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Lecture Notes on Systemic


Histology
For
Medical Students

Naama Abdulgader, MD, PhD, Professor


Department of Histology and Medical Genetics
Faculty of Medicine
Tripoli University
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Table of Contents

Subject Page

1. Digestive system 3
2. Digestive system associated glands 44
3. Respiratory system 69
4. Urinary system 90
5. Endocrine system 115
6. Male reproductive system 145
7. Female reproductive system 162
8. Special senses 195
9. Central nervous system 222
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The digestive system


The digestive system is composed of:
Oral cavity (lips, tongue, palates, cheeks, teeth and pharynx)
Gastro-intestinal tract (GIT) (esophagus, stomach, small
intestine, large intestine and anal canal)
The associated glands (liver, pancreas, salivary glands, and
glands present in the walls of the organs)

The digestive system develops from endoderm. Its main functions:


Ingestion
Digestion
Absorption of the nutritive elements
Excretion of the residues
GIT plays an important role in immunity by: low pH of
stomach, mucus secretion, enzymes, saliva, bile and the gut
associated lymphoid tissue.

Oral cavity
The oral cavity or mouth is lined with oral mucosa (epithelium and
lamina propria)
The epithelium: stratified squamous epithelium covers the entire
oral cavity of mucous type but keratinized in some areas subject to
friction such as palate and filiform tongue papillae.
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The lamina propria: connected to the underlying muscles by


loose submucosal supporting tissue in mobile areas (soft palate and
the floor of the mouth); overlies the bony hard palate and tightly
bound to the periosteum by thin dense fibrous submucosa.
The submucosa: contains numerous small serous and mucous
accessory salivary glands.
The oral cavity consists of:
Lips and cheeks
Tongue
Palates
Teeth and oropharynx.

The lips
The lips are good examples of muco-cutaneous junction; they have
three surfaces:
- An outer surface made of thin skin
- A free surface of red area and
- An inner mucosal surface.
1. The outer surface is covered by thin skin with hair follicles,
sebaceous and sweat glands.
2. The inner surface lies opposite to the outer surface and is
covered by mucous membrane of thick non-keratinized stratified
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squamous epithelium with nucleated surface cells which slough


into the mouth cavity (important in buccal smears).
3. The transitional zone of the lip constitutes free vermilion
border or the red margin; devoid of hair follicles, sweat and
sebaceous glands and is covered by modified thin skins. This
margin is a transition zone which lies between the skin on the outer
surface and the inner surface mucous membrane.
The connective tissue papillae of the red margin are tall and highly
vascularized. The circulating blood in the numerous small blood
vessels gives the lips its red color.
The lamina propria is rich in fine fibrous connective tissue and lies
beneath the epithelium.
4. The submucosa is made of coarse connective tissue fibers and
the large tubulo-alveolar labial glands which function in
moistening the oral surface where their ducts open. Small blood
vessels and nerves are scattered throughout the connective tissue.
** Lips are the most common site of oral cancer.

Cheeks
The cheeks are covered externally by thin skin and lined internally
by mucous membrane. The lamina propria contains numerous
buccal minor salivary glands.
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Tongue
The tongue is divided anatomically into anterior two thirds or the
body, and a posterior one third or the root by a posteriorly oriented
V-shaped groove called sulcus terminalis.
The foramen cecum is located at the apex of the sulcus terminalis;
it is the point of attachment of the thyroglossal duct and is formed
during the embryological descent of the thyroid gland.
The anterior two thirds of the tongue dorsal surface contain three
types of papillae, filiform, fungiform and circumvallate , while the
posterior one third is irregular and contains lymphoid nodules and
lingual tonsils in its lamina propria.
The superior or dorsal surface of the tongue is covered by stratified
squamous epithelium partly keratinized, while its inferior ventral
surface is covered with stratified squamous nonkeratinized
epithelium.

Tongue Features
1. The dorsal surface of human tongue contains lingual papillae;
their types:
a. Filiform papillae: Numerous, 2 - 3 mm. long and their tips
are partly keratinized with some desquamated cells. The core of
the papillae is made of lamina propria. The main function of these
papillae is to increase the surface friction during mastication.
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b. The fungiform papillae are less numerous and larger than


the filiform papillae and irregularly dispersed among them. The
fungiform papillae are rounded, slightly elevated and look like
mushroom with a broad cap and a stalk, their covering epithelium
is non-keratinized. Their connective tissue core shows secondary
papillae and it is highly vascular giving reddish color to the
papillae. Taste buds are present in the epithelium of the papilla
sides and apex.
c. The circumvallate papillae are 7 12 in number, located at
the posterior part of the tongue; there are trenches around the
papillae into which the ducts of the serous Von Ebner`s glands
empty. Taste buds lie in the lateral walls of the circumvallate
papillae (no taste buds on the dorsal surface of the papilla).
Taste buds are oval or barrel-shaped structures present in the
epithelium of tongue papillae (except foliform), soft palate,
epiglottis and lower pharynx.
By LM, the taste buds appear to be composed of:
Gustatory (taste) cells, responsible for taste perception,
comprise about 50% of the total cells; they are slender
elongated, lightly-stained cells with life span of 7 10 days.
They have apical microvilli projecting through the taste pore.
The afferent sensory nerve fibers enter the base of taste buds
and synapse with these cells.
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Supporting cells: immature, dark, slender elongated with


secretory granules; their function is not well-defined.
Undifferentiated basal stem cells located basally and
peripherally, they divide to give rise to the other cells types.

Taste modalities:
Salty for metal ions
Sour for acids
Sweet for sugars
Bitter for alkaloids
Umami for glutamate

d. Foliate papillae, poorly-developed in adults, but best-


developed in young children. They are ridge-like located on the
sides of the tongue, and have lateral deep trenches to receive the
ducts of Von Ebner`s glands. Foliate papillae have numerous taste
buds on the lateral surface and long epithelial ridges extending into
their connective tissue core.

2. The lingual tonsils are located behind the circumvallate


papillae. They are composed of numerous lymphatic nodules
which form bulges on both sides of the dorsum of the tongue. The
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lymphatic nodules are aggregated around broad deep crypts of the


mucous membrane.
3. The anterior lingual glands lie near the ventral surface and are
embedded in the muscle. They are mixed glands with serous,
mucous and mixed alveoli; their ducts open on the ventral surface.
Von Ebners glands, purely serous, lie in the region of
circumvallate (and foliate) papillae and their ducts open into the
trenches of circumvallate papillae to dissolve the substances to be
tasted and to remove food particles.
4. The posterior lingual glands, purely mucous, located at the root
of the tongue extending deeply into the muscle. Most of their
ducts open into the crypts of the circumvallate papillae and some
of them open onto the surface.
5. The intrinsic muscles of the tongue consist of fine skeletal fibers
arranged in longitudinal, transverse and vertical planes. A median
lingual fibrous septum incompletely divides the intrinsic muscles
into right and left halves.

The Palate
The palate consists of two parts, hard anterior and soft posterior.
The hard palate is covered by stratified squamous epithelium partly
keratinized, while the soft is covered with non-keratinized
stratified squamous epithelium and contains taste buds.
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The Teeth
In adult human being, there are 32 permanent teeth, 8 teeth in each
quadrant (2 incisors, 1 canine, 2 premolars and 3 molars).
Baby teeth (deciduous) are 20 in total with no molars; they are
replaced with permanent teeth between the ages of 6 and 25 Years.
The maxilla and the mandible have bony ridges called alveolar
processes which provide strong sockets for the teeth.
The alveolar processes are covered with a mucous membrane
called gum or gingiva.
A tooth lies in its socket and held by a fibrous structure called
periodontal membrane or ligament.
Each tooth is composed of a crown, a root and the neck.
The crown is the part of tooth which projects above the gingiva; it
is covered by enamel.
The root is the part of the tooth which dips below the gingiva into
the bony socket; it is covered by cementum.
The cementum and enamel meet at the tooth neck which is the
junctional zone between the crown and the root.
The tooth internal structure is formed of calcified material called
dentin which surrounds the pulp cavity.
The pulp cavity extends to the apex of the root as the root canal.
Blood vessels, lymphatics and nerves of the tooth pulp enter and
leave through the apical foramen at the apex of the root canal.
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Dentin and odontoblasts


Dentin is composed of organic and inorganic components.
The organic component is mainly collagen type I and some
glycosaminoglycans (GAGS).
The inorganic component is made of calcium salts, hydroxy-
appatite (70% of its dry weight).
Dentin is produced by odontoblasts initially as unmineralized
substance called predentin.
Odontoblasts line the internal surface of the tooth separating
dentin from the pulp cavity.
Each odontoblast is a tall columnar secretory cell with a long
cytoplasmic process extending inside a fine canal called
dentinal tubule.
The dentinal tubules and the odontoblast processes within
them traverse the mass of dentin perpendicularly and reach
the junction between the dentin and the enamel in the crown
or cementum in the root.
Dentin can be renewed and compensated in adult life by
odontoblasts.

Enamel and ameloblasts


Enamel is the hardest component of human tissue, composed
of the inorganic hydroxyapatite crystals (95 - 98%) which
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can absorb fluoride ions producing the acid-resistant


fluorapatite which resists the micro-organisms of dental
caries.
The organic matrix of the enamel is formed of unique
proteins (enamelins and amelogenins) but no collagen.
Enamel is produced before tooth eruption by apical Toms
processes of tall columnar ectodermally-derived cells called
ameloblasts.
Ameloblasts degenerate when tooth erupts, so enamel cannot
be repaired or renewed after its damage.
Enamel is made of structural subunits called enamel rods and
inter-rods.
Cementum
Cementum is avascular calcified tissue; it resembles the bone in
structure except lacking the Haversian systems and blood vessels.
Cementum is produced by cells called cementocytes which reside
in lacunae but do not communicate together by canaliculi.
Cementum over the neck region is acellular. It is firmly attached
to the bony sockets by periodontal ligaments.
Periodental ligament
Periodental ligament is composed of a special type of dense
connective tissue; its collagen fibers penetrate the cementum of the
tooth and bind it to the bony walls of the socket (alveolus).
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Periodental ligament permits slight movement of the tooth such as


biting on something hard to avoid transmission of pressure directly
to bone.
Tooth Pulp
Tooth pulp consists of loose connective tissue richly supplied by
small blood vessels and nerve fibers; it extends along the pulp
cavity to the apical foramen. Through the apical foramen, blood
vessels, nerves and lymphatics enter and leave the pulp.
Gingiva:
Gingiva is a fibrous, masticatory oral mucosa, surrounding the
necks of teeth and binds them firmly to maxilla and mandible for
support.
Gingival has free and attached parts. Between the free gingiva
and the enamel, there is a small gingival sulcus (0 - 3 mm deep)
surrounding the crown; this sulcus is important clinically as a sign
of periodontal disease. The attached gingiva is firmly attached to
the underlying bone to withstand the masticatory forces.
The gingival epithelium is stratified squamous, keratinized, except
at the junctional epithelium, it is nonkeratinized stratified
squamous and is bound to tooth enamel by cuticle which looks like
a thick basal lamina. Its lamina propria is dense and contains
collagen, reticulin, elastin and oxytalin fibers.
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Alveolar bone
Alveolar bone is a primary immature non-lamellar bone; the sites
where the roots of teeth reside are called sockets.
Many of the collagen fibers of periodontal ligament are arranged in
groups traversing alveolar bone and cementum (Sharpeys fibers)
for tooth support.
Perforating blood vessels enter the alveolar bone, penetrate the
periodontal ligament and some of which enter the pulp through the
apical foramen.

Pharynx
Pharynx is a common pathway for both respiratory and digestive
systems. It is divided into:
Oropharynx and laryngopharynx which are lined with
stratified squamous non-keratinized
Nasopharynx lined with pseudostratified columnar ciliated
epithelium.
The lamina propria contains mucous glands, blood vessels, nerves
and lymphatics. The posterior wall of nasopharynx contains
lymphoid aggregates known as adenoids.
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The digestive tract


The gastro-intestinal tract (GIT) has uniform general histological
features with some differences due to specialization in function.
The wall of GIT is composed of 4 concentric layers:
Mucosa
Submucosa
Muscularis externa
Adventitia or serosa

Mucosa
The mucosa is the innermost layer of GIT surrounding its lumen.
It is directly in contact with food and responsible for absorption,
secretion and digestion.
The mucosa is composed of the following:
The epithelium may be protective (stratified squamous in
esophagus), secretory (simple columnar mucous secreting in
stomach) or absorptive (simple columnar with striated border
in small intestine).
The lamina propria is made of loose connective tissue
containing blood vessels, lymphatic capillaries to transport
the absorbed food to the circulation, and solitary or
aggregates of lymph nodules. It also contains antibody-
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producing plasma cells which play an important role in


immunity and defense mechanism.
Muscularis mucosae made of 2 thin layers of smooth muscle,
an inner circular and outer longitudinal.
The mucosa is highly specialized in each part of the GIT: gastric
pits in the stomach, villi and plica circularis in the small intestine.

Submucosa
The submucosa consists of dense irregular connective tissue with
blood vessels, lymphatics and nerves. It contains Meisseners
nerve plexus made of autonomic ganglion cells.
In duodenum and esophagus, the submucosa contains mucous-
secreting glands.

Muscularis externa
Muscularis externa is the muscle coat of the GIT which supports
its wall; it consists of an inner circular and outer longitudinal
muscle layers.
The coordinated contractions of these layers create peristaltic
movement of the gut to move the luminal contents along the tract.
Myenteric or Auerbach`s nerve plexus lies between the two muscle
layers.
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Adventitia or Serosa
The serosa is the outermost layer; it is made up of thin layer of
loose connective tissue rich in blood and lymphatic vessels and is
covered by a single layer of simple squamous epithelium called
mesothelium. Gut mesenteries are suspensory serosal folds made
of 2 layers of peritoneum mesothelium with a thin layer of loose
connective tissue sandwiched in between.
The outermost layer is called adventitia when there is no
mesothelium.

Esophagus
Esophagus is a long narrow muscular tube extending from the
cricoid cartilage to the opening of the stomach in the diaphragm;
its lumen is compressed except when a bolus passes from the
pharynx to the stomach. Esophageal wall is composed of:
1. Mucosa:
Epithelium: is relatively thick stratified squamous
nonkeratinized.
Lamina propria: It is composed of loose connective tissue
containing collagen fibers, few elastic fibers, fibroblasts, plasma
cells and lymphocytes.
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Lamina propria contains variable number of mucosal glands


which resemble the cardiac glands, being mucus-secreting
simple tubular glands, mainly in lower third.
The mucosal glands are lined with simple columnar epithelium
and they are common sites for esophageal ulcers and cancer;
they are called esophageal cardiac glands.
Muscularis mucosa: marks the outer border of the mucosa and
consists of smooth muscle fibers arranged as an outer
longitudinal and an inner circular.
2. Submucosa is a fibro-elastic layer which lies between the
muacularis mucosa and the muscularis externa. The elasticity of
this layer is important in food swallowing. It contains large blood
vessels, submucosal nerve plexuses and variable number of
tubuloalveolar mucus-secreting esophageal glands; their ducts
penetrate the mucosa to carry secretions to the surface to act as a
lubricant for food swallowing.
3. Muscularis externa consists of two layers, an inner circular
layer and an outer longitudinal layer.
The muscle layer is wholly skeletal in the uppermost one-third,
gradually becomes mixed with smooth muscle fibers in the middle
one-third, and consists wholly of smooth muscle fibers in the lower
one-third. Myenteric nerve plexus (Auerbach plexus) lies between
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the inner and outer muscle layers. Close to the stomach, the
musculosa forms the lower esophageal sphincter.
4. Adventitia or fibrosa: is the outermost layer, composed of loose
connective tissue. It functions in binding the esophagus to the
surrounding connective tissue and contains blood vessels and
nerves.

Stomach
The stomach is the dilated segment of the GIT.
When viewed by naked eye, the interior of undistended empty
stomach shows longitudinal folds (rugae) containing mucosa and
submucosa and disappear in full stomach.
When the stomach interior is viewed by low microscopic
magnification, large number of small circular openings of gastric
pits in the mucosal lining is noticed.
Anatomically, the stomach is divided into:
Cardiac region: forms a small narrow ring surrounding the
entrance of esophagus.
Fundus: the bulging part above the body.
Corpus: the body below the fundus; it forms the major
gastric region.
Pyloric region (pyloric antrum, pyloric canal and pylorus):
forms the entrance to the small intestine.
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Stomach functions: (Exocrine & endocrine functions)


o temporary storage of food
o mechanical breakdown of food to viscous fluid
chyme through powerful mixing waves
o Secretes HCl, KCl and intrinsic factor
o starts protein and triglycerides digestion

Pepsin
Proteins Polypeptides
HCl

At the transition from esophagus to the stomach, the gastro-


esophageal junction, there are:
1. An abrupt change from the stratified squamous epithelium of
esophagus to the simple columnar mucous-secreting epithelium
lining the cardiac region.
2. The lamina propria of the cardia contains cardiac glands which
are similar to mucosal cardiac glands occurring in the lamina
propria of the lower part of esophagus.
3. The muscularis mucosa, submucosa and muscularis externa are
continuous from esophagus to stomach with appearance of third
oblique layer of muscularis in the stomach.
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4. The gastric glands are short and slightly coiled and the pits are
wide and deep. The acid-secreting parietal cells are very few or
absent from the gastric glands of the cardia, but become more
numerous distally as the cardia passes into the fundus of the
stomach. Mucous secreting cells are abundant.

Stomach fundus
1. The mucosa:
The mucous membrane of the stomach shows no villi but it shows
gastric pits (faveolae) which are shallow and narrow.
The epithelial lining of stomach, as well as the pits, is simple
columnar (surface mucous cells) which secretes alkaline mucus
and bicarbonates, and also absorbs salts, water, alcohol, glucose
and some drugs.
The epithelial cells form a mucosal protective barrier (against the
enzymes and HCl) of the stomach through the following
mechanisms:
The mucus consists of water, glycoproteins and lipids, together
forming a hydrophobic protective gel.
The mucus firmly adheres to the epithelial cells.
The bicarbonates secreted by the epithelial cells create a pH
gradient between the luminal and the cell surfaces.
The intercellular tight junctions
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The previous mechanisms are aided by the rich submucosal


blood supply which helps in superficial wound healing
(mucosal restitution), provides oxygen and bicarbonates to the
lining epithelium and helps to remove the toxic and waste
products.

The gastric or fundic glands


The gastric or fundic glands are simple branched tubular with
narrow lumen; they occupy the lamina propria and extend down to
the muscularis mucosae.
The fundic glands open into the gastric pits which represent of
the glands. Below the pits, each gland is divided into a neck and a
base.
At the neck region, the gastric glands contain mainly stem cells,
mucous neck cells and parietal cells. At the base, the glands
contain chief cells, enteroendocrine cells and fewer parietal cells.
1. Mucous neck cells: They are columnar cells with basal ovoid
nuclei, stain positively with PAS, and present at the necks of the
gastric glands. They secrete acid mucous which helps in the
protective mechanism of the stomach.
2. Parietal cells (oxyntic):
By LM, these cells are large, spherical or pyramidal in shape with
one centrally located spherical nucleus (sometimes binucleated)
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and acidophilic cytoplasm. They are located at the periphery of the


gastric glands and bulge into the lamina propria.
By EM, the parietal cells appear rich in mitochondria, SER and
have tubulovesicles on their apical surface.
Parietal cells are characterized by intracellular canaliculi which are
formed by circular invaginations of the plasma membrane with
microvilli projecting into the canaleculi.
Parietal cells secretion is stimulated by parasympathetic stimuli,
histamine and gastrin; they secrete:
a. Hydrochloric acid by the activity of carbonic anhydrase
Carbonic anhydrase
CO2 + H2O H2CO3 (carbonic acid)

Dissociates
H2CO3 HCO3 + H+

Hydrogen ions leave the cell by active transport to the canaliculi


outside the cell in exchange with K ions, and Cl ions are actively
transported across the cell from the blood capillaries in the
connective tissue of the lamina propria to the canaliculi in
exchange with the bicarbonate ions.
The chloride ions combine with hydrogen ions and HCl is formed
in the canaliculi outside the parietal cells.
b. Potassium chloride
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c. The gastric intrinsic factor (a glycoprotein that binds to


vitamin B12 to facilitate its absorption); its deficiency leads
to pernicious anemia.

