Carte Finala 2015

Ioana Cristina AMIHĂESEI
Liliana CHELARU
Elena COJOCARU
HISTOLOGY
Organs and Systems
- PRACTICAL WORKS -
Descrierea CIP a Bibliotecii Naţionale a României
AMIHĂESEI, IOANA CRISTINA
Histology – Organs and Systems. Practical Works /
----------------------------------------------
Editura şi tipografia STEF

700705, Iaşi, Bd. Carol I nr. 8 (în clădirea Academiei Române)
Tel/fax: 0232-216829, Mobil: 0745-236413
E-mail: office@editurastef.ro, http://www.editurastef.ro
Ioana Cristina AMIHĂESEI
Liliana CHELARU
Elena COJOCARU
HISTOLOGY
Organs and Systems
- PRACTICAL WORKS -
Editura Stef
Iaşi, 2015
TABLE OF CONTENTS
TABLE OF CONTENTS................................................................5
I. Lymphoid (immune) system..............................................7
I.1. Thymus.................................................................................7
I.2. Lymph node........................................................................12
I.3. Spleen................................................................................17
I.4. Mucosal attached lymphoid tissue/MALT..........................21
II. Endocrine system.............................................................24
II.1. Pituitary gland....................................................................24
II.2. Thyroid..............................................................................28
II.3. Parathyroid glands............................................................31
II.4. Adrenal (suprarenal) glands..............................................33
III. Digestive system...............................................................37
III.1. The lips.............................................................................37
III.2. Tongue.............................................................................39
III.3. General organization of the digestive tract......................43
III.4. Esophagus.......................................................................44
III.5. Stomach...........................................................................46
III.6. Small Intestine..................................................................51
III.7. Appendix..........................................................................57
III.8. Large Intestine/colon........................................................58
III.9. Glands of the digestive system. The Liver......................60
III.10. Pancreas........................................................................64
III.11. Major Salivary glands.....................................................67
IV. Respiratory System..........................................................73
IV.1. Nasal cavity......................................................................73
IV.2. Olfactory mucosa.............................................................74
IV.3. Larynx..............................................................................75
IV.4. Trachea............................................................................75
IV.5. Bronchial tree...................................................................79
IV.6. Lung alveoli......................................................................82
V. Urinary System..................................................................85
V.1. Nephron............................................................................86
V.2. Collecting tubules.............................................................91
V.3. Juxtaglomerular apparatus...............................................92
V.4. Urinary passages..............................................................93
VI. Female Reproductive System..........................................97
VI.1. Ovaries.............................................................................97
VI.2. Oviducts/fallopian tubes.................................................105
VI.3. Uterus............................................................................107
VI.4. Mammary Glands..........................................................110
VI.5. Placenta.........................................................................113
VII. Male Reproductive System............................................116
VII.1. Testes...........................................................................116
VII.2. Male genital ducts.........................................................120
VII.3. Seminal vesicles...........................................................123
VIII. Integument.......................................................................126
IX. References.......................................................................133
I. LYMPHOID (IMMUNE) SYSTEM
I.1. THYMUS
Thymus is a primary lymphoid organ, where are dividing

and maturing T lymphocytes; it has double epithelial
(endodermic) and mesenchymal origin being located in the upper
part of the mediastinum. From the outer dense connective tissue
capsule are deriving septa, which are dividing the thymus into
incomplete lobules; thymic lobules are communicating through
their central medullary zones.
Each thymic lobule is a unit of the thymus and it shows two
zones: a deep basophilic peripheral cortex, and a lighter more
acidophilic central medulla. Cell population is grossly the same in
the cortex and in the medulla of the thymic lobule, only the
proportion of the cell types is different; in the cortex are
predominating T lymphocytes originating in the bone marrow,
here submitted to a complex process of differentiation and
maturation. In the medulla there are fewer T cells and more
numerous epithelial reticular cells of the stroma and
macrophages.
Thymus is the sole organ which shows a stroma of epithelial
nature; stromal cells have processes by which they establish
junctions one with another and they are forming the stroma of the
thymus, being also most important component of the blood-
thymus barrier. The development of the immunological
competence of the T cells, elimination of the self-reactive T
7
Ioana Cristina AMIHĂESEI • Liliana CHELARU • Elena COJOCARU
lymphocytes and recognition of MHC antigens take place in the

thymus cortex. Large number of T lymphocytes found in the
cortex is responsible for its deep basophilic aspect in light
microscopy; besides lymphocytes, in the thymic cortex are found
macrophages and epithelial reticular cells.
Fig. 1. Thymic lobule HEx40
8
HISTOLOGY - Organs and systems • Practical Works
Fig. 2. Thymus HEx40
In the cortex of the thymus are present three types of

epithelial reticular cells:
1. Type I cells are isolating the parenchyma from the
connective tissue capsule and the trabeculae arising
from the capsule and are surrounding the blood vessels
of the cortex, they show occluding junctions between
them, being an important part of the blood-thymus
barrier.
2. Type II cells show long processes which are establishing
desmosomal junctions between the cells, forming
compartments where are hosting T cells during their
differentiation (anciently known as nurse cells).
3. Type III epithelial reticular cells are found at the
corticomedullary junction; besides hosting T
lymphocytes, they isolate the cortex from the medulla.
The stromal cells are developing an antigen-free
environment for the proper maturation of the T
lymphocytes; type II and type III cells, as well as antigen
presenting cells known as interdigitating cells are
presenting the self antigens of the major histo-
compatibility (MHC) complex to the developing T cells.
Cells which TCRs recognize the self, or which CD4 or
CD8 markers cannot identify MHC I, respectively MHC II
molecules are excluded by apoptosis; 98 % of the cortex
T cells die here and are phagocytosed by macrophages.
The small surviving percentage of T cells is reaching the
medulla or is leaving the thymus through the
postcapillary HEV (high endothelial venule) found at the
9
corticomedullary junction and is further colonizing the

secondary lymphoid organs.
In the medulla are predominating the epithelial reticular cells

and the macrophages, conferring a lighter acidophilic stain to this
zone of the thymic lobule. In the medulla are present the
Hassall’s corpuscles, which are most characteristic for the
thymus and its recognition in light microscopy. Epithelial reticular
cells in the Hassall’s corpuscle show a concentric disposition and
they become keratinized and even calcified; the number and size
of the Hassall’s corpuscles are increasing with the age of the
individual (from 25 -30 μm to 100 μm or more). In the medulla are
present epithelial reticular cells type IV which with type III, are
forming the corticomedullary junction; epithelial reticular cells
type V are forming the stroma of the medulla, while type VI are
forming the Hassall’s corpuscles.
Fig. 3. Thymus Hassall corpusclex40
10
Fig. 4. Thymus Hassalll's corpuscles HEx100
Fig. 5. Thymus medulla HEx100
11
The high endothelial venules are found at the limit between

cortex and medulla; they show tall cuboidal endothelial cells
which may recognize fully matured T lymphocytes and allow them
to pass in the general circulation, without reaching the medulla.
Blood–thymus barrier provided by epithelial reticular cells, mainly
type I, encircling the vessels and isolating the parenchyma of the
thymus from the capsule and its septa, by the occluding junction
of the endothelial cells of the thymic capillaries and by the
macrophages phagocytosing any antigenic material which yet
escaped into the parenchyma is less effective in the medulla than
in the cortex.
Thymus is submitted to a process of involution, with age the
lymphoid tissue being replaced by adipose and connective tissue;
nevertheless small territories of T lymphocytes here developing
are found in the thymus, even in advanced age individuals.
Recognition criteria in light microscopy:
- presence of thymic lobules, triangular shaped, limited by
septa, with basophilic cortex and rather acidophilic
medulla in periphery;
- Hassall’s corpuscules in the medulla of the thymic
lobules;
- absence of the lymphoid nodules in the thymus is the
main criterion which is differentiating it from the
secondary lymphoid organs, such as lymph node, spleen
etc.
I.2. LYMPH NODE
Lymph nodes are small bean-shaped structures found as

small stations on lymphatic circulation, which are filtering the
12
lymph. They are located in the neck, axilla, groin, along largest
blood vessels and in the body cavities.
They are secondary lymphoid organs (as are also the
spleen, tonsils, appendix) meaning main sites of humoral and
cellular immune responses development in the organism. They
show less than 3 cm in diameter and exhibit the common
histologic organization of the lymphoid organs – a dense
connective tissue capsule, a stroma and a parenchyma. The
convex margin is penetrated by the afferent lymph vessels, while
at the concave margin is found the hilum, through which are
exiting the efferent lymph vessels; here are present the blood
vessels and nerves of the organ.
In histologic section we observe a dense lymphoid area in
periphery, surrounding the node just below the capsule, with the
exception of the hilum, known as the cortex or cortical area of
the lymph node and a more loose lymphoid (with a low density of
lymphocytes) area in the center, representing the medulla or
medullary zone. Medulla is occupied mainly by large, dilated
medullary sinuses, well visible in light microscopy.
The cortex is subdivided into two zones – a peripheral
cortex, known as superficial/nodular cortex and a deeper zone
– the deep cortex or paracortex. The superficial cortex is
colonized by B lymphocytes originating in the bone marrow; B
lymphocytes are characteristically disposed into spherical
structures, known as lymphoid nodules. Paracortex or deep
cortex is populated by T lymphocytes, which show instead a
diffuse disposition; T lymphocytes do not form lymphoid
nodules.
13
Fig. 6. Lymph node capsule; secondary lymphoid nodule HEx40
Lymphoid nodules may show two different aspects

according to their estate of activity or repos. Primary lymphoid
nodules are inactive, meaning B lymphocytes there were not
submitted to any antigenic stimulation. Their aspect in
microscopy is rounded, basophilic and homogenous, these
nodules being made mainly by mature small B lymphocytes.
Secondary lymphoid nodules are the result of the
antigenic stimulation of the B lymphocytes; they show a pale
center, known as germinal or clear center and a deep
basophilic crown of lymphocytes in periphery. The clear center
is made especially of B lymphocytes regressed into a younger
stage, as result of the antigenic stimulus – B lymphoblasts; these
cells have a larger amount of cytoplasm and a paler nucleus than
that of the small mature lymphocytes, being responsible for the
pale acidophilic nuance of the clear center of the lymphoid
nodules. Clear center is also containing macrophages, plasma
14
cells (effectors of the humoral immune response, antibody

secreting cells).
Fig. 7. Lymph node supeficial cortex x 40
Fig. 8. Lymph node paracortex; medulla HEx40
15
The lymphocytic crown in periphery is made almost entirely

of small mature B lymphocytes, with their characteristic deep
basophilic aspect. Outer nodular cortex of the lymph node is the
site of ruling out of the humoral immune response in the
organism.
Inner/deep cortex or paracortex is a thymus dependent
area colonized with T lymphocytes, which show characateristic
diffuse disposition; usually is underdeveloped compared to
outer/nodular cortex. This is the site where is ruled out the
cellular immune response in the organism (against tumor cells,
viruses, fungi, intracellular bacteria etc.)
Medulla of the lymph node is made of large lymph sinusoid
capillaries, the medullary sinuses and the so-called medullary
cords, improperly named cords, in fact crowding of cells
circulating in the lymph aligned along the sinuses – B and T
lymphocytes, macrophages and plasma cells.
Fig. 9. Medulla; medullary cord medullary sinus HEx100
16

- ovoid section with better stained periphery – the cortex
and much paler center – the medulla;
- well visible large secondary lymphoid nodules, with clear
germinal centers in periphery – the outer/superficial
cortex of the lymph node;
- in the center are present large empty lumens of
medullary sinuses, interposed with the cells of the
medullary cords, forming the medulla of the organ;
- difference with the thymus and with the spleen, we do
not find neither lobules in the lymph node, like in the
thymus, nor arterioles surrounded by numerous
lymphocytes, like in the spleen. Crypts or digestive
mucous layer are also absent here, differentiating the
lymph node from the palatine tonsils, the Peyer patches
of the ileum or the appendix;
I.3. SPLEEN
The spleen is the largest lymphoid organ of the human

organism, with a weight of approximately 150-180 g in adults.
Spleen is filtering the blood, capturing antigens penetrated in it.
With the naked eye we observe in the spleen two big territories –
most of it is made of a red-brownish tissue, like a blood-filled
sponge; this is the red pulp of the spleen which is following the
venous circulation of the organ. In this sponge mass filled with
blood, here and there are appearing small white-yellowish
nodules, representing the white pulp of the spleen, organized
around the arteriolar branches of the organ. Histologically, we
find a dense connective tissue capsule, a stroma and a
17
parenchyma. From the capsule are arising septa which do not

define lobules in human specie.
Fig. 10. connective tissue septum; spleenHEx 100
Fig. 11. Spleen lymphoid nodule; arteriole; white pulpx40
18
Fig. 12. Spleen; white pulp surrounded by red pulp HEx40
White pulp is represented by thymus dependent areas – T

lymphocytes crowding around an arteriole and forming so-called
periarteriolar lymphoid sheath/PALS, a site of cellular immune
response of the organism. To the outside of this first zone is
appearing a thymus independent area, colonized with B
lymphocytes, lymphoid nodule of the spleen/Malpighian
corpuscle of the spleen. We observe that in the white pulp of
the spleen are present sites of both humoral and cellular immune
responses, surrounding directly the arteriolar branches of the
splenic artery. At the periphery of the lymphoid structures forming
the white pulp of the spleen is present the so-called
marginal/mantle zone; this is an important site of antigenic
contact of the organism, here are trapped blood-circulating
antigens and also from this zone are passing into the venous
sinuses, like that reaching in the general circulation activated
lymphocytes, developed in the white pulp of the spleen.
19
Red pulp is mainly formed by the system of venous

sinusoid capillaries of the spleen, interposed with crowding of
cells, known as the Billroth cords of the red pulp of the spleen.
Fig. 13. Spleen red pulp; Bilroth cord, sinusoid HEx 100
Venous sinusoid of the spleen is a typical sinusoid

capillary, with a discontinuous wall, in what concern both the
basement membrane and the endothelial cells. The wall of the
sinusoid capillary is basically made of a wire of reticular fibers
disposed in a longitudinal direction and intersected by others
which show a perpendicular disposition on the first (compared
with the doves and the circles of a barrel). Between the reticular
fibers are left free spaces of approximately 2 μm in diameter,
through which blood cells are passing freely. Aged red blood cells
becoming rigid are trapped in these small spaces, afterwards
being phagocytosed by extremely active splenic macrophages.
Spleen is the main site of removal from the circulation of the aged
blood cells.
20
Billroth cords may contain besides immune cells

(lymphocytes, macrophages and plasma cells) any circulating
blood cell.
- lymphoid nodules centered by an arteriole; sometimes
the arteriole appears eccentrically placed toward the
crowding of lymphocytes of the white pulp of the spleen;
- large predominating area made of the venous sinusoids,
which may appear empty or sometimes may contain
blood cells in their lumen, forming most of the red pulp;
between them the crowding of cells are representing the
Billroth cords; presence of thick connective tissue septa,
sectioned in different incidences, deep acidophilic in light
microscopy.
- difference with the thymus – absence of lobules, with
cortex and medulla; difference with the lymph node –
absence of outer cortex and medulla and presence of
arterioles (more often cross sectioned, sometimes
obliquely or more longitudinally sectioned).
I.4. MUCOSAL ATTACHED LYMPHOID

