Conducting
cardiomyocytes are anaerobic cells; therefore, they are more tolerant of oxygen deficiency.

Central Organs of Hemopoiesis: Red Bone Marrow and Thymus

1. The red bone marrow macrophages take part in erythropoiesis and are called nurse cells.
The nurse cells capture iron in the spleen (after erythrocyte degradation), migrate to the red bone
marrow, and supply the erythropoietic cells with iron.
2. It is the red bone marrow. Megakaryocytes are the precursors of platelets.
3. Adipose cells of the red bone marrow take part in the creation of microenvironment,
because they produce some hemopoietic growth factors. With age, the red bone marrow in the
diaphyses of tubular bones is replaced by the yellow bone marrow mostly consisting of white
adipose cells. The yellow bone marrow retains the hemopoietic potential.
4. The student has made a mistake. The reticular tissue forms the stroma of the red bone
marrow. The thymic lobule stroma is composed of the epithelial tissue (epithelioreticular cells).
5. This is a morphological picture of age-related thymus involution.
6. The kidney graft was not rejected due to the absence of T killer cells arising in the thymus.

Peripheral Organs of Hemopoiesis and Immunogenesis

1. The lymph nodes, the tonsils, and the spleen have lymphatic nodules consisting of
lymphocytes at different stages of development. The distinctive feature of the splenic nodule is the
acentrically located central artery. The periarterial sheath is a T-dependent zone.
2. Gut-associated lymphatic tissue (GALT) including the palatine tonsils, the appendix, and
lymphatic nodules can be used for this purpose. In these organs, lymphocytes infiltrate both the
lamina propria and the tunica mucosa epithelium. For example, the intestinal epithelium contains
M-cells presenting antigens to lymphocytes.
3. In inflammation, regional lymph nodes receive lymph rich in antigens. Antigen-
dependent proliferation and differentiation of lymphocytes are activated. B-lymphocyte
differentiation results in the formation of numerous plasma cells producing immunoglobulins.
4. Droplets of the dye injected into the afferent lymphatic vessel are found in the cytoplasm
of macrophages. Lymph filtration and removal of foreign particles occur in the lymph node sinuses
containing numerous macrophages.
5. In the period of active digestion, antigens are absorbed in the small intestine and reach
the mesenteric lymph nodes. The antigens stimulate antigen-dependent proliferation and
differentiation of lymphocytes. The cells increase in number causing the lymph node to enlarge.

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 Endocrine System
1. The second gland is endocrine, because it is ductless and releases hormones into the
blood. The endocrine glands are characterized by the fenestrated type of blood capillaries.
2. The hormones mentioned above are produced by the hypothalamus and affect the
adenohypophysial endocrine cells. Somatostatin inhibits the somatotropes (acidophils) producing
GH. Gonadoliberin activates the gonadotropes (basophils) producing LH and FSH. Thyroliberin
stimulates the thyrotropes (basophils) producing TSH.
3. The first field of view shows the neurohypophysis (the pars nervosa) consisting of
neurosecretory axons, their endings, and small glial cells called the pituicytes. The second field of
view shows the adenohypophysis (the pars distalis) consisting of different endocrine cells:
acidophils, basophils, and chromophobes.
4. Two endocrine glands were affected by the intervention: the thyroid gland whose
parafollicular cells (calcitoninocytes) arise from the neural crest and the adrenal medulla whose
chromaffin cells also originate from the neural crest.
5. The slide treated by silver impregnation shows the parafollicular cells secreting
calciotonin. These cells are nonadenohypophysis-dependent. The experiment with an injection of
radioactive iodine reveals the follicular cells producing the iodide-containing hormones T4 and T3.
The follicular cells depend on the adenohypophysis and are stimulated by TSH.
6. The small follicles, columnar thyrocytes, and vacuolated colloid are the morphological
features of the thyroid gland hyperfunction.
7. The large follicles, flat thyrocytes, and dense colloid are the morphological features of
the thyroid gland hypofunction.