3. Chief cells (zymogenic cell): These cells are cuboidal or low


columnar and more numerous at the lower part of the glands. They
have rounded basally located nuclei and apical zymogen granules
containing the inactive enzyme pepsinogen. They have basophilic
cytoplasm due to presence of RER and ribosomes.
Functions of chief cells: They produce the inactive pepsinogen
which is converted to the active pepsin when released into the
acidic environment of the stomach. They also produce rennin
(chymosin) which curdles milk, leptin hormone and lipase enzyme.

4. Enteroendocrine cells: They are present at the bases of the


gastric glands, and need special stain like silver to be demonstrated
(argyrophilic).
They belong to diffuse neuroendocrine system previously
called amino precursor uptake and decarboxylation cells
(APUD cells).
They secrete gastrin, serotonin, somatostatin and endorphin.
They give rise to tumors called carcinoids.
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5. Undifferentiated stem cells in neck or isthmus of glands; they


are low columnar with oval nuclei and few organelles.
They have high rate of mitosis, and their main function is
regeneration and differentiation into other types of cells.

The lamina propria:


It is composed of delicate collagenous and reticular fibers and
numerous cells such as fibroblasts, lymphocytes, plasma cells,
mast cells, eosinophils and macrophages (loose connective tissue)
and highly rich in blood supply. It is occupied by gastric or fundic
glands.

Muscularis mucosae:
It is made of two layers of smooth muscle fibers, an inner circular
and an outer longitudinal.

2. Submucosa: It is made of relatively coarse connective tissue


fibers, fibroblasts, macrophages, mast cells, plasma cells, and
lymphocytes. It is rich in blood supply and lymphatic vessels,
nerves, and small parasympathetic ganglia of submucosal plexus
(Meissner`s plexus).
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3. Muscularis externa: It is composed of three layers, an inner


oblique, a middle circular and an outer longitudinal layer of
smooth muscles. Large parasympathetic ganglion cells of the
myenteric plexus present between the circular and the longitudinal
muscle layers.

4. Serosa: It is the outermost layer of the stomach; it is composed


of a thin layer of fine connective tissue covered with mesothelium.

Stomach pylorus
The wall of pylorus is composed of four layers (mucosa,
submucosa, musculosa and serosa) with some modifications if
compared to the layers of the fundus:
1. Mucosa:
The lining epithelium of pylorus and the pits is simple columnar
mucus-secreting epithelium.
The lamina propria is occupied by pyloric glands which are
shorter, branched and more coiled than the fundic glands. The
pyloric glands are loosely packed with abundant connective tissue
in between and their gastric pits (faveolae) extend to half of the
thickness of the mucosa (short and narrow pits in fundic glands).
Typical pyloric glands are lined with:
Mucous-secreting columnar cells
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Enteroendocrine cells, gastrin-producing (G) cells and


somatostatin-producing (D) cells which cannot be
distinguished by routine stains at the light microscopy level.
No chief cells and no parietal cells; but at body-pyloric
transition area, parietal cells might be numerous in the
glands.
The cells in the coiled part of the pyloric glands appear filled with
mucin, with basal flattened nuclei, compared to the cells lining the
gastric pits or the surface.
The muscularis mucosa is relatively thick, it consists of two
layers of smooth muscles (inner circular and outer longitudinal).
2. Submucosa: contains blood and lymphatic vessels and nerves.
3. Muscularis externa: is composed of two layers of smooth
muscle fibers, an inner circular and an outer longitudinal layer.
The circular layer is very thick and forms the pyloric sphincter.
4. Serosa: is made of mesothelium with underlying fine connective
tissue.

Control of gastric secretion and motility


The gastric secretion and motility is controlled by:
I. Impulses from vagus nerve which stimulate the gastric secretion.
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II. Hormones secreted by cells of GIT belonging to diffuse


neuroendocrine system (APUD) or Enteroendocrine Cells (EC).
These cells are of two types:
The open type (in small intestine) where the cells have
microvilli and reach the lumen of the organ
The closed type where the cells lie between the basement
membrane and the lining epithelium and do not reach the
lumen of the organ.
The Enteroendocrine cells (EC) of GIT secrete:
1. 5-hydroxy-tryptamine or serotonin secreted by EC cells of
GIT; it increases gut motility and causes vasoconstriction.
EC cells also secrete substance P.
2. Gastrin secreted by G cells of the stomach pylorus and
duodenum; it stimulates HCl and pepsinogen and promotes
gastric motility and mucosal growth.
3. Ghrelin secreted by stomach; it stimulates hunger sensation.
4. Cholecystokinin (CCK) secreted by I cells of duodenum; it
stimulates pancreatic enzyme secretion and gall bladder
contraction.
5. Somatostatin secreted by D cells of pancreas; it inhibits the
release of endocrine, exocrine and neurotransmitters by other
cells (secretin by small intestine and gastrin by stomach).
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6. Secretin secreted by S cells of duodenum; it stimulates


pancreatic and biliary bicarbonate and water secretion.
7. Gastric inhibitory peptide (GIP) secreted by K cells of small
intestine; it inhibits the gastric secretion.
8. Vasoactive intestinal peptide (VIP) secreted by D1 cells of
GIT; it stimulates ion and water secretion and increases gut
motility.
9. Motilin secreted by Mo cells of small intestine; it increases
the gut motility.
10. Glucagon-like peptide secreted by L cells of small
intestine; it inhibits HCl secretion and stimulates insulin
release.
11. Neurotensin is secreted by N cells of large intestine; it acts as
a neurotransmitter. Neurotensin stimulates the release of
glucagon and inhibits the release of insulin.

At the transition from stomach pylorus to small intestine, pyloro-


duodenal junction, there will be:
1. An abrupt change of pyloric mucosa to intestinal mucosa with
villi.
2. The duodenal muscularis mucosa is continuous with that of the
stomach.
3. Appearance of Brunner`s glands in the duodenal submucosa
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4. The thick pyloric sphincter changes to thinner muscle layer in


the duodenum.

Small intestine
The small intestine is about 21 23 feet (~ 5 m) long; it is divided
into three subdivisions: the duodenum, the jejunum and the ileum
with similar general microscopic structure.
Functions of small intestine:
To complete the digestive process
Selective absorption of the digestion end products
Secretion of gastrointestinal hormones which regulate the
functions of the digestive system.

General features of the small intestine:


The wall of the small intestine is made of 4 layers, mucosa,
submucosa, musculosa and serosa.
I. Mucosa:
With the naked eye, the lining of small intestine shows spiral
permanent folds called plicae circularis made of mucosal folds
with submucosal core, most developed in the jejunum. The
mucosa also shows the intestinal villi in large number giving a
velvet-like appearance to the small intestine.
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1. The epithelium is simple columnar, absorptive (enterocyte) with


microvilli forming the striated border with irregularly scattered
goblet cells. The microvilli increase the surface area of the lining
cells by at least twenty times.
The goblet cells produce acid mucus to protect and lubricate the
intestinal lining.
2. Plica circularis (Kerckring`s valves) which are visible circular
folds of mucosa and submucosa. These folds are most prominent
in the distal part of the duodenum and the proximal part of the
jejunum, and extend to the mid-ileum. They increase the intestinal
surface area by three folds.
3. The intestinal villi:
These are finger-like projections or evaginations in the mucosa of
the small intestine, about 0.5 - 1.5 mm. in height. They are
covered mainly by columnar cells with striated or brush borders
and goblet cells (simple columnar absorptive epithelium plus
goblet cells).
Each villus contains a central core of loose connective tissue
of the lamina propria, a lymphatic capillary (central lacteal),
an arteriole, two venules and a dense network of fenestrated
blood capillaries which are involved in nutrient absorption.
The core of the villi contains also, smooth muscle cells
extending from the muscularis mucosa. Contraction of these
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muscle cells increases the efficiency of the absorptive


process and helps the central lacteals to empty their contents
into the large lymphatics in the lamina propria.
The length of the villi is maximal in the proximal part of the
duodenum, and they decrease gradually towards the terminal
part of the ileum.
The villi increase the absorptive area of the small intestine in
man up to ten folds.
4. The intestinal glands (crypts of Leiberkuhn):
These are simple tubular glands occupying the lamina propria; they
open between the bases of the villi and extend to the muscularis
mucosae. The crypts add to the increase of surface area of the
villi; their epithelium is continuous with the epithelium of the villi.
In addition to absorptive cells, they contain goblet cells, paneth
cells at the bases of the glands, scattered enteroendocrine cells
(argentaffin cells) and undifferentiated stem cells.
5. Microvilli:
The apical surface of the simple columnar absorptive cells is
covered by large number of microvilli known as brush or
striated border.
These microvilli increase the surface area by 20 folds and
constitute the major specialization which facilitates
absorption.
33

6. The lamina propria:


It is highly cellular, fills the spaces between the glands of
Lieberkuhn, extending into and forming the core of the villi.
It contains mainly argyrophilic reticular, some elastic and
fine collagenous fibers, large number of lymphocytes, plasma
cells, other white blood cells, mast cells and some scattered
smooth muscle fibers.
The lymphocytes may be organized into solitary nodules
scattered along the whole length of the intestine.
In ileum, aggregates of lymph nodules known as Peyer`s
patches are found in its mucosa and submucosa.
7. Muscularis mucosa:
It is a thin layer of smooth muscle, composed of inner circular and
outer longitudinal layers. It sends few fibers into the lamina
propria.

II. Submucosa:
1. It is composed of loose connective tissue and lies between the
muscularis mucosa and the muscularis externa.
2. It contains large blood vessels, lymphatics, nerve plexuses and
small parasympathetic ganglia.
3. Only in the duodenum, the submucosa contains Brunner`s
glands.
34

III. Muscularis externa:


It is made of inner circular and outer longitudinal smooth muscle
layers, with myenteric nerve plexus in between.

IV. Serosa:
It is made of simple squamous epithelium (mesothelium) covering
a thin layer of loose connective tissue.

Duodenum
I. The mucosa of the duodenum consists of lining epithelium,
lamina propria and muscularis mucosa.
The mucosa is characterized by the following:
It shows plica circulares (permanent spiral folds consisting of
mucosa and submucosa seen by the naked eye), and leaf-like
villi and simple tubular glands which empty into the lumen
between the villi.
The surface epithelium consists of goblet cells and simple
columnar absorptive cells with striated (brush) border. The
striated border is PAS-positive due to presence of the surface
coat (glycocalyx) associated with microvilli.
The intestinal glands (crypts of Lieberkuhn) open between
the bases of the villi and their bases reach the muscularis
mucosa. The glands are lined with simple columnar
35

absorptive cells, goblet cells, Paneth cells, APUD cells and


stem cells.
The lamina propria is made of loose connective tissue and
GALT (gut-associated lymphoid tissue).
Muscularis mucosa is a thin layer of smooth muscles formed
of inner circular and outer longitudinal layers, some of which
may extend up into the villi.

The lining cells of duodenum:


1. The absorptive cells (enterocytes) are simple tall columnar
cells with oval nuclei at their bases and striated border at their
apices.
By EM, the striated (brush) border appears to be formed of
microvilli. Each microvillus is an apical cytoplasmic protrusion of
the cells containing a core of actin microfilaments and covered
with cell membrane. Microvilli are about 1 um long and 0.1 um in
diameter; there are 3000 microvilli / cell.
Plica circularis, villi, intestinal crypts and microvilli increase the
intestinal surface area enormousely.
2. Goblet cells become scarce in the lower part of intestinal
glands.
Goblet cells are less abundant in duodenum and become
more numerous in ileum.
36

They produce acid glycoprotein (mucin) to lubricate and


protect the intestinal lining.
3. Paneth cells are present at the blind ends of the glands.
Paneth cells are large pyramidal or columnar cells with round
or oval nuclei at their basal part and large acidophilic
granules in their apical parts.
Their granules contain lysozymes which are antibacterial
enzymes capable of digesting bacterial cell wall and
controlling the intestinal flora.
4. Enteroendocrine cells have orange staining granules in their
infranuclear position. (The GIT ECs were discussed earlier).
5. Stem cells show mitotic figures to replace the cells shed from
the tips of the villi. All other epithelial cells of the mucosa are
believed to be derived from the stem cells; so there is a continuous
renewal of the intestinal epithelial cells, every 3-6 days.

II. The submucosa is composed of loose connective tissue and


contains blood vessels, lymphatics, Meissner parasympathetic
nerve plexuses and Brunner's glands. The ducts of duodenal
Brunners glands open into the crypts of Lieberkuhn after they
penetrate the muscularis mucosa. Brunner`s glands secrete
alkaline mucus and urogastrone which inhibits HCL production by
the stomach.
37

III. Muscularis externa is composed of two muscle layers, inner


circular and outer longitudinal with Aurbach myenteric nerve
plexus lying in between.

IV. Serosa (adventitia) is formed of simple squamous epithelium


overlying a thin layer of loose connective tissue.

Jejunum
1. The villi of the jejunum are finger-like with rounded ends; they
are lined with goblet cells and simple columnar absorptive cells
with striated (brush) border. The striated border is reduced at the
bases of the crypts of Lieberkuhn.
The cells lining the crypts (glands) are shorter or less columnar
than the cells lining the villi. Besides simple columnar epithelium,
the glands have goblet, APUD, Paneth and stem cells.
2. The goblet cells are more numerous than in the duodenal
mucosa, their nuclei stain darker than the nuclei of the adjacent
absorptive cells. They are narrower and more triangular in shape
than the absorptive cells.
3. No submucosal glands of Brunner. Large ganglion cells of the
submucosal nerve plexus (Meissner`s plexus) are present.
4. Between the two layers of muscularis externa, the ganglion cells
of the myenteric plexus are present.
38

Ileum
1. The villi of the ileum are numerous short fingers-like, lined with
simple columnar absorptive epithelium showing typical normal
structure and the striated border is prominent. Goblet cells are
more numerous than in the jejunum.
The glands are lined with simple columnar, goblet, Paneth (at the
bases of the glands), APUD and stem cells.
The aggregated lymphatic nodules are covered with simple
cuboidal epithelium containing microfolds called M cells and no
goblet cells.

Peyers Patches and the M cell (Microfold cell):


The lamina propria of the ileum is composed of loose connective
tissue containing eosinophils with reddish granules, numerous
plasma cells and aggregates of lymph nodules (Peyer`s patches).
Peyer`s patches are present in the anti-mesenteric wall of the
ileum. They originate in the lamina propria and may extend
through muscularis mucosa to submucosa.
Sometimes, the Peyer`s patches reach the lumen of the ileum, if so
they are covered with a single layer of columnar cells (M) and no
villi. So the M cells overly peyers patches where the basal lamina
is discontinuous to facilitate the transport between the M cells and
lymphoid nodules in lamina propria.
39

M cells have basal invaginations forming pits where intraepithelial


cells (lymphocytes and macrophages) reside.
M cells are able to uptake antigens by endocytosis for transport to
the underlying lymphocytes and macrophages. They are believed
to have a role in the immunological reactions of the intestinal
mucosa acting as antigen presenting cells.
2. The submucosa has no Brunner`s glands; it contains submucosal
Meissner`s nerve plexuses and sometimes Peyer`s patches.
3. Muscularis externa is composed of two muscle layers: inner
circular and outer longitudinal with myenteric nerve plexuses lying
in between.
4. Serosa or adventitia is composed of mesothelium (simple
squamous epithelium, and a thin layer of loose connective tissue
containing lymph and blood vessels, and adipose connective tissue.

Colon (Large Intestine)


The large intestine consists of cecum, ascending, transverse,
descending and sigmoid colons and the rectum; its main function is
water absorption, secretion of mucus and some peptide hormones.
Large intestine is characterized by the absence of the plica
circularis, the villi and paneth cells.
1. Mucosa
40

The surface epithelium is absorptive simple columnar with


very thin striated border (irregular short microvilli).
Lamina propria is made up of loose connective tissue and
contains the intestinal glands.
Intestinal glands (of Lieberkuhn) are straight tubular, larger
and more numerous than in the small intestine, and contain
more numerous goblet cells, few enteroendocrine and stem
cells at their bases.
Muscularis mucosa is made of 2 thin layers of smooth
muscles, inner circular and outer longitudinal.

2. The submucosa contains large blood vessels and the cell bodies
of neurons in the submucosal plexus.

3. Muscularis externa
The inner smooth circular layer of the muscularis externa is
continuous, while the outer longitudinal layer is modified to form
three separate thick longitudinal bands of muscle called taeniae
coli.

4. Serosa: serous membrane covers the colon except at the


retroperitoneal surface, where it is covered by adventitia. The
41

serous membrane encloses masses of adipose tissue called


appendices epiploicae.

Rectum and Anal Canal


Rectum is the lower part of large intestine; it is connected to the
anal orifice by the anal canal.
1. The layers of the upper rectum are similar to those of the colon,
but taeniae coli are absent since the outer longitudinal layer of the
muscularis externa becomes continuous.
2. The circular layer of smooth muscle becomes thicker and forms
the involuntary internal anal sphincter.
3. In the upper part of the anal canal or lower rectum, the outer
layer of the smooth muscle is replaced by skeletal muscle which
serves as the external anal sphincter.
4. Longitudinal ridges appear and form the rectal columns of
Morgagni, which overlie small veins (responsible for the formation
of internal hemorrhoids). The rectal columns are connected at
their bases by the anal valves which are transverse folds of
mucosa.
5. The intestinal glands become very short and disappear at the
level of the anal valves where the epithelium becomes stratified
squamous non-keratinized.
42

Near the anal orifice, the epithelium becomes keratinized, highly


pigmented and contains hairs, sebaceous and sweat glands.

Appendix
The appendix has the basic histological structure of large intestine;
it is characterized by the following:
1. The lumen of the appendix is small and irregular.
2. The appendix lacks the villi and plica circularis.
3. The crypts of Lieberkuhn contain absorptive columnar cells,
goblet cells, few paneth cells and enteroendocrine cells.
4. The lamina propria is completely infiltrated with lymphocytes,
macrophages with vacuolated acidophilic cytoplasm and
eosinophils with bilobed nuclei and acidophilic cytoplasm.
5. The inner circular layer of muscularis externa is thicker than the
outer longitudinal one.
43

The Glands Associated


With The Digestive System
44

The Glands of the Digestive System


There are two types of glands associated with the digestive system,
intramural and extramural glands.
The intramural glands are located in the wall of the digestive
tract such as: esophageal, gastric, Brunner's and intestinal
glands.
The extramural glands such as salivary glands, pancreas and
liver.

Salivary glands
The salivary glands are divided into two main groups:
The accessory or minor salivary glands (labial, buccal,
lingual, palatine) which lie within the submucosal connective
tissue of the oral cavity. They secrete continuously and
directly through their ducts to moisten the oral surface.
The extrinsic or major salivary glands are three pairs: the
parotid, the submandibular and the sublingual glands.
1. Extrinsic salivary glands lie outside the walls of the oral
cavity and convey their secretions by means of excretory
ducts which pass through the mucosa.
2. The major salivary glands are classified as tubuloalveolar,
exocrine glands.
45

3. Their secretory alveoli are wholly serous (parotid)


producing watery secretion, or mixed as submandibular
(mainly serous) and the sublingual glands (mainly
mucous).