TISSUE/MALT
Main characteristics of the MALT are:

 absence of a proper capsule, being covered by the
tissues of the organ where they are situated;
 absence of a proper stroma and a proper circulation,
being vascularized by the vessels of the organ and
21
sharing with the organ where it appears the same

stroma;
These structures are functioning as secondary lymphoid

organs; such organs are the tonsils, the appendix, ileum. MALT is
best developed in the digestive tract, but is also present in the
respiratory tract, in the skin, in the genito-urinary tract (BALT –
bronchial attached lymphoid tissue; SALT – skin attached
lymphoid tissue).
Palatine tonsils are masses of lymphoid tissue situated on
the lateral walls of the pharynx; they are covered by oral type
epithelium – stratified squamous nonkeratinized epithelium which
is invaginating to form crypts, each tonsil is showing 10-15 crypts,
main criterion for identification of the palatine tonsil in light
microscopy. Beneath the epithelium are appearing numerous,
crowded secondary lymphoid nodules; between this thymus
independent areas are appearing small thymus dependent areas,
zones of T lymphocytes which show the usual diffuse disposition.
At the base of the tonsil is found a layer of dense connective
tissue – the capsule of the palatine tonsil, limiting the spreading
of the tonsil’s infections in the deeper regions of the neck.
Pharyngeal tonsil is situated in the superior part of the
naso-pharynx being made of a single mass of lymphoid tissue
covered by respiratory epithelium (pseudostratified ciliated
columnar); it does not show crypts. The hypertrophy of this tonsil
results in the appearance of the adenoids.
Lingual tonsils are very small lymphoid structures situated
at the base of the tongue; they present each just one crypt.
22
 oral type epithelium forming crypts and covering

numerous, crowded secondary lymphoid nodules;
absence of lobules, cortex and medulla or arterioles to
center the lymphoid nodules.
Fig. 14. Palatine tonsil; secondary lymphoid nodule; palatine glandx40
23
Fig. 15. Crypt palatine tonsil;trichromex40
II. ENDOCRINE SYSTEM
Endocrine system is one of the main control systems of

the organism; endocrine cells may form proper endocrine glands
(pituitary, thyroid, adrenal, parathyroids) or may appear as
isolated cells spread between the lining epithelial cells of different
tracts (digestive, respiratory, urinary) forming the diffuse
neuroendocrine system/DNES and somehow similar to the
DNES, in the case of the Langerhans islets of pancreas and the
endocrine cells of the gonads.
24
II.1. PITUITARY GLAND
Pituitary gland is controlling the activity of the others

endocrine glands and also different functions of the organism,
behaving like an endocrine brain of the organism. It is a very
small gland of only 0.5-1 g in adult, situated in a depression of
the sphenoid bone, the sella turcica. As histologic organization,
pituitary is made of cords of endocrine cells which show a
reticular arrangement, with some zones with glomerular aspect.
Between the cords of endocrine cells are present fenestrated
capillaries, through the wall of which the pituitary hormones are
passing into the blood stream. An expansion of the dura mater
forms the capsule of the gland. Pituitary is linked with the
hypothalamus by the infundibulum/the stalk, thus forming the
hypothalamic-pituitary system. The activity of the pituitary is
controlled by neurohormones secreted in the hypothalamus –
releasing-factors, which are stimulating the secretion of different
pituitary hormones (like GH-RH, TRH or CRH) and inhibiting-
factors (like somatostatin, dopamine or inhibins) which are
inhibiting the secretion of some pituitary hormones. The
neurohormones are reaching to pituitary cells via the circulating
blood, through the hypothalamic-pituitary portal system.
In light microscopy, using special staining methods are
identifiable two big categories of cells – cells which show affinity
for dyes, known as chromophils, representing 60 % of the
pituitary cell population and cells which show no affinity for dyes,
chromophobs, with grayish aspect and representing 40 % of the
pituitary cell population.
25
Choromophils according to their affinity are divided into

acidophilic cells linking acidic dyes and basophilic cells, with
affinity for basic dyes.
Acidophilic cells are secreting hormonal polypeptides and
are represented by GH (growth hormone) secreting cells, are
most numerous of the acidophilic cells, situated mainly in the
periphery of the anterior lobe of the pituitary/pars distalis (the
endocrine active, secretory part of the pituitary) and are linking an
orange dye. GH is stimulating the growth and ossification of the
growth cartilages/epiphyseal plates, till the end of the growth
period, thus determining the final stature of the individual. It is
also an anabolic hormone, influencing the metabolism. The lack
of hormone is leading to the pituitary dwarfism, a severe
dwarfism, but unlike other types of dwarfism, with a normal
mental development. The secretion in excess during growth
period is resulting in gigantism; afterwards will determine the
development of acromegaly, with overgrowth of the extremities.
Secretion of GH/somatotrop (STH) is stimulated by the
hypothalamic GH-RH and inhibited by somatostatin, produced by
both hypothalamus and DNES (mostly DNES of the digestive
tract and pancreas).
Another category of acidophilic cells are represented by
the prolactin secreting cells, which are linking a carmine dye;
they stimulate the secretion of milk in the mammary glands, at the
final part of pregnancy and after parturition. Outward lactation,
prolactin secreting cells are inhibited by the dopamine secreted in
the hypothalamus (known also like prolactin inhibiting factor –
PIF); with the pregnancy the inhibitory power of dopamine is
overcome and the mammary gland starts to secrete milk. Stop of
26
the breast-feeding is leading to the increase of the dopamine

secretion and inhibits the prolactin secretion.
Chromophobes cells are reserve cells or degranulated
chromophils, but an important part of them is represented by
adrenocorticotropin/ACTH secreting cells. These cells become
basophilic when the adrenal cortex of the adrenal glands is
destroyed. ACTH stimulates zone fasciculata and zone reticularis
of the adrenal cortex, stimulating the secretion of glucocorticoids,
mainly cortisol, respectively of adrenal androgens. The feed-back
of control is achieved by cortisol which is acting directly on the
hypothalamic releasing hormone – CRH /corticotropin releasing
hormone, through a high/long loop of retrocontrol. First is
secreted a larger molecule, known as big ACTH, from which are
resulting by cleavage ACTH, MSH (melanocyte stimulating
hormone) and endorphins (endogenous opiate/opium-like
substances).
Basophilic cells secrete hormonal glycoproteins being
stained with PAS method. There are two categories of basophilic
pituitary cells; a small number of deep basophilic, angular cells,
arranged in small clusters near capillaries secrete
thyrotropin/TSH (thyroid-stimulating hormone). TSH
stimulates the development and function of the thyroid gland; the
feed-back is done by the thyroid hormones – T4/thyroxine and
T3/triiodthyronine, through a short loop of control; they are acting
directly on the pituitary TSH.
Another category of basophils are the gonadotropin-
secreting cells; they are more numerous, rounded and lower
basophilic than throtropin-secreting cells; in both sexes they
secrete the two gonadotropins FSH/follicle-stimulating
hormone and LH/luteinizing-hormone (known in male sex as
27
ICSH – interstitial cells stimulating hormone). In female, FSH

stimulates from puberty to menopause the development of the
ovarian follicles till the stage of mature follicle, capable to release
an ovum and the secretion of estrogens by the endocrine thecae
of the ovarian follicles; LH is triggering ovulation under the
positive feed-back of the increasing estrogen levels and is
stimulating the development of the corpus luteum/progestative
body, from the ex-mature follicle, after ovulation. In male, FSH
initiates spermatogenesis, stimulating mitoses of spermatocytes,
while LH/ICSH stimulates secretion of testosterone by interstitial
Leydig cells of the testes and the final stages of
spermatogenesis, till liberation of mature spermatozoa.
Gonadotropin secretion is stimulated by hypothalamic
factor– LH-RH; FSH secretion is inhibited by estrogens in female
and by inhibins in male, while LH is inhibited by progesterone in
female and by testosterone in male.
Nervous lobe of the pituitary/pars nervosa is made of the
terminals of the hypothalamic neurons of the supraoptic and
paraventricular nuclei, which are forming the infundibulum, the
pituitary stalk/ hypothalamic-pituitary tract; the end bulbs of the
neurons are PAS positive, the so-called Herring bodies. Herring
bodies are made of neurosecretory granules, containing two
hypothalamic neurohormones here stocked – antidiuretc
hormone (ADH)/vassopresin and oxytocin. ADH stimulates the
facultative water absorption at the level of the collecting tubules
of the nephrones; the lack of ADH is leading to diabetes
insipidus, with incapacity to concentrate the urine and an
overexcretion/polyuria of up to 30 liters of urine daily. Oxytocin
stimulates the contraction of the muscular wall of the uterus at the
end of the pregnancy, triggering parturition and the ejection of the
28
milk from the mammary gland, stimulating the activity of the

myoepithelial cells of the lactiferous ducts.
II.2. THYROID
Thyroid is the largest endocrine gland, situated at the base

of the neck, in front of the larynx and of the first tracheal rings. It
has the shape of letter H being made of two lobes united by an
isthmus. The gland is covered by a dense connective tissue
capsule; the stroma is made of a fine network of reticular fibers.
The morphologic and functional unit of the thyroid is the thyroid
follicle, an approximately spherical structure limited by a simple
cuboidal epithelium, in a normal functioning gland.
The microscopic image of the thyroid is appearing like that
of a mosaic, being made entirely of thyroid follicles, which
crowded one in another are often assuming a polyhedral aspect.
In the interior, the follicles contain a gelatinous material, the
thyroid colloid, which is a way of extracellular stocking of the
precursor of the thyroid hormones, the thyroglobulin.
29
Fig. 16. Thyroid HE x40
The thyroid cells or thyrocytes show basophilic cytoplasm,

nuclei with visible nucleoli, colloid appears acidophilic in H&E
staining method; in electron microscopy thyroid/follicular cells
have developed RER, Golgi complex, lysosomes, involved in the
synthesis of the thyroid hormones. Toward apical pole, the cells
show numerous short microvilli through which they absorb the
colloid, during hormonal synthesis. Iodide is indispensable for the
synthesis of T3 and T4, being trapped inside the cells from the
blood. In the synthesis process, the cell is functioning through
both its apical and basal pole, uptaking precursors from the blood
through the basal pole, discharging the thyroglobulin inside the
follicle through the apical pole, further re-uptaking the colloid
(through apical pole), synthesizing the thyroid hormones, which
are finally discharged into the blood through the basal pole of the
thyroid cells. Synthesis stages are primarily depending on
pituitary TSH, main stimulus for the activity of the gland.
30
Fig. 17. Thyroid follicles; parafollicular cells HE x100
Thyroid follicles are surrounded by arched and spiral

arranged capillaries, the gland is extremely well vascularized.
A second category of cells is represented by the
parafollicular cells, C cells or clear cells, which appear isolated or
in small clusters between the thyroid follicles; they are few in
number and they do not reach in the lumen of the follicles. They
are two to three times larger than follicular cells and they show
pale cytoplasm, which contains small secretory granules of
calcitonin, synthesis product of the parafollicular cells. Calcitonin
is a hormonal peptide which inhibits bone lyses performed by
osteoclasts, thus decreasing blood calcium levels. High blood
calcium level is triggering the release of calcitonin; calcitonin is
antagonistic to parathyroid hormone.
Thyroid hormones: triiodthyronine/T3 and thyroxine/T4
are maintaining a normal catabolism and are ensuring a normal
oxygen consumption all over organism.
31
In hypofunction of the gland/hypothyroidism, the gland

shows low cuboidal/squamous follicular epithelium and abundant
colloid inside the follicles, with the development of a goiter. Main
cause of hypothyroidism in the world is the lack of iodide in the
drinking water.
Hyperfunction/hyperthyroidism is characterized by columnar
follicular epithelium and a small amount of colloid inside the
thyroid follicles. The main cause of hyperthyroidism is
represented by the development of stimulator autoantibodies
acting on the TSH receptor of the thyroid cells, resulting in
Graves-Basedow disease.
- thyroid follicles are occupying almost entirely the
microscopic field; they are bordered by simple cuboidal
epithelium and the interior of the follicles is filled with an
acellular acidophilic material, the colloid looking
acidophilic/pink in H&E method (it may appear bluish or
others in trichrome methods of staining); the characteristic
image of mosaic conferred by the follicles is making
thyroid easily recognizable in light microscopy;
II.3. PARATHYROID GLANDS
Parathyroid glands are usually four small glands situated at

the four poles of the two thyroid lobes. At the outside, the glands
are enveloped by a dense connective tissue capsule which sends
septa inside the parenchyma. The cell population is mainly made
by chief cells, basophilic cells which are secreting the
parathyroid hormone/PTH. The basophilic principal cells
show an aspect very similar to lymphocytes/ lymphocyte-like
32
aspect; they are arranged in cords crowded together, conferring a

compact aspect to the parenchyma of the parathyroid.
Fig. 18. Parathyroid gland HEx 40
PTH is acting on bone, kidney and intestine, assuring the

maintenance of a normal blood calcium level. On bone, PTH is
stimulating bone lyses performed by osteoclasts; together with
vitamin D3, it is increasing the absorption of calcium in the
intestine and calcium reabsorption in the kidney.
Another category of cells is represented by the oxyphil
cells are acidophilic, with abundant mitochondria in electron
microscopy and larger than principal basophilic cells. Even if their
function is not yet understood, they are believed to be
quiescent/inactive principal cells. With age advance, up to 60 %
of the parenchyma may be occupied by adipose tissue.
- compact aspect of the gland, made entirely of cords
of basophilic, principal cells, with lymphocyte-like
33
appearance; parathyroid parenchyma is usually

surrounded by thyroid follicles, this proximity making
easier the recognition of the parathyroid.
II.4. ADRENAL (SUPRARENAL) GLANDS
Adrenal glands are pair organs situated on the superior pole

of the two kidneys, demilune-shaped. In their structure are found
two different glands, in what concerns the origin, the type of
secreted hormones, functional dependence. Outer part of the
gland is represented by the adrenal cortex, which has
mesodermal origin, is secreting steroids and is depending
functionally upon pituitary ACTH and renin-angiotensin-
aldosterone system. The deep inner part is known as the adrenal
medulla, with origin in the neural crest, secreting catecholamines
(epinephrine and norepinephrine) and depending upon
sympathetic nervous system, under brain control.
Adrenal cortex exhibits three zones, with different
arrangement of the endocrine-secreting cellular cords: zona
glomerulosa, zona fasciculata and zona reticularis.
34
Fig. 19. Adrenal cortex HEx40
Zona glomerulosa is made of short, curved cords of

endocrine cells, taking the aspect of glomeruli. This zone is
reduced, representing only 10-12 % of the adrenal cortex.
Endocrine cells are cuboidal and better stained than cells of the
following zone. This zone is secreting mineralocorticoids, most
important aldosterone. Aldosterone is stimulating sodium and
water reabsorption at the level of the distal convoluted tubule of
the nephron, main stimulus for its secretion being the decrease of
the blood pressure in the afferent arteriole of the kidney
corpuscle.
Zona fasciculata is best represented, accounting for
approximately 80 % of the adrenal cortex. Fasciculata is made of
cords of cells almost parallel one to another, arranged in a radial
manner toward the surface of the gland. Cells are slightly larger
and vacuolar, stocking lipid material (cholesterol) precursor in the
hormonal synthesis. This zone is secreting glucocorticoids, most
35
important cortisol. Cortisol is acting on all metabolisms (protein,

lipid and carbohydrate); at the same time is one of the stress
hormones of the organism, being released during stress
response and supporting the stress adaptive mechanisms of the
organism.
Zona reticularis is a small area situated next to adrenal
medulla (approx. 7 %) with cords disposed in network; frequently
the cells contain lipofuscin pigment inclusions. This zone secretes
androgens, mainly dehydroepiandrosterone, with reduced
physiological significance.
Fig. 20. Adrenal gland; cortex reticularis; adrenal medullax40
Adrenal medulla is the innermost part of the adrenal gland,

made of short cords or clusters of better stained granular cells.
The gland is secreting catecholamines – epinephrine/adrenaline
and norepinephrine/noradrenaline; from the two, adrenaline is the
main stress hormone of the organism, developing the so-called
fight– or –flight reaction, during stress exposure and it represents
36
at least 70 % of the secretion of the adrenal medulla. Cells show

marked affinity for chromaffin salts, conferring to them a deep
brown color, for that they are known as chromaffin cells. Cellular
cords of endocrine cells are separated by large dilated capillaries.
In the gland are present large sympathetic neurons since the
gland is under nervous sympathetic dependence.
Fig. 21. Adrenal medulla HEx 40