Digestive System: Oral Cavity and Esophagus

1. On the dorsal surface of the tongue, the mucosa forms papillae; the papillary epithelium
contains the taste buds; the epithelium covering the filiform papillae is keratinized; the submucosa
is absent. On the lower surface of the tongue, the mucosa lacks papillae; there are no taste buds;
the mucosal epithelium is nonkeratinized; the submucosa is present.
2. In the oral cavity, antigen-dependent proliferation and differentiation of lymphocytes
occur in the tonsils, e. g., in the palatine tonsils.
3. The enzymes breaking down carbohydrates in the oral cavity are synthesized by the
salivary glands and released with saliva.
4. Yes, it is possible. The parotid glands are serous and lack mucous cells; they do not stain
with this method. The submandibular and sublingual salivary glands are mixed, contain mucous

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cells, and stain with this method. But, the submandibular glands are more serous, include some
mixed acini arranged in groups, and partially stain with this method. The sublingual glands are
more mucous, include many mixed and mucous acini, and almost completely stain with this
method.
5. The enamel is the hardest tooth component due to its high mineralization (about 98%).
The dentin is less mineralized (about 70%) and includes collagen fibrils as well as the amorphous
substance. Odontoblasts are located in the peripheral region of the dental pulp, but their processes
project into the dentinal tubules.
6. The student’s explanation is not correct. The esophageal muscularis externa contains the
skeletal muscle tissue in the upper third and the smooth muscle tissue in the distal third of the
organ. The esophageal middle third consists of both striated muscle fibers and smooth muscle
cells.
7. The esophageal cardiac glands are linked to ulcer development. These glands can be
found in the mucosal lamina propria in the proximal and terminal portions of the esophagus.

Digestive System: Stomach and Small Intestine

1. In the first slide, the pyloric region of the stomach is seen; in the second slide, the fundic
part. Gastric glands produce gastric juice and are found in the mucous membrane. Glandular
mucous cells secrete mucus, the chief cells secrete enzymes, mainly pepsinogen, and the parietal
cells produce hydrochloric acid and the intrinsic factor.
2. The method described reveals mucus-secreting cells in the mucosa of the stomach and
the small intestine. In the stomach, these cells are the covering epitheliocytes and the mucous cells
in the gastric glands. In the small intestine, these cells are the goblet cells of the intestinal
epithelium.
3. The hypoacidity of gastric juice results from functional inhibition of the parietal cells of
gastric glands. Hydrochloric acid converts the inactive enzyme pepsinogen to active pepsin-
digesting proteins. The patient’s poor protein digestion is due to low acidity of gastric juice.
4. The targets for gastrin are the parietal cells of gastric glands. The activation of G-cells
and the increased gastrin production result in hyperacidity of gastric juice.
5. The cambial epithelial cells in the small intestine are called intermediate cells located in
crypts.
6. The cells containing granules at the apical cytoplasmic pole are Paneth cells. These cells
secrete enzymes and lysozyme and take part in the regulation of normal intestinal bacterial flora.
The basally granulated cells are endocrine cells (cells of the APUD system). These cells produce
hormones regulating secretory, proliferative, and contractile activity of the small intestine cells.

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 7. The duodenal glands located in the submucosa.

Digestive System: Large Intestine, Liver, and Pancreas

1. The epithelium lining the large intestine mucosa is simple columnar striated. It is
characterized by the predominance of goblet cells. The columnar cells of this epithelium possess
the brush border and take part in the absorption of some substances (water, electrolytes, vitamins,
glucose) including medications.
2. The palatine tonsil is found in the oral cavity mucosa and includes the stratified squamous
epithelium. The appendix is part of the large intestine and includes the simple columnar
epithelium.
3. Both statements are true. The triad is a center of the portal hepatic lobule, while the central
vein is a center of the classic hepatic lobule.
4. The hepatocyte sER is responsible for detoxication of different substances, including
bacterial poisons.
5. Arterial oxygenated blood flows from the periphery to the center in the classic hepatic
lobule and from the center to the periphery in the portal hepatic lobule. In venous blood congestion,
the center of the classic lobule and the periphery of the portal lobule are the first to be affected.
6. Venous portal blood flows from the periphery to the center in the classic hepatic lobule
and from the center to the periphery in the portal hepatic lobule. In such a case, the periphery of
the classic lobule and the center of the portal lobule are the first to be affected.
7. Experimental ligation of the main pancreatic duct causes the death of exocrine
glandulocytes. The endocrine cells of the pancreatic islets survive after the operation, because they
are not associated with the duct system and release hormones into the islet blood capillaries.
8. In this case, B cells of the pancreatic islets function with overstrain. B cells are
adenohypophysis-independent and regulated by glucose blood levels. If people eat a lot of sweets,
their blood glucose levels rise and stimulate B cells to produce insulin.