The basic components of the major salivary glands:


In the glands, the secreting epithelial cells constitute the
parenchyma and the supporting connective tissue and other
elements constitute the stroma.
1. Connective tissue stroma is made of capsule surrounding the
whole gland and sends trabeculae or septa dividing the gland into
lobes and lobules; these septa are called interlobar and interlobular
septa respectively carrying ducts, blood vessels and nerves. The
whole gland is supported by delicate network of fine reticular
connective tissue.
2. Parenchyma is made of secretory acini and exceretory duct
system. There are three types of acini: serous, mucous and mixed.

Serous Acini
The serous acini (alveoli) are rounded or oval units composed
of simple cuboidal to low columnar cells surrounding very
small central lumen.
46

The cells appear pyramidal in shape with rounded nuclei


located at the bases of the cells.
The cells are darkly-stained, filled with secretory zymogen
granules.
Myoepithelial cells (basket cells) lie between the basement
membrane and the bases of the serous cells. These cells can
be distinguished by their horizontally-oriented flattened
nuclei. They have contractile processes which embrace the
serous cells to help in expelling the secretion.
By EM, the cells lining the acini exhibit the features of
protein synthesizing cells; abundant RER and well-developed
Golgi complex, ribosomes, mitochondria and seceretory
granules at the apical parts of the cells.
The main function of serous acini is production of serous
watery secretion rich in proteins and enzymes

Mucous Acini
The mucous acini are composed of cuboidal or pyramidal
cells.
The cells have well-distinct boundaries with pale acidophilic
foamy (vacuolated) cytoplasm.
The nuclei are flat and basally located
The lumens are relatively wide
47

The acini are surrounded with myoepithelial (basket) cells


which are located between lining cells of acini and their
basement membrane. Basket cells contract and squeeze the
secretion of acini into the duct system.
At EM level, the cytoplasm is rich in RER and mitochondria,
well-developed Golgi and apical mucous secretory granules.
Their main function is production of mucus (glycoprotein)

Mixed Acini
These acini are usually mucous with serous demilunes (resemble a
crescent), i.e. mucous acini with cap of serous cells. They produce
seromucous (mixed) secretion.

The Duct System


The duct system together with nerves, lymphatics and blood
vessels are running in the connective tissue septa. The duct system
includes intralobular (intercalary, striated), interlobular, interlobar
and the main ducts.
1. Intralobular ducts: composed of two portions
a. The intercalated ducts are very narrow (5-7 cells), arise from
the lumen of acini and unite the acini with striated ducts; they are
lined with low simple cuboidal epithelium.
48

b. The striated ducts also called salivary ducts or secretory ducts;


they are dispersed among the alveoli (acini) within the lobules.
These ducts are lined with a simple columnar epithelium.
They are called striated due to the presence of vertically
oriented striations at the bases of the cells; these striations
represent the mitochondria lined up between the basal
invaginations of the basal lamina.
The duct cells have rounded nuclei, granular acidophilic
cytoplasm and apical microvilli. The lateral cell membranes
show interdigitations and tight junctions near the lumen to
prevent the backflow of the secreted enzymes.
The cells are ion transporting; they absorb sodium and
release potassium. They also contribute to the serous
secretions coming from the secretory cells of the acini.
2. Interlobular ducts: they are running in the interlobular
connective tissue septa and are lined with simple columnar
epithelium which becomes taller as the ducts become wider.
3. Interlobar ducts are located in the interlobar connective tissue
septa; they are lined by psuedostratified or stratified columnar
epithelium.
4. The main duct receives the secretion from the interlobar ducts
and pours it into the mouth cavity. It is lined by stratified
squamous epithelium nonkeratinized.
49

Parotid gland
Parotid gland is paired, it is the largest salivary gland and it is
purely serous. It is composed of connective tissue stroma and
parenchyma.
1. The stroma is composed of a well-developed capsule,
surrounding the whole gland and sends connective tissue septa rich
in fat cells, and dividing the gland into lobes and lobules. The
glandular tissue is supported by fine network of reticular
connective tissue.
2. Parenchyma is composed of pure serous acini and the elements
of the previously discussed duct system. Intercalated ducts are
long and numerous. Striated ducts are also present and the main
ducts open into the mouth cavity opposite the upper 2nd molar
teeth.
Submandibular gland
The submandibular gland is a mixed gland but primarily serous. It
is composed of stroma and parenchyma.
1. The stroma is composed of connective tissue capsule and septa
dividing the gland into lobes and lobules. Fat cells are usually
absent.
2. The parenchyma is composed of secretory acini and duct
system. There are serous acini with scattered groups of mucous
alveoli or acini. The mucous acini are composed of lightly-stained
50

cells. There are also some mixed mucous alveoli with serous
demilunes; demilunes are serous cells grouped on the periphery of
mucous alveoli. The duct system is well developed, intercalated
ducts are short and not easy to locate; the main ducts open into the
floor of the mouth posterior to the incisor teeth.

Sublingual gland
Sublingual gland is a paired mixed gland, primarily mucous. It is
composed of stoma and parenchyma.
1. The stroma is composed of thin capsule surrounding the gland
and sending septa dividing the gland into lobes and lobules.
2. Parenchyma is composed of mainly mucous acini, few serous
acini and some mixed acini. Numerous intralobular ducts are
present among the acini. The main ducts open in the mouth cavity
close to submandibular ducts.

Pancreas
The pancreas is considered as both an endocrine (Islets of
Langerhans) and an exocrine gland (pancreatic acini).

A. The exocrine part


The exocrine part of the pancreas is composed of compound
tubuloalveolar glands consisting of serous secretory acini. The
51

exocrine part secretes water, ions, and digestive enzymes. The


exocrine part is composed of two components:
I. Connective tissue stroma
The underdeveloped capsule sends thin septa to divide the
pancreas into lobes and lobules.
Delicate networks of reticular connective tissue carry the blood
vessels and nerves to the lobes and lobules and impart support to
the glandular tissue; the basal laminae of the acini are also
supported by reticular fibers.
II. Parenchyma
The parenchyma is composed of pancreatic acini and the duct
system.
The pancreatic acini:
The pancreatic acini are serous acini, variable in size and shape,
with small lumens lined by the centroacinar cells. The centro-
acinar cells represent the terminal ends of intercalated ducts.
The acini are lined with simple high cuboidal epithelium.
By LM:
The acinar cells appear cuboidal or pyramidal in shape with
rounded basally located nuclei.
The cytoplasm of the acinar cells exhibits differences in the
staining between the basal and the apical portions.
52

The apical parts contain the zymogenic granules which are


acidophilic, whereas the basal portions contain the rough
endoplasmic reticulum and highly basophilic.
By EM:
The acinar cells show the typical features of protein
synthesizing cells: large vesicular basal nuclei, well-
developed supranuclear Golgi complex, very rich in RER and
mitochondria, numerous secretory vesicles at the apical part
and luminal short microvilli.
The lateral borders of the cells are joined by junctional
complexes with the tight junctions just below the cell surface
to close the intercellular space and prevent the passage of
secretion to the intercellular space.

The duct system:


The main pancreatic (excretory) duct and, the accessory
pancreatic duct which, in some persons, open into the main
duct before reaching the duodenum, are lined with simple
columnar epithelium, join the common bile duct and open
into the duodenum at the ampulla of Vater.
The main duct extends along the entire length of the pancreas
giving off the interlobular ducts to the individual lobules,
which then give off the intralobular ducts.
53

The intralobular ducts are very few, small narrow intercalated


ducts lined by low simple cuboidal epithelium, and open
directly into the interlobular ducts.
The acinar portions of the intercalated ducts are formed by
the centroacinar cells seen in cut sections lining the lumens
of the acini.
No secretory striated ducts in the pancreas.

Functions of the exocrine pancreas:


1. Production of the digestive enzymes such as protrypsin,
prochymotrypsin, lipase, amylase, elastase, and phospho-lipase.
Protrypsin is activated by duodenal enterokinase into trypsin which
in turn activates prochymotrypsin into chymotripsin.
2. Secretion of bicarbonates to neutralize stomach acidic secretion.
3. Pancreatic secretion is controlled by vagus nerve as well as by
two hormones secreted by enteroendocrine cells of small intestine,
secretin and cholecystokinin.

B. The endocrine part of the pancreas (Islets of Langerhans)


The islets of Langerhans are lightly-stained areas or cell masses
scattered among the darkly-stained pancreatic acini.
The islets are composed of connective tissue stroma and
parenchyma.
54

The stroma:
The islets of Langerhans are not surrounded by a capsule but they
are supported by fine reticular connective tissue frameworks.
The parenchyma:
The islets of Langerhans are formed of anastomosing cords of
cells, and numerous fenestrated capillaries in between; they are
surrounded by the pancreatic exocrine acini.
The types of endocrine cells can be demonstrated by the use of
immunohistochemical techniques; there are four types of cells in
the islets of Langerhans:
1. Beta cells ( cells)
B cells are the most numerous cells lying at the central region of
the islets; they represent 60 75% of the total cells. They are
small in size and oval in shape with basophilic cytoplasm.
By EM; cells have well developed Golgi complex and RER,
numerous secretory granules and irregular crystals.
Function: secretion of insulin which lowers the blood glucose
level.
2. Alpha cells ( Cells)
They are larger and less in number than B cells representing about
15-20%; they have acidophilic cytoplasm and present at the
periphery of the islets. They have secretory granules with electron
dense central area.
55

Function: secretion of glucagon hormone which elevates the


blood glucose level.
3. Delta cells ( cells)
They constitute less than 5% of the islet cells, scattered between
other cells.
Function: secretion of somatostatin which inhibits the release of
other islet cell hormones (insulin and glucagon) by local paracrine
effect; they also inhibit the release of growth hormone.
4. F cells or pancreatic polypeptide cells (PP cells)
These are rare cells present in the islets as well as in pancreatic
acini; they secrete pancreatic polypeptides which control the
gastric and pancreatic acini secretion, and hence help in protein
and carbohydrate metabolism.

Liver
The liver is the largest internal organ of the body and the largest
gland. It serves as an exocrine gland in secreting the bile, and as
an endocrine gland in synthesizing and storing several products to
be released directly into the blood stream such as plasma proteins
(albumin), coagulation factors and growth factors.
Anatomically, the liver consists of four lobes which, in man, are
incompletely divided into lobules.
56

Histologically, the liver is composed of two elements: the stroma


and parenchyma.
I. Connective tissue stroma:
The connective tissue septa divide the liver into lobules and
carry into the liver, branches of hepatic arteries, portal veins,
bile ducts, nerves and lymphatics.
These septa (interlobular) are continuous with the Glisson`s
capsule which covers the whole liver.
A delicate network of reticular fibers supports hepatocytes
and sinusoidal endothelial cells of liver lobules.
A serosa (visceral layer of peritoneum) covers the whole
capsule of Glisson`s in most areas (except the bare areas).
II. Parenchyma:
The classic liver lobules are the structural and functional units of
liver.
Liver lobules consist of similar parynchymal cells (hepatocytes)
arranged radially in hepatic plates, with anastomosing hepatic
sinusoids.
The classic liver lobules are prismatic or hexagonal in shape,
irregularly distributed throughout the liver.
The axis of the lobule is the central vein which receives blood from
the hepatic sinusoids and drains it into the sublobular veins.
57

The portal spaces containing the portal triads are triangular and
present at the corners of the liver lobules. The triad consists of an
arteriole (a branch of the hepatic artery), a venule (a tributary of
the portal vein), and a branch of the bile duct and lymphatic
vessels. The portal spaces provide important landmarks in liver
structure.

Histology of hepatocytes:
By LM:
Hepatocytes are large polyhedral cells with large centrally
located nuclei. Some hepatocytes are binucleated; the nuclei
are vesicular with one or two nucleoli.
The cytoplasm is acidophilic (abundant mitochondria), with
areas of basophilia due to presence of RER.
The cytoplasm shows vacuolated areas of dissolved fat,
glycogen and pigment granules.
By electron microscope:
The hepatocytes appear highly rich in all cell organelles:
mitochondria for energy production, free ribosomes and RER
for protein synthesis, and SER for detoxification, lipid and
steroid metabolism. Well-developed Golgi complex,
lysosomes and peroxisomes are also present in hepatocytes.
58

Bile canaliculi are formed between the plasma membranes of


two adjacent hepatocytes through which the bile secreted by
hepatocytes passes. At bile canaliculi, the cell membranes of
hepatocytes show short microvilli and the adjacent cells are
sealed with tight junction to prevent the bile leakage.
The cell membrane of hepatocytes adjacent to sinusoids
exhibits long microvilli for absorption and secretion.

Functions of hepatocytes:
1. Hematopoietic function during intrauterine life
2. Metabolic functions such as: deamination of aminoacids,
synthesis of plasma protein and very low density lipoprotein
(VLDL), carbohydrate and lipid metabolism.
3. Detoxification of drugs, liver cytotoxic chemicals such as
chlorinated hydrocarbons (pesticides) and a range of common
organic solvents and anaesthetics.
4. Bile synthesis.

Hepatic sinusoids:
The hepatic blood sinusoids are intralobular vascular blood
channels lined by two main types of cells:
The endothelial cells
The phagocytic stellate cells (Kupffer cells).
59

The space between hepatocytes and hepatic sinusoids


(subendothelial space) is called space of Disse. Besides blood, it
contains some reticular fibers, microvilli of hepatocytes, fat-storing
cells (Ito cells) and the pit cells. Blood elements are not allowed
to pass into the space of Disse.
The endothelial cells:
- They are smaller and more flattened than the stellate
Kupffer cells.
- They have small amount of cytoplasm and small ovoid
dark nuclei.
- They are fenestrated and have no basal lamina but they are
supported by the reticular fibers in the space of Disse.
The phagocytic or stellate cells (Kupffer cells):
- They are typical fixed macrophages situated among the
endothelial cells sharing them in lining the hepatic
sinusoids.
- They belong to mononuclear phagocytic system.
- Their processes extend between the endothelial cells into
the lumen of the sinusoid.
- They engulf and breakdown the bacteria in the blood and
take part in breaking down the aged erythrocytes.
The fat-storing cells or Ito cells or lipocyte:
60

- Located in the peri-sinusoidal space of Disse which is


fluid-filled space lying between the hepatocytes and the
sinusoids.
- They have the ability to accumulate lipid droplets
- They are considered the main source of storage of
retinoids (vitamin A) in the body.
- They help in healing of liver wounds (hepatic
fibrogenesis) by secreting the extracellular proteins,
proteoglycans and growth factors.
The pit cells:
- Present in the space of Disse
- They belong to immune system
- Mobile, and believed to be a form of natural killer or
lymphokine-activated killer cells (LAK cells).
Bile canaliculi
They are small channels between the plasma membranes of the
adjacent hepatocytes which have short microvilli and sealed by
tight junctions to prevent bile leakage.
Bile canaliculi form networks of anastomosing channels; these
channels open, at the periphery of the lobule, into small bile
ductules called cholangioles or canals of Hering.
Cholangioles are tiny ductules lined by low cuboidal epithelium
and then open into the bile ducts.
61

Bile secretion
Bile is composed of water and bile salts (sodium glycocholate and
sodium taurocholate).
Synthesis of the bile salts takes place in the SER of hepatocytes,
- The bile, which is excreted via the bile duct to the
duodenum, is responsible for the emulsification of fats.
- The bile also serves as a vehicle for the excretion of
components of aged erythrocytes. The breakdown of
erythrocytes by Kupffer cells of the liver, or macrophages
of the spleen, results in the heme pigment converted to
biliverdin, then to bilirubin.
- Bilirubin, water-insoluble, toxic, is conjugated with
glucuronic acid in the SER of hepatocytes to form non-
toxic water-soluble bilirubin glucuronide, which is
secreted in the bile.
- In the duodenum the bilirubin is converted by bacteria to
urobilinogen, which is reabsorbed in the distal small
intestine and recaptured in the liver.
- About 90% of the bile is recycled, with about 10% de
novo formation.
- The bile provides the characteristic dark color of the feces.
62

Liver lobules:
1. The classic liver lobule
2. Portal lobule
3. The liver acinus

The Classic liver Lobule:


It is polygonal or hexagonal in shape made of plates of
hepatocytes arranged radially in relation to central vein
which lies in the middle of the lobule.
Blood sinusoids are running in between the plates of
hepatocytes to drain into the central vein.
At the periphery of each lobule, there are three to six
triangular areas of connective tissue (portal tracts or portal
areas) containing the portal triad (a branch of hepatic
artery, a branch of portal vein and a bile duct) plus nerves
and lymphatic vessels.

The Portal lobule:


The idea of portal lobule is based on the fact that liver is
considered as an exocrine gland in secreting the bile
It is a triangular area stretching between three central veins
and has no clearly defined borders.
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The bile duct in the portal triad lies in the center of the portal
lobule, and the regions of adjoining hepatic lobules drain into
the bile duct of the central portal triad.

The Liver Acinus:


This lobule is based on the blood flow and metabolic functional
areas of the liver.
The acinus is a diamond shape and its borders are not well-
defined, but its physiological zones are defined as three zones
(zone I: periportal, zone II: transition, zone III: centrilobular).
In this lobule, the central veins are located at its periphery,
while, the branches of hepatic artery lie in its center.
Accordingly, the cells in its center are the first to receive
blood supply whereas the cells at its periphery are the last to
receive the blood supply.
This concept is important to understand several
histopathological conditions.

Metabolic Zones of Liver:


The classic liver lobules can be divided into areas of different
metabolic activities. The most peripheral areas of the lobules have
the highest blood supply containing more oxygen metabolites.
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This peripheral area is called the zone of permanent


function (zone I).
The middle zone of the lobules has reduced metabolic
activities and is known as the zone of intermediate
function (zone II).
The most central zone, closest to the central vein, has the
least metabolic function and is called the zone of
permanent repose or inactivity (zone III).
This is reflected by the greater numbers and activities of
mitochondria in the peripheral zone (perilobular cells)
compared to the number of mitochondria in the inner zone
(centrolobular).

Blood Supply of the Liver


The liver has a double blood supply, portal venous blood carrying
nutrients from the intestine, except complex lipids, by the portal
vein (75%), and an arterial oxygenated blood by hepatic artery
(25%). Chylomicrons (complex lipids) are carried to liver by
lymph vessels.
In liver, the blood flows from the periphery to the center
(centripedal).
1. The portal venous system:
The portal vein branches into interlobular veins
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The interlobular veins give off small distributing veins which


run at the periphery of the lobules
Distributing veins branch into inlet venules which empty
directly into the sinusoids.
The sinusoids converge in the center of the lobule forming
the central vein.
The central veins drain into the sublobular veins which
converge to form the hepatic vein.
Hepatic veins join the inferior vena cava.
2. Arterial system:
The hepatic artery branches into interlobular arteries.
Some of interlobular arteries supply the portal spaces; others
break down into inlet arterioles which empty directly into the
blood sinusoids thus providing a mixture of arterial and
portal venous blood in the liver blood sinusoids.

Liver Regeneration:

Parenchymal cells of the liver have a great capacity, although


slow, to regenerate after injury in organized way.
The healthy liver cells undergo compensatory hyperplasia to
replace the damaged cells exposed to toxic agents.
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If a lobe of the liver is removed surgically and donated by an


individual for transplantation, the liver tissue can regenerate
and return to full liver functions in both the donor and the
recipient.
Liver stem cells can regenerate into liver cells in
experimental animals; also oval cells which are present in
bile ductules near the portal area can give rise to hepatocytes
and cholangiocytes.
In case of sustained exposure of liver cells to toxins, and
infection by parasites or viruses, disorganized mass of
hepatocytes surrounded by a great quantity of connective
tissue resulting in liver cirrhosis.