- presence of the three different zones in the adrenal
cortex – glomerulosa, fasciculata and reticularis, with their
typical aspect, in light microscopy. Difference between
adrenal cortex and medulla, which is made of larger and
better stained cells.
37
III. DIGESTIVE SYSTEM
Digestive system consists of the digestive tract and

attached glands (liver, pancreas and major salivary glands).
III.1. THE LIPS
The lips are muscular folds which are limiting the opening
of the oral cavity. They present two faces – an outer skin-covered
face; in the dermis of the skin are found sweat glands, hair
follicles and sebaceous glands. The inner face of the lip is
covered by a continuously moisten stratified squamous
nonkeratinized epithelium/oral type epithelium; in the under-
epithelial connective tissue of support are found numerous minor
salivary glands, made mostly of mucous acini, but also serous
and mixed. The transition from the outer to the inner face of the
lip is known as the vermilion zone, which is covered by thin skin,
but is devoid of sweat glands and hair follicles and may contain
only some nonfunctional sebaceous glands.
38
The dermal papillae of this region are well developed and

contain numerous capillaries, being responsible for the reddish
color of the lips. In the axis of the lip is found striated skeletal
muscle – muscle orbicularis of the lip, accompanied by vascular
and nervous elements.
Fig. 22. Lip outer face HEx 40
39
Fig. 23. Lip center He x40
Fig. 24. Lip inner face HEx40
40
- presence of the two versants – outer, where one

may identify the thin skin, with its epidermis and dermis
(containing sweat glands, sebaceous glands and hair
follicles) and inner, where are observable acini of the
minor salivary glands.
III.2. TONGUE
Tongue is a muscular organ present in the oral cavity,

involved in mastication, deglutition, phonation, reception of the
gustative sensations.
The dorsal surface of the tongue is divided into two regions
by the presence of a V-shaped groove, separating anterior two
thirds of the tongue of the posterior one third, called sulcus
terminalis; the apex of the V is posteriorly oriented. The anterior
two thirds of the dorsal surface of the tongue is covered by small
projections – the tongue or lingual papillae. Lingual papillae are
made of lamina propria covered by the oral epithelium – stratified
squamous, mostly nonkeratinized, but in some cases presenting
small areas of keratinization. Four types of papillae are
identifiable in humans – filiform, fungiform, foliate and
circumvallate.
Filiform papillae are the most numerous of all; they appear
thin and slender and show a sharp edge, most often inclined
toward the surface of the tongue. They are covered by a stratified
squamous epithelium, keratinized to the edge, serving as a
mastication area and giving to the tongue surface its hairy
aspect. They do not contain taste buds.
Fungiform papillae are mushroom–shaped, with a long
slender stalk inserting them to the tongue surface. They are
41
covered by stratified squamous nonkeratinized epithelium; they

are well vascularized, with reddish aspect and they contain taste
buds toward their top.
Fig. 25. Tongue filiform papilla trichrome x 40
Folliate papillae are present on the posterior and lateral

side of the tongue. They appear as waved prominences
separated by shallow furrows; they do contain taste buds,
especially in children till 3 years of age, which are degenerating
afterwards.
Circumvallate papillae are disposed in V shape, anterior to
the sulcus terminalis; they are 8 to 12. They are deepened in the
surface of the tongue, being surrounded by a groove in which are
opening the excretory ducts of glands of von Ebner, pure serous
minor salivary glands (serous acini); the acini of von Ebner
glands are observable in the lamina propria at the base of the
circumvallate papillae. They contain numerous taste buds on
their lateral sides and in the epithelial lining of the groove
42
surrounding them. In light microscopy, the taste buds appear as

small pale ovoid structures (80 μm high/ 40 μm thick), found in
the thickness of the oral epithelium, much paler than the
epithelium surrounding them.
Fig. 26. Tongue circumvallate; fungiform papillae trichrome x40
43
Fig. 27. Tongue cicumvallate taste buds HE x 40
In the axis of the tongue are found intertwined striated

skeletal muscle, vascular and nervous elements. Acini of minor
salivary glands are appearing all over the lamina propria of the
dorsal face of the tongue; toward the apex of the tongue we find
all types of acini – serous, mucous and mixed, at the lingual V are
found serous acini of von Ebner’s glands and toward the base of
the tongue are present exclusively mucous acini.
- the presence of the tongue papillae on the
superior/dorsal surface of the tongue makes it easy
recognizable in light microscopy; the inner face of the lip is
smooth-surfaced, as it is as well, the lining epithelium of
the esophagus, which may present only some large folds.
III.3. GENERAL ORGANIZATION OF THE

DIGESTIVE TRACT
From the esophagus to anal canal, digestive tract shows the

same structure, represented by four concentrically disposed
tunics which from the innermost part toward outside are: a
mucosa/mucous tunic, a submucosa, a muscularis
externa/muscular wall and a serosal lining or an adventitia
according to the localization.
Mucosa consists of epithelium and lamina propria; lining
epithelium of the digestive tract is simple columnar epithelium,
from the esophageal-gastric junction to the anal canal, while
esophagus and anal region are lined by stratified squamous
44
nonkeratinized epithelium. Lamina propria is consisting of loose

connective tissue and is rich in migrated cells of immune defense,
a so-called lamina propria of defense, especially in the intestine.
In the lamina propria are found glands – mucous cardiac
glands in the upper and lower part of the esophagus; fundic and
pyloric glands in the stomach; simple tubular straight
glands/Lieberkühn glands all the length of the intestine: Brunner’s
mucous glands in the duodenum. Lymphoid structures –
lymphoid nodules and thymus dependent small areas are
numerous in the ileum and in the appendix, which are acting as
secondary lymphoid organs and isolated and transitory, in the
jejunum and in the colon. The limit between mucosa and
submucosa is given by muscularis mucosae, a thin layer of
smooth muscle fibers, subdivided into two layers, an inner
circular and an outer circular layer.
Submucosa is made of loose connective tissue and
contains mucous glands all the length of the esophagus, the
proper esophageal glands and in the duodenum, the Brunner’s
glands. Lymphoid structures are abundant also in the ileum and
in the appendix. Nervous microganglia of this tunic form the
Meissner’s nervous plexus.
Muscular tunic/muscularis externa is made all over
intestine by two layers of smooth muscle fibers, an outer
longitudinal layer and an inner circular layer. In the stomach we
find a third smooth muscle layer, an oblique innermost layer. In
the upper and middle third of the esophagus, at this level are
present skeletal muscle fibers. Between the muscular layers of
the digestive tube are found microganglia which are forming the
myenteric nervous plexus of Auerbach.
45
Serosal lining is covering the digestive tract, with the

exception of the esophagus and anus, where is present an
adventitia, made of loose connective tissue continuous with the
connective tissue around.
III.4. ESOPHAGUS
Esophagus is a muscular tube of approximately 25 cm in

length, connecting the pharynx with the stomach. Histologic
structure presumes the four tunics already described.
Mucosa is forming folds distended during the passage of
the alimentary bolus; besides swallowing process, the lumen of
the esophagus is closed. Lining epithelium is stratified squamous
nonkeratinized and consequently lamina propria is not so rich in
immune defense cells. In the lamina propria, in the upper part,
close to the pharynx and next to cardiac region of the stomach
are found the cardiac glands tubular-branched mucus-secreting
glands; the mucus here secreted and the mucus secreted by the
proper esophageal glands is lubricating the mucous lining of the
esophagus, facilitating deglutition. Muscularis mucosae seems to
consist of just one longitudinally oriented layer of smooth muscle
fibers. The abrupt passage from the stratified squamous
epithelium lining the esophagus to the simple columnar
epithelium forming crypts of the stomach is representing the
esophageal-gastric junction.
46
Fig. 28. Esophageal-gastric junction HE x 40
Submucosa is made of slightly denser connective tissue

than the lamina propria and contains all its length tubular –acinar
mucus-secreting glands, the proper esophageal glands. In this
layer is found the Meissner’s submucosal plexus.
Muscularis externa is made mostly of skeletal striated
muscle in the upper third of the esophagus, of a mixture of both
skeletal and smooth muscle fibers in the middle third and of only
smooth muscle fibers in the lower third of the esophagus. Here is
found the Auerbach’s myenteric plexus.
47
Fig. 29. Esophagus; proper glands HE x 40
Adventitia made of loose connective tissue is the outer

tunic of the esophagus; after penetrating through the diaphragm
into the abdomenum, esophagus shows a serosa to the outside.
- stratified squamous nonkeratinized epithelium
supported by a layer of lamina propria and the presence of
the fine layer of muscularis mucosae separating mucosa
from the submucosa; the striated skeletal muscle fibers
found in the muscular tunic.
III.5. STOMACH
Stomach is the dilated part of the digestive tract, where the

ingested food mixed with the gastric juice it forms a viscous
product, the gastric chyme. Simple columnar epithelium of the
48
stomach is invaginating and forms gastric pits/crypts. Epithelium

lining the stomach is mucus-secreting homogenous type; tall
columnar cells show ovoid nuclei at the base and mucus
granules are filling two apical thirds of the cytoplasm; mucus
secretion is forming a gel which is protecting the mucosa against
the low acid ph of the stomach.
Histologically, stomach is divided into three regions –
cardia, fundus and pylorus. Region of the cardia is reduced,
situated at the opening of the esophagus into the stomach; it
contains short gastric pits and tubular-branched mucus- secreting
glands which are opening at the base of the pits.
Fundic region is made of short gastric pits and long simple
tubular fundic glands, opening at the base of the pits; glands are
numerous, 2-3 glands are opening at the base of one pit and 4-5
times longer than the pits. In the structure of the fundic gland one
may identify 5 cell types – undifferentiated regenerative cells;
mucous cells of the neck; parietal/oxyntic cells; chief/zymogenic
cells; cells of the DNES.
49
Fig. 30. Stomach fundus HEx40
Fig. 31. Fundic glandsx100
The fundic gland shows a neck, a body and a base; at the

neck of the gland are present cells of regeneration, which by
mitosis are responsible for the renewal of the lining epithelium,
showing a rapid turnover; with a slower rhythm they renew also
the cell population of the glands.
Mucous neck cells/accessory mucous cells are located
at the neck of the fundic glands interspersed with the
regenerative cells here placed; they show a basal flattened
nucleus, the apical cytoplasm is filled with mucus granules,
mucus being different from that secreted by the epithelial linig
cells of the gastric mucosa.
Parietal/oxyntic /acidophilic cells are located mainly in
the upper part of the body of the glands, toward the periphery.
They are large, round /polyhedral, with large central located
50
nuclei (because of their aspect, they are compared to a fried egg)

and they show intense acidophilia, given by the richness of
mitochondria. The cells are synthesizing hydrochloric acid from
sodium chloride and carbonic acid uptaken from the plasma.
They also synthesize the gastric intrinsic factor, which combined
with vitamin B12 is making it absorbable in the small intestine; the
lack of vitamin B12 is resulting in pernicious anemia.
Fig. 32. Parietal cells, basophilic cells fundus glands x 100
Chief/zymogenic/basophilic cells are forming most of the

body and the base of the glands; the cells are columnar, with
basal nuclei, basophilic cytoplasm and secretory granules which
contain the precursor of pepsin – pepsinogen.
Cells of the DNES are interspersed between the other cell
types; they are stained with silver salts, for that known as
argentaffin and in electron microscopy they contain endocrine
secretory granules; hormones released by these cells are usually
acting in vicinity, on the paracrine way. In the stomach, such cells
51
are secreting especially gastrin and histamine, both stimulators of

the hydrochloric acid secretion.
Pyloric region unlike fundic region shows deep pits and
short mucus secreting branched-tubular glands opening at the
base of the pits. The pits are usually longer than the glands,
occupying at least half of the thickness of the mucosa. Mucus-
secreting cells of the glands are also secreting here lysozyme,
with bactericidal activity.
Fig. 33. Stomach pylorus HE x 40
Muscularis mucosae is a continuous uninterrupted layer in

the stomach; both fundic and pyloric glands are ending in the
proximity of muscularis mucosae; sometimes a third inner circular
smooth muscle layer may appear at this level, in the stomach.
Smooth muscle fibers of the muscularis mucosae may arise to
insert on the basal lamina of the lining epithelium; their
contraction helps the emptying of the glands content.
Submucosa is well vascularized and contains the
submucosal nervous plexus of Meissner. Migrated cells may
52
encounter eosinophils and mast cells more numerous than in

other regions.
Muscular tunic/muscularis externa is made in the
stomach of three layers of smooth muscle fibers – inner oblique,
middle circular and outer longitudinal. The innermost oblique
layer is best developed in the cardia. The myenteric nervous
plexus of Auerbach is located between the middle circular and
the outer longitudinal layer.
Serosa is covering stomach to the outside, showing the
usual structure – thin layer of loose connective tissue and a
simple squamous epithelium.
 presence of gastric pits lined by simple columnar pale –
looking, mucus-secreting epithelium; in the fundus are
observable short pits and a high density of long simple
tubular fundic glands with different cell types, differently
stained – basophilic the zymogenic chief cells, acidophilic,
the parietal oxyntic cells. In the pylorus are found deep pits
and short mucus-secreting branched-tubular glands; the
gland is paler looking than the gastric pit.
 to differentiate stomach from the intestine – in the stomach
are not present the villi or the Lieberkühn glands; the lining
epithelium do not contain enterocytes or goblet cells.
III.6. SMALL INTESTINE
Small intestine is the main site of digestion and absorption

of nutrients; it may reach to 7 meters long and has three distinct
regions – duodenum, jejunum and ileum, which show particular
features each.
53
Common histologic structure

Main adaptive feature of the intestinal mucosa is
represented by the enlargement of its surface through the
presence here of plicae circulares/ Kerckring valves, villi,
microvilli of the absorptive cells and glands/crypts of Lieberkühn).
Plicae circulares represent folds of the mucosa and
submucosa, semicircular or helical as shape, of up to 8 mm tall
and 5 cm long.
Intestinal villi are finger-like or leaf-like prominences of the
lamina propria, covered by the intestinal epithelium. In their axis
are present an arteriole, a venule, a capillary network and a blind-
ended lymphatic vessel and a few smooth muscle fibers. Lamina
propria is rich in migrated cells of immune defense, a so-called
lamina propria of defense. They measure from 0.5 to 1.5 mm in
length, giving velour –like aspect to intestinal mucosa. They
increase 10 folds the surface of the mucosa. Morphologically and
functionally, the villi represent the units of the small intestine.
Microvilli of the absorptive cells increase 20 folds the
surface of the mucosa, for a better contact between the mucosa
and the intestinal content. Intestinal glands or glands/crypts of
Lieberkühn, simple tubular glands found at the base of the villi all
the length of the intestine are further increasing intestinal surface.
Absorptive cells/enterocytes are most numerous cells of
the intestinal lining epithelium. They are tall columnar, with basal
ovoid nuclei, basophilic cytoplasm, showing at their apical pole
the striated border/brush border, given by the presence of
microvilli, approximately 3000/cell. Microvilli are covered by a
glycoprotein layer – the glycocalyx, which is PAS positive. They
have well developed organelles and junctional complexes
54
between one another. They are involved in digestion (secreting

enzymes) and absorption of nutrients, synthesis of chylomicrons.
Goblet cells are more numerous toward ileum; they are
mucus-secreting unicellular glands. Their classical shape, with a
dilated apical cytoplasm filled with mucus granules, pale-looking
in usual staining methods in light microscopy and a narrow basal
nucleus, led to the comparison with “glass of champagne”. They
are dispersed between absorptive cells.
DNES cells are numerous in the small intestine, compared
to other epithelial linings, representing around 1 % of the lining
cells. They secrete various hormonal substances and are named
by majuscules – A cells secrete glucagon, G cells secrete gastrin,
D cells secrete somatostatin, S cells – secretin; EC cells –
serotonin and substance P etc.
M cells/microfolded cells are squamous cells, with long
processes, replacing enterocytes at the level of the lymphoid
structures, especially in the ileum. They are part of the
phagocyte- mononuclear system and are able to capture,
phagocyte and transport antigens toward the lymphoid tissue of
the intestine.
Crypts/glands of Lieberkühn are simple tubular glands
which are opening between the intestinal villi, further increasing
the surface of the intestinal mucosa: their lining is composed of
absorptive cells, goblet cells, DNES cells, regenerative cells and
Paneth cells. The base of the glands contains numerous
regenerative cells responsible for the renewal of the epithelium
up to the top of the villi, with a turnover of 5-6 days.
Paneth cells are pyramidal cells, present at the base of the
Lieberkühn glands, mostly in the duodenum. They contain large,
55
acidophilic and refringent granules. The cells secrete lysozyme,

with bactericidal activity.
Duodenum is the shortest portion of the small intestine; it
has most numerous villi. The villi are larger and branched,
resembling to leaves. In the duodenum are discharged bile
secretion of the liver and the pancreatic juice, most important in
the digestion. In the submucosa and in the lamina propria are
present branched tubular acinar glands, the Brunner’s glands.
They secrete mucus with an alkaline ph which helps to neutralize
the acidity of the gastric chyme. Muscularis mucosae is
discontinuous in the duodenum, being interrupted by Brunner’s
glands.
Fig. 34. Duodenum HE x 40
Jejunum shows thinner villi, with a classical aspect of

fingers; Lieberkühn glands show a regular aspect, at the base of
the villi. Muscularis mucosae is a continuous layer in the jejunum.
56
Isolated lymphoid nodules may appear at the base of the

intestinal/Lieberkühn crypts.
Fig. 35. Jejunum intestinal glands x 40
Fig. 36. Jejunum; villi HE x 40
57
Ileum shows sparse and short villi and deviated Lieberkühn

glands; this aspect is given by the presence of the Peyer’s
patches, made of clusters of lymphoid nodules, which are bulging
from the submucosa and tend to wipe the accidents of the
mucous layer. Presence of the Peyer’s patches is disrupting
muscularis mucosae, which in the ileum is more difficult to
observe.
Fig. 37. Ileum Peyer pathches x 40
58
Fig. 38. Ileum; villi, Lieberkuhn glands x 40
Muscular tunic/muscularis externa and serosa of the small

intestine show no peculiar features. Muscular tunic is made of
two layers of smooth muscle fibers – an inner circular layer and
an outer longitudinal layer.
- Presence of the villi and of Lieberkühn glands lined
by intestinal epithelium with goblet cell; mucus-secreting
Brunner’s glands occupying most of the submucosa, in the
duodenum; Peyer’s patches made of numerous lymphoid
nodules in the ileum. Numerous long villi in the jejunum.
Rare and short villi; more rare intestinal crypts/glands of
Lieberkühn, in the ileum, where the number of goblet cells
tends to become important, in the proximity of the
colon/large intestine.
59
III.7. APPENDIX
Appendix is a glove finger shaped diverticulum of the

cecum; the submucosa and the lamina propria are occupied by
numerous secondary lymphoid nodules, thus the Lieberkühn
glands are more rare, shorter and deviated. Besides enterocytes,
goblet cells, M cells and DNES cells, in the appendix may appear
Paneth cells. Muscularis mucosae is discontinued by the
presence of the lymphoid tissue, sometimes being more difficult
to identify.
Muscular tunic of the appendix is common and shows no
taeniae coli, usually present in the large intestine. The organ is
functioning as secondary lymphoid organ; the inflammation of
appendix is known as appendicitis and is treated surgically, with
removal of the appendix – appendectomy.
Fig. 39. Appendix; lymphoid nodule x 40
60
III.8. LARGE INTESTINE/COLON
Since the absorption is almost finished at the level of the

colon, here villi are not present, instead are found numerous
Lieberkühn glands; they are placed one next to another. The
intestinal epithelium shows numerous goblet cells, here tending
to predominate over absorptive cells. The brush border/striated
border of enterocytes is not so developed like in the small
intestine. Isolated, transitory lymphoid nodules may appear in the
submucosa, at the base of the Lieberkühn glands. The outer
longitudinal layer of smooth muscle fibers is concentrated here in
there longitudinal bands known as taeniae coli. In the colon are
absorbed fluids, electrolytes and vitamins.
Fig. 40. Intestinal glands colon HE x 40

 appendix is usually cross-sectioned and appears as a thick
circular lymphoid mass made mostly of lymphoid nodules;
61
to the lumen is visible the intestinal epithelium forming a

few deviated and short Lieberkühn glands.
 colon is characterized by the numerous Lieberkühn
glands, which appear one next to another, longitudinally
and/or obliquely or cross-sectioned. Usually isolated
lymphoid nodules are visible in the submucosa.
III.9. GLANDS OF THE DIGESTIVE SYSTEM.