Respiratory System
1. Inspired air is filtered out in the respiratory passages by the mechanism called the
“mucociliary escalator.” Goblet cells of the epithelium lining the respiratory passages produce
mucus that precipitates dust and foreign particles from inspired air. The cilia of the epithelial
ciliated cells sweep the mucus with dust particles towards the nasal cavity. The particles reaching
the alveoli are phagocytosed by pulmonary macrophages. The macrophages subsequently migrate
from the alveolar space to interalveolar connective tissue.
2. This blood vessel belongs to the pulmonary circulation.

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 3. This is a type II pneumocyte. Its main function is surfactant production. In extensive
destruction of alveoli, type II pneumocytes act as stem cell precursors for type I alveolar cells.
4. Elastic fibers of the interalveolar septa actively reduce the volume of the pulmonary
alveoli on expiration. Lysis and destruction of the interalveolar elastic fibers are associated with
pulmonary emphysema.
5. Smooth muscle cells of the lamina muscularis mucosa cause a sudden spasm in bronchial
asthma. The constriction of small bronchi is markedly pronounced, because their muscularis
mucosa is well-developed but there are no cartilage plates.

Integumentary System: Skin and Appendages

1. The epidermis lacks blood vessels and is supplied by diffusion from the underlining loose
connective tissue. But the epidermis contains macrophages (Langerhans cells) and T lymphocytes
migrating from the dermis.
2. This skin area is the thick skin covering the palms and the soles. The glands revealed in
the biopsy material are the sweat glands. They are simple nonbranched tubular coiled glands with
the merocrine mode of secretion.
3. The so-called “goose flesh” results from constriction of the arrector pili muscle attached
to the connective tissue sheath of the hair follicle. The muscles raise the hair causing goose pimple
appearance.
4. Melanocytes located in the epidermis of the thin skin are responsible for this reaction.
These cells produce melanin and provide keratinocytes with it. Melanin protects the skin from
ultraviolet light and the ionizing effect of electromagnetic radiation.
5. The choice is not correct. The thick skin contains sweat glands with the merocrine mode
of secretion and lacks holocrine sebaceous glands.
6. The finger skin is characterized by the unique papillary print, because its papillary dermis
layer consists of numerous high (up to 2 mm) papillae. In the face skin, the dermal papillae are
small, sparse, and may disappear with age.

Urinary System
1. This is the renal cortex, because the renal medulla lacks renal corpuscles. The cortex
contains the following tubules: convoluted (proximal and distal) tubules and straight tubules of the
medullary rays (the initial parts of collecting tubules and straight nephron tubules).
2. Mesangial cells are located in the renal corpuscles between the capillary loops. An
increase in the number of mesangial cells decreases the surface of the filtration barrier and reduces
filtration.

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 3. In such a case, the filtration barrier is damaged, because the filtration barrier prevents
erythrocytes from passing into the primary urine.
4. In such a case, the proximal convoluted tubules are affected, because glucose is
reabsorbed by the epithelial cells of the proximal tubules. The epitheliocyte brush border that takes
part in reabsorption is damaged.
5. The first renal corpuscle belongs to the juxtamedullary nephron, which hardly takes part
in filtration and urine production. The second renal corpuscle belongs to the cortical nephron,
which is very active in filtration.
6. The morphofunctional disorder of the juxtaglomerular apparatus may lead to the
development of renal hypertension.
7. Both of them are right. The renal macula densa consists of the epithelial cells of the distal
convoluted tubules and belongs to the juxtaglomerular apparatus where it functions as sodium
osmoreceptors.

Male Reproductive System

1. Spermatogenic cells are sensitive to temperature. The temperature in the peritoneum is
higher than in the scrotum; therefore, in cryptorchism spermatogenesis fails to occur.
2. The testis trauma damages the blood–testis barrier that maintains immune homeostasis in
the seminiferous tubules. An autoimmune reaction develops and specific antibodies against
spermatogenic cells desolate the seminiferous tubules.
3. The cell is a primary spermatocyte that represents the spermatogenic stage of growth.
4. The cell is a spermatid that represents the spermatogenic stage of formation.
5. The FSH acts on Sertoli cells stimulating ABP production. The LH acts on Leydig cells
stimulating the secretion of testosterone. In the experiment described, the secretory activity of
these testicular cells is inhibited.
6. This prostate gland structure is typical of elderly and old men.