Gall bladder
The gall bladder is a pear-shaped structure showing great variation
in size and shape among different individuals.
It is composed of a neck, body and fundus.
Its wall consists of mucosa, muscularis, a perimuscular layer of
connective tissue and a serosa or fibrosa.
a. Mucosa
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The mucosa is highly folded; the epithelium is tall simple


columnar, absorptive in nature, with basal ovoid nuclei and striated
border (EM).
The lamina propria is a delicate loose connective tissue containing
many blood vessels. No muscularis mucosa. No submucosa.
b. Muscular layer
It is a thin layer composed of smooth muscle bundles in all
directions to help emptying its contents.
c. Adventitia:
The adventitia lies external to the muscular layer, made of thick
irregular connective tissue and contains large blood vessels, nerves
and lymphatics. Serosa is present where gall bladder is covered by
peritoneum.
Functions of gall bladder:
Storage of bile
Concentration of bile by absorbing its water
Releasing bile when needed by contraction of the smooth
muscles which is under the effect of cholecystokinin of
enteroendocrine cells of small intestine. The wall of gall
bladder has receptors for cholecystokinin hormone.
68

The Respiratory System


69

Respiratory system
The respiratory system is composed of conducting and
respiratory portions. The conducting portion is formed of nasal
cavities, nasopharynx, larynx, trachea, bronchi, and bronchioles,
while the respiratory portion is formed of the lungs containing
alveoli, alveolar sacs and ducts and respiratory bronchioles.
The main function of the respiratory system, beside blood-air (gas)
exchange, is to clean, warm or cool and moistens the inspired air
(air conditioning) and sound production.

I. The Conducting Part


The structure of the conducting part of the respiratory system:
Generally, the wall of the conducting portion is made of:
1. Mucosa:
Epithelium: the conducting portion is lined by respiratory
epithelium (pseudostratified columnar ciliated with goblet
cells) in trachea and bronchi, becomes simple columnar and
cuboidal in bronchioles.
Lamina propria is made of loose connective tissue rich in
elastic fibers and contains blood vessels, nerves and
lymphatics
Fibro-elastic layer.
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2. Submucosa contains blood vessels, lymph nodules and mixed


gland.
3. Cartilage
4. Adventitia

Nasal cavity
The nasal cavity is divided by the bony nasal septum into two
halves (2 cavities).
Arising from the lateral wall of each cavity, three bony projections
called conchae. The middle and inferior conchae are lined with
respiratory epithelium and the superior is lined with olfactory
epithelium.
Large venous plexuses, called swell bodies, and thin-walled
venules are present in the lamina propria of the conchae to warm
and condition the inspired air.
Nasal cavity is divided into:
1. Vestibule
2. Paranasal sinuses
3. Respiratory area
4. Olfactory area
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The vestibule of the nose


The vestibule is the anterior dilated part of the nose following the
nostrils; it opens to the exterior by two nostrils and it is lined with
keratinized stratified squamous epithelium.
The lining skin contains sebaceous and sweat glands, also contains
thick short hairs called vibrissae which filter the inspired air from
the dust particles.
The posterior part of the vestibule is lined with stratified squamous
nonkeratinized.

Respiratory area
The respiratory area follows the vestibule, where the epithelium
changes from stratified squamous nonkeratinized to become
pseudostratified columnar ciliated with goblet cells (respiratory
epithelium). The lamina propria contains mucous glands and is
highly vascular.

Olfactory area
It is a specialized area of the mucous membrane lying in the roof
of the nasal cavity (in the upper posterior part just lateral to nasal
septum).
It is responsible for the sense of olfaction or smell.
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It is lined by pseudo stratified ciliated columnar epithelium


consisting of olfactory cells, supporting (sustentacular) cells,
and basal cells.
1. The olfactory cells are bipolar neurons whose axons are
gathered to form the fila olfactoria. They have long non-motile
cilia containing chemoreceptors to recognize the smell differences.
2. The sustentacular (supporting) cells are tall cells present in the
upper part of the epithelium; they have broad rounded apices and
narrow bases. They have apical microvilli and well-developed
Golgi apparatus and junctional complexes.
3. The basal cells are small with rounded nuclei. They form a
single basal layer. They act as stem cells and might differentiate
into the other cell types.

The lamina propria


The lamina propria is made of loose connective tissue containing
Bowman`s glands which are branched tubuloalveolar serous glands
and their secretion acts as a solvent to clear the cilia to facilitate
the access of the new odoriferous substances. The glandular cells
are cuboidal to columnar with rounded nuclei and granular
cytoplasm; their ducts might be seen passing through the
epithelium. The lamina propria merges with the periosteum of the
underlying bone.
73

The Paranasal Sinuses


The paranasal sinuses are closed dilated cavities in the frontal,
maxillary, ethmoid and sphenoid bones of the skull. They are
lined with pseudostratified columnar ciliated epithelium with
goblet cells.
The lamina propria is bound tightly to the underlying periosteum
and is made of loose connective tissue rich in lymphocytes and
lymph follicles and mucous glands.
The produced mucus is drained into the nasal fossa through small
openings.

The Nasopharynx
The nasopharynx communicates the nasal cavity with the larynx
and continues with the oropharynx caudally.
Nasopharynx is lined with pseudostratified columnar ciliated
epithelium with goblet cells.
The lamina propria is made of loose connective tissue containing
mucous glands, blood vessels and pharyngeal tonsil.
The pharyngeal tonsil is a single collection of lymphatic tissue and
is covered with respiratory epithelium.
When the pharyngeal tonsil is infected, it enlarges (adenoid) and
obstructs the airway leading to mouth breathing.
74

The Larynx
The larynx is an irregular tube that connects the pharynx to the
trachea.
The wall of the larynx is lined with respiratory epithelium
and is supported by connective tissue and several laryngeal
cartilages.
The laryngeal cartilages are of two types, hyaline (thyroid,
cricoid and arytenoid), and elastic (cuneiform, corniculate,
epiglottis and tips of arytenoid).
During swallowing, the laryngeal opening is protected by
epiglottis.
Below the epiglottis the laryngeal mucosa forms 2 pairs of
folds which extend into the lumen of the larynx forming the
false and true vocal cords.
The false vocal cords:
The false vocal cords are the upper vestibular folds; they are lined
with respiratory epithelium and their lamina propria contains
numerous serous glands.

The true vocal cords:


The true vocal cords are made by the lower mucosal folds.
They contain large bundles of parallel elastic fibers.
They are covered by stratified squamous nonkeratinized.
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The lamina propria contains laryngeal cartilages and skeletal


muscle (vocalis muscle).

The Epiglottis
1. The epithelium is stratified squamous nonkeratinized, on the
lingual surface, which changes gradually to pseudo stratified
columnar ciliated epithelium with goblet cells on the laryngeal
surface. Occasional taste buds might be encountered on the lingual
surface..
2. The lamina propria is made of loose connective tissue with
diffuse lymphatic tissue, adipose tissue, groups of tubuloalveolar
mixed glands, small blood vessels and nerves.
4. A single elastic cartilage forms the central plate of epiglottis.

Trachea
The trachea is an airway tube extending from the base of the larynx
to its point of bifurcation (C4) into the right and left main bronchi.
It is about ten centimeters long, consists of a series of C-shaped
plates of hyaline cartilage for support.
The smooth muscle (trachealis) is present only between the ends of
the C-shaped cartilage plates.
The wall of trachea is made of the following layers:
I. Mucosa
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a. The epithelium is typical respiratory epithelium (pseudo


stratified columnar ciliated with goblet cells).
Respiratory epithelium:

The mucosa of most of the conducting portion of the respiratory


system is lined by a pseudo stratified columnar ciliated epithelium,
often referred to as respiratory epithelium. [In areas of high
turbulence (abrasion), the mucosa is lined by a stratified squamous
epithelium.]
Respiratory epithelium contains 6 cell types, some of which are
also found in the respiratory portion of the system.
1. Ciliated columnar cells each of which has ~ 300 cilia on its
apical surface. The cilia move in unison to sweep mucous and its
trapped particular matter towards the pharynx.
2. Mucous or goblet cells are unicellular mucous glands
interspersed among the ciliated cells. They have a basal nucleus
and apical mucinogen granules forming a mucous cup.
3. The basal cells are the epitheliums stem cells found along the
basal lamina. Their apices do not reach the lumen, thus creating
the pseudostratified appearance of the epithelium.
4. The brush cells are columnar cells whose apices are covered
with blunt microvilli. Their basal surfaces are in synaptic contact
with afferent (sensory) nerve endings; however, the sensory
function of these receptors is unclear.
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5. Small granule cells correspond to the enteroendocrine cells of


the gut and, like their intestinal counterparts, contain small, dense
vesicles or granules that are visible in EM. These vesicles contain
neurotransmitters and hormones. Many of these cells are
innervated by nerve terminals to form neuroepithelial bodies.
Acting in paracrine fashion, they are thought to regulate the air and
vascular channel diameters.
6. Clara cells are present in the terminal and respiratory
bronchioles. They are non-ciliated, cuboidal cells with a
characteristic apical dome and an EM profile typical of protein
synthesizing cells. These cells secrete glycoseaminoglycans and
surfactant-like substance to protect the bronchiolar lining.
b. The lamina propria is formed of loose connective tissue with
scanty diffuse lymphatic tissue and abundant elastic fibers.
c. Thick dense elastic membrane
II. Submucosa
The submucosa extends from the elastic membrane to the
perichondrium of tracheal cartilage. It consists of collagen and
elastic fibers, blood and lymphatic vessels.
III. The tracheal cartilage
The tracheal cartilage is made of 16 20 C-shaped rings of hyaline
cartilage with perichondrium which blends with connective tissue
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of submucosa and fibrosa. The open portion of the C-shaped


cartilage is directed posteriorly towards the esophagus.
IV. Trachealis muscle is attached to the posterior ends of the
cartilage plates, its smooth muscle fibers run mainly transversely.
V. Fibrosa is made of connective tissue external to the
perichondrium; it blends with the loose connective tissue
connecting it with the adjacent structures.

The Bronchi
The trachea bifurcates into two primary extrapulmonary bronchi;
each bronchus enters the corresponding lung through the hilum.
Inside the lungs, each primary bronchus divides into a number of
secondary or lobar bronchi to each lobe.
The lobar or secondary bronchi divide into a number of segmental
then sub-segmental bronchi.
1. The layers in the walls of the primary bronchi are similar to
those of the trachea.
2. The lobar (secondary, intrapulmonary) bronchi have the
following feattures:
a. The epithelium is pseudo stratified ciliated columnar with goblet
cells. The lamina propria is made up of loose connective tissue
rich in elastic fibers and lymph nodules.
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b. The submucosa is thinner than that in the trachea, but it contains


the same type of glands (tubuloalveolar).
c. The smooth muscle forms a complete layer around the bronchus.
d. The cartilage plates are made of hyaline cartilage and are
arranged irregularly, not in the form of rings. Note that the amount
of cartilage decreases, in contrast to the amount of smooth muscles
which increases as the size of bronchi decreases.
e. The fibrosa separates the bronchus from the lung tissue.
3. The tertiary or segmental bronchi (branches of the lobar
bronchi) which branch successively to give the bronchioles.
The epithelium is still pseudo stratified columnar ciliated with
goblet cells.
The cartilage plates are few in number and widely separated from
each other.
The subsegmental or smaller branches of the segmental bronchi
have very little cartilage with fewer glands.
4. The bronchioles:
There are four to five divisions of the bronchioles with convoluted
lumens; but do not contain cartilage or glands.
The pseudo stratified ciliated columnar epithelium decreases in
height and the goblet cells disappear in the first divisions of
bronchioles coming from the subsegmental bronchi.
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The rest of bronchioles divisions are lined by simple columnar


ciliated epithelium which becomes cuboidal in the terminal
bronchioles.
5. The terminal bronchioles are the smallest terminal branches of
the conducting portion; they are lined with ciliated simple cuboidal
epithelium with Clara cells and no goblet cells.
The Clara cells present in the lining epithelium of the terminal
bronchioles; they have secretory granules of glycoseaminoglycans
to protect the bronchiolar lining. Clara cells do not have cilia.

II. The Respiratory Portion


The respiratory portion is made of respiratory bronchioles, alveoli
and alveolar ducts.
1. The respiratory bronchioles are subdivisions of the terminal
bronchioles.
The respiratory bronchioles are lined with simple ciliated cuboidal
epithelium with Clara cells and a myoelastic layer lying beneath
the epithelium.
The bronchiolar epithelium is interrupted by the pulmonary alveoli
lined by simple squamous epithelium which is continuous with the
bronchiolar epithelium.
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2. The alveolar ducts coming off the respiratory bronchioles. They


are large tubular air spaces; their walls are made up by pulmonary
alveoli.
Both, alveolar ducts and alveoli are lined by very thin simple
squamous epithelium. Alveolar ducts end in alveolar sacs which
are composed of groups of alveoli.
3. Pulmonary alveoli are the fundamental lung tissue.
The alveoli appear as cup-shaped structures with an open end; they
are lined with simple squamous epithelium (pneumocytes type I
and II) with interalveolar septa between the alveoli.
Pneumocytes type I:
The type I pneumocytes are simple squamous epithelium lining
about 97% of the alveolar surface.
By LM, pneumocyte type I cells appear flat simple squamous
epithelium with flat nuclei.
By EM, pneumocyte type I cells look very thin 25 -100 nm in
width; their nuclei occupy the wide central part. The cytoplasm
contains very few organelles (Golgi complex, mitochondria and
ER) around the nucleus, and pinocytotic vesicles.
Cells are bound together by tight junctions and desmosomes to
prevent the leakage of tissue fluid into the alveolar air spaces.
Function: gas exchange and air-blood barrier.
82

Clinical Note
Pneumocyte type I cells are fully differentiated and cannot divide
and cannot be replaced, thus massive damage of lung tissue heals
by the process of fibrosis, a scar of connective tissue e.g.
tuberculosis

Pneumocytes type II
Pneumocytes type II are few in number lining about 3% of the
alveolar wall interspaced among type I pneumocytes with which
they are bound by occluding junctions.
By LM, the pneumocyte type II cells appear cuboidal or rounded in
shape with round central nuclei and vesicular or foamy cytoplasm.
By EM, they appear to have microvilli on their free surface and
attached to adjacent cells by occluding junctions.
The cytoplasm contains Golgi complex, ribosomes, RER,
mitochondria and lamellar dense bodies.
The dense bodies are membrane bound structures, 1 2 um in
diameter and contain phospholipids, glycosaminoglycans and
proteins (pre-surfactant).
Functions: they divide to replace damaged cells of type I and II.
Pneumocyte type II cells secrete the pulmonary surfactant by
exocytosis.
83

The surfactant is an aqueous mixture of lipoprotein rich in


phospholipids, glycosaminoglycans and specific proteins; it is
secreted by pneumocytes type II and is responsible for lowering
the surface tension of the lung alveoli, and preventing their
collapse. In intrauterine life, the surfactant develops in the last
weeks of pregnancy (the 30th w).

Clinical Note
Surfactant deficiency in pre-mature infants is the major cause of
death due to respiratory distress or respiratory failure which could
be treated by administration of exogenous surfactant.

The inter-alveolar septum


An interalveolar septum consists of two simple epithelial layers of
the adjacent alveoli, rich anastomosing pulmonary capillary
networks supported by reticular and elastic meshworks, fibroblasts,
and macrophages lying between the epithelial layers.
The basal laminae of both capillary endothelial and alveolar
epithelial cells fuse together in one structure.
The interalveolar septum contains pores of 10 - 15 um in diameter
to connect the neighboring alveoli and equalizes air pressure in
them.
84

The alveolar macrophages (The dust cells):


The alveolar macrophages are large phagocytic cells which belong
to the mononuclear pahgocytic system; they are derived from the
blood monocytes.
They are called dust cells when they phagocytose dust or carbon
particles, and called heart failure cells when they phagocytose
RBCs in heart failure.
By LM, macrophages appear as large irregular cells with large
nucleus and acidophilic cytoplasm.
By EM, they appear very rich in mitochondria and lysosomes.

The blood-air barrier


The air in alveoli is separated from the capillary blood by
components referred as blood-air barrier 0.1 1.5 um in diameter,
which consists of:
1. The surface lining and cytoplasm of pneumocytes type I.
2. The fused basal lamina of closely opposed alveolar and
capillary endothelial cells.
3. The cytoplasm of capillary endothelial cells.

The Lungs
There are two lungs lying in the thoracic cavity and covered by
the pleura.
85

Each lung is divided into lobes which are divided into segments.
The right lung has 3 lobes while the left has only 2 lobes.
Each lung is formed of intrapulmonary branches of bronchial tree
and the respiratory portion (respiratory bronchioles, alveolar ducts,
alveoli and alveolar sacs), pulmonary and bronchial blood vessels,
nerves and lymphatics which enter and leave the lung through the
hilum.
There are about 300 million alveoli in each lung; they provide a
vast surface area for gas exchange. Oxygen passes from alveoli to
capillary blood though the blood-air barrier, while carbon di-oxide
passes in the opposite direction liberated from the carbonic acid by
the action of carbonic anhydrase of the RBCs.
Regeneration of alveolar lining:
Death of pneumocyte type I nd II by toxic gases, activates type II
cells to start mitosis to renew both types of alveolar cells;
increased toxicity activates Clara cells too to divide and give rise
to alveolar cells.

The Blood Supply of the Lungs:


Pulmonary arteries carry the unoxygenated blood from the
right ventricle to the lungs for gas exchange.
Pulmonary veins carry the oxygenated blood from the lungs
to the left atrium.
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Bronchial arteries carry the oxygenated blood and nutrients


to the lung tissue, and bronchial veins carry the
unoxygenated blood from the lungs to the azygos vein.

The Lymphatic Drainage of the Lungs:


The lymphatic drainage of both lungs is carried by the lymphatic
vessels which accompany the branches of the bronchial tree (deep
lymphatic network) and drain to the hilar lymph nodes.
The lymph drainage of the visceral pleura runs through the
superficial network to the hilar lymph nodes

The Nerve Supply:


Parasymapathetic motor fibers through Vagus nerve to the
smooth muscles of the bronchial tree promoting constriction.
Sympathetic fibers act as broncho-dilators to the smooth
muscle fibers in the bronchial tree.
Sympatho-memetic drugs (adrenaline) are used in bronchial
asthma to bring bronchodilation to the constricted smooth
muscle fibers of bronchioles.

The Fetal Lung


The lower part of respiratory passages develops from the foregut in
the 4th week of gestation as laryngotracheal tube.
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The laryngotracheal tube divides into 2 lung buds; the tube lining
will give rise to the epithelial lining of the respiratory portion
while the rest of the structures develop from the splanchnic
mesoderm.
The prenatal growth of the lungs is divided into three stages:
The glandular stage in which, the bronchi grow and branch;
this stage lasts until the 17th week of gestation. Alveoli are
not present at this time.
The canalicular stage, up to 25th week, during which the
bronchi and bronchioles expand, branch and begin to form
the primitive alveoli lined with cuboidal and squamous cells.
Pulmonary blood vessels appear, and respiration may start.
The alveolar stage, 26th w to full term, starts by the increase
in number of the terminal sacs and the development of the
capillary networks in between the terminal sacs.
Late in the alveolar stage, development of mature alveoli
and formation of the terminal sacs will take place.
This period begins shortly before birth, but the first
appearance of mature alveoli occurs only after birth. The
alveolar sacs continue to be formed during early childhood
up to the age of 8 years, and their maturation and growth
continue for another decade, but there is no increase in their
numbers.
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A histological section of the fetal lung depends on the fetal age,


but generally, it is characterized by the following:
1. The section is occupied mostly by glandular-like structures
representing the successive divisions of bronchial branches and
lined with simple columnar epithelium.
2. The respiratory portions are made of saccular spaces which
correspond to alveolar ducts.
3. The alveoli are absent or represented by shallow indentations in
the duct walls.
4. Branches of pulmonary artery accompany the bronchial tree.