THE LIVER
Liver is the largest parenchymal organ of the human body,

with a weight of up to 1.5 kg in adult. Hepatocytes are fulfilling
both exocrine and endocrine functions; bile secretion in the
duodenum on an exocrine pattern and metabolic functions, which
are fulfilled on an endocrine pattern. The connective tissue
capsule of the liver is known the Glisson’s capsule.
Liver cells are disposed in plates arranged radial toward a
central vein, the central vein of the classical liver lobule, a
hexagonal area of liver cells, which in humans is not limited by
connective tissue. In three of the six angles of this hexagon are
appearing triangular spaces, the portal spaces, which are
hosting three elements, the so-called portal triad – an arteriole,
branch of the hepatic artery, a venule, branch of the portal vein
62
and a small bile duct, recognizable by its lining simple cuboidal

epithelium.
Fig. 41. Liver lobules with central vein HE x 40
Liver cells/hepatocytes are the main elements of the liver

parenchyma, since liver has a very small amount of connective
tissue in its structure; a fine network of reticular fibers, which is
forming the stroma of the organ. Liver cells are polygonal cells of
20-30 μm in diameter arranged in plates; in light microscopy, they
show acidophilic cytoplasm with lipid vacuolar inclusions and
basophilic droplets, central large nuclei with visible nucleoli.
Sometimes they may be binucleated. Between liver cells plates
are visible the lumens of the venous sinusoids, which are
surrounding the plates of cells. In electron microscopy, liver cells
show very well developed organelles, areas with abundant RER,
numerous Golgi complexes, smooth ER, lysosomes and a large
number of mitochondria. Between the liver cells and the sinusoid
capillaries is appearing the microscopic space of
63
Disse/perisinusoidal space, where are found microvilli of the

hepatocytes. Through the space of Disse, interposed between
the liver cells and the bloodstream, hepatocytes are exchanging
materials with the blood, fulfilling their metabolic functions (e.g.
synthesis and discharge of plasma proteins, like albumin). The
billiary pole of the hepatocyte is showing a depression of the
plasma membrane, with few microvilli, which together with the
similar membrane of the adjacent liver cell is forming the bile
canaliculus, limited by the membranes of the adjoining liver cells.
At this level are present tight junctions/occluding junctions,
impairing the bile to leak into the blood.
Capillary sinusoids are appearing as radiating free lumens,
between the plates of liver cells of the classical liver lobules; they
end to the central vein of the lobule, where they empty. They
show all the known characteristics of sinusoid capillaries – a
sinuous passage, more dilated areas followed by narrower zones
and above all a discontinuous wall; at this level are present gaps
of approximately 0.5 μm, where are missing both endothelial cells
and the basement membrane of the capillary wall. Endothelial
cells show fenestrae which are clustered to form sieve areas.
Through the discontinuous wall of the sinusoid the blood is
coming into contact with the liver cell through the Disse’s space.
In the liver sinusoids are present resident macrophages, the
Kupffer cells. Kupffer cells contain phagosomes; in light
microscopy they are recognizable under the condensed and
rounded aspect of their nucleus. Perisinusoidal space also
contains Ito cells/fat-storing cells/stellate cells; these cells are
involved in storage of vitamin A, secretion of reticular fibers and
of growth factors needed for regeneration of the liver cells. A
64
small number of cells with granular cytoplasm, believed to be

natural killer cells are also present in the perisinusoidal space.
Billiary ducts system begins by the small intercellular bile
canaliculus; in the periphery of the classical liver lobule, low
cuboidal epithelial cells are forming a discontinuous wall – the
cholangioles. Cholangioles are continued by the canals of
Herring, with a continuous lining of flattened cuboidal epithelial
cells. The anastomosing interlobular bile ducts are gradually
uniting to form the left and the right hepatic ducts, which are
uniting to form the common hepatic duct. The common hepatic
duct is uniting with the cystic duct of the gallbladder to form the
common bile duct, which is opening into the duodenum by the
sphincter of Oddi. The bile ducts are lined by simple columnar
epithelium; larger ducts show a mucosa, with a thin lamina
propria and a thin muscular layer.
Fig. 42. Liver; portal triad HE x 100
65
Gallbladder is a pear-shaped organ, united to the inferior

face of the liver by connective tissue; it may store up to 70 ml of
bile. Its mucosa is made of ion-transporting simple columnar
epithelium, being able to concentrate or to dilute the bile. Lining
epithelial cells contain mucus granules in the apical cytoplasm. A
few mucus-secreting tubuloacinar glands are present at the neck
of the gallbladder. The muscular layer is mostly obliquely
oriented. The inferior face of the gallbladder, which is not
attached to the liver is covered by peritoneum.
- liver is most typical parenchymal organ, made
almost entirely of plates/cords of liver cells; they radiate to
the central vein of the classical liver lobule. Liver cells
appear acidophilic, arranged in unicellular cords,
separated by the free lumen of liver venous sinusoid.
Opposite to the central vein of the lobules, we may
observe the portal triad, located in the portal space,
containing three sectioned elements – a venule, an
arteriole and a bile duct (usually lined by simple cuboidal
epithelium).
III.10. PANCREAS
Pancreas is at the same time an exocrine gland, by its

serous acini, producing the pancreatic juice involved in digestion
and an endocrine gland, by the presence of Langerhans islets
which are secreting hormones, discharged into the blood.
Exocrine pancreas is a compound tubuloacinar gland; it is
situated outside peritoneum and is covered by a thin connective
tissue capsule from which arise trabeculae limiting lobules in the
66
parenchyma. The serous acini of the pancreas are different from

those of the parotid or of the others acinar glands, in the way that
the smallest excretory ducts – intercalated ducts begin inside
the serous acini; in light microscopy are visible some nuclei in the
center of the serous acini, nuclei of centroacinar cells.
Intercalated ducts are lined by simple cuboidal epithelium; they
join to form larger interlobular ducts, lined by simple columnar
epithelium. Finally, the ducts are forming principal duct of
Wirsung, lined also by simple columnar epithelium, with some
goblet cells. Serous acini of the pancreas are typical serous acini,
made of pyramidal cells, with basal rounded nuclei at their base
and basophilic cytoplasm, containing zymogenic granules in its
apical two thirds.
Fig. 43. Pancreatic serous acini; Langerhans islets x 100
Pancreatic juice contains the most powerful digestive

enzymes – trypsin, pancreatic lipase and amylase; exocrine
secretion of pancreas is controlled by cholecystokinin (providing
67
an enzyme-rich secretion) and secretin (stimulating a secretion

poor in enzymes and rich in fluid and bicarbonate) secreted by
cells of the DNES of the intestine. Parasympathetic nervous
system/vagus nerve is promoting the synthesis and secretion of
the pancreatic juice.
Endocrine pancreas is made by approximately one million
conglomerations of endocrine cells – the islets of Langerhans.
Islets are made of short anastomosed cords of endocrine cells,
situated on a fine reticular fibers stroma; between the cords of
endocrine cells are present numerous capillaries. In routine
methods of staining, the islets appear paler than the serous acini
of the exocrine pancreas, which are surrounding them.
Fig. 44. Pancreas; Langerhans islets x 40
Immunocytochemical techniques are differentiating five

types of cells which are forming the endocrine islets:
 β cells represent approximately 70 % of the cell
population of the islets; these cells appear situated
68
mainly in the center of the islets, they secrete insulin,

hormone indispensable for life, which is decreasing the
level of the blood glucose, stimulating its entrance into
the cells.
 α cells are forming 20 % of the cells of the islets; these
cells are secreting glucagon, which is increasing the
level of the blood glucose. The cells appear in the
periphery of the islets.
 δ cells/D cells - only 5 % of the islets cell population;
they secrete somatostatin, which here is inhibiting
paracrine way the release of the other islets hormones
and vasoactive intestinal peptide/VIP (involved in the
regulation of the intestinal motility).
 G cells represent 1 % of the cells; they secrete gastrin,
which stimulates the secretion of the hydrochloric acid
by the parietal cells of the fundic glands in the stomach.
 PP cells/F cells represent only 1 % of the cells of the
islets; these cells secrete pancreatic polypeptide,
which inhibits the exocrine secretion of the pancreas.
D cells, as well as G an PP/F cells are dispersed between

the first two cell types.

- presence of serous acini, well stained, with granular
cytoplasm; in the mass of the serous acini are appearing
scattered the Langerhans islets, appearing paler than the
acini, with usual staining techniques – main criterion for
the recognition of pancreas. In the parotid, which is also a
pure serous gland, we do not find such islets and we
69
observe more numerous excretory ducts than in the

pancreas. In the pancreatic acini are present the
centroacinar cells, which are not present in the salivary
glands.
III.11. MAJOR SALIVARY GLANDS
Major Salivary glands are represented by three pair of

organs – parotid, submandibular and sublingual glands. They are
branched tubuloacinar glands enveloped with a connective tissue
capsule from which are deriving septa dividing the parenchyma of
the glands into lobules.
Fig. 45. Parotid; striated ducts x 40
70
Fig. 46. Parotid; large interlobular duct x 40
The acini of the salivary glands are typical serous, mucous

and mixed acini. Serous acinus is rounded, made of pyramidal
cells, limiting a small star-shaped lumen; nuclei of the serous
cells are rounded, at the base of the cells, the cytoplasm is
basophilic and granular, containing zymogenic granules. Best
developed are the organelles involved in the protein synthesis.
Mucous acini are larger, ovoid or irregular, their cells are
pyramid trunk-shaped cells, with flattened nuclei at the base; the
rest of the cytoplasm is filled with mucus granules, with pale
aspect in light microscopy.
Mixed acini are large, sometimes branched, are made
mostly of mucous cells; at one pole of the acinus are present a
few serous cells, arranged in demilune, forming Gianuzzi’s
demilune. At the base of the secretory acinar cells of the salivary
glands are found myoepithelial cells/basket cells, which show a
71
small cell body where is located the nucleus; their long processes
are surrounding the acinar cells and the small excretory
ducts/intercalated ducts of Boll. The processes of these cells
contain actin and myosin filaments; contracting they help the
release of the secretory product into the ducts. Unlike salivary
glands, pancreas does not contain myoepithelial cells (pancreas
is originating in the endoderm, while salivary glands have their
origin in the ectoderm).
Fig. 47. Mixed salivary gland ; interlobular duct HE x 40
72
Fig. 48. Mixed salivary gland; striated ducts x 100
Parotid is a pure serous gland being made exclusively of

serous acini; submandibular is a mixed gland with serous
predominance (containing serous, mixed and only a few mucous
acini); sublingual is a mixed gland with mucous predominance (it
contains mucous, mixed and a few serous acini).
Excretory ducts begin in the salivary glands at a pole of the
acini, here are not present the centroacinar cells found in
pancreas. The intercalated ducts of Boll are small intralobular
ducts lined by simple cuboidal/flattened cuboidal epithelium. They
fuse to form larger intralobular ducts – striated ducts/Pflüger
ducts; the striated aspect of these ducts (visible in light
microscopy) is given by the presence of microvilli at the apical
pole of the lining epithelial cells and folds of the basal cellular
membrane, this being an ion-transporting epithelium, responsible
for the concentration/dilution of the saliva. In the septa of
73
connective tissue parting the glands into lobules are present

larger interlobular ducts lined by bistratified cuboidal epithelium.
In the principal duct of the gland, like Stennon canal of the
parotid, the lining epithelium is stratified columnar with goblet
cells. In the stroma of the salivary glands are present vascular
and nervous elements, small lymphoid structures and variable
amount of white adipose tissue.
Saliva is secreted in an amount of one liter daily; it has
numerous roles – lubricating oral cavity, antibacterial properties,
involved in taste perception by solving food compounds, initiation
of digestion through its content of amylase and lipase, formation
of the alimentary bolus, neutralizing the local acid ph by its
alkaline content. 60 % of the saliva is secreted by submandibular
glands, 30 % by the parotids and only 5 % by the sublingual
glands (5 % is secreted by the minor salivary glands found in the
mucosa and submucosa of the oral cavity).
- mixed salivary glands are easily recognizable by the
presence in the parenchyma of all types of acini –
predominantly serous and mixed in the submandibular
gland and predominantly mucous and mixed in the
sublingual gland.
- parotid gland should be differentiated from the
pancreas, by the presence of more numerous ducts, than
in the pancreas and the absence of the Langerhans islets,
which are most characteristic for pancreatic parenchyma.
74
IV. RESPIRATORY SYSTEM
Respiratory system is made of the airways/respiratory

passages and the lungs, where the gases exchanges take place.
Respiratory passages are divided into a conducting portion,
bringing air to the lungs and situated outside and also within the
lungs and a respiratory portion, found inside the lungs, where
are taking place the gases exchanges.
Conducting portion of the respiratory passages is
represented by – nasal cavity, pharynx, larynx, trachea, bronchi
and bronchioles, including terminal bronchioles.
Respiratory portion of the respiratory passages is
represented by – respiratory bronchioles and lung alveoli.
IV.1. NASAL CAVITY
Nasal cavity is divided into the two nasal fossae by the

nasal septum. The anterior and dilated part of the nasal cavity is
known as the vestibule which is skin-covered and contains
sebaceous and sweat glands, as well as short hairs that are
preventing the penetration of large particles into the air passages;
these hairs are called vibrissae. Dermis is firmly anchored by
collagen bundles to the cartilaginous wall of the nose. The
posterior part of the nasal cavity is lined by respiratory
epithelium/pseudostratified columnar ciliated epithelium,
with the exception of a small superior and posterior area, which is
forming the olfactory mucosa. Mucosa of the nasal cavity is
75
attached through its lamina propria to the bony and cartilaginous

wall of the nasal cavity. In the lamina propria are present large
arterial plexuses and venous sinuses and mixed (seromucous)
acinar glands, the secretion of which is moistening the mucosa.
Cleansing cilliary beat of the respiratory epithelium is oriented
toward the pharynx.
IV.2. OLFACTORY MUCOSA
Olfactory mucosa is located toward the roof of the nasal

cavity, showing a macroscopically yellowish aspect. Olfactory
epithelium is pseudostratified columnar epithelium, made of three
types of cells – sensory/ olfactory, supporting and
basal/regenerative. Olfactory cells are bipolar neurons with a
modified dendrite which forms the olfactory vesicle, from where
are arising 6-8 nonmotile olfactory cilia lying on the epithelium
surface; cilia show receptors for the odoriferous molecules; only
the substances which are soluble in the local secretion may be
perceived as odorous. The nuclei of the olfactory neurons are
basal located and their axons are forming the olfactory nerve.
Supporting cells of the olfactory mucosa are tall columnar
cells with nuclei situated toward the apical pole, above the level
of the nuclei of the olfactory neurons. They show microvilli at their
apical pole and in the apical cytoplasm they contain granules of a
yellow pigment (aldehyde of vitamin A) which expelled in the local
secretion is facilitating the sensorial activity of the olfactory
neurons. Basal cells are round cells with intense proliferative
capacity which are replacing both supporting cells and olfactory
sensorial cells.
76
IV.3. LARYNX
Larynx is involved in phonation and prevention of the