Female Reproductive System

1. The first slide shows the ovary morphology typical of prepuberty; the second slide, of the
reproductive period; the third slide, of the preclimacteric period.
2. In such a case, the ovarian cycle lacks the ovulation (anovulatory cycle), because the LH
peak fails to occur. The ovaries contain follicles at different stages of development (except
Graafian follicles), atretic follicles, and atretic bodies but lack the corpus luteum. The ovaries
produce estrogens during the whole cycle.

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 3. The endometrium morphology corresponds to the secretory (premenstrual) phase of the
menstrual cycle. The ovarian corpus luteum is characteristic of this phase. Progesterone is
predominantly produced during this phase.
4. This ovary morphology is not normal, because the corpus luteum is absent on the 22nd
day of the cycle. It means that ovulation did not occur; therefore, pregnancy is impossible.
5. Progesterone production by the corpus luteum of pregnancy was impaired inducing the
miscarriage.
6. Oxytocin is responsible for milk release in a breast-feeding woman; milk secretion is
regulated by prolactin. In this case, the circulating oxytocin levels decrease, but the prolactin levels
are normal.

Human Embryology: Initial Stages of Embryonic Development

1. The enzymes released from the acrosome facilitate the sperm passage through the oocyte
envelopes. If acrosome formation is impaired, the sperm cannot penetrate an ovum.
2. All the students are right.
3. This cell is a human zygote called a synkaryon, because it contains two (male and female)
pronuclei. The zygote is surrounded by the zona pellucida. The zygote corresponds to the final
stage of fertilization.
4. The embryo corresponds to the final stage of cleavage (blastula formation). The human
blastula is called a blastocyst, because it looks like a vesicle. The blastocyst is implanted into the
endometrium.
5. Human fertilization is characterized by monospermy due to the cortical reaction
preventing multiple sperm penetration. Identical twins result from separation of two blastomeres
and the embryoblast or primitive streak duplication.
6. After the first or the second cleavage divisions, blastomeres retain the zygote
totipotentiality and may develop into an embryo. The blastula blastomeres undergo determination,
become pluripotential, but cannot give rise to an embryo.
7. The first student is right. In human gastrulation, all the three germ layers (ectoderm,
mesoderm, and endoderm) arise from the epiblast. The hypoblast does not take part in the
formation of the embryo body proper and is displaced to extraembryonic regions.
8. The mesenchyme arises from the mesoderm at the stage of the axial organ formation. The
mesenchyme gives rise to blood vessels, blood, all types of connective tissue, smooth muscle cells,
microglial cells, and the endocardium.
9. It is not a human embryo. In human embryogenesis, only the body folds develop; the
amniotic folds fail to appear, because the amnion forms earlier, in the second week of gestation.

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 Human Embryology: Embryonic Period, Provisory Organs, and Placentation
1. The embryo is in the second week of development. The embryo looks like a bilaminar
disk that corresponds to the first stage of gastrulation. The embryo is associated with the amniotic
vesicle and the yolk sac.
2. The female sex hormone progesterone prepares the endometrium for implantation.
Progesterone is produced by the ovarian corpus luteum. After the ovariectomy, the experimental
female rat lacks progesterone, which makes implantation impossible.
3. The urine of a pregnant woman contains human chorionic gonadotropin (hCG) that
stimulates folliculogenesis in the ovaries of immature female mice. This hormone is secreted by
the chorionic syncytiotrophoblast into maternal blood and then excreted in maternal urine. Human
chorionic gonadotropin maintains the maternal corpus luteum and stimulates it to continue
progesterone production. The detection of hCG in the woman’s urine is an early pregnancy test.
4. No, the student is not right. The placental intervillous spaces or lacunae contain maternal
blood from the eroded endometrial arteries. Fetal blood flows in the blood vessels of the chorionic
villi.
5. In placenta, fetal blood never mixes with maternal blood owing to the placental barrier
that is characterized by selective permeability. Most medicines may pass through the placental
barrier and be found in the fetal body. Some of them, e.g., thalidomide, cause congenital
malformations.
6. The picture is correct. By the end of the second month of gestation, the yolk sac and the
allantois degenerate; after that, their remnants exist as parts of the umbilical cord.