The pleura
The pleurae are serous sacs covering the lungs.
Each pleura is formed of two membranes enclosing a cavity
containing a thin film of liquid for lubrication.
The outer pleural membrane lines the thoracic cavity and is called
parietal pleura and the inner membrane which covers the lungs, is
called the visceral pleura.
Each layer of the pleura consists of mesothelium and a very thin
layer of underlying connective tissue.
89

The Urinary System


90

The Urinary System


The urinary system is composed of two kidneys, two ureters, one
urinary bladder and one urethra.
Functions of Urinary system:
The main function of urinary system is to produce, store and
eliminate urine (~ 1500 ml urine produced/day), thus sharing
in maintenance of homeostasis.
Urinary system also regulates the fluid and electrolyte
balance.
Produces rennin (helps to regulate BP), prostaglandins, and
erythropoietin (stimulates the production of RBCs).
Hydroxylates the pro-vitamin D produced in skin, into the
active calcitriol (1,25-dihydroxyvitamin D3).

The Kidney
Kidneys are located retroperitoneally on the posterior abdominal
wall; they are bean-shaped, with convex and concave borders.
The convex border is directed laterally while the concave border is
directed medially and contains the hilum.
Blood vessels, nerves, lymphatics and ureters enter and leave the
kindneys through the hilum.
The hilum encloses a space called the renal sinus which contains
the calyces and adipose tissue.
91

The renal pelvis is the expanded upper part of the ureter located in
the kidney hilum; it divides into 2 3 major calyces, each of which
divides into 2 3 minor calyces.
The kidneys are considered as compound tubular glands; they
consist of stroma (thin capsule and septa) and parynchma
(uriniferous tubules).

The kidney general structure


1. The kidneys are covered by a fibrous, pain-sensitive capsule and
peri-renal adipose connective tissue. Within the kidney, the renal
capsule gives off very thin connective tissue septa which
accompany the blood vessels.
2. By the naked eye (NE), a coronal section of the kidney reveals
its internal structure; the kidney consists of an outer dark granular
area called cortex and an inner pale area called medulla.
3. Histologically, the kidney is composed of uriniferous tubules
(the nephrons and the collecting tubules).
4. The cortex contains renal corpuscles, convoluted tubules,
peritubular capillaries and medullary rays.
5. The medulla is the inner pale area with radial striations due to
the presence of loops of Henle, straight collecting tubules and
vasae rectae.
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Medulla is formed of 10 18 medullary pyramids whose bases are


directed to the cortico-medullary junction and covered with
cortical tissue.
Each medullary pyramid base gives medullary ray which passes
into the cortex.
The apex of the pyramid is called renal papilla which protrudes
into the minor calyx and is perforated, thus called area cribrosa.
6. The medullary rays or pars radiata are cortical tissue composed
of small blood vessels and loops of Henle (straight segments of the
proximal and the distal convoluted tubules and the straight
collecting tubules).
7. Pars convoluta is the cortical tissue lying between the pars
radiata. It contains renal corpuscles, proximal convoluted tubules,
distal convoluted tubules and blood vessels.
8. A renal lobe is formed of a medullary pyramid and the adjacent
associated cortex.
9. A renal lobule consists of a medullary ray and the associated
cortical tissue or the nephrons draining into it.
10. The renal columns of Bertini are the cortical tissue found
between the medullary pyramids.
11. Large blood vessels (arcuate arteries and veins) are running at
the corticomedullary junction.
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The Nephron
Nephron is the structural and functional unit of the kidney; there
are 1 1.4 milion nephrons per kidney. Most of the nephrons are
cortical in position, but about one seventh of them are
juxtamedullar in location (near the corticomedullary junction).
The latter nephrons have long loops extending into the medulla.
The nephron consists of:
Renal corpuscle
Proximal convoluted tubule
Loop of Henle
Distal convoluted tubule
Collecting tubules (added by some authors like Basic
Histology)

The renal corpuscles:


The renal or Malpighian corpuscles are rounded structures present
in the renal cortex. Each corpuscle is formed of tuft of capillaries
called glomerulus surrounded by glomerular or Bowman`s capsule.
The renal corpuscle has two poles, vascular and urinary (tubular)
poles. The afferent arteriole enters and the efferent arteriole leaves
the glomerulus at the vascular pole. The proximal convoluted
tubule leaves the glomerulus at the urinary (tubular) pole.
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The glomerulus
The glomerulus is made of loops of fenestrated capillaries of both
afferent and efferent arterioles which meet at the vascular pole.
The capillaries are surrounded by a basement membrane. The
afferent arteriole which supplies blood to the glomerulus to be
filtered is larger than the efferent arteriole; afferent arteriole
divides into 2 5 glomerular capillaries. The blood leaves the
glomerulus through the efferent arteriole which in turn either gives
the peritubular plexus (to supply the convoluted tubules), or
continues as vasae rectae in the medulla.
The endothelial cells line the capillary lumen; they have well
developed basal lamina. They are large, fenestrated cells with no
diaphragm, and they have thin cytoplasm which becomes thicker
around the nucleus. Their nuclei appear bulging into the capillary
lumen. The glomerular capillaries are covered with podocytes
(visceral layer of Bowman`s capsule).
The mesangial cells are modified type of pericytes surrounded by
mesangial matrix, and located inside the interstitial spaces between
the glomerular capillary loops.
The mesangial cells are stellate in shape with cytoplasmic
processes; they contain actin and myosin filaments.
The mesangial matrix, produced by the mesangial cells, resembles
the material of basement membrane.
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There are two types of mesangial cells, intraglomerular and


extraglomerular.
Functions of mesangial cells:
They act as supporting cells,
Act as phagocytic for the turnover of the basement membrane
and the material accumulating on it
Contractile, may regulate blood flow
Act as antigen presenting cells.
They also have surface receptors for atrial natriuretic factor.
Secrete cytokines and prostglandins
The Bowman`s capsule
The Bowman`s capsule has an outer (parietal) layer, and an inner
(visceral) layer with urinary or capsular space lying between the
two layers. The outer layer consists of a simple squamous
epithelium which is continuous with the epithelial lining of the
proximal convoluted tubules at the neck region and with the
visceral layer at the vascular pole. The inner visceral layer covers
the glomerular tuft of capillaries. It is made of modified epithelial
cells called podocytes.
The podocytes
The podocytes are modified epithelial cells lining the visceral layer
of Bowman`s capsule.
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By LM, podocytes appear as flat branched cells with large nuclei.


By EM, podocyte cytoplasm contains Golgi complex, RER,
ribosomes, microtubules and actin filaments. The visceral
epithelium or podocytes posses numerous feet-like primary
processes which give secondary processes called pedicles.
Pedicles embrace and adhere to the basal lamina of blood
capillaries and interdigitate with the pedicles of the adjacent
podocytes, while the podocyte cell body does not contact the
capillary basement membrane.
The spaces between pedicles are called filtration slits which are 30-
40 nm wide. The slits are spanned with diaphragms 5 nm thick
called slit membranes. The slit membrane (diaphragm) is formed
by the basal lamina extending between the pedicles; it is
semipermeable, uniform in thickness, highly specialized
intercellular junction with large transmembrane protein called
nephrin which project on both sides of the membrane.
Nephrin proteins impart the membrane porous feature which
prevents the passage of albumin and the larger molecules into the
filtrate.
By EM, the basal lamina between the glomerular capillary
endothelium and the podocyte is 0.1 um thick composed of
electron-dense central lamina densa with an electron-lucent layer
lamina rara on each side.
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The basal lamina is mostly made of collagen type IV, laminin and
heparin sulfate. Heparin sulfate is a charge barrier because it is a
strong negatively-charged polyanion which keeps the albumin in
the blood stream.
In some diseases such as diabete mellitus and glomerulonephritis,
the filtration membranes become more permeable to proteins, so
the proteins passes into the urine, a condition known as
protinurea.

The Blood-Renal Barrier


Renal blood barrier is a functional barrier between the blood in
glomerular capillaries and the filtrate in the capsular (urinary)
space; it is meant to obtain an ultrfiltrate containing the waste
products.
The glomerular filtrate (180 L/day or 125 ml/min) is under neural
and hormonal control; it contains water, ions, salts and low
molecular weight substances. Particles greater than 10 nm in
diameter or with a molecular weight more than 69kd (albumin) are
not allowed to pass into the filtrate. The glomerular filtrate is
reabsorbed by the renal tubules and 1.5 2 L of urine/day is
excreted as urine.
The renal (filtration) barrier is composed of the following:
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1. Fenestrated endothelial cells of glomerular capillaries to prevent


the passage of blood cells into the filtrate.
2. The fused basal lamina of podocytes and capillary endothelium.
3. The filtration slit membrane (diaphragm)

The Proximal Convoluted Tubules


The proximal convoluted tubule (PCT) begins at the urinary
(tubular) pole of the renal corpuscle; it is about 15 mm long and 60
um wide. It is composed of convoluted part lying in the cortex and
straight part lying in the medullary ray.
PCT function is:
Reabsorb water (65%), sodium chloride (85%), glucose,
amino acids and small molecular weight proteins from the
glomerular filtrate.
Active transport of sodium, calcium and potassium ions.
Involved in vitamin D hydroxylation.
Tubular secretion: the PCT cells can move forign substances
like drugs (penicillin) and organic anions from peritubular
capillaries into the tubular lumen.

The structure of proximal convoluted tubule


By LM, the PCT appears rounded with narrow lumen, lined with
3-5 pyramidal cells (simple cuboidal epithelium) with striated
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border. The cytoplasm is acidophilic and the nucleus is spherical


and located close to the base of the cell, basal striations, and no
distinctive borders of the cells due to lateral intercellular
interdigitations.

The ultrastructure (EM) of PCT:


The cells lining the PCT are the best example for ion transport
cells; the sodium pump responsible for ion transport is located in
the basolateral compartment of the cell. The PCT cells show the
following modifications for the optimum function:
1. The apical microvilli (brush or striated border) to increase
the surface area for absorption; pinocytotic vesicles
containing small molecular weight are present near the
microvilli bases.
2. The intercellular interdigitations along the lateral walls of the
cells.
3. The basal deep infoldings where abundant longitudinally
oriented long mitochondria are residing giving the
characteristic cellular basal striations and the basal
eosinophilia. Mitochondria provide the energy needed for
the active transport of some ions from the basal part of the
cells (compartmentalization).
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When the amount of glucose in the filtrate is too high exceeding the
PCT absorbing capacity, the extra glucose passes in urine as in
diabetes mellitus.

The Loop of Henle


When the PCT is completed, it passes to the medulla then returns
to the cortex making a U loop (Henleys loop). Henle`s loop
consists of:
A thick descending limb (some books consider it as part of
PCT). It is lined by simple cuboidal cells which resemble the
structure of the PCT; it is about 60 um in diameter.
A thin descending limb of 12 um in diameter; it is lined by
simple squamous epithelium.
A thin ascending limb of 12 um in diameter; it is lined by
simple squamous epithelium.
A thick ascending limb is lined by simple cuboidal
epithelium and resembles the structure of distal convoluted
tubule (DCT). It is about 60 um in diameter and is
considered as the straight segments of DCT.
Functions of Henle`s loop
Water retention and creation of hypertonic medium in the
medullary interstitium needed to produce hypertonic
concentrated urine.
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The Distal Convoluted Tubule (DCT)


The DCT begins at the thick ascending part of Henle`s loop at the
cortico-medullary junction; it ascends in the cortex (straight
segment) where it comes in close contact with the renal corpuscle
at the vascular pole forming the macula densa of the JG system
after which the convoluted part starts.
Light microscopic structure of DCT:
a. The DCT cross sections appear smaller (25 um in diameter) with
wider lumen and fewer in number in than the PCT.
b. The cells of DCT are simple cuboidal and lightly-stained.
c. The cells of DCT appear smaller with 5 - 8 cells in cross section.
d. The cell boundaries in DCT are ill-defined.
e. The DCT cells show no brush border.

The EM (ultrastructure) of DCT cells:


a. The apical surface of the cells has very few short microvilli
b. Extensive deep basal invaginations with longitudinally oriented
mitochondria.
c. Presence of lateral cellular interdigitations but less numerous
than in PCT.
Functions of DCT are under the aldosterone hormone control:
1. Reabsorb the remaining sodium and water from the glomerular
filtrate.
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2. Secretion of hydrogen, ammonium and potassium ions to


maintain the acid-base balance.

The Juxta Glomerular System


The juxtaglomerular (JG) apparatus can be found adjacent to the
renal corpuscles where the straight segment of DCT is located
close to the afferent arteriole of the glomerulus at the vascular
pole.
The JG apparatus is composed of the macula densa of DCT, lacis
cells (extraglomerular mesangial cells) and juxtaglomerular cells
(JG cells).
a. The JG cells are modified smooth muscle cells in the tunica
media of the afferent arteriole. They are secretory in nature
containing secretory granules, 40 nm in diameter, and are
separated from the cells of macula densa only by the basal lamina.
At this area the internal elastic membrane of the afferent arteriole
disappears. The JG cells secrete the enzyme renin which plays a
role in maintenance of blood pressure.
b. The cells of macula densa of DCT are tall narrow cells with
closely packed small apical nuclei giving the appearance of dense
spot and basal Golgi complex. Their function is to monitor the
sodium and other ions in the DCT.
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c. The lacis cells (extraglomerular mesangial cells) are small,


granular, lightly-stained cells located in the triangular area between
the afferent and efferent arterioles. They are pericyte-like cells.
Their functions: phagocytic, supportive and may transmit signals
from macula densa to glomerulus for vasoconstriction.

Functions of the JG system:


The main functions of JG system are the autoregulation of
glomerular filtration rate and controlling the systemic blood
pressure.
High blood pressure increases the glomerular filtration rate which
in turn increases the tubular concentration of sodium and chloride
ions monitored by macula densa.
Increased sodium and chloride ions in the tubules, lead to
liberation of ATP and vasoconstrictors by tubular cells which
trigger vasoconstriction of afferent arterioles and reduction of
glomerular filtration rate, reduction tubular ion concentration and
cessation of vasoconstrictors release.
On the other hand, decreased arterial blood pressure causes the JG
cells to secrete renin enzyme which changes angiotensinogen into
inactive decapeptide angiotensin I. The inactive angiotensin I is
activated into angiotensin II by the action of ACE (Angiotensin
Converting Enzyme) present on lung capillaries.
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Angiotensin II raises directly the blood pressure and stimulates


aldosterone secretion by adrenal cortex to raise blood volume and
pressure and stop renin secretion.

The Collecting Tubules


The collecting tubules receive urine from the DCTs and run in the
medullary rays in the cortex then enter the medullary pyramids
where a group of them joins to form papillary ducts of Bellini. The
ducts of Bellini open on the apices of renal papillae into the minor
calyces.
The histological features of collecting tubules:
By LM, the cells lining the tubules range from high simple
cuboidal to columnar epithelium in converging tubules (200um in
diam.) depending on the size of tubule, and changes to transitional
epithelium in minor calyces.
The tubule cross sections show, large diameter about 40 um diam,
wide lumens, made of principal cells, well distinct cells with pale
acidophilic cytoplasm and rounded to oval centrally located nuclei.
By EM, the cells exhibit very few organelles, no microvilli, no
interdigitations but they have basal infoldings.
There are dark cells present among the pale cells called
intercalated cells which contain numerous vesicles and abundant
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mitochondria; they help in regulation of acid-base balance by


secretion of hydrogen and absorption of bicarbonate ions.
Function:
The main function of collecting tubules is to help producing
concentrated urine through the following mechanisms:
The cells of collecting tubules selectively absorb water
because they have an integral membrane protein in their cell
membrane called acquporin which acts as selective pores for
water passage.
The collecting tubules are under the control of antidiuretic
hormone (ADH) which increases the permeability of the
collecting ducts to water to be pulled osmotically from the
duct lumens to the vasae rectae, thus retaining the fluid and
reducing the urine volume.

The Blood Supply of the Kidney


The renal arteries (from abdominal aorta) divide in the hilum
into anterior and posterior segmental branches which give the
interlobar arteries.
At the corticomedullary junction, the interlobar arteries give
two arcuate arteries (accompanied by the arcuate veins).
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The interlobular arteries arise from the arcuate arteries and


run perpendicular to the renal capsule and accompanied by
the interlobular veins.
The interlobular arteries give off to afferent glomerular
arterioles (small intralobular arteries) which break into
glomerular capillaries at the vascular pole.
Efferent arterioles arise from the tuft of glomerular
capillaries and carry the blood away from the glomeruli.
In the cortical nephrons, the efferent arterioles soon break up
into peritubular capillary network to supply PCTs and DCTs.
In the juxtamedullary nephrons the efferent arterioles give
rise into 2 capillary networks: the intertubular capillary
network to supply the renal tubules in the medulla, and the
long thin straight capillaries running in the medulla as vasae
rectae then loop back as venules to corticomedullary
junction.
The blood capillaries in the outer cortex supply the capsule
with stellate arteries.

The renal venous drainage:


The stellate veins from the capsule and peritubular capillaries
drain into the interlobular veins which drain into the arcuate
veins.
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The venous blood returns from peritubular capillaries into the


capillaries of vasae rectae of the medulla into the arcuate
veins.
The arcuate veins drain into the renal veins.

The Renal Interstitium


The renal iterstitium is the connective tissue filling the spaces
between the renal parenchyma; it is poorly developed. It is best
seen associated with blood vessels, nerves and lymphatics. It is
more abundant in the medulla more than the cortex.
Renal interstitium consists of:
Fine collagen and reticular fibers with fibroblasts,
macrophages.
Mucopolysuccharides
Some specialized cells called interstitial cells. It is believed
that the interstitial cells produce prostaglandin and ground
substance. Type I interstitial cells are elongated cells
resembling fibroblasts, with several processes connected to
each other. Type II interstitial cells are large round cells
with large nuclei; they belong to mononuclear phagocytic
system. Type III interstitial cells are pericyte-like cells
associated with blood vessels.
108

The Urinary or Exceretory Passages


The urinary or excretory passages are: Calyces, pelvis, ureters and
urinary Bladder.

Ureters
The ureters are paired small muscular tubes which carry the urine
from the kidneys to the bladder by peristaltic contraction. On
approaching the kidney, the upper end of each ureter expands into
the pelvis which gives major then minor calyces. Calyces, pelvis
and ureter have the same histological structure. The ureter has a
small stellate-shaped lumen; its wall consists of three layers, a
mucosa, a musculosa and a fibrosa.
1. The mucosa
The mucosa consists of transitional epithelium and a lamina
propria.
The transitional epithelium (urothelium) is a stratified epithelium
composed of:
A single basic layer resting on very thin basement membrane.
Intermediate layers: composed of 5 - 6 layers of cells in
empty organ and 2 3 layers in empty organ.
The surface or the apical or the luminal cells are called the
cap or umbrella cells, bi-or multi-nucleated, and in direct
contact with urine.
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They are well-developed, and modified to protect the


underlying cells from urine leakage.
- large, about 100 um in diameter,
- Apical cells have unique apical membrane made of
asymmetric unit membrane in which the outer leaflet is
twice thick as the inner lipid leaflet and the integral
membrane protein uroplakins assembled in 16 nm hard
plaques.
- When the organ is full, the plaques are hinged together to
protect the underlying cells from urine.
- When organ is empty, the umbrella cells fold and
internalize the plaques into disc-like vesicles
- When the organ refills, the discoid vesicle join the
membranes of apical cells which become flat and the
number of epithelial layers becomes less.
The lamina propria is made of loose to dense connective tissue
containing collagen fibers, connective tissue cells and numerous
elastic fibers which produce marked folding of lumen mucousa
when the ureter is empty.
2. Muscularis externa or musculosa.
In the upper two-thirds of the ureters, the muscularis is made of an
inner longitudinal and an outer circular smooth muscle layer. In
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the lower one-third of the ureters, a third outer longitudinal layer of


smooth muscles is added.
3. The fibrosa is made of loose connective tissue containing blood
vessels, nerves, lymphatics and fat cells.