penetration of food and fluids into the trachea. Larynx is
appearing like a small tube of approximately 4 cm long. The
medium tunic of the larynx contains hyaline cartilages (thyroid,
cricoids, partially the arytenoids); elastic cartilages (epiglottis,
corniculate and cuneiform cartilages, tips of the arytenoids).
Cartilages are connected one to another by ligaments and
membranes and by the striated skeletal muscles of the larynx,
which are controlling their movements (muscles are maintaining
an open airway and are acting as a valve, preventing food or
fluids to pass into the trachea).
Mucosa of the larynx has two pairs of folds – a superior pair:
vestibular folds/false vocal cords, which are immovable; they
are covered by respiratory epithelium and in the lamina propria
are found seromucous glands. The inferior pair is forming the
vocal folds/true vocal cords; they are covered by stratified
squamous nonkeratinized epithelium and a dense lamina propria
adherent to the subjacent plan. They are connected by the vocal
ligament and vocalis muscles, being main structures of the
phonation (as air is conducted between the vocal folds, muscles
contraction is responsible for sounds production). The outside of
the larynx is covered by an adventitia, which is connecting it at a
certain degree with the surrounding structures.
77
IV.4. TRACHEA
Trachea is a partially flexible tube of approximately 12 cm

long and of 2 cm in diameter, which is extending from the larynx
to where it bifurcates into the two primary bronchi.
The trachea is made of three concentrically disposed tunics,
which are (from the innermost part to the outside) – mucosa,
medium tunic and adventitia. The wall of the trachea contains in
its medium tunic C-shaped/horse-shoe hyaline cartilage rings.
Respiratory epithelium of the trachea is typical,
pseudostratified ciliated columnar epithelium composed by
several cell types:
Ciliated columnar cells are best represented of all cell
types; they show each approximately 300 motile cilia. The
movement of the cilia is oriented toward outside, toward the
pharynx; this movement is cleansing the trachea by removal of
the secretion and of the particulate material trapped in it.
Fig. 49. Trachea trichrome x 40
78
Goblet cells represent approximately 30 % of the cell

population; they are similar to other goblet cells (in the digestive
tract) show their typical shape of champagne glass and their
apical cytoplasm is filled with mucus granules; they develop after
birth, their number being determined by the degree of pollution of
the inspired air.
Brush border cells show microvilli to their apical pole;
there are brush cells of two types – type I shows fewer organelles
and nerve endings to their base, they are sensory cells. Type II
cells are future ciliated cells.
Small basal cells are cells of regeneration which are able
to differentiate into different cells types.
DNES cells are located to the basement membrane, they
show a granular cytoplasm in electron microscopy; here they
secrete serotonin, calcitonin, also endogenous opiate substances
(endorphins). The number of cells which are secreting
endogenous opiates is particularly abundant before birth, being
involved in local vasodilatation and increase of the local blood
flow, for a better development of the pulmonary circulation,
almost absent before birth.
Lamina propria of the trachea is rich in elastic fibers and
contains mixed acinar glands, which are providing secretory fluid
involved in the cleansing of the mucosa through the cilia
movements. Lymphoid structures, also lymphoid nodules are
present in the lamina propria of the trachea, part of the mucosal
local immune defense (BALT – bronchial associated lymphoid
tissue). At least to the posterior part of the trachea is present a
submucosa, separated from the lamina propria by a thick elastic
lamina made of elastic fibers.
79
Medium tunic of the trachea is made of C-shaped/horse-

shoe hyaline cartilage rings held together by the perichondrium
and an elastic membrane. Cartilage rings are maintaining the
lumen of the trachea open; the incomplete cartilage rings are
completed by smooth muscles fibers going from one end of the
cartilage ring to the other and forming the tracheal muscle. The
concavity of the cartilage rings is oriented toward posterior, where
esophagus is located.
Fig. 50. Trachea medium tunic and adventitia trichrome x 40
Adventitia of the trachea is made of loose connective

tissue, rich in white adipose tissue (sometimes here is also found
brown adipose tissue), vascular and nervous elements. At some
degree adventitia of the trachea is common with that of the
esophagus.
- trachea is recognizable in light microscopy
especially on the presence in the medium tunic of the thick
80
hyaline cartilage ring with its typical aspect – chondrocytes

in chondroplasts and the homogenous cartilage matrix;
another criterion for the recognition of the trachea is
represented by the presence of the lining respiratory
epithelium – pseudostratified ciliated columnar epithelium.
Sometimes in the vicinity of the section through trachea
are present thyroid follicles, or a small portion of
esophagus, since anatomically these organs are situated
in the same region.
IV.5. BRONCHIAL TREE
Bronchial tree is gradually branching after the penetration

of the bronchi inside the lung. From trachea are first arising the
two primary bronchi which show a structure similar to that of the
trachea, the sole difference being the presence in the wall of the
primary bronchi of a complete cartilage ring, instead of C-shaped
cartilage rings of the trachea.
81
Fig. 51. Segmentary bronchus x 100
From the primary bronchi, as they enter into the lungs are
resulting the lobar bronchi – 2 for the left and 3 for the right lung.
From the lobar bronchi are further branching segmental/tertiary
bronchi, leading air toward a pulmonary segment. Large bronchi
show a structure similar to that of the trachea, the difference
concerns the cartilage ring which becomes fragmented to form
hyaline cartilage plates/islets united by connective tissue and
smooth muscle fibers. Lining epithelium of the large bronchi is of
respiratory type and in the lamina propria are still present mixed
acinar glands and lymphoid structures.
Fig. 52. Lung; segmentary bronchus; bronchiole;

alveoli HE x 40
Bronchioles are conducting air to a pulmonary lobule; they

are primary/intra-lobular bronchioles showing a diameter of
less than 1 mm and being devoid of hyaline cartilage in their wall.
82
Lining epithelium of the intra-lobular bronchiole is simple ciliated

columnar, without goblet cells. Replacing goblet cells, here are
appearing Clara cells, cells with microvilli to their apical pole,
which are secreting a material similar to the pulmonary
surfactant, protecting the epithelium and reducing the surface
tension at this level, to maintain the bronchioles open. Lamina
propria of bronchioles is devoid of glands and lymphoid
structures. Medium tunic of bronchioles is made of smooth
muscle fibers with helical or circular orientation. Absence of the
cartilage plates in the wall of the bronchioles explains their folding
after death; for that, in the microscopic specimens the lumen of
the bronchioles appears deeply scalloped, with characteristic
crenels, given by the rigidity of the muscular layer after death, the
rigor mortis.
From each intra-pulmonary bronchiole are arising 3-5
terminal bronchioles which show a simple ciliated cuboidal
lining epithelium, with Clara cells and a circular smooth muscle
fibers layer in their wall. Adventitial tunic of the bronchioles has
elastic fibers which are partially continuous with elastic fibers of
the alveolar wall or of the adventitia of others bronchioles,
ensuring the dilation of the bronchiolar lumen during inspiration.
83
Fig. 53. Lung alveoli HE x 100
The terminal bronchiole with its respiratory bronchioles is

considered a pulmonary acinus; main morphologic unit of the
lung parenchyma.
From each terminal bronchiole are deriving 2-3 respiratory
bronchioles, making part already of the respiratory portion of the
respiratory system. Respiratory bronchioles show simple cuboidal
epithelium which tends to flatten, as epithelial lining; their wall
shows discontinuities given by the opening of alveoli at this level.
Smooth muscle fibers are still present, even in the walls of the
alveolar ducts. They further divide into alveolar ducts, which are
continued by lung alveoli. Clusters of alveoli tributary to one
alveolar duct form the alveolar sac.
Bronchial tree by its extensive, gradual branching is
involved in decreasing the speed of the inspired air and uniform
distribution of the air inside the lung; the glands secretion is
humidifying the inspired air, while the rich vascularization of the
84
lamina propria is warming the air, which at the alveolar level will
have the temperature of the body. We may conclude that the
bronchial tree is functioning as a device which is conditioning the
inspired air, to ensure optimal level of gases exchanges at the
level of the lung.
IV.6. LUNG ALVEOLI
Lung alveoli are giving to the lung the sponge–like or lace-

like microscopic image or compared to the honeycomb of a
beehive. Alveolus is a small pocket of around 200 μm in diameter
where the gases exchanges take place: they communicate one
with another through alveolar pores/pores of Kohn, of up to 60
μm in diameter.. In the alveolar structure are found: connective
tissue compound – rich mainly in elastic and reticular fibers; an
extensive capillary network resulted from the ultimate branching
of the pulmonary artery, bringing to the lung the venous blood
which must be oxygenated and the epithelial lining of the alveoli,
represented mainly by two types of alveolar cells – type I
pneumocytes and type II pneumocytes.
Type I pneumocytes/membranous pneumocyte (or
squamous alveolar cells) represent up to 95 % of the lining
surface of the alveoli. They extend their cytoplasm on such a big
surface that this is appearing as a very thin veil, reaching
sometimes only 80 nm in thickness. The organelles of these cells
are restricted toward around the central placed nucleus, the rest
of the cytoplasm being mainly the place of the gases exchange.
The surface of the pneumocytes is covered by a layer of
surfactant.
85
Type II pneumocytes/granular pneumocytes form only 5

% of the alveolar lining, being spread among type I alveolar cells.
They appear as cuboidal cells, usually isolated in the corners of
the alveoli; these cells show microvilli at their apical pole and
small granules in the cytoplasm – lamellar bodies, containing
the pulmonary surfactant. Alveolar lining being covered by a
watery fluid, the surfactant is needed to impair the collapse of the
alveoli during expire through reduction of the surface tension.
Biochemically surfactant is made especially of phospholipids; it
shows a structure comparable to that of the myelin sheath.
Alveolar macrophages/dust cells are deriving from the
blood monocytes, they migrate inside the alveoli, where they
phapocytose particles and bacteria which penetrated inside the
lungs; around 100 million macrophages are eliminated each day
by swallowing or are expectorated. Because at the level of the
lung they frequently phagocytose powders, dust particles and
they do appear in light microscopy with their cytoplasm filled with
small black granules, they are known as dust cells.
To enter into the blood gases must cross the
blood-air/blood-gas barrier, made of: the film of surfactant, the
cytoplasm of the type I pneumocytes, the fused basal laminae of
the pneumocytes and of the capillary endothelium and the
cytoplasm of the endothelial cells.
 unique aspect of the lung alveoli, with their lace-like
aspect makes lung easily recognizable in light
microscopy; in the mass of lung alveoli are present
sections through bronchi and bronchioles; bronchi show
cartilage plates in their wall, while bronchioles have a
smaller caliber, a folded lumen and do not show
86
cartilage plates in their wall. Dust cells/alveolar

macrophages are visible in the lung, as cells charged
with black particles.
87
V. URINARY SYSTEM
Urinary system is the main excretory system which is

removing catabolic products from the blood and is eliminating
urine to the outside. It is consisting of the two kidneys and the
urinary passages – ureters, urinary bladder and the urethra.
Kidneys are bean-shaped organs situated with the convex
margin toward exterior and the convex margin, where they
present the hilum to the vertebral column. At the hilum are found
the ureter, renal artery and renal vein. Each kidney has a weight
of around 150 g in adult and is covered by a thin connective
tissue capsule, which under normal conditions may be easily
removed from the organ. In section, we observe a granular
reddish area in periphery – the renal cortex and small triangular
structures to the center – the renal medulla, made by 6-12
Malpighian pyramids, pale colored. Each renal/Malpighian
pyramid is covered at its base by a zone of cortex – the cortical
arch. The apex of the pyramid, known as renal papilla forms
minor calyces which unit to form major calyces, which are
emptying into the upper dilated portion of the ureter, known as
the renal pelvis. From the base of the pyramids are extending
into the cortex small areas of medullary tissue – medullary rays
of Ferrein; the cortex between the renal pyramids is forming the
cortical columns of Bertin.
Each renal pyramid withs the surrounding cortex forms a
renal lobe and each medullary ray with its surrounding cortex
forms a renal lobule.
88
V.1. NEPHRON
The nephron is considered the morphological and functional

unit of the kidney; it shows a globular portion known as the renal
corpuscle and tubules of the nephron. Renal corpuscle is
continued by the proximal convoluted tubule, followed by the
loop of Henle, which is continued by the distal convoluted
tubule, opening into the collecting tubules. The kidney
corpuscle is always situated in the cortex of the kidney; the
tubules of the nephrons are situated in both cortex and medulla,
while the collecting tubules are situated exclusively in the
medulla, forming most of it.
According to their situation in the cortex, nephrons are
cortical nephrons, which in their turn are superficial and medium
nephrons and the juxtamedullary nephrons, which show loops
of Henle descending deep in the medulla; this last type of
nephrons is the most important in concentration and formation of
the urine.
89
Fig. 54. Cortex kidney HE x 40
In the structure of the renal corpuscle are found three

components – a vascular component represented by tufts of
capillaries resulting from the afferent arteriole, entering in the
corpuscle through the vascular pole; from the capillaries is
resulting the efferent arteriole, exiting from the corpuscle
through the same vascular pole. Capillaries show pores/fenestrae
of around 70-90 nm in width, with no diaphragms. In light
microscopy, in some corpuscles is visible the vascular pole, with
its entrance and exit of the two arterioles. The epithelial
component is represented by the double-layered Bowman’s
capsule; during embryonic development the vessels are
invaginating into the spherical end of the tubules of the nephrons,
for that the two layers of the Bowman’s capsule are in
continuation, one with another. The inner/visceral layer of the
Bowman’s capsule shows greatly modified cells – the
podocytes, which are participating in the filtration process,
especially through their basal lamina. The basal lamina of the
podocytes is fused with that of the capillaries to form a thick
common basal lamina – the filtration membrane, showing a
central dense lamina surrounded on each face by two laminae
lucidae/rarae; on the lamina lucida interna are situated the
endothelial cells of the capillaries and on the lamina lucida
externa are situated the podocytes. Podocytes show processes,
which become gradually thinner – primary, secondary and
tertiary/pedicels, embracing the capillaries, between these are
appearing small spaces forming the filtration slits.
The outer/parietal layer of the Bowman’s capsule shows a
simple squamous epithelium, which is continuous at the urinary
90
pole of the kidney corpuscle directly with the proximal convoluted

tubule of the kidney. The outer/parietal layer of the Bowman’s
capsule shows a basal lamina to its exterior and the simple
squamous epithelium to its interior. Between the parietal layer of
The Bowman’s capsule and the capillary tufts is appearing the
urinary space, a virtual, microscopic space; in light microscopy
this space appears larger due to the collapse of the capillary
tufts, which in vivo are turgid.
The third component of the kidney corpuscle is represented
by the mesangial cells; they are intraglomerular mesangial cells,
another type being the extraglomerular mesangial cells. These
cells are situated between the capillary tufts, providing support for
those and they are phagocytosing the filtration membrane which
is continuously produced by podocytes and endothelial cells and
continuously removed by mesangial cells, being damaged during
continuous filtration process.
In light microscopy are visible nuclei of podocytes,
endothelial cells and mesangial cells, but they cannot be
differentiated with the light microscope.
91
Fig. 55. Macula densa, proximal and distal tubule,

kidney HE x 100
Filtration process is filtrating plasma, without blood cells and

molecules which are exceeding 68 kDa, the molecular weight of
albumin. Through filtration are produced 150-180 liters of
ultrafiltrate daily, yet kidneys are eliminating only 1.5 liters of
urine/day; the final urine is obtained after important reabsorption
process, taking place in the tubules of the nephrons.
Proximal convoluted tubule is beginning at the urinary
pole of the renal corpuscle and is responsible for more than 90 %
of reabsorption process. It is longer than the distal convoluted
tubule; for that in the cortex, most of the sectioned tubules
surrounding the renal corpuscles are through the proximal
convoluted tubules; its lining epithelium is tall cuboidal with brush
border/microvilli at the apical pole of the cells. For that, the lumen
of the sectioned proximal convoluted tubule is small, unclear or
even absent. Usually the section does not pass through all nuclei,
92
so in section, not all the nuclei are visible in light microscopy.