CONTROL TESTS: KEY

Cytology
1 E 11 C 21 E 31 B
2 D 12 E 22 E 32 B
3 B 13 C 23 A 33 A
4 C 14 A 24 B 34 E
5 B 15 B 25 E 35 C

327
6 A 16 D 26 E 36 D
7 C 17 C 27 E 37 E
8 E 18 B 28 A 38 D
9 C 19 A 29 E
10 A 20 D 30 C
Epithelial Tissues
1 D 7 C 13 A 19 A
2 B 8 A 14 A 20 D
3 B 9 D 15 E 21 B
4 A 10 C 16 C 22 A
5 C 11 A 17 B
6 E 12 E 18 A
Blood and Lymph
1 D 7 E 13 E 19 B
2 A 8 C 14 B 20 C
3 D 9 D 15 C 21 B
4 D 10 B 16 D 22 A
5 B 11 E 17 D 23 B
6 A 12 A 18 B 24 B
Connective Tissues
1 A 7 B 13 A 19 A
2 B 8 E 14 E 20 A
3 C 9 C 15 A 21 A
4 E 10 D 16 E 22 B
5 D 11 B 17 E 23 C
6 A 12 C 18 E 24 A
Skeletogenic Tissues: Cartilage and Bone Tissues
1 D 8 A 15 E 22 A
2 B 9 E 16 E 23 B
3 D 10 C 17 D 24 E
4 C 11 D 18 A 25 B
5 E 12 B 19 E 26 D
6 A 13 A 20 A 27 E
7 D 14 E 21 B 28 E

328
Muscle Tissues
1 E 8 D 15 E 22 E
2 B 9 C 16 E 23 A
3 A 10 E 17 C 24 A
4 C 11 C 18 E 25 E
5 B 12 D 19 E 26 A
6 D 13 B 20 E 27 C
7 E 14 E 21 A
Nervous Tissue
1 D 8 A 15 A 22 A
2 E 9 E 16 A 23 E
3 C 10 D 17 C 24 A
4 B 11 B 18 A 25 A
5 C 12 C 19 E 26 A
6 E 13 B 20 E 27 C
7 C 14 D 21 B 28 E
Nervous System
1 B 8 A 15 E 22 C
2 D 9 E 16 B 23 A
3 C 10 E 17 E 24 A
4 A 11 D 18 A 25 A
5 D 12 B 19 E 26 E
6 B 13 B 20 E 27 A
7 D 14 C 21 A 28 A
Primary Sentient Sense Organs: Organ of Vision and Organ of Smell
1 E 9 E 17 E 25 B
2 B 10 B 18 A 26 E
3 A 11 D 19 E 27 E
4 C 12 A 20 E 28 E
5 B 13 D 21 A 29 A
6 E 14 E 22 E 30 A
7 C 15 D 23 A 31 E
8 B 16 A 24 C

329
Secondary Sentient Sense Organs: Organ of Hearing, Organ of Equilibrium,
and Organ of Taste
1 C 8 D 15 B 22 D
2 B 9 E 16 E 23 A
3 D 10 B 17 A 24 A
4 A 11 D 18 E 25 A
5 E 12 A 19 C 26 A
6 C 13 E 20 A
7 B 14 C 21 B
Cardiovascular System
1 C 9 C 17 E 25 A
2 B 10 D 18 E 26 C
3 E 11 E 19 A 27 A
4 A 12 B 20 B 28 A
5 B 13 A 21 C 29 A
6 C 14 B 22 D 30 C
7 D 15 A 23 A 31 E
8 D 16 E 24 A 32 E
Central Organs of Hemopoiesis: Red Bone Marrow and Thymus
1 D 8 D 15 E 22 B
2 C 9 B 16 E 23 A
3 A 10 E 17 E 24 A
4 E 11 C 18 C
5 B 12 E 19 D
6 D 13 E 20 A
7 E 14 A 21 E
Peripheral Organs of Hemopoiesis and Immunogenesis
1 C 8 B 15 D 22 D
2 C 9 D 16 A
3 E 10 A 17 A
4 B 11 D 18 E
5 C 12 E 19 A
6 B 13 B 20 A
7 D 14 A 21 A