Urinary bladder
The urinary bladder is a muscular organ lying in the pelvis
immediately behind the pelvic bones. It acts as a urine reservoir
before voiding it through the urethra.
The wall of urinary bladder consists of a mucosa, a muscularis
externa and a fibrosa or serosa (on the superior surface where the
bladder is covered with peritoneum).
1. The mucosa is made of transitional epithelium (urothelium) and
lamina propria.
The transitional epithelium is a stratified epithelium resting on a
basement membrane. Its number of layers depends on the state of
fullness of the bladder.
In the empty (undistended) bladder, the mucosa is folded and the
epithelium consists of five to eight layers of cells, and the surface
cells or the cap cells resemble those of the ureters. They appear
dome-shaped or rounded and sometimes binucleated.
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When the bladder is full of urine or distended, the surface cells


become flattened or squamous and the number of cell layers is
reduced to three or four.
By EM, the cells of the surface layer show thick plasma
membrane, membranous vesicles and plaques attached to large
number of microfilaments. The cells of transitional epithelium are
attached to each other by abundant intercellular occluding
junctions. The mentioned modifications in the urothelium help the
cells sliding over each other to allow volume changes and act as a
barrier to prevent dilution of urine and protect the tissue from the
hypertonic urine.
The lamina propria is highly vascular, made of loose connective
tissue underlying the transitional epithelium. Occasional solitary
lymphatic nodules might be present.
2. The musculosa is made of three poorly-defined layers of
smooth muscles separated by abundant connective tissue and
arranged into an inner longitudinal, a middle circular and an outer
longitudinal.
The middle layer is the thickest one; it forms the internal urethral
sphincter at the neck of the bladder.
Musculosa has a rich blood supply and the muscle bundles are
separated by abundant connective tissue.
3. Advetitia
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The upper portion of the bladder which projects into the peritoneal
cavity is covered with mesothelium. The rest of the bladder is
covered with fibrosa containing fat, blood vessels, nerves and
lymphatics.
Urethra
I. The female urethra
The female urethra is very short, 4 5 cm long; its upper part is
lined with transitional epithelium, and the lower part is lined with
stratified squamous non-keratinized epithelium.
The mucosa show shallow pouches lined with mucus-secreting
cells (glands of Littre in male).
The lamina propria is loose connective tissue rich in elastic fibers
and veins forming a plexus.
The musculosa is made of inner longitudinal and outer circular
which will form the external urethral sphincter at the end of the
urethra.

II. The male urethra is about 20 cm long; it conducts urine as


well as semen to the outside of the body. It is composed of three
portions:
1. The prostatic urethra, 3-4 cm long, lies within the prostate; it is
lined with transitional epithelium.
113

2. The membranous urethra is the shortest segment, extends from


the apex of prostate to the beginning of the bulb of corpus
spongiosum of the penis passing through the urogenital diaphragm.
It is lined by pseudo stratified or stratified columnar epithelium
and is surrounded by striated muscle fibers of the external urethral
sphincter.
3. The penile urethra is the longest part (12 cm) of male urethra; it
runs through the corpus spongiosum of the penis. It is lined by
stratified columnar and pseudostratified columnar epithelium, and
by stratified squamous at the fossa navicularis. The mucosa show
shallow pouches containing mucus secreting glands of Littre.
114

The Endocrine System


115

Endocrine system
The endocrine system includes all endocrine glands and hormone-
secreting cells of other organs (thymus, kidney, brain, heart, small
intestine, adipocytes secreting leptin, endothelium secreting
endothelins promoting vasoconstriction).
The endocrine system and the central nervous system are
responsible for the proper co-ordination of the body functions.
The endocrine glands share certain features such as:
1. The endocrine glands have no ducts (ductless).
2. They secrete hormones which selectively affect some target cells
which have surface receptor proteins for specific hormone.
3. The endocrine glands have rich vascularization to transport
quickly the secreted hormones to the other parts of the body.
4. The endocrine parenchyma is usually made of epithelial cells
arranged as cords or as follicles (thyroid).
5. The stroma consists of few collagen fibers, fibroblasts and
reticular fibers.
Mode of endocrine secretion:
- Paracrine: when endocrine secretion acts very quickly at a
short distance (pyloric G cells action on fundic cells).
- Juxtacrine: where the secreted molecules remain on the
secreting cell surface or close by until contact occurs with
the target cells.
116

- Autocrine: where the cells produce secretion which acts on


them or on the same cell type (insulin-like growth factor
produced by liver cells).

The endocrine glands are:


Pituitary
Adrenals
Thyroid and parathyroids
Pineal body

Hypophysis cerebri (Pituitary gland)


Pituitary gland is the master control gland of the endocrine system.
Its hormones regulate the essential body functions as the basal
metabolic rate, the other endocrine organs (thyroid and adrenals),
sexual development and reproduction and the overall growth of the
body.
Hypophysis lies in the sella turcica of sphenoid bone below the
brain; it develops from two sources:
Oral ectoderm of Rathke`s pouch (hypophyseal pouch) of
embryonic pharynx, gives rise to adenohypophysis
Neural ectoderm of the floor of diencephalon gives rise to
neurohypophysis.
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Anatomically, hypophysis is divided into two divisions:


1. Adenohypophysis: forms the major part of hypophysis (75% of
the gland). It is composed of pars distalis (anterior lobe), pars
intermedia and pars tuberalis.
2. Neurohypophysis: is connected to hypothalamus via
infundibular stalk which contains the hypothalamo-hypophyseal
tract made of unmyelinated nerve fibers. It is formed of pars
nervosa, stalk and infundibulum.

Adenohypophysis
Pars Distalis:
Pars distalis is composed of parenchyma (cells arranged in clusters,
groups or cords) which are separated from each other by sinusoidal
capillaries and small amount of stroma (fine reticular fibers).
According to affinity to stains, there are two types of cells:
1. The chromophobes:
They are small cells with indistinct cell boundaries
Poorly-stained, pale colorless cytoplasm and no apparent
granules.
They are present in groups interspersed between the other
cell types.
They make about 50% of the pars distalis cells.
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They include stem cells, undifferentiated progenitor cells and


degranulated cells.
2. Chromophils which contain granules and stain acidophilic
(acidophils) or basophilic (basophils).
Acidophils (alpha cells) which are large cells filled with
prominent eosinophilic granules. They make about 37% of
the pars distalis cells.
They consist of 2 types of cells:
-Somatotropes, most abundant (50%), secreting growth
hormones (somatotropin) which regulates the cellular
growth and metabolism of muscles, bone and adipose
tissue.
- Mammotropes (15-20%) secreting prolactin which
stimulates milk secretion.
Basophils which are the least numerous forming about 10%
of the pars distalis cells.
They have variable sizes with lightly stained basophilic
(bluish) cytoplasmic granules.
There are 3 cell types: gonadotropes secreting 2 hormones,
FSH and LH, thyroptropes (5%) secreting thyrotropin
(TSH), and corticotropes secreting ACTH (corticotropin).
1. FSH stimulates ovarian follicle formation and estrogen
secretion in females and stimulates spermatogenesis in males.
119

2. LH stimulates maturation of ovarian follicles and


progesterone secretion in females and stimulates Leydig cells
to secrete androgens in males.
3. TSH stimulates formation, storage and liberation of
thyroid hormones.
4. ACTH stimulates secretion of adrenal cortex hormones,
lipotrophins regulate lipid metabolism. These hormones
result from cleavage of proopiomelanocortin (POMC).
5. -MSH: secreted by basophils of pars intermedia, acts on
melanocytes and stimulates synthesis of melanin pigment.

Clinical notes:

** Tumors arising in the adenohypophysis are usually benign.


Most of the tumors produce hormones that cause clinical
manifestations such as growth hormone, prolactin,
adrenocorticotropin, and thyroid-stimulating hormone.

Diagnosis is confirmed by immunocytochemical methods.

** Overproduction of growth hormone before puberty leads to


gigantism.

** Overproduction of growth hormone after puberty leads to


acromegally.
** Deficient production of growth hormone leads to dwarfism.
120

Pars intermedia are a slender structure lying between pars distalis


and pars nervosa. It consists of weakly-stained basophilic cells
arranged in cords and follicles and colloid-filled cysts.
The melanotropic cells secrete -Melanocyte-stimulating hormone
(MSH, LPH, and endorphin). -MSH acts on melanocytes and
stimulates synthesis of melanin pigment.

Pars tuberalis surrounds the infundibulum and consists of cells


arranged in cords along the blood vessels; they secrete
gonadotropins (LH, FSH).

Control of adenohypophysis:
The hormones secreted by pars distalis is controlled by three
mechanisms:
The main mechanism of control is through hypothalamic
hormones (releasing and inhibitory) secreted by
hypothalamic nuclei and stored in the median eminence then
released to anterior pituitary through the hypothalamo-
hypophyseal system. This mechanism is aided by CNS
stimuli affecting the function of pituitary and many other
organs. Examples:
121

- Thyroid releasing hormone (TRH) of hypothalamus


stimulates pituitary thyrotropes to secrete TSH and
prolactin.
- Gonadotropin releasing hormone (GnRH): stimulate the
release of LH, and FSH
- Somatostatin: inhibits release of somatotropin and
thyrotropin
- Growth hormone releasing hormone (GHRH): stimulates
synthesis and release of somatotropins
- Dopamine or prolactin inhibiting hormone (PIH): inhibits
the release of prolactin
- Corticotrophin releasing hormone (CRH): stimulates the
release of corticotrophin and lipotropin (LPH).
Negative feedback mechanism from the target organs
on the hypothalamic secretion and on hormone
secretion by pituitary cells. As an example,
hypothalamic thyrotropin-releasing hormone (TRH)
stimulates the secretion of thyrotropin (TSH), which
stimulates the secretion of thyroid hormone (TH). On
the other hand, TH inhibits TSH secretion from the pars
distalis and TRH secretion from the hypothalamus by
negative-feedback mechanism.
122

Hormones secreted by cells of other organs rather than


the feedback mechanism such as:
Inhibin and activin produced by gonads control
the release of FSH and LH.
Ghrelin produced by stomach mucosa stimulates
GH secretion
Oxytocin increases the secretion of prolactin.

Neurohypophysis
Neurohypophysis is made up of pars nervosa and infundibulum.
The pars nervosa consists of unmyelinated axons of neurons lying
in supraoptic and paraventricular hypothalamic nuclei, pituicytes,
Herring bodies, few blood vessels and few connective tissue fibers.
Pituicytes are the most abundant, modified neuroglial cells; they
are highly branched cells with oval nuclei, resemble astrocytes.
Herring bodies contain light eosinophilic granules of
neurosecretory material produced by supraoptic and
paraventricular nuclei and propagated to pars nervosa. Herring
bodies are seen by light microscope; they are located close to
blood vessels.
The neurosecretory material contains two hormones: vasopressin
or antidiuretic hormone (ADH) and oxytocin bound to carrier
proteins called neurophysin I and II.
123

Oxytocin, of paraventricular nuclei, stimulates the contraction of


myoepithelial cells of mammary gland alveoli thus increasing milk
ejection and stimulates the contraction of uterine smooth muscles
during baby delivery.

Vasopressin (ADH), of supraoptic nuclei, acts on the collecting


tubules increasing their permeability to water resulting in more
water reabsorption, thus helping in regulation of the osmotic
balance of body fluids.

Diabetes insipidus is a disease resulting from destruction of


neurons secreting ADH, and presenting with polyuria (about
20L/day).

Blood supply of pituitary gland:


The blood supply of pituitary gland comes from two branches of
the internal carotid artery; it is involved in the control process of
the gland itself.
Inferiorly, the internal carotid artery gives the inferior
hypophyseal arteries which supply mainly the
neurohypophysis.
Superiorly, the internal carotid artery gives several superior
hypophyseal arteries which branch and anastomose forming a
primary plexus of fenestrated capillaries extending into the
124

median eminence of hypothalamus and the pituitary stalk.


These capillaries return to the surface of median eminence
and stalk and rejoin into venules and veins, run downward
and supply the sinusoidal capillaries of adenohypophysis
forming a secondary capillary plexus.
The venules that connect capillaries in the median eminence
with the sinusoidal capillaries of anterior lobe are called
hypophyseal portal system.
The hypophyseal portal system is very important carrying
three known groups of hormones:
1. Hormones produced by the hypothalamic nuclei (supra-optic
and paraventricular), released by exocytosis and carried
along the neuron axons to their terminal ends in
neurohypophysis. These hormones are oxytocin and ADH.
2. Hormones produced by dorsal medial, ventral medial and
infundibular nuclei of hypothalamus, released along the
axons ending in the median eminence, enter the primary
plexus, and then transported along the hypophyseal system to
adenohypophysis. These hormones are: thyrotropin releasing
hormone (TRH), gonadotropin releasing hormone (GnRH),
somatostatin, growth hormone releasing hormone (GHRH),
prolactin inhibiting hormone (PIH) and corticotrophin
releasing hormone (CRH).
125

3. Hormones secreted by pars distalis pass into the secondary


capillary plexus, then to general circulation to reach their
specific target organs.

Thyroid gland
The thyroid gland consists of two lateral lobes connected by an
ismuth. It lies over the superficial part of the trachea just below
the larynx.
Thyroid gland develops very early in gestation as thyroid
diverticulum from the midventral wall of the pharynx (gut
endoderm).
Thyroid gland is highly vascular and its size differs according to
sex, age, nutrition, temperature and iodine content of the food.

Thyroid gland produces thyroid hormones (T3 and T4). Thyroid


hormones are important for growth, cell differentiation, oxygen
consumption and basal metabolic rate control (carbohydrate,
protein and lipid metabolism).

Thyroid gland consists of stroma and parenchyma.

Stroma:
Thyroid gland is surrounded by a true thin fibroelastic capsule
which sends fine connective tissue septa dividing the lobes of the
gland into lobules.
126

Each lobule is surrounded by delicate connective tissue containing


blood vessels and contains thyroid follicles supported by fine
reticular fibers.

Parenchyma:
The thyroid glandular tissue is present in the form of follicles of
variable size and shapes. Each follicle is lined by glandular cells
of simple cuboidal epithelium endodermal in origin and few
parafollicular cells (ectodermal in origin). The follicular cavity is
filled with colloid.
Colloid is a semi-fluid homogenous substance rich in iodine and
thyroglobulin which is the stored form of thyroxine.
In the resting state, the follicles have wide lumen full of secretion
and are lined with simple squamous epithelium; in the active state,
the lining epithelium is tall columnar.
The secretion is poured directly into the capillaries which are of
fenestrated type. The follicles contain two types of cells: the
follicular cells which are predominant and produce the two thyroid
hormones (T3 and T4) and parafollicular cells or C-cells which
secrete calcitonin. Calcitonin is a hormone which lowers the blood
calcium level and thus opposing the parathyroid hormones.
127

The follicular cells:


By LM, the thyroid follicular cells might be simple squamous
(inactive gland), cuboidal or tall columnar epithelium (active
gland) surrounding the follicular lumen together with few short
parafollicular cells.
The lumen is filled with pink-staining colloidal substance and the
follicles appear of variable diameters.
By EM, the follicular cells have apical junctional complexes with
luminal short microvilli; they have round nuclei and present all the
features of protein-synthesizing cells: abundant RER and
ribosomes, mitochondria, well-developed Golgi complex, large
number of secretory granules, rich in mitochondria and lysosomes.

Synthesis of thyroid hormone:


Thyroglobulin is synthesized by follicular cells and stored in
follicular lumen as colloid which will be activated into thyroid
hormone according to cellular needs. This process is under the
control of TSH.
Synthesis of thyroid hormone involves an exocrine and endocrine
phases:
1. Formation of thyroglobulin
Thyroglobulin (protein) is synthesized in RER of follicular cells,
then addition of carbohydrates in RER and Golgi complex where
128

secretory granules are formed. The contents of secretory granules


(thyroglobulin) are released into the lumen by exocytosis (exocrine
phase).
2. Uptake and oxidation of iodine
The follicular cells absorb iodide from the blood of capillary bed at
the base of cells, and liberate it into the follicular lumen carried by
the protein pendrin to be oxidized into active iodine by the enzyme
peroxidase present at the cell surface.
3. Iodination of thyroglobulin (tyrosine residues)
Iodination of thyroglobulin occurs in the lumen of thyroid follicle
(extracellularly) where the tyrosyl group of thyroglobulin
combines with iodine to form mono- and di-iodotyrosine. Finally,
molecules of mono- and di-iodotyrosine couple to produce tri-
iodothyronine (T3) and tetra-iodothyronine (T4) which are stored
in colloid.
If two di-iodotyrosine molecules couple together, the result is the
formation of thyroxin (T4). If a di-iodotyrosine and a mono-
iodotyrosine are coupled together, the result is the formation of tri-
iodothyronine (T3).
4. Liberation of thyroid hormones
In the endocrine phase and under the effect of TSH, the follicular
cells take up colloid (inactive T3& T4) by endocytosis
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(pinocytosis). Pinocytotic vesicles fuse with primary lysosomes


and move to basolateral compartment of the cell.
Inside lysosomes, the iodinated thyroglobulins are digested,
degraded and hydrolyzed by lysosomal proteases resulting in
liberation of mono- and di-iodotyrosine into the cytoplasm. . The
active T3 and T4 cross the cell membrane into capillaries.
T4 is more abundant (90%) than T3 but less potent and can give
rise to T3 when neede, on the other hand T3 forms only about 10%
of thyroid hormone but more potent.

Parafollicular (Clear or C-cells):


C- Cells are present in the walls of thyroid follicles between
follicular cells and the basal lamina, or as clusters (groups)
between the follicles. They dont reach the follicle lumen.
By LM, they are not easily distinguished. They are rounded,
larger and stain lighter than the follicular cells; they have pale or
clear cytoplasm.
By EM, the cells appear to be rich in RER, mitochondria, well-
developed Golgi complex and numerous small granules containing
the hormone calcitonin which inhibits bone resorption by
osteoclasts and thus lowering blood calcium levels opposing the
parathormones.
130

Control of Thyroid Secretion

Thyroid-stimulating hormone (TSH; thyrotropin), secreted


by pars distalis. TSH increases the follicular activity to
produce and release thyroid hormones.
Thyroid hormones inhibit the release of TSH, and
maintain an enough amount of T4 and T3. TSH receptors
are present on the basal membrane of follicular cells.
Exposure to cold increases TSH secretion and exposure to
heat and stress decrease TSH secretion.
Production of an excess amount of reverse T3 (rT3),
which interferes with the production of T3.