Richness of mitochondria confers a deep acidophilia to proximal
convoluted tubule; presence of lateral folds of the plasma
membrane of the epithelial cells makes invisible the intercellular
limits, with the light microscope. Also this tubule shows a larger
diameter than the distal one.
Loop of Henle is situated between the proximal and distal
convoluted tubules of the kidney. It is U-shaped and has a thin
segment and a thick segment, which is similar in structure with
the distal convoluted tubule. Cortical nephrons show short loops,
while the juxtamedullary nephrons show long loops deeply
penetrating into the medulla. The short loops have their
conturnation at the level of the thick segment; in the long loops,
the conturnation appears in the thin segment of the loops. Hence,
the long loops have a thick descending limb, a long thin
descending and ascending limb and a thick ascending limb. Short
loops of the cortical nephrons show a short thin descending limb,
followed by the thick segment with the conturnation and they do
not have any thin ascending limb. The thin segment of the loop of
Henle is lined by a simple squamous epithelium, resembling with
the endothelium of the capillaries; the difference is represented
by a thicker epithelium than in the case of the capillary. Thick
segment of the loop of Henle shows a structure identical with that
of the distal convoluted tubule. In the thin segment of the loop of
Henle, water and sodium are passively absorbed, according to
the difference of gradient between the lumen and the interstitium,
while at the level of the thick segment of the loop sodium is
transported actively with ionic pumps, being followed by water,
here under the influence of aldosterone urine is concentrated
against the gradient.
93
Distal convoluted tubule is found more rarely in the

histologic specimens since it is shorter than the proximal, thus
are appearing fewer sections through this tubule. It has also a
smaller diameter than the proximal tubule. It has a larger and
better contoured lumen, because microvilli are not so well
developed like in the proximal tubule. Intercellular limits are
distinguishable with the light microscope, and because
mitochondria are not so numerous like in lining cells of the
proximal convoluted tubule, this tubule appears lower acidophilic
in light microscopy. In the distal convoluted tubule is acting
mainly aldosterone, stimulating active absorption of water and
sodium. This active sodium transport is controlled by the renin-
angiotensin-aldosterone system.
V.2. COLLECTING TUBULES
Collecting tubules in which are opening the distal

convoluted tubules are first lined by simple cuboidal epithelium;
as they become larger, they are lined by simple columnar
epithelium, forming the ducts of Bellini which are opening at the
area cribrosa of the tip of the pyramids/renal papilla, conducting
the urine to the calyces and finally to the ureter. Collecting
tubules are forming most of the medulla of the kidney; their lining
epithelium shows a pale aspect with clear intercellular limits and
they may be observed in both cross sections/longitudinal
sections. Collecting tubules are absorbing water under the
influence of the ADH (antidiuretic hormone/vasopressin); if water
consumption is restricted, then ADH is stimulating facultative
water absorption from the urine.
94
Fig. 56. Kidney medulla HE x 40
V.3. JUXTAGLOMERULAR APPARATUS
Juxtaglomerular apparatus shows three main components

– juxtaglomerular cells of the afferent arteriole, macula densa
of the distal convoluted tubule and extraglomerular mesangial
cells/ polkissen/ lacis cells/polar cushion.
Juxtaglomerular cells are modified smooth muscle cells
situated in the wall of the afferent arteriole (more rarely in the
efferent arteriole of the renal corpuscle) showing endocrine
secretory properties; they show round nuclei and they contain
secretory granules. Cells are in close contact with the
endothelium, since at this level the internal elastic limiting
membrane is missing.
Cells of the macula densa are narrow, tall columnar cells
lining the portion of distal convoluted tubule which is in close
95
contact with the juxtaglomerular cells of the afferent arteriole.

Nuclei of these cells are better stained and because the cells are
narrower they seem more numerous, giving in light microscopy
the image of a colored spot, from where the name of macula
densa. The basal lamina common in every epithelium is missing
at the level of macula densa, hence the cells are in contact with
juxtaglomerular cells in the wall of the afferent arteriole.
Extraglomerular/external mesangial cells are situated
in the angle beween afferent and efferent arteriole of the
kidney corpuscle, they are in continuity with
intraglomerular/internal mesangial cells; they have processes
between juxtaglomerular cells. They are difficult to observe in
light microscopy.
Juxtaglomerular cells secrete hormonal substances such
as renin, erythropoietin and others. They are monitoring the
filtration process through rennin secretion. When blood
pressure in the afferent arteriole is high enough to ensure a
normal filtration, juxtaglomerular cells do not release the renin.
When the blood pressure decreases, cells release the rennin
which is acting on the plasma angiotensinogen, forming
angiotensin I; on angiotensin I is acting angiotensin-
converting enzyme (ACE) with the formation of angiotensin II
a potent vasoconstrictor, which constricting arterioles is
increasing the blood pressure, thus ensuring an effective
filtration pressure. On the other hand, angiotensin II is
stimulating the secretion of aldosterone in zone glomerulosa
of the adrenal cortex, which stimulates absorption of sodium
and water in the distal convoluted tubules of the kidney; like
this blood pressure will once more increase, to ensure a
normal filtration pressure.
96
Cells of the macula densa may stimulate secretion of

renin by juxtaglomerular cells through monitorization of
sodium and chloride ions concentration in the lumen of the
distal convoluted tubules.
External mesangial cells show sympathetic innervations
and may stimulate rennin secretion via nervous system.
V.4. URINARY PASSAGES
Urinary passages are represented by calyces uniting to

form the pelvis, which is the dilated upper portion of the ureters;
ureters are opening into the urinary bladder, where urine is
gradually accumulated; urinary bladder is opening to the exterior
through the urethra, ultimate portion of the urinary passages.
Urinary passages show a common histologic structure:
mucosa, muscular layer and an adventitia/serosa to the outside.
97
Fig. 57. Urinary bladder HE x 40
Mucosa has transitional/ urinary epithelium/

paramalpighian epithelium/urothelium; this is a pseudostratified
epithelium. In light microscopy are visible 5-6 layers of nuclei;
columnar basal cells appear situated on the basal lamina and are
forming a regenerative layer. The intermediary layers are made of
rocket-like cells, with nuclei disposed perpendicularly face to the
basal lamina. Superficial cells are rounded at the apical pole, the
so-called umbrella-like cells. All cells are anchored to the basal
lamina through long cytoplasm pillars; this is visible in electron
microscopy. When the bladder is distending to fill with urine, cells
of transitional epithelium are rearranged on only 2-3 layers and
superficial cells become flattened or squamous. Apical pole of the
superficial cells has a peculiar adaptive structure, called cuticle
by ancient histologists.
In electron microscopy was revealed that the apical cellular
membrane has zones of thicker plaques, which are interposed
with areas of common cellular membrane; when urinary bladder
is empty, the common cellular membrane is plicate forming folds.
As the bladder is filling with urine, the folds of the superficial
cellular membrane are redressed, with the enlargement of the
inner surface of the epithelium (like a reserve of cellular
membrane). This adaptive feature is characteristic for the urinary
bladder, where is really needed and not so well expressed in
other segments of the urinary passages. Lamina propria is
common, thicker in the urinary bladder, where it is made of
denser connective tissue in its superficial aspect and of rather
loose connective tissue deeper, next to the muscular layer.
98
Muscular layer is made in the ureter by a helical layer at

the pelvis; in the upper two thirds of the ureters there are two
layers of smooth muscle fibers, an inner longitudinal layer and an
outer circular layer (an arrangement opposite to that of the
intestine’s muscular tunic), while in the lower/inferior one third are
present three layers of smooth muscle fibers – inner and outer
longitudinally disposed and a middle circular layer. The muscular
layer of the bladder shows a plexus-like disposition, smooth
muscle fibers being here interspersed with abundant connective
tissue, rich in elastic fibers.
Adventitia made of loose connective tissue is present at
the outside, only in the bladder some regions are covered by
peritoneum /serosal lining.
Female urethra is short, of about 3-4 cm long; it is lined to
the bladder by transitional epithelium, the rest of it being lined by
stratified squamous nonkeratinized epithelium, with small areas
of pseudostratified columnar epithelium.
Male urethra is longer of 15 -20 cm long, with three regions
– prostatic urethra is surrounded by prostate gland; it is lined by
transitional epithelium and here are emptying the ducts of the
prostate alveoli. Membranous urethra and spongy/penile
urethra are lined by stratified columnar epithelium, with zones of
pseudostratified columnar epithelium. To its end is lined by
stratified squamous nonkeratinized epithelium.
Urethra has two sphincters – inner involuntary and an outer
sphincter which contains striated skeletal muscle fibers and is
under the voluntary control of the individual.
- cortex of the kidney is recognizable by the presence
here of the renal corpuscles; in the medulla are found
99
exclusively sectioned tubules, mainly collecting tubules.

Distal convoluted tubule appears more rarely in the cortex
than the proximal tubule; distal tubules show a larger
lumen, well contoured, a paler acidophilia and all the
nuclei of the lining epithelium are visible in microscopy,
while proximal tubule shows a very small lumen,
sometimes no lumen at all, a deep acidophilia of its lining
cells and not all the nuclei are visible in histologic section.
Sections through proximal tubules are much more
numerous, because the proximal tubule is longer than the
distal one.
- Urinary bladder shows as lining the transitional
epithelium, with its characteristic umbrella-like superficial
cells, and intermediate rocket-like cells. Mucosa has folds;
the muscular layer shows abundant connective tissue
interspersed between smooth muscle fibers.
100
VI. FEMALE REPRODUCTIVE SYSTEM
Female reproductive system is made of the gonads, the

ovaries and of the female genital ducts – uterine tubes/oviducts,
uterus with its lower portion, the cervix and vagina. Through their
function, mammary glands are associated to the female genital
system.
VI.1. OVARIES
Ovaries are pair organs situated in the low part of the

abdomen/pelvis; they are flattened – ovoid structures, of around
3-4 cm long, 2 cm wide and 1 cm thick. They are classically
compared with almonds, since they show an irregular surface,
with prominences and depressions. In section, they present two
zones – a more compact periphery, the cortex and a looser zone
to the center, the medulla.
The surface of the ovary is covered by a simple low
cuboidal epithelium, the germinal epithelium, in fact part of the
peritoneum. First histologists wrongly believed this should be the
origin of oogonia/germ cells, nevertheless the name was kept.
Right under germinal epithelium is found tunica albuginea, a
dense connective tissue capsule, rich in collagen fibers and
showing a whitish appearance.
In the cortex, stroma is abundant, rich in fibroblasts showing
a helical disposition; in this highly cellular stroma are found the
ovarian follicles, in different stages of development. Oogonia
101
arising from the endoderm, the yolk sac are colonizing the genital
ridges/future ovaries; here they continue to divide up to
approximately 5-7 million, at the end of the 5 th month of
pregnancy. One to three million oogonia are surrounded by
stromal fibroblasts, known as follicular cells, to form primordial
follicles at the moment of birth; the rest of oogonia are
degenerating, submitted to so-called atresia. In the primordial
follicles, germinal cells are entering in the first meiosis, blocked in
its first phase by local paracrine factors; these are the primary
oocytes, resting in this phase till puberty. From 1 to 3 million
primordial follicles at birth, only 300-400 thousand are reaching
the age of puberty; the rest are becoming atretic. From this large
number of primordial follicles only one will reach the stage of
mature follicle, each month, releasing an ovum, for 30-40 years,
from menarche to menopause, which means the fertile life of a
female. Remaining follicles will degenerate through atresia,
during this time period.
Fig. 58. Ovary; primordial, primary follicles trichrome x 40
102
Before the age of puberty, in the ovaries are found

exclusively primordial follicles. Initiation of puberty is triggered
especially by the pulsatile release of GnRH/gonadotropin-
releasing hormone from the hypothalamus, leading to the same
pulsatile discharge of gonadotropins - FSH and LH from the
anterior pituitary; this is resulting in evolution of the ovarian
follicles till the stage of ovulation and ovarian hormonal secretion
of female sexual hormones, estrogens and progesterone.
Ovarian follicles show four stages of evolution –
primordial, primary, secondary and mature/graafian/tertiary.
Primordial follicles are most numerous follicles; they are
located in the periphery of the ovaries, right beneath tunica
albuginea. Primary oocyte has approximately 25 μm in diameter,
an eccentrically placed pale nucleus, with well visible nucleolus; it
contains well developed organelles. Follicular cells surrounding
the oocyte are flattened, squamous cells, connected one with
another by desmosomal junctions, forming a single layer around
the oocyte and separated from the ovarian stroma by a fine
vitrous membrane – membrane of Slavjanski.
Primary follicles show larger oocytes, of approximately
100 μm in diameter; follicular cells become cuboidal and are now
called granulosa cells. First, they form a single layer around the
oocyte – the unilaminar follicle; as they proliferate and form
several layers around the oocyte, this will be a multilaminar
follicle. In this stage, between oocyte and granulosa cells is
appearing an amorphous glycoprotein material, forming zona
pellucida, secreted by the oocyte. Inside zona pellucida are
present processes of the granulosa cells, establishing gap
junctions with the oocyte. At the outside of the multilaminar
primary follicles, stromal cells are forming the two thecae of the
103
ovarian follicle – an inner theca interna which has endocrine

activity; its cells are linking pituitary LH, under the influence of
which, here are secreted androgens (androstenedione).
Granulosa cells (linking pituitary FSH) are secreting enzyme –
aromatase which is converting the androgen into estrogen –
estradiol. This is the so-called principle of the two cells in what
concerns the hormonal secretion of the ovary. The outer theca
externa is a fibrous sheath, made of connective tissue, devoid of
endocrine activity.
Secondary/antral follicles shows a large oocyte of up to
200 μm in diameter, surrounded by numerous layers of granulosa
cells; first between the granulose cells appear in this stage
several small cavities filled with so-called follicular fluid,
containing GAG, GP and hormones – estradiol, progesterone,
inhibin (inhibiting FSH), activin (regulating the release of FSH and
LH). Gradually, inside the follicle will develop a single cavity filled
with follicular fluid/antrum. Granulosa cells which are surrounding
the oocyte are bulging into the antrum, forming cumulus
oophorus. Granulosa cells which are directly surrounding the
oocyte, being disposed perpendicularly on zona pellucida are
forming corona radiata. All these features are characteristic for
the late stage of secondary follicle; at the end of this stage theca
interna is well developed and abundantly vascularized, ensuring
the hormonal secretion of the ovary. Many such follicles are
degenerating, becoming atretic, but small parts of granulosa cells
are persisting in the ovary to form the interstitial gland, as they
further secrete androgens and estrogens, also after menopause.
104
Fig. 59. Ovary; mature and secondary follicles trichrome x 40
Mature/graafian follicles are the largest ovarian follicles,

they may reach 2.5 cm in diameter by the time of ovulation,
especially through accumulation of follicular fluid in the antrum.
The mature follicle is prominent on the surface of the ovary – the
zone of stigma. Granulosa cells pushed in periphery of the
follicles are forming the membrana granulosa. The cumulus
oophorus containing the oocyte may detach from the rest of the
granulosa cells and to float in the follicular fluid. The main factor
triggering ovulation, (meaning the release of a secondary
oocyte, first meiosis being completed during ovulation) is
represented by the gradual elevation of the plasma levels of
estrogens; this is inducing inhibition of the pituitary FSH and most
important – a sudden surge of LH from the anterior pituitary,
known as the ovulatory cascade of LH. It is taking place around
14th day of an ovarian and menstrual cycle of usually 28 days; the
105
discharge of LH is preceding ovulation with approximately 24

hours.
Fig. 60. Ovary; mature follicle HE x 40
Corpus luteum or progestative body is resulting from the

ex-mature follicle after ovulation; expelling of the oocyte, cumulus
oophorus and follicular fluid makes the walls of the follicle to
collapse and become folded. The ruptured blood vessels are
resulting in the formation of a central blood clot; as the clot is
removed by macrophages, a highly vascularized endocrine
structure will form, the corpus luteum, its development being
stimulated by high levels of LH. 80 % of the cells of the corpus
luteum are at origin granulosa cells which become large, pale-
looking, steroid secreting endocrine cells; they are called
granulosa-lutein cells and they secrete progesterone and they
convert androgens secreted by theca-lutein cells into estrogens.
Theca- lutein cells are originating in the theca interna of the
ovarian follicle, they represent around 20 % of the cell population
106
of the corpus luteum, being smaller and darker stained and

peripheral disposed, compared to granulosa -lutein cells. These
cells secrete progesterone, androgens and small amounts of
estrogens.
Fig. 61. Ovary; corpus luteum trichrome x 40
If pregnancy does not occur, the drop of LH (inhibited by

progesterone) will lead to involution of the copus luteum, with the
gradual formation of a scar rich in collagen fibers, called corpus
albicans. This structure appears in light microscopy as an
irregular, acellular, fibrous, collagen-rich formation which is
gradually resorbed advancing toward the medulla of the ovary. In
case of fertilization of the ovum and pregnancy, secretion of LH-
like human chorionic gonadotropin by the placenta maintains
corpus luteum several months in the ovary; this is the corpus
luteum of pregnancy, growing at about 5 cm in diameter and
secreting large hormonal amounts to ensure the development of
pregnancy.
107
Fig. 62. Ovary; atretic follicles; remnants of zona pellucida

trichrome x 40
Atresia of the ovarian follicles is a physiologic

phenomenon involving all the stages of development of the
ovarian follicles. Numerous primordial follicles become atretic;
generally, in later stages of development main observable events
of atresia are – ceasing of proliferation of granulosa cells, their
detachment one from another and eventual float in the follicular
fluid of the antrum; proliferation of fibrous connective tissue which
is invading the atretic follicles; long persistence of zona pellucida
devoid of oocyte (which is submitted to autolysis) with a
characteristic aspect of flat wheel, important for recognition of the
atretic follicles in light microscopy.
Medulla of the ovary contains especially large blood
vessels in an atmosphere of loose connective tissue; large
muscular arteries and arterioles are clearly visible in microscopy.
Hilus cells are steroid-secreting endocrine cells very similar with
108
the endocrine Leydig cells of the testes; here too, they secrete
androgens.
Fig. 63. Ovary; medulla x 40