330
Endocrine System
1 D 10 B 19 C 28 A
2 B 11 D 20 A 29 E
3 A 12 E 21 A 30 E
4 D 13 A 22 A 31 E
5 C 14 D 23 B 32 A
6 B 15 D 24 B 33 B
7 D 16 B 25 B 34 E
8 A 17 A 26 A
9 D 18 A 27 E
Digestive System: Oral Cavity and Esophagus
1 D 8 B 15 B 22 E
2 A 9 A 16 E 23 E
3 C 10 C 17 A
4 B 11 E 18 D
5 E 12 A 19 E
6 B 13 E 20 B
7 D 14 C 21 D
Digestive System: Stomach and Small Intestine
1 C 8 B 15 E 22 E
2 A 9 D 16 D 23 A
3 E 10 A 17 A 24 A
4 B 11 D 18 E 25 E
5 D 12 E 19 D 26 E
6 B 13 D 20 A 27 E
7 E 14 E 21 E
Digestive System: Large Intestine, Liver, and Pancreas
1 B 9 C 17 C 25 E
2 E 10 E 18 B 26 D
3 C 11 E 19 A 27 A
4 D 12 B 20 A 28 A
5 A 13 D 21 E 29 E
6 B 14 C 22 E
7 D 15 B 23 A

331
8 A 16 E 24 B
Respiratory System
1 D 8 E 15 E 22 E
2 B 9 C 16 E
3 E 10 B 17 D
4 C 11 A 18 D
5 A 12 E 19 A
6 D 13 A 20 E
7 B 14 A 21 E
Integumentary System: Skin and Appendages
1 D 6 A 11 E 16 A
2 C 7 D 12 E 17 B
3 B 8 A 13 A 18 A
4 E 9 B 14 E 19 B
5 C 10 C 15 E 20 E
Urinary System
1 C 8 D 15 E 22 E
2 B 9 E 16 A 23 E
3 E 10 D 17 C
4 D 11 C 18 E
5 A 12 A 19 A
6 C 13 E 20 A
7 B 14 E 21 A
Male Reproductive System
1 C 8 D 15 E 22 E
2 B 9 A 16 E 23 E
3 E 10 D 17 B 24 A
4 A 11 D 18 D 25 E
5 D 12 B 19 B 26 A
6 C 13 A 20 C
7 E 14 C 21 E
Female Reproductive System: Ovaries
1 E 7 C 13 A 19 E
2 C 8 D 14 A 20 A

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3 B 9 B 15 E 21 E
4 E 10 E 16 B
5 D 11 A 17 E
6 A 12 E 18 E
Female Reproductive System: Reproductive Cycle, Uterus, Oviducts, Vagina,
and Mammary Glands
1 B 7 E 13 A 19 A
2 D 8 A 14 B 20 B
3 E 9 B 15 E 21 E
4 C 10 C 16 B 22 E
5 A 11 E 17 E 23 C
6 E 12 E 18 E
Human Embryology: Initial Stages of Embryonic Development
1 C 8 A 15 B 22 E
2 A 9 D 16 E 23 A
3 E 10 C 17 A 24 C
4 D 11 E 18 E 25 E
5 B 12 D 19 E
6 C 13 A 20 A
7 E 14 E 21 E
Human Embryology: Embryonic Period, Provisory Organs, and Placentation
1 D 9 B 17 A 25 A
2 A 10 D 18 C 26 E
3 C 11 B 19 E 27 B
4 D 12 A 20 C 28 B
5 A 13 A 21 E 29 E
6 E 14 A 22 A
7 D 15 E 23 C
8 A 16 E 24 E

CONTENTS:
Cytology
Epithelial Tissues
Blood and Lymph

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Connective Tissues
Skeletogenic Tissues: Cartilage and Bone Tissues
Muscle Tissues
Nervous Tissue
Nervous System: Peripheral Nervous System and Spinal Cord
Nervous System: Brain
Primary Sentient Sense Organs: Organ of Vision and Organ of Smell
Secondary Sentient Sense Organs: Organ of Hearing, Organ of Equilibrium, and Organ of
Taste
Cardiovascular System
Central Organs of Hemopoiesis: Red Bone Marrow and Thymus
Peripheral Organs of Hemopoiesis and Immunogenesis
Endocrine System
Digestive System: Oral Cavity and Esophagus
Digestive System: Stomach and Small Intestine
Digestive System: Large Intestine, Liver, and Pancreas
Respiratory System
Integumentary System: Skin and Appendages
Urinary System
Male Reproductive System
Female Reproductive System: Ovaries
Female Reproductive System: Reproductive Cycle, Uterus, Oviducts, Vagina, and
Mammary Glands
Human Embryology: Initial Stages of Embryonic Development
Human Embryology: Embryonic Period, Provisory Organs, and Placentation
Control Problems: Answers and Explanations
Control Tests: Key

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