Clinical notes:
1. Hypothyroid function:
a. Infantile hypothyroidism results in short stature (cretinism) or
dwarfism, mental retardation and abnormal reproductive function.
b. Adult hypothyroidism or myxedema results in Hashimoto
disease.
2. Iodine deficiency goiter due to deficiency of iodine uptake in
diet resulting in follicular hypertrophy and accumulation of colloid
in the follicles.
131

3. Grave`s disease or exophthalmic goiter resulting from


hyperthyroid function despite of subnormal level of TSH. The
follicles show hyperplasia without colloid accumulation and high
level of circulating thyroid hormone. This condition is believed to
be due to immunologic dysfunction caused by circulating
immunoglobulins whose effect resembles that of the TSH.
Parathyroid glands
The parathyroids are four in number embedded in the dorsal
surface of the thyroid gland, and separated from it by a thin
connective tissue capsule.
Ectopic parathyroids may be present anywhere from the base of
skull to the arch of aorta especially in the thymus, in the
mediastinum or in the neck external to thyroid gland.
The superior pair develops from the endoderm of the fourth
pharyngeal pouch, while the inferior pair develops from the third
pharyngeal pouch. This fact explains the ectopic presence of
parathyroids in the thymus gland. The glands are composed of
stroma and parenchyma.
Stroma:
Each parathyroid is invested by a delicate connective tissue
capsule which sends trabeculae into the gland without dividing it
into distinct lobules; blood vessels, nerves and lymphatics
supplying the gland are running in these trabeculae.
132

Parenchyma:
The gland parenchyma consists of two types of cells: the chief
cells and oxyphil cells.
1. The chief cells (Principal cells):
By LM, chief cells appear as small polygonal cells with round
vesicular nuclei and pale-staining basophilic or clear cytoplasm.
By EM, chief cells have abundant RER and ribosomes, well-
developed Golgi complex, numerous mitochondria and secretory
granules.
Chief cells secrete parathyroid hormones (parathormones) which
oppose calcitonin effect. The function of parathormones is to
regulate the calcium and phosphate ions level in the blood.
If the blood calcium level is lowered, parathormones will increase
blood calcium level by:
Stimulating bone resorption by osteoclasts
Increasing calcium reabsorption by distal convoluted tubules
of kidney
Increasing calcium absorption by the intestine.
No evidence of pituitary control over the parathyroid glands.
Complete removal of parathyroid glands in mammals is fatal.
2. The oxyphil cells are polygonal and larger than chief cells and
present singly or in clusters. Their cytoplasm has fine acidophilic
granules, large number of mitochondria and small dark pyknotic
133

nucleus. Oxyphil cells appear around the age of puberty and


gradually increase in number by age; their function is unknown.

Clinical Note:
1. Hyperparathyroidism:
This leads to increase of blood calcium levels and reduced blood
phosphate levels resulting in deposition of calcium in several
organs such as kidneys and arteries; while calcium is withdrawn
from bones leading to their fracture.
2. Hypoparathyroidism:
This condition occurs in accidental removal of parathyroid glands
resulting in decrease of blood calcium level and increased blood
phosphate level and thus bones become denser with excessive
calcium deposition. This causes spastic generalized skeletal
muscle contraction (tetany); this condition can be treated with
calcium and vitamin D.
134

Suprarenal (adrenal) glands


The suprarenal glands are paired glands lying on the superior poles
of the kidneys. They are composed of cortex and medulla which
differ in embryonic origin, structure and function.
The adrenal cortex arises from mesoderm and is very essential for
life; it forms about 90% of the total volume of the suprarenal.
The adrenal cortex is under the control of the hormones of
adenohypophysis and the kidney; it produces steroid hormones
which affect protein and carbohydrate metabolism and electrolyte
distribution.
The medulla arises from neural crest ectoderm and is under
nervous control, it secretes catecholamines which affect the heart
rate, smooth muscles of blood vessels and viscera, carbohydrate
and lipid metabolism.

Adrenal cortex
Stroma:
Each gland is encapsulated by a thick collagenous connective
tissue capsule that sends trabeculae into the gland parenchyma
carrying blood vessels and lymphatics. Outside the capsule, there
is a pad of fat enclosing the blood vessels.
135

Parenchyma:
The cortex completely surrounds the medulla; and is composed of
three distinguished zones which are zona glomerulosa, zona
fasiculata, and zona reticularis.
a. Zona glomerulosa
This is the outermost layer of the cortex; it lies just beneath the
capsule and comprises about 15% of the cortex thickness.
By LM, the cells of this layer appear columnar or pyramidal with
oval basal nuclei, arranged in closely packed arched clusters and
surrounded by capillaries. By EM, the cells have the features of
steroid secreting cells, abundant SER, numerous mitochondria with
tubular cristae, lipid droplets and Golgi complex. This zone
produces mineralocorticoids mainly aldosterone which controls
water and electrolyte balance by stimulating sodium reabsorption
from distal convoluted tubules of the kidney and intestninal
mucosa.
b. Zona fasiculata
This layer lies in the middle zone; it is the widest zone forming
about 78% of the cortex thickness.
By LM, the cells appear polyhedral and arranged in cords with
fenestrated blood capillaries in between. The cytoplasm contains
large number of lipid droplets which dissolve during tissue
136

preparation, thus the cytoplasm appears vacuolated and the cells


are called spongiocytes.
By EM, the cells appear very rich in SER, mitochondria with
tubular cristae, lipid droplets and well developed Golgi complex.
Together with zona reticularis, they secrete glucocorticoids and
androgens (sex hormones), but zona fasiculata mainly secretes
glucocorticoids (mainly cortisol) which regulate carbohydrate,
protein and fat metabolism.
c. The zona reticularis
This layer is the innermost layer, it lies adjacent to the medulla and
it forms about 7% of the cortex thickness.
By LM, the cells appear smaller than the cells of the other two
layers and are arranged in irregular cords which anastomose
forming reticulum and enclosing fenestrated blood capillaries in
between.
By EM, the cytoplasm appears very rich in SER, mitochondria
with tubular cristae, lipid droplets, numerous lipofuscin granules
(pigment), and apoptotic cells with small dark pyknotic nuclei are
seen in this layer.
Zona reticularis secretes androgens (dehydroepiandrosterone) and
possibly cortisol.
Glucocorticoids action:
137

Stimulates gluconeogenesis (formation of glucose from


amino acids or fatty acids).
Decreases cellular uptake of glucose and increase glucose
production leading to hyperglycemia.
Maintains blood glucose level during stress and starvation.
Suppresses the immune response

Adrenal medulla
The adrenal medulla can be distinguished from the cortex by being
stained more basophilic. The majority of cells in the medulla are
chromaffin cells, also called pheochrome cells or pheochromocytes
which give rise to the tumor pheochromocytoma.
By LM, the cells of the adrenal medulla (the chromaffin cells) are
large polyhedral with large vesicular nuclei and granular basophilic
cytoplasm (the granules contain ATP and the protein
chromogranins which may act as binding protein for
catecholamines). Chromaffin cells are arranged in cords with
fenestrated capillaries in between. Some sympathetic ganglion
cells might be present in the medulla.
By EM, the cytoplasm contains few RER, well developed Golgi
complex, numerous mitochondria, and abundant secretory granules
containing catecholamines (pale epinephrine granules and dense
norepinephrine granules).
138

Clinical notes:
1. Hyperfunction of adrenal cortical hormones is manifested as:
Cushing syndrome: due to excessive secretion of
glucocorticoids leading to obesity, moon face and
hyperglycemia.
Conn`s disease due to excessive production of aldosterone
Excessive androgen production in females leads to abnormal
hair growth (hairsutism) and to precocious puberty in males.
2. Hypofunction of adrenal cortex (insufficiency) will result in:
hypoglycemia, weakness, and weight loss and skin hyper-
pigmentation.
3. Pheochromocytoma is a tumor of medulla chromaffin cells
leading to paroxysmal elevation of blood pressure.

Pineal gland
The pineal gland or epiphysis cerebri is a small endocrine gland
located above the posterior part of the third ventricle. Its function
is believed to be regulation of certain biologic rhythms such as the
onset of puberty, since the pineal tumors in males are associated
with precocious puberty.
Stroma: It is covered by pia matter which sends connective tissue
septa into the gland carrying blood vessels and unmyelinated nerve
fibers.
139

Parenchyma:
The gland is composed of two types of cells, pinealocytes and
astrocytes.
The pinealocytes are arranged in cords, they have basophilic
cytoplasm and large irregular nucleus with prominent nucleolus.
These cells produce melatonin, an active derivative of serotonin
which exerts a suppressive effect on the release of gonadotrophin
releasing factor and may also decrease the response of
gonadotrophs to their hypothalamic releasing factor.
The astrocytes are supportive neuroglial cells rich in
microfilaments.
Calcified concretions appear in the gland; they are called corpora
arenacea or brain sand. These concretions contain
hydroxyapatite; they become more evident with age. They
constitute a good medical landmark in X-rays, CT scan and
magnetic resonance imaging.

Islets of Langerhans
It is the endocrine part of the pancreas; it is the islets of
Langerhans which are lightly-stained areas or cell masses scattered
among the darkly-stained pancreatic acini. The islets are
composed of connective tissue stroma and parenchyma.
140

The stroma:
The islets of Langerhans are not surrounded by a capsule but they
are supported by fine reticular connective tissue frameworks.

The parenchyma:
The islets of Langerhans are formed of anastomosing cords of
cells, and numerous fenestrated capillaries in between; they are
surrounded by the pancreatic exocrine acini. The types of cells can
be demonstrated by the use of immunohistochemical techniques;
there are four types of cells in the islets of Langerhans:
1. Beta cells ( cells)
Beta cells are the most numerous cells lying at the central region of
the islets; they represent 60 75% of the total cells. Using LM,
cells appear small in size and oval in shape with basophilic
cytoplasm. By EM; they have well developed Golgi complex and
RER, numerous secretory granules and irregular crystals.
Function: secretion of insulin which lowers the blood sugar
(glucose) level.
2. Alpha cells ( Cells)
Alpha cells are larger but less than cells representing about 15-
20%; they have acidophilic cytoplasm and present at the periphery
of the islets. They have secretory granules with electron dense
central area.
141

Function: secretion of glucagon hormone which elevates the blood


glucose level.
3. Delta cells ( cells)
Delta cells constitute less than 5% of the islet cells; they scattered
between other cells.
Function: secretion of somatostatin which inhibit the release of
other islet cell hormones (insulin and glucagon) by local paracrine
effect.
4. F cells or pancreatic polypeptide cells (PP cells)
These are rare cells present in the islets as well as in pancreatic
acini.
Function: production of pancreatic polypeptides which control the
gastric secretion and the secretion of pancreatic acini.
142

Hormones secreted by non-endocrine organs


1. Male gonads
Intersitial cells of Leydig secrete testosterone
Sertoli cells secrete inhibin and androgen binding proteins
2. Female gonads
The ovaries secrete estrogen and progesterone
3. Placenta secretes estrogen, progesterone, chorionic gonadotropin
and chorionic somatomammatropin.
4. Thymus secretes thymosin
5. Kidney secretes rennin and erythropoietin
6. Diffuse neuro-endocrine system (DNES) or APUD system
The cells of this system are scattered in different systems and they
are able to uptake amino acid precursors and synthesize amines by
amino acid decarboxylase enzyme. Because some of the cells are
not able to concentrate amine precursors, so the name DNES is
more appropriate.
Most of the cells are derived from neural crest and stain with
silver, so they are called argentaffin or argyrophil cells.
The cells of DNES are present in respiratory and urinary systems,
gastro-intestinal tract, thyroid gland and hypophysis cerebri.
By LM, the cells appear ovoid or pyramidal with wide base and
narrow apex. By EM, the cytoplasm has few RER, Golgi complex
spherical mitochondria and numerous secretory granules.
143

The mode of action of DNES cells:


Paracrine acting locally upon the neighboring cells
Endocrine through the blood by acting on target organs
Neuroendocrine acting as chemical mediators in nerve tissue
Classes of DNES cells:
1. The open type which reaches the lumen and the apex has villi.
2. The closed type in which the cell apex is covered by other
epithelial cells.
The sites or locations of DNES cells are:
1. Enteroendocrine cells of Stomach (secreting gastrin,
enteroglucagon, somatostatin, serotonin, and endorphin) and
small intestine (secreting secretin, enteroglucagon,
cholecystokinin, somatostatin, serotonin, and endorphin).
2. Bronchiolar neuroepithelial bodies made of 80-100 cells
which contain secretory granules and receive cholinergic
nerve endings.
3. Parafollicular cells of thyroid
4. Chromaffin cells of adrenal medulla
5. Corticotropic and melanotropic cells of pituitary gland
6. Paraventricular and supraoptic hypothalamic nuclei.
7. Myocardial neuroencrine cells secreting atrial natriuretic
hormone.
144

The Male Reproductive System


145

Male reproductive system


The male reproductive system consists of two testes, the excretory
genital ducts, the accessory glands and the penis.

The testis
The testes are ovoid, paired, primary male sex organs located in
the scrotum; their function is to produce spermatozoa (act as
exocrine glands) and the hormone testosterone (endocrine glands).
Testosterone is essential for normal development, maturation and
competence of the male reproductive system. Each testis is
covered by three tunics:
1. The tunica vaginalis is the outermost tunic; it covers the tunica
albuginea and is made of one layer of squamous cells and a thin
layer of loose connective tissue. Tunica vaginalis is a serous sac of
peritoneum that was trapped by the descended testis during
development. This tunic is lacking in the posterior wall of the
testis.
2. The tunica albuginea is the middle tunic; it is made of tough
fibrous layer of connective tissue surrounding the testis. It is
thickened at the posterocephalic part forming the mediastinum
testis through which ducts, blood vessels and nerves pass.
Connective tissue trabeculae project from the mediastinum into the
146

parenchyma dividing the testis into about 250 pyramidal-shaped


lobules.
3. The tunica vasculosa is made of thin layer of loose connective
tissue highly vascular, and lies internal to tunica albuginea.
Each testicular lobule contains 1 - 4 convoluted seminiferous
tubules which are the structural and functional units of the testes.
At the apices of the lobule, seminiferous tubules unite with the
straight tubules which in turn unite with the rete testis.
The stroma of the testis lying between the seminiferous tubules
(the interstitial tissue) is a continuation of the tunica albuginea and
contains fibroblasts, collagen fibrils, macrophages, lymphatics,
mast cells, blood vessels and interstitial cells of Leydig. The
Leydig cells produce the androgenic steroid hormone testosterone.
Testosterone production is stimulated by luteinizing hormone (LH)
which is produced by basophils of the anterior hypophysis.

The seminiferous tubules:


The seminiferous tubules are the exocrine part of the testes which
produce spermatozoa; their wall is made of three layers:
a. An outermost layer of fibro elastic connective tissue.
b. A basement membrane on which the spermatogonial cells rest.
c. The stratified epithelium lining the seminiferous tubules, 2
types:
147

Sertoli cells
The spermatogenic cells
Sertoli cells:
The supporting cells of Sertoli lie within the stratified
epithelium of seminiferous tubules.
By LM:
1. They rest on the seminiferous epithelial basal lamina and
reach the lumen.
2. They are elongated pyramidal cells with numerous lateral
processes which partially embrace spermatogenic cells.
3. By LM, the cytoplasm stains pale with fat droplets. Their
boundaries are not clear, but can be identified by their nuclei
which are basal, large, ovoid, euchromatic (lightly-stained)
and contain one or two nucleoli.
By EM: the cells have abundant SER, some RER, well
developed Golgi complex, lipid droplets, lysosomes,
numerous mitochondria, euchromatic nucleus, and their
adjacent processes are connected together by occluding
junctions at their basolateral borders forming the blood-testis
barrier thus dividing the seminiferous tubules into basal and
ad luminal compartments.
The spermatogonia lie at the basal compartment below the blood-
testis barrier. The spermatocytes and spermatids lie in the deep
148

lateral and apical invaginations of Sertoli cells in the ad luminal


compartment above the blood-testis barrier.

Functions of Sertoli cells:


Supporting, protection and nutrition to spermatogenic cells
Phagocytosis of the excess cytoplasmic fragments of
spermatid during spermiogenesis Produce anti-mullerian
hormone
The blood-testis barrier is formed by the tight (occluding)
junctions between Sertoli cells in order to protect the
spermatogenic cells from noxious blood-borne substances
and auto-immune responses.
Secretion of fluid that helps in sperm transport to genital
ducts.
Secretion of inhibin B which inhibits the release of FSH by
pituitary gland.
Secretion of androgen-binding protein (ABP) which binds
testosterone to keep its high concentration for
spermiogenesis; ABP is under the effect of FSH.

The spermatogenic cells:


These cells line the seminiferous tubules. At puberty,
spermatogenic cells undergo successive divisions to give rise to
149

spermatids by a process called spermatogenesis. The resulting


cells stay connected by intercellular cytoplasmic bridges until
complete maturation of sperms.
a. The spermatogonia: these are small cells resting on the
basement membrane of seminiferous tubules. They are diploid
cells (46 chromosomes) with 2N amount of DNA; there are two
types of spermatogonia:
Type A cell contains one or two peripherally located nucleoli
within their nuclei. This type of cells might be dark or light.
The light type is divided into 2 halves (half of cells stays as
stem cells and the other half differentiates into type B
spermatogonia.
Type B nucleus contains a centrally located nucleolus. They
are progenitor cells which differentiate into primary
spermatocytes.
b. The primary spermatocytes: these cells are the largest of the
spermatogenic cells arranged in 2-3 layers. They lie next to
spermatogonia and are easily identified due to presence of mitotic
figures within the cells; they contain 46 chromosomes with 4N
amount of DNA.
c. The secondary spermatocytes: these are small cells about one-
half the cells of primary spermatocytes. They are difficult to
observe in sections as they are short-lived cells; they rapidly divide
150

to form spermatids. Secondary spermatocytes contain 23


chromosomes with 2N amount of DNA.
d. The spermatids: they occupy the recesses of the supporting
cells near the lumen. They are small cells with darkly-stained
nuclei containing 23 chromosomes with 1N amount of DNA.
They differentiate into spermatozoa by the process of
spermiogenesis.
e. The spermatozoa: these are the sperm cells; their heads are very
small containing very small, dark, heterochromatic ovoid to
elongated nuclei. Their heads are directed towards the
spermatogenic cells with their tails projecting into the lumen of the
seminiferous tubules. They contain 23 chromosomes with 1N
amount of DNA.
Spermiogenesis:
The process of spermatid transformation into sperm; no cell
division occurs in this process. Spermiogenesis is divided into 3
phases:
1. The Golgi phase:
The spermatids contain well developed Golgi complex,
mitochondria, centrioles, SER, free ribosomes and small secretory
granules called proacrosomal granules. Proacrosomal granules
unite to form single acrosomal granule within the acrosomal
vesicle and the centrioles migrate opposite to the future acrosome.
151

2. The acrosomal phase:


The acrosomal vesicle enlarges to cover the anterior half of the
nucleus and is known as the acrosome. The acrosome contains
carbohydrates (PAS-positive) and hydrolytic lysosomal enzymes
such as hyaluronidase and protease. The acrosomal enzymes help
the sperm to penetrate the cells of corona radiata and digest the
zona pellucida in the process of fertilization where the acrosome
fuses with the sperm cell membrane at several places leading to
liberation of acrosomal enzymes in the extracellular space
(acrosomal reaction).
The spermatid nucleus (sperm head) become denser and more
elongated and directed to the base of seminiferous tubules, on the
opposite side of the nucleus the 2 centrioles are located
perpendicular to each other. One centriole will elongate and form
the flagellum (axoneme); the mitochondria will aggregate around
the proximal end of flagellum forming the middle piece.
3. Maturation phase:
The forming sperm is covered by a thin layer of cytoplasm and the
residual cytoplasm is shed and phagocytosed by Sertoli cells.
Mature free spermatozoa are released into the lumen of
seminiferous tubules.
152

Morphology of mature sperm:


The mature sperm consists of head, neck, middle piece or body and
tail.
The head has a smooth oval configuration; it is about 6 microns
long and 3 microns wide. Sperm head contains densely packed
heterochromatic nucleus and the acrosome covers about 40-70% of
the head anterior.
The neck is a constriction between the head and the middle piece;
it contains 2 centrioles perpendicular on each other.
The middle piece has an internal structure of axoneme (9 + 2); it is
covered mitochondrial sheath and externally by the cell membrane.
It is around 8 microns long and 1 micron in diameter.
The tail is straight, uncoiled slightly thinner than the middle piece
abbot 45 micron in length. It has an internal structure like the
middle piece and cilia and externally is covered by cell membrane
and fibrous sheath.
The connective tissue stroma of the testis:
The stromal (connective) tissue lies in the angles between the
seminiferous tubules; it contains the interstitial cells of Leydig
which are present in small clusters, nerves and blood and
lymphatic vessels. Testicular capillaries are fenestrated to allow
the free passage of macromolecules.
153

The interstitial cells of Leydig:


By LM, the interstitial cells of Leydig appear polyhedral in shape,
with acidophilic cytoplasm and central rounded nucleus that
usually contains one or two prominent nucleoli. The cytoplasm
may appear vacuolated due to dissolved lipid droplets during
preparation. The cells may contain brownish deposits of
lipochrome pigments.
By EM, the cytoplasm contains abundant SER, some RER, well
developed Golgi complex, numerous tubular mitochondria, and
lipochrome pigments.
Function:
Leydig cells secrete the male hormone, testosterone. This
hormone is important for spermiogenesis and the appearance of
secondary male sex characters.