- presence of the ovarian follicles in different stages
of development, in the cortex of the ovary is unique
aspect, making it easy recognizable in light microscopy.
Occasionally, corpus luteum, a large structure made of
pale-stained cells is visible, as well as atretic follicles. The
central medullary zone is occupied mainly by large arterial
blood vessels.
VI.2. OVIDUCTS/FALLOPIAN TUBES
Oviducts/fallopian tubes are paired muscular tubes 12 cm

long, connecting the surface of the ovary with the uterine cavity.
109
Anatomically they show four regions – the infundibulum, which is

fringed, showing projections – fimbriae toward the ovary and
helping in the capture of the oocyte during ovulation; a dilated
part – the ampulla, where fertilization usually occurs; an isthmus
and an intramural part, opening in the uterine wall.
Histologically, the structure of the wall is consisting of
mucosa, musculosa and serosa.
Mucosa has numerous folds, conferring a labyrinth aspect
in cross section. Simple columnar lining epithelium is made of two
cell types – ciliated cells, with motile cilia and secretory cells with
no cilia/peg cells. Number of ciliated cells in the uterine tube
epithelium is greater during first, estrogenic phase of the ovarian
cycle, while during second, progesteronic phase, peg cells are
predominating. The beat of the cilia is oriented toward uterine
cavity, helping the advance of the fertilized ovum to uterus. Peg
cells are secreting nourishing products for the ovum and are
ensuring capacitation of the spermatozoa, making them capable
to fertilize the ovum. Lamina propria is rich in blood vessels
undergoing an edema phenomenon around the time of ovulation,
which is approaching more the fimbriae to the ovarian surface for
the capture of the oocyte.
Musculosa is made of two layers of smooth muscle fibers –
inner circular and outer longitudinal.
Serosa is common, with no peculiar features.
- the folded, labyrinth-like image of the lumen of the
oviduct is characteristic; ciliated cells are distinguishable
with the light microscope.
110
VI.3. UTERUS
VI.3. Uterus is a pear-shaped, unpaired muscular organ. Its

lower portion, prominent in the vagina is called uterine cervix.
Histologic structure of the uterine wall includes mucosa –
endometrium, musculosa – myometrium and serosa/adventitia
to the outside.
Endometrium is called the thick mucosa of the uterus; its
lining epithelium is simple columnar with two cell types, similar to
that of the oviducts, however in the case of the uterus secretory
nonciliated cells are predominating, independently of the phase
of the ovarian cycle. Simple columnar epithelium is deepening to
form simple tubular glands, the endometrial glands which are
extending to most basal part of the mucosa, next to myometrium.
Lamina propria is richly cellular, containing mainly proper cells of
the connective tissue – fibroblasts, modifying their aspect
according to the phases of the hormonal cycle.
Two layers are differentiable in the endometrium – a basal
layer/basalis, which is not expelled with the menses and
regenerates mucosa each month; it represents ¼ up to 1/3 of the
thickness of the endometrium and is irrigated by the straight
arterioles, not showing hormone dependency. The functional
layer/functionalis is eliminated with the menstruation each
month and regenerated from the basal layer; it represents 2/3 up
to ¾ of the endometrium and is nourished by the coiled
arterioles, strongly hormone dependent vessels.
At the beginning of the menstrual bleeding, with expulsion of
the functional layer and lasting for 3-5 days, under the influence
of the estrogens secreted by the ovaries, endometrium begins to
grow from the base of the glands found in the basal layer and
111
from the uncovered basal lamina propria. The glands are almost
straight during first phase of the cycle – lasting from the 1 st day of
the menstrual bleeding to the 14 th day – known as proliferative
/follicular/estrogenic phase.
Fig. 64. Endometrium 1st phase; endometrial

glands trichrome x 40
Accumulation of glycogen in the epithelial lining cells is first

moving the nucleus to the apical pole, afterwards nucleus regain
its basal position and cytoplasm appears paler at the apical pole.
In the second secretory/luteal/progesteronic phase of the
endometrial cycle, lasting from 14th to the 28 day, or first day of
the following cycle, edema of the lamina propria and
accumulation of secretion in the glands is leading to their tortuous
and dilated aspect, characteristic for this phase of the cycle. Their
aspect is compared to a corkscrew or to the teeth of a saw.
Cellular lamina propria is also modified as aspect in microscopy;
lamina propria cells which were accumulating glycogen,
becoming rounded are crowded beneath lining epithelial cells,
112
forming the compact zone of the endometrium/decidual layer of

the endometrium. Deeper, the lamina propria is made of rather
dissociated cells and fibers – the spongy zone of the
endometrium.
Fig. 65. Endometrium 2nd phase HE x 40
In premenstrual phase, further coiling of the coiled arteries

which are irrigating the functional layer of the endometrium is
leading to ischemia and necrosis of this layer, finally expelled with
a small amount of blood, the menstrual bleeding. Drop of the
plasma levels of progesterone is main factor which results in the
coiling and spasms of the coiling arteries of the functional layer of
the endometrium.
Myometrium shows a rather plexus-like disposition of its
smooth muscle fibers; nevertheless three layers may be
differentiated in the myometrium; an outer and an inner
longitudinal layers and a middle circular layer, which is containing
numerous vessels, known also as the vascular layer. From the
arcuate arteries of this layer result the straight and the coiled
113
arterioles, irrigating endometrium. Adventitia of the blood vessels

of the uterus is poorly developed allowing their firm tight under
muscular contraction and this way impairing hemorrhages after
parturition.
Serosal lining of peritoneum is covering uterus in its
upper and posterior part, while to the anterior part and laterally,
we find adventitial loose connective tissue.
Uterine cervix is the cylindrical lower portion of the uterus,
prominent inside the vagina. The inner lumen of this canal is lined
by simple columnar mucus-secreting epithelium, also forming
branched tubular glands. The quality of the mucus is modified
according to the phases of the ovarian cycle; around moment of
the ovulation mucus is fluid, easily penetrated by spermatozoa,
due to high estrogenic levels. In the second progesteronic phase
and mostly during pregnancy, the mucus is viscous; in pregnancy
it forms a mucus plug which is obliterating the uterine cavity. The
part of the cervix which is prominent in the vagina is covered by
stratified squamous nonkeratinized epithelium, continuous with
the same epithelium, lining the vagina. Muscular tunic of the
cervix is thin, containing abundant connective tissue, rich in
elastic fibers.
- first, proliferative/follicular phase of the endometrial
cycle is recognizable on presence of almost straight, thin
endometrial glands; second, secretory/luteal phase is
characterized by coiled and tortuous glands, with the
aspect of corkscrew or teeth of a saw.
114
VI.4. MAMMARY GLANDS
Mammary glands are compound tubuloalveolar glands

made of 15-20 lobules separated one from another by adipose
and collagen-rich connective tissue. In light microscopy are
observable the differences between the resting/non-lactating
glands and the active/lactating glands.
Fig. 66. Resting mammary gland trichrome x 40
115
Fig. 67. Resting mammary gland x 40 HE
Secreting alveoli are absent in inactive glands, since they

develop only during pregnancy. In the resting glands are found
only excretory ducts embedded in abundant connective tissue
and white adipose tissue, otherwise also responsible for the
characteristic shape of the organ, beginning with the puberty.
Small intralobular ducts are lined by simple cuboidal/columnar
epithelium, while larger ducts known as lactiferous ducts are lined
by stratified cuboidal epithelium; they open at the nipple, where
they are lined by stratified squamous keratinized epithelium.
Myoepithelial cells are found between the basal lamina and the
epithelial cells, in the ducts and in the alveoli of the gland. Just
before their opening, lactiferous ducts show a dilated portion –
the lactiferous sinus, for milk storage.
116
Fig. 68. Lactating mammary gland x 40 trichrome
During pregnancy, under the influence of growing plasma

levels of estrogens and progesterone secreting alveoli are
gradually developing in such a manner that they occupy most of
the gland, replacing the connective and adipose tissue which is
filling the gland before pregnancy. Alveoli first secrete colostrum,
rich in proteins and immune factors. At birth, under the influence
of prolactin, secreted by the anterior pituitary, milk secretion is
initiated within the alveoli of the gland. Oxytocin is contracting the
myoepithelial cells of the ducts and alveoli inducing the ejection
of milk from the mammary gland.
- extensive connective tissue and white adipose
tissue hosting just a few excretory ducts, clustered in some
small areas is the main criterion for the recognition of the
resting mammary gland; larger ducts are lined by stratified
cuboidal epithelium.
117
- presence of alveoli filling entirely the lobules is the

aspect of the lactating gland. In the lactating gland is
difficult to observe any ducts, because they are masked by
extremely numerous alveoli.
VI.5. PLACENTA
VI.5. Placenta is a transitory organ present only in

pregnancy. After fertilization of the ovum, rapid cellular division of
the zygote is leading to the formation of the morula; the next
stage is that of blastocyst made of a fluid-filled cavity and a
cluster of cells at one pole. The cells surrounding the fluid-filled
cavity form the trophoblast, from which fetal placenta is
developing.
Implantation in the endometrium takes place in the
blastocyst stage; besides eroding the endometrium, trophoblasts
is developing on its surface processes known as chorionic villi,
the base of the villi forms the chorionic plate of the placenta.
The erosion of the endometrium done by the trophoblast is
opening the maternal blood vessels, forming large blood-filled
spaces called lacunae. Most of the chorionic villi are floating
freely in the maternal blood – the free villi, while others are
anchored in the decidua basalis (anchoring villi), which is the
name of the endometrium profoundly modified by hormonal
pregnancy status and where chorionic villi are developing.
Epithelium of the trophoblast is first made of two layers –
the outer layer is a syncytium, a band of cytoplasm with nuclei
showing no intercellular limits – the syncytiotrophoblast.
Syncytiotrophoblast is up-taking nutrients from the maternal blood
and is discharging waste products of the fetus into it through its
118
microvilli/brush border. Furthermore this layer shows endocrine

activity, secreting human chorionic gonadotropin/hCG,
progesterone, estrogens,chorionic somatomammotropin (growth
and lactogenic hormone), essential in the normal evolution of
pregnancy. Inner layer of the epithelium of the trophoblast is the
cytotrophoblast which shows mitotic activity and provides the
full, normal development of the placenta. Cytotrophoblast layer is
gradually disappearing in the second semester of pregnancy,
when placenta reaches its complete development.
Chorionic villi may be primary villi, made only of the
trophoblastic epithelium; as the connective tissue of the chorionic
plate is penetrating inside the villi, are appearing secondary villi;
finally fetal blood vessels are penetrating inside the villi to form
the tertiary villi. Maternal blood is separated from fetal blood by
the placental barrier which consists of syncytiotrophoblast (and
cytotrophoblast only in the first 3-4 months of pregnancy),
connective tissue inside the villi and the endothelium of the fetal
blood capillaries with its basal lamina. G immunoglobulin is
passing through the placental barrier and is ensuring the
immunity of the fetus and of the newborn. Placental barrier is
generally not crossed by bacteria but is crossed by viruses,
alcohol, nicotine and most of the medications.
119
Fig. 69. Placenta; chorionic villi first half of pregnancy HE x 40

- on the microscopic specimen are usually present
fragments of chorionic villi; if they are bordered by a bi-
layered epithelium – syncytio- and cytotrophoblast it is a
placenta in the first semester of pregnancy; if instead we
observe one layer of nuclei bordering the chorionic villi,
only the syncytiotrophoblast, then it is placenta during
second half of pregnancy; presence of well developed
blood vessels inside the villi is also characteristic for
second semester of pregnancy placenta.
120
VII. MALE REPRODUCTIVE SYSTEM
Male reproductive system consists of the two testes and

male genital ducts, which according to their situation are intra-
and extratesticular – rete testis, ductules efferentes, epididymis,
vas/ductus deferens and associated glands – seminal vesicles
and prostate. Similar to the ovaries, testes show both exocrine
and endocrine function, production of gametes (spermatozoa) on
one hand, and on the other secretion of male genital hormones,
mainly testosterone.
VII.1. TESTES
Suspended in the scrotum, testes are paired organs

covered by tunica vaginalis which is part of the peritoneum
brought into the burses by the testicle during its migration along
the inguinal canal. At the outside, testis is enveloped by a thick
collagenous connective tissue tunic, tunica albuginea which
shows a thickening at its posterior inner face - the mediastinum
testis from which are running septa dividing the interior of the
testis into approximately 250 lobules. Each lobule contains 1-4
seminiferous tubules highly coiled, beginning with a blind end
inside the testicle and opening with the other end in the
mediastinum, in the tubuli recti, continued by a system of
anastomosed canaliculi – the rete testis, intratesticular male
genital ducts. Between seminiferous tubules are present clusters
of endocrine cells Leydig cells which are secreting male sexual
hormone, testosterone.
121
Fig. 70. Testis; seminiferous tubules; leydig cells HE x 100
Seminiferous tubule is made of a stratified epithelium –

germinal/seminiferous epithelium with a thick basal lamina
surrounded to the outside by a thin layer of connective tissue
which may contain rare myoid cells showing characteristics of
smooth muscle fibers and contractile capacity.
Seminiferous epithelium is made of two cell types – Sertoli
cells, cells of support and cells of the spermatogenic lineage.
Sertoli cells are tall columnar cells which are occupying
entirely the thickness of the epithelium, with the basal pole on the
basal lamina and the apical pole in the lumen. In light
microscopy, only nuclei of different cells of the seminiferous
epithelium are visible. Nucleus of the Sertoli cell is recognizable
being the sole which is ovoid/triangular since the nuclei of the
spermatogenic cells are rounded; it is appearing pale, with
obvious nucleolus and 1-2 associated chromatin clumps. Besides
being a cell of support for the sperm cells (showing lateral
122
compartments in which are hosted spermatogenic cells) Sertoli

cells accomplish other important functions for spermatogenesis –
they establish a blood-testis barrier through occluding junctions
between one another determining a basal compartment hosting
solely spermatogonia and an ad-luminal compartment where are
sheltered all the other cells involved in spermatogenesis; they
nourish all the cells found in the ad-luminal compartment; they
secrete hormonal substances – antimüllerian hormone (inhibiting
the development of the müllerian duct and thus suppressing the
spontaneous development of the embryo toward female sex) and
inhibin ( inhibiting FSH) and other important fractions – ABP
(androgen-binding protein ensuring concentration of testosterone
in the seminiferous tubule, needed for spermatogenesis process)
and fructose, important for the nourishment of spermatozoa.
Spermatogenic cells are representing most of the cell
population of the seminiferous tubules. Spermatogonia are small
diploid cells situated on the basement membrane; there are three
types of spermatogonia – type A dark, with dense nuclei (these
are reserve cells), type A pale with pale nuclei (containing
euchromatin) and type B deriving through mitosis from type A
pale spermatogonia. Through mitoses, type B spermatogonia
give rise to primary spermatocytes. Primary spermatocytes
have the largest nuclei of all the sperm cells, looking round and
showing large chromatin clumps conferring them an image of a
ball with large spots. They are situated to the mid part of the
germinal epithelium; they are engaged in the first meiosis in
which is taking place the crossing-over phenomenon supposing
genes exchanges between homologous chromosomes, modifying
the genetic material and ensuring the variability of the specie.
Thus cells engaged in meiosis are not anymore recognized as
123
self by the immune system, for that is needed a blood-testis

barrier (if exposed to immune system, autoimmunity with
autoantibodies against these cells would develop; spermatozoon
is a sequestered/segregated antigen). Secondary
spematocytes are small short-living cells as they enter rapidly in
the second meiotic division, for that they are not easily
observable in microscopy.
Fig. 71. Seminiferous tubules HE x 100
Spermatids are small haploid cells showing small

condensed nuclei; they appear to the lumen of the seminiferous
tubules, intercalated with spermatozoa. Through a complex
process of differentiation without cellular division known as
spermiogenesis, from spermatids are resulting spermatozoa.
Spermatozoa are made of a head, a middle piece and a
tail; they are measuring around 65 μm in length, with the tail the
longest part of all. In the anterior part of the head is found the
acrosome containing enzymes capable to digest zona pellucid of
124
the oocyte during fertilization. The tail is a single flagellum with

the structure of a motile cilium; dynein responsible for the mobility
of the tail of the spermatozoon is activated inside epididymis,
before reaching epididymis, spermatozoa are unmotile cells. In
the seminiferous tubules spermatozoa are sitting with their heads
in depressions at the apical pole of Sertoli cells and with their tails
toward the lumen. A complete spermatogenesis process is
accomplished in 65-70 days; process which is found in different
stages in different seminiferous tubules. One ejaculate contains
2-5 sperm ml, with an average of 60-120 million
spermatozoa/sperm ml.
Interstitial Leydig cells are situated in small clusters
between seminiferous tubules, in a well vascularized connective
tissue environment. They are polygonal cells measuring 15 μm in
diameter; they show central located nucleus, sometimes they are
binucleate. They show lipid vacuoles in the cytoplasm, being
typical steroid-secreting endocrine cells. They secrete
testosterone, main male sexual hormone under ICSH/LH
stimulation. Testosterone is responsible for the development of
the male sex in the embryo, otherwise the development is
resulting in formation of female sex. From puberty is inducing the
development of secondary male traits and of normal process of
spermatogenesis.
VII.2. MALE GENITAL DUCTS
Male genital ducts are divided into intra- and extratesticular;

intratesticular – tubuli recti and rete testis; the rest (ductuli
efferentes, epididymis, vas deferens, ejaculatory duct) are
extratesticular male genital ducts.
125
Tubuli recti are continuing seminiferous tubules at their

opening into the mediastinum testis; these are short and straight
tubules which are first lined by Sertoli cells, while toward their
opening in the rete testis they are lined by simple cuboidal
epithelium, with microvilli at the apical pole of the epithelial cells.
Rete testis appears as narrow labyrinth space dig in the
dense connective tissue of the mediastinum testis; it is lined by
simple cuboidal/simple squamous epithelium.
Ductuli efferentes are 15-20 highly coiled tubules in a con-
shape, forming together the head of the epididymis. Lining simple
epithelium is made of groups of cuboidal nonciliated cells
alternating with groups of tall columnar ciliated cells; this confers
a characteristic scalloped aspect to the lumen of these tubules, in
cross section. Cuboidal cells show absorptive activity absorbing
fluid from the sperm, while cilia are moving the sperm toward
epididymis. At the outside is present a thin sheath of circularly
arranged smooth muscle fibers.
Epididymis is a long tortuous duct of 4-6 m; epithelial lining
is represented by pseudostratified columnar epithelium, with short
basal cells of regeneration, which are regenerating principal tall
columnar cells. Columnar cells show ovoid large basal nuclei and
stereocilia at the apical pole; stereocilia are very long microvilli
which appear in light microscopy clustered together (they were
compared with a “candle flame”). Columnar cells are absorbing
the fluid in which spermatozoa are reaching epididymis, thus
concentrating the sperm and creating a negative pressure
capable to move spermatozoa to the distal end of the male
genital ducts. To its outside epididymis is surrounded by a
circular layer of smooth muscle fibers which peristaltic
contractions propel the sperm toward vas deferens.
126
Fig. 72. Epididymis x 100
Ductus/Vas deferens is a muscular tube which is linking

epididymis with the ejaculatory duct. It is lined by pseudostratified
columnar epithelium with stereocilia, similar to that of the
epididymis and has a thick muscular tunic made of three
muscular layers – inner and outer longitudinal layers and a
middle circular layer. The presence of this thick muscular layer is
explaining the star-shaped image of the cross section through
vas deferens; muscular contraction after death is contracting the
lumen giving this irregular image of the vas deferens in light
microscopy. Terminal portion of vas deferens is dilated forming
the ampulla, continued with the seminal vesicle, opening into the
ejaculatory duct. Ejaculatory duct is a straight, short tubule lined
by simple columnar epithelium; it is opening into the prostatic
urethra.
127
Fig. 73. Vas deferens HE x 40
VII.3. SEMINAL VESICLES
Seminal vesicles are highly coiled tubular spaces of

around 15 cm long. Mucosa of the seminal vesicles shows a
fringed epithelium, responsible for the labyrinth-like image of the
microscopic section. Lining epithelium is simple
columnar/pseudostratified columnar; tall columnar cells are
producing a yellowish, viscous fluid which is rich in fructose,
representing main source of energy for spermatozoa. Fluid here
secreted represents approximately 70 % of the volume of semen.
Macroscopically, epithelium shows a yellow nuance caused by
the lipochrome pigment secreted by the lining epithelial cells. A
thin muscular tunic is found in the wall of the seminal vesicles.
Prostate gland has three lobes and the middle one is
surrounding the first portion of the urethra. The gland consists of
30-50 tubuloalveolar glands and besides dense connective
tissue, the capsule and the stroma of the gland contain numerous
128
smooth muscle fibers. Tubuloalveolar glands are arranged in

three concentric layers facing the urethra – mucosal glands show
short excretory ducts; submucosal glands are situated external to
the mucosal glands and are larger; main glands are the outer-
most glands, being the largest and most numerous of all they are
forming most of the parenchyma. The lumen of the alveoli
appears partially divided by fringes of the epithelial cells of the
pseudostratified columnar epithelium; each alveolus has its own
excretory duct lined by simple columnar epithelium, emptying
separately into the urethra. In the lumen of the alveoli and of
excretory ducts are found characteristic rounded or ovoid
structures, made of calcified glycoproteins called corpora
amylacea/prostatic concretions. Secretion of the gland is part
of the seminal fluid, an opalescent, serous secretion, containing
lipids, enzymes (acid phosphatase), citric acid, lecithin etc. The
gland is strongly hormonal-dependent.
- Testis is recognizable under the presence of
seminiferous tubules sectioned in various incidences;
seminiferous tubules are lined by the polymorphous
seminal/germinal epithelium. Ovoid/triangular large, pale
nuclei of Sertoli cells are visible interspersed with
spermatogenic cells nuclei. First spermatocyte nucleus is
easily recognizable being rounded, large with clear large
chromatin bulges. To the lumen are visible spermatozoa
with their tails toward the lumen of the tubules. Between
the tubules are visible clusters of large polyhedral cells,
with vacuolar cytoplasm, the Leydig interstitial cells. To
one pole of the testes usually are found sections through
epididymis – the tall columnar epithelium slightly
129
pseudostratified, shows clearly visible stereocilia projecting

into the lumen.
- prostate is made of alveoli with a partially divided
lumen by the fringed epithelium; stroma of the gland is rich
in smooth muscle fibers. Presence of oval/rounded
prostatic concretions is important criterion of recognition
for the gland.
Fig. 74. Prostate x 40
130
Fig. 75. Prostate; prostatic concretions HE x 40
VIII. INTEGUMENT
Skin represents approximately 15 % of the body weight,

being the heaviest organ of the human body. It is covering the
entire body and is continuous with the mucous membranes of the
digestive, respiratory and urogenital system, where these tracts
show openings in contact with the exterior.
Skin is made of epidermis and of its connective tissue of
support – the dermis. It is providing functions of mechanical and
thermo isolation and is acting as a hydro-electrolytic and immune
barrier.
Epidermis forms two varieties of skin – thin skin covering
most of the body and thick skin, covering only the palms of hands
and soles of the feet. It is stratified squamous keratinized
131
epithelium, made of four layers in the thin variety of skin –

basale/germinativum; spinosum/thorny; granulosum and
corneum; in the thick skin are found five layers in the structure of
epidermis, the supplementary layer lucidum appears between
layer granulosum and layer corneum.
Stratum basale/germinativum is made of a single layer of
low columnar/cuboidal cells situated on the basement membrane;
the basement membrane is folded, like generally in the case of
stratified epithelia. They renew through mitotic divisions all the
superficial layers; cells are basophilic, with large nuclei. They are
attached to the basement membrane through hemidesmosomes.
Stratum spinosum is made of basal keratinocytes which
still divide for the renewal of the superficial layers. Cells are
generally polyhedral and they tend to flatten to the surface; they
contain tonofilaments and tonofibrils of cytokeratin which are
attached on desmosomes, appearing as intercellular bridges and
conferring to cells a prickle/ thorny appearance, giving the name
of this layer. This layer is the thickest of all, made of 5-6 rows of
cells in the thin epidermis, up to 10-12 in the thick variety.
Stratum granulosum is composed of 2-3 layers of flattened
keratinocytes, but may be discontinuous in the thin variety. This is
the ultimate layer where nuclei are still present in the cells. Cells
contain large basophilic granules of keratohyalin, a keratin
precursor, giving the name of this layer. Cells also contain lipid
granules which content is discharged in the extracellular space
forming the hydro-electrolytic barrier at thus providing this
function of the skin.
Stratum lucidum is present only in the thick skin; cells do
not contain anymore nor nuclei, neither organelles, they contain
132
eleidin, a product developed from keratohyalin. It is a very thin

discontinuous layer, shining/refringent in light microscopy.
Stratum corneum is the most superficial layer, much
thicker in the thick than in the thin variety of skin, where it is
formed by only a few keratin lamellae. It is made of dead cells,
filled completely with keratin; desquamation is done as keratin
sheaths/lamellae. However, deeper cells still contain
desmosomes, while the more superficial ones lose their
desmosomal junctions and are known as horny cells. Langerhans
cells are antigen-presenting and phagocytic cells situated in layer
spinosum; melanocytes are producing the pigment of the skin –
melanin, afterwards transferred to keratinocytes and conferring
the color of the skin, providing protection against UV radiations,
they appear in the basal layer; Merkel cells found in stratum
basale, are sensory cells of the epidermis, associated with nerve
endings. All these cells are not recognizable in usual methods of
staining, in light microscopy.
Fig. 76. Thick epidermis HE x 40
133
Fig. 77. Hypodertmis HE x 40
Dermis is the supporting connective tissue of the skin,

found just beneath the epidermis. It shows prominences toward
the epidermis known as dermis papillae. We differentiate a
papillary dermis or superficial dermis, made of loose connective
tissue, a proper/reticular dermis made of dense irregular
connective tissue and representing the thickest part of the dermis
and a deep dermis or hypodermis, made of loose connective
tissue and white adipose tissue.
The thick, coarse collagen type I bundles of the proper
dermis are characteristic for the dense irregular connective tissue
variety and appear in light microscopy as an aquarelle paint.
134
Fig. 78. Thin epidermis; sebaceous glans; hair follicle HE x 40
Eccrine sweat glands are secreting the sweat via

merocrine way; they are coiled tubular glands situated deep in
the dermis or in the hypodermis. The secretory portion shows a
simple cuboidal/pseudostratified epithelium, while the excretory
duct is lined by bistratified cuboidal epithelium. The coiled tubular
duct is ascending to open at a pore of the skin, where is emptying
the sweat. At the base of the secretory cells are present
myoepithelial cells (containing myosin and actin contractile
filaments) which through their contraction are facilitating the
discharge of the sweat.
Sebaceous glands are associated with the hair follicles
and are present exclusively in the dermis of the thin skin
(glabrous skin of the palms and soles is devoid of sebaceous
glands and hair follicles). The gland is acinar, with a sack-shaped
secretory portion; the excretory duct is short, rather a neck of the
gland than a real duct. At the base of the gland is present a
135
single layer of low regenerative cells which are proliferating

continuously ensuring the rapid turnover of the sebaceous cells.
Sebaceous cells are filling the gland; they are large polyhedral
cells with vacuolar cytoplasm and central located nuclei. As the
cells are filling with lipid droplets (triglycerides composing the
sebum) the cells are degenerating; to the neck of the gland the
nucleus is shrinked and picnotic. Finally the cells are dying and
are expelled with the sebum. A third category of cells is
represented by large keratinized cells which show processes and
are forming a skeleton of support for the gland, maintaining it
permanently opened. This way of secretion is known as a
holocrine way. On the surface of the skin sebum is decomposed
by saprophytic bacteria forming fatty acids and conferring a low
acid ph to the surface of the skin which bactericidal activity.
Fig. 79. Thin skin; sebaceos gland, hair follicle He x 40
Hair follicles are elongated keratinized structures

projecting from the surface of the skin. They are surrounded by a
136
connective tissue sheath with a thickened glassy membrane

surrounding the hair follicle. The end of the hair root is dilated
forming the hair bulb; in the hair bulb are penetrating blood
capillaries to nourish the hair and thus forming the hair papilla. In
cross section is visible the outer root sheath made of the basal
cell layers of the epidermis and showing in microscopy the same
aspect as these; the inner root sheath is made of single-layered
Henle’s layer and Huxley’s layer and the cuticle of the inner root
sheath made of shingle-like cells overlapping each other. Inner
root sheath is ending at the opening of the sebaceous gland
attached to the hair follicle. Hair shaft is made of a central
medulla and a peripheral cortex. At its periphery the hair has also
a cuticle, the cuticle of the hair, made of shingle-like cells
matching with the shingle cells of the cuticle of the inner root
sheath, since they show the opposite disposition than these.
- different layers of the epidermis are easily
recognizable in light microscopy; thick aspect of the
epidermis with its gradually surface flattening cells is
characteristic. Thick epidermis shows a keratin layer
corneum which is usually overpassing in thickness, the
whole thickness of all the other layers.
- sections through sweat glands are clustered in the
deep part of the dermis; excretory ducts are better stained
than the sections through the secretory portion and are
lined by bistratified cuboidal epithelium – two layers of
nuclei are clearly visible.
- sebaceous glands show a sack-like aspect and are
made mainly by large polyhedral vacuolar unstained cells
with central nuclei (lipid material being removed during
137
technique, sebum vacuoles appear empty, unstained in

microscopy).
- sections through hair follicles appear ovoid,
rounded or elongated, when longitudinally sectioned. Inner
root sheath is better stained in light microscopy than the
outer root sheath which is made of basal epidermal cells.
138
IX. REFERENCES
1. Michael H. Ross, Gordon I. Kaye, Wojciech Pawlina,

Histology – A text and atlas, Lippincott Wilkins, 2011.
2. Gartner L.P., Hiatt J.L., Color Textbook of Histology,
Saunders Elsevier, Philadelphia, third edition, 2007.
3. Henrikson R.C., Gordon I.K., Mazurkiewicz J.E.,
Histology, International edition, National Medical Series
for Independent Study, Williams & Wilkins, Baltimore,
USA, 1997.
4. Junqueira L.C., Carneiro J., Kelley R.O., Basic Histology,
Appleton & Lange, Stamford, 11th edition, 2003.
5. Eroschenko V.P., diFiore’s Atlas of Histology with
Functional Correlations, 9th edition, Lippincott Williams &
Wilkins, 2000.
6. Luca (Amihăesei) Ioana Cristina, Histology Organs and
Systems, editura Dosoftei, Iaşi, 2000.
7. Wolfgang Kuhnel, Color Atlas of Cytology, Histology
and Microscopic Anatomy, Thieme Verlag, 4th edition,
2003.
139

Carte Finala 2015

Uploaded by

Document Information

Original Description:

Original Title

Copyright

Available Formats

Share this document

Share or Embed Document

Sharing Options

Did you find this document useful?

Is this content inappropriate?

Copyright:

Available Formats

Carte Finala 2015

Uploaded by

Copyright:

Available Formats

Ioana Cristina AMIHĂESEI

Editura şi tipografia STEF

Thymus is a primary lymphoid organ, where are dividing

lymphocytes and recognition of MHC antigens take place in the

Fig. 1. Thymic lobule HEx40

Fig. 2. Thymus HEx40

In the cortex of the thymus are present three types of

corticomedullary junction and is further colonizing the

In the medulla are predominating the epithelial reticular cells

Fig. 3. Thymus Hassall corpusclex40

Fig. 4. Thymus Hassalll's corpuscles HEx100

Fig. 5. Thymus medulla HEx100

The high endothelial venules are found at the limit between

I.2. LYMPH NODE

Lymph nodes are small bean-shaped structures found as

Fig. 6. Lymph node capsule; secondary lymphoid nodule HEx40

Lymphoid nodules may show two different aspects

cells (effectors of the humoral immune response, antibody

Fig. 7. Lymph node supeficial cortex x 40

Fig. 8. Lymph node paracortex; medulla HEx40

The lymphocytic crown in periphery is made almost entirely

Fig. 9. Medulla; medullary cord medullary sinus HEx100

Recognition criteria in light microscopy:

The spleen is the largest lymphoid organ of the human

parenchyma. From the capsule are arising septa which do not

Fig. 10. connective tissue septum; spleenHEx 100

Fig. 11. Spleen lymphoid nodule; arteriole; white pulpx40

Fig. 12. Spleen; white pulp surrounded by red pulp HEx40

White pulp is represented by thymus dependent areas – T

Red pulp is mainly formed by the system of venous

Venous sinusoid of the spleen is a typical sinusoid

Billroth cords may contain besides immune cells

I.4. MUCOSAL ATTACHED LYMPHOID

Main characteristics of the MALT are:

sharing with the organ where it appears the same

These structures are functioning as secondary lymphoid

 oral type epithelium forming crypts and covering

Fig. 14. Palatine tonsil; secondary lymphoid nodule; palatine glandx40

Fig. 15. Crypt palatine tonsil;trichromex40

II. ENDOCRINE SYSTEM

Endocrine system is one of the main control systems of

II.1. PITUITARY GLAND

Pituitary gland is controlling the activity of the others

Choromophils according to their affinity are divided into

the breast-feeding is leading to the increase of the dopamine

ICSH – interstitial cells stimulating hormone). In female, FSH

milk from the mammary gland, stimulating the activity of the

Thyroid is the largest endocrine gland, situated at the base

Fig. 16. Thyroid HE x40

The thyroid cells or thyrocytes show basophilic cytoplasm,

Fig. 17. Thyroid follicles; parafollicular cells HE x100

Thyroid follicles are surrounded by arched and spiral

In hypofunction of the gland/hypothyroidism, the gland

II.3. PARATHYROID GLANDS

Parathyroid glands are usually four small glands situated at

aspect; they are arranged in cords crowded together, conferring a

Fig. 18. Parathyroid gland HEx 40

PTH is acting on bone, kidney and intestine, assuring the

appearance; parathyroid parenchyma is usually

II.4. ADRENAL (SUPRARENAL) GLANDS

Adrenal glands are pair organs situated on the superior pole

Fig. 19. Adrenal cortex HEx40