The genital ducts


1. The tubuli recti (straight tubules):
These tubules lie in a narrow region between the ends of
seminiferous tubules and the rete testis. The seminiferous tubules
empty the mature sperms into the straight tubules whose initial part
is lined only by Sertoli cells, and the rest of it is lined by simple
cuboidal epithelium.
154

2. The rete testis is the structure where the tubuli recti empty. It is
lined with simple cuboidal epithelium and unites the straight
tubules with efferent ductules.

3. The efferent ductules are composed of 10 - 15 ductules where


the rete testis empties into. They convey the secretory product of
the testis into the epididymis. The efferent ductules are lined with
alternating groups of nonciliated cuboidal cells and tall columnar
ciliated cells giving the scalloped or undulated appearance.

4. The ductus epididymidis (epididymis) lies at the posterior


aspect of the testis.
Mucosa:
The lining epithelium is pseudo stratified columnar with stereocilia
(modified microvilli). The epithelium rests on thin basal lamina; it
consists of tall columnar cells and short pyramidal basal cells. The
stereocilia extend from the apices of the columnar cells.
The lamina propria is formed of thin layer of loose connective
tissue which contains blood capillaries, lymphatics and nerves.
Musculosa:
Surrounding the epithelium is surrounded by a thin layer of smooth
muscles.
Function: Storage of spermatozoa.
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5. The ductus (vas) deferens is a thick muscular tube which


begins at the tail of epididymis and ascends upward within the
inguinal canal as one component of the spermatic cord. The other
components of the spermatic cord are the artery of the ductus
deferens, testicular artery, cremasteric artery, pampiniform venous
plexus, lymphatic vessels and nerves.
The wall of ductus deferens is composed of mucosa, muscularis
and fibrosa.
Mucosa:
a. Epithelium: It is lined pseudostratified columnar epithelium
with stereocilia.
b. Lamina propria is made of loose connective tissue
Musculosa:
The muscularis is thick and is made of three layers, a thin inner
longitudinal, a thick middle and a thicker outer longitudinal layer.
Fibrosa (adventitia):
The fibrosa lies external to the muscularis and blends with the
connective tissue of the spermatic cord.
Functions:
Transport sperms to ejaculatory duct.
6. The ejaculatory duct
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The ductus deferens ends in the ejaculatory duct which opens in


the prostatic urethra. It is lined by simple columnar epithelium
which becomes transitional at the opening.

The accessory genital glands


A. Prostate gland:
It is an accessory unpaired sex gland of males that surrounds the
urethra on leaving the bladder (prostatic urethra). The prostate
gland is made of aggregations of 30 - 50 branched tubulo-alveoalr
glands. These glands are arranged into three groups:
Mucosal
Submucosal
The main group.
1. The stroma:
The glands are surrounded with thick fibromuscular stroma which
makes a thick distinctive feature of the prostate gland. Strands of
smooth muscles intermixed with collagenous and elastic fibers.
2. Parenchyma:
The prostatic urethra, a U-shaped groove, is lined with transitional
epithelium. The ejaculatory ducts are found on both sides of the
urethra.
The mucosal (central) group lies next to the urethra and the
submucosal lies just peripheral to the mucosal group.
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The main glands lie outside the submucosal glands. They


form the main bulk of the prostate (70%) and it is the major
site of prostate cancer. The glands are made of acini lined
with pseudostratified columnar epithelium. The lumins of
the glands are irregular and may contain eosinophilic
concretions (corpora amylacea).
Function:
Prostatic gland secretes milky fluid rich in citric acid and acid
phosphatase and empties this secretion into the prostatic urethra.
Prostatic secretion comprises about 75% of semen.

B. The seminal vesicles:


These are paired sex glands of the male lying posterior to the
prostate. Its wall is made of mucosa, muscularis and fibrosa. The
gland has numerous lumins due to the numerous convolutions of
the gland appeared at the plane of cutting during processing.
1. The mucosa shows primary folds with secondary and tertiary
branching. The epithelium is low pseudo stratified columnar
epithelium rich in secretory granules. The lamina propria is a wide
layer of loose connective tissue.
2. The muscularis is made of an inner circular and an outer
longitudinal smooth muscle layer.
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3. The fibrosa is rich in elastic fibers and contain blood vessels and
nerves.
Function:
Seminal vesicles secrete yellowish secretion rich in ascorbic acid,
alkaline phosphatase, prostaglandin, proteins and fructose

C. Bulbo-urethral glands (Cowper`s gland):


These are small tubuloalveolar glands located at the base of the
penis. They are lined with simple cuboidal mucus-secreting cells.
They empty their secretion into the membranous urethra. They
secrete viscous mucous secretion which lubricates the penile
urethra.
The penis
The penis is the male copulatory organ made of three masses of
erectile tissue surrounding the urethra, and is covered externally
with thin hairless skin. Glans penis is an extension of corpus
spongiosum at the terminal end of the penis; it is covered by a skin
fold called prepuce which is removed by circumcision.
The erectile tissue consists of 2 corpora cavernosa and one corpus
spongiosum.
Corpora cavernosa:
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There are two corpora cavernosa lying on the dorsal side of


the penis connected together by an incomplete median
connective tissue septum.
Each corpus cavernosum is covered with the thick layer of
dense connective tissue (tunica albuginea).
They contain irregular blood spaces called cavernous blood
sinuses separated by connective tissue trabeculae containing
bundles of smooth muscle and elastic fibers.
Branches of the deep artery of the penis run the trabeculae
and end in small arteries (helicine arteries) which open
directly in the cavernous sinuses. Helicine arteries are spiral
with longitudinal folding in the intima.
The cavernous sinuses are drained by small vein plexus
The deep dorsal vein of the penis lies dorsally in the midline
between the two corpora cavernosa embedded in the fascia
penis with the dorsal arteries on both sides.

Corpus spongiosum:
The corpus spongiosum lies on the ventral midline of the penis
containing the penile urethra along its whole length. The penile
urethra urethra is lined by pseudostratified columnar epithelium
with areas of stratified columnar.
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Semen and sperm count:


The normal ejaculate volume of semen is around 3 ml; about 65%
of it is produced by seminal vesicles. Semen is slightly alkaline
and liquefies in 20-25 min. It contains ~ 100 million sperms /ml.
When sperm count is less than 20 million /ml, it is called
oligospermia and absence of sperms in the semen is called
azospermia.
161

The Female Reproductive System


162

The female reproductive system


The female reproductive system consists of two ovaries, two
uterine tubes, a uterus, a vagina, the external genitalia,
placenta and the mammary glands. The ovaries produce the
female germ cells (the ova) and certain hormones. The uterine
tubes are important in transporting the sperms to ova for
fertilization, then transporting the zygote to the uterus for
implantation. Uterus is important for growth and maturation of the
fetus.
The ovary
The ovaries are paired almond-shaped organs (2x4cm) which
produce the female germ cells or ova and the female sex hormones,
estrogen and progesterone. It lies in the pelvis and suspended by
the broad ligament of the uterus by the mesovarium which carries
ovarian blood vessels, nerves and lymphatics to ovarian hilum.
The outermost covering of the ovary is simple cuboidal epithelium
germinal epithelium although it does not produce germ cells.
Immediately deeper to germinal epithelium there is a white
collagen capsule called tunica albuginea. Each ovary is formed of
cortex and medulla.
The medulla is smaller than cortex and lies in the central part of
ovary; it is composed of loose connective tissue which contains
numerous blood vessels, nerves, lymphatics and interstitial stromal
163

cells. Blood vessels, nerves and lymphatics enter and leave the
ovary through its hilum.
The cortex is the wide outer zone of the ovary, highly cellular and
covered by tunica albuginea. It contains different stages of ovarian
follicles and stromal cells (long spindle shaped cells).

Development of the ovary:


During early intrauterine life, the primordial germ cells
migrate from the endoderm of yolk sac to the ovary where
they differentiate into oogonia.
By the 3rd month of intrauterine life, the oogonia divide by
mitosis and differentiate into primary oocyte containing 46
chromosomes and 4 N amount of DNA. Primary oocytes
enter the first meiotic division and arrested at the diplotene
stage of prophase throughout intrauterine life, childhood and
puberty.
In adult female, one oocyte usually reaches the mature stage
and completes its first meiotic division shortly before
ovulation, despite the large number of follicles stimulated to
grow each month.
The resulting secondary oocyte (and 1st polar body)
immediately enters the second meiotic division where it is
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arrested at the metaphase and will be completed (into mature


ovum) if fertilization process takes place.
The resulting 3 polar bodies are insignificant.

Types of ovarian follicles:


A. The primordial follicle is made of the primary oocyte
surrounded by a single layer of squamous follicular cells.
By LM, the primary oocyte appears large, spherical, ~ 25 m in
diameter, surrounded by a single layer of flat or cuboidal epithelial
cells. It has a large pale vesicular eccentric nucleus with
prominent nucleolus.
By EM, the primary oocyte contains several Golgi complexes,
numerous mitochondria, RER and free ribosomes.
At birth, the ovary contains only primordial follicles about
600,000, most of which degenerate by the process of atresia, and
only 300,000 primordial follicles are left to puberty. At
menopause (the age of 40-45 years), the number of primordial
follicles decreases to 8,000 only and the rest degenerate and
become atretic follicles.
B. The primary follicles which are:
i. The unilaminar primary follicle which consists of an oocyte
surrounded by simple cuboidal to low columnar follicular cells.
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ii. The multilaminar (pre-antral) primary follicle: at this stage the


follicular cells proliferate by mitosis to form stratified epithelium
or granulosa cell layer which rests on basal lamina surrounding the
follicle and separating it from the surrounding tissue. A thick coat,
the zona pellucida, secreted by oocyte and follicular cells, made of
glycoproteins, PAS-positive, appears and immediately surrounds
the plasma membrane of the oocyte. Zona pellucida is not present
in the small growing follicles. The stromal cells surrounding the
follicles differentiate into theca interna and theca externa cells
which have the characteristics of steroid secreting cells.
C. The secondary, antral or vesicular follicles. The follicles
consist of primary oocytes surrounded by 6 - 12 layers of
granulosa cells, and fluid-filled spaces called antra. The filopodia
of granulosa cells communicate with each other and with the
microvilli of the oocyte through gap junctions; the granulosa cells
are under the control of FSH.
D. The mature (graafian) follicle. It appears as large transparent
vesicle (2.5 cm in diameter) bulging from the surface of the ovary.
The mature follicle contains large follicular cavity containing
follicular fluid, and the mature ovum. The ovum (primary oocyte)
reaches its maximum size about 150 microns in diameter with
large, pale and centrally-located nucleus with prominent nucleolus.
The mature ovum is surrounded by a clear zone called zona
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pellucida and external to it a cluster of granulose cells called


corona radiata. The ovum is pushed by liquor folliculi to one
side of the follicle and the granulosa cells surrounding the follicle
are separated from theca cells by a thick basement membrane; they
are reorganized to form the antrum, cumulus oophorus and corona
radiata.
Comulus oophorus is a group of granulosa cells extending
between the ovum and the follicular wall, forming a hillock
supporting the ovum. The mature follicle is surrounded by theca
interna cells and external to it, the theca externa cells. The cells of
theca interna have the characteristics of steroid secreting cells such
as: abundant SER, numerous mitochondria with tubular cristae,
and lipid droplets
The theca interna cells secrete androstenedione hormone which is
transported to granulose cell layer where it is transformed into
estrogen.

Ovulation:
Ovulation means liberation of the mature ovum into the peritoneal
cavity due to rupture of the wall of the mature Graafian follicle
Normally the ovulation occurs on the 14th day (mid-cycle) of
a 28 days menstrual cycle.
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Normally one ovum is released, occasionally 2 or rarely more


than 2 ova.
Sometimes the cycle is not associated with ovulation and is
called anovulatory cycle.
The ovum and the granulose cells of corona radiata get
loosened from the cumulus oophorus and float freely in the
follicular fluid.
The amount of follicular fluid increases tremendously and
become watery leading to thin follicular wall and the
appearance of a weak translucent spot in the ovarian wall
called stigma.
At the stigma, the blood flow stops, the epithelium becomes
discontinuous and the follicle ruptures expelling the ovum,
with the corona radiata, to the peritoneal cavity.
The ovum is captured by the fimbriated end of oviduct, and
drawn into it by the cilia of the lining epithelium.
After expulsion of the ovum, the follicular wall collapses
giving irregular narrow cavity which is invaded by blood
from the ruptured thecal blood vessels. The blood clots then
invaded by connective tissue cells which later will be
phagocytosed leaving an empty cavity.
The first period of menstrual cycle is called menarche occurs
at the age of 11 13 years old, on the other hand,
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menopause means the cessation of menstrual cycle occurs at


the age of 45 50 years old. After menopause, gradual
involution of the female genital organs occurs.

Hormonal control of ovulation:


The ovulation is controlled by a complicated mechanism between
hypothalamus, pituitary gland and ovary.
The gonadotrphic hormones of hypothalamus act upon
pituitary gland to secrete FSH and LH which promote
maturation of ovary and ovarian follicles.
High levels of circulating estrogen produced by the growing
follicles (membrane garnulosa cells) lead to additional LH
release.
At the mid-cycle, a surge of LH will cause rupture of the
follicle and ovulation; LH is secreted by anterior pituitary in
response to high levels of circulating estrogen.
The ruptured follicle is transformed into corpus luteum which
secretes large amount of progesterone and small amount of
estrogen.
The ovarian hormones inhibit the hypothalamus and pituitary
gland to release gonadotropins.
If no fertilization occurs, corpus luteum will be transient and
involutes and the ovarian hormones will not be secreted;
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menstruation will follow and the hypothalamus and


hypophysis will start their functions again.
The use of oral contraceptives (birth control pills) composed
of estrogen and progesterone, depends on inhibition of FSH
and LH release and hence inhibition of LH midcycle surge
and ovulation.
Maturation of primary oocytes:
The primordial follicle needs 14 days from the beginning of the
cycle to reach maturity. The primary oocyte (46 chromosomes,
4N) is arrested in the diplotene stage of prophase of first meiotic
division and just before ovulation, the primary oocyte; completes
its first meiotic division to give the first polar body and the
secondary oocyte (23 chromosomes, 2N). The secondary oocyte
immediately undergoes a second meiotic division which is arrested
at metaphase, which will be completed on or immediately after
fertilization to give rise to the haploid mature ovum containing 23
chromosomes, 1N amount of DNA and the second polar body. If
no fertilization, the secondary oocyte will degenerate without
completing the second meiotic division.
The corpus luteum (yellow body):
Corpus luteum is a temporary endocrine organ which appears
immediately after ovulation and maintained by LH of
adenohypophysis.
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Corpus luteum is large in size, consists of a thick folded wall and a


central cavity filled with loose connective tissue. Most of its wall
is formed by granulosa and theca lutein cells derived from the
granulosa and theca interna cells of the mature follicle.
The lipid droplets in the lutein cells of corpus luteum are dissolved
during routine preparation, giving the appearance of vacuolated
cytoplasm by LM examination.
By EM, examination, the lutein cells exhibit features of steroid
secreting cells (abundant SER, numerous tubular mitochondria).
Types of cells in corpus luteum:
1. Granulose lutein cells are large with pale cytoplasm and
vesicular nucleus containing prominent nucleolus. They
secrete progesterone.
2. Theca lutein cells derived from the theca interna; they are
small darkly stained cells which lie at the periphery of the
corpus luteum. They secrete estrogen.
If the ovum is not fertilized within 24 hours, it degenerates, and
the corpus luteum of menstruation is formed; it lasts only 14
days.
If the liberated ovum is fertilized, corpus luteum of pregnancy is
formed; it lasts for 6 months.
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Both types of corpora lutea undergo fibrotic changes and replaced


by dense connective tissue giving white scars called corpora
albicans.

Interstitial tissue of the ovary:


The interstitial cells of the ovary are isolated groups of theca
interna cells in the ovarian cortical stroma which persist after
degeneration of the follicles. The interstitial cells of the ovary are
present from childhood to menopause; they are under the control of
LH and they secrete steroid hormones.

Atretic follicles:
Despite the large number of ovarian follicles stimulated to grow,
only one follicle is destined to mature stage each month.
The total number of mature ova liberated during the normal female
fertile life is about 450 ova; the rest of the follicles undergo
follicular atresia which can occur at any stage of follicular
development.
The atretic follicles can be seen by LM, as small, irregular
intensely stained structures with hypertrophied zona pellucida.

The ovarian cycle:


The ovarian cycle passes through three phases:
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1. Follicular or estrogen phase (1st -13th day)


FSH promotes the growth and maturation of primordial
follicles to mature graafian follicles which secrete estrogen.
2. Ovulation (day 14th)
Increase blood level of estrogen stimulates LH secretion
which triggers ovulation to occur on 14th day of the cycle
3. Luteal or progesterone phase (15-28th day)
After ovulation, corpus luteum is formed and under the effect
of LH, corpus luteum secretes progesterone which inhibits
LH secretion. If no fertilization, the corpus luteum
degenerates and the estrogen level decreases and FSH
secretion is stimulated again.

The uterine tube


There are 2 uterine tubes (oviducts or fallopian tubes), about 10 -
12 cm long and function mainly to receive the ovum and transport
it if fertilized to uterine cavity by the aid of cilia and peristaltic
movement. Also, the oviduct cilia and its movement help in sperm
transport beside the secretion of nutritive substance to sperm
activation (capacitation) and fertilized ovum. The uterine tube is
composed of 4 anatomical parts:
Intramural part: inside the uterine wall
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Isthmus is the narrow part immediately outside the uterine


wall.
The ampulla is the middle segment where fertilization takes
place.
The infundibulum is the lateral funnel-shaped part which
opens into the peritoneal cavity and is lying close to ovary
and has finger-like processes called fimbriae.
Histological structure:
The wall of uterine tube is composed of mucosa, musculosa and
serosa.
1. Mucosa is highly folded with primary, secondary and tertiary
folds especially in the ampulla.
The lining epithelium consists of two types, simple columnar
ciliated type and simple columnar non-ciliated secretory type
(peg cells) which secrete fluid to protect the ovum, facilitate
its movement and nourish the zygote.
The lamina propria consists of thin layer of cellular loose
connective tissue.
2. The muscularis is an inner circular and an outer longitudinal
layer of smooth muscles.
3. The serosa forms the outermost layer; it is made of loose
connective tissue covered with simple squamous epithelium
of visceral peritoneum.
174

The uterus
The uterus is a pear-shaped single organ composed of a dilated part
called body containing the uterine cavity, and a cylindrical part
called cervix. The dome-shaped part of the body is called fundus;
the internal os lies between the body and the cervix, and the
external os lies between the cervix and the vagina.
The uterus has a thick wall composed of 3 layers: the endometrium
(mucosa), the myometrium (muscularis), and the perimetrium
(serosa or adventitia).
1. The endometrium consists of epithelium and lamina propria
containing simple tubular glands.
The thickness of endometrium depends on the phase of menstrual
cycle; it is composed of two layers:
Stratum basalis is the deep compact layer adjacent to
myometrium; it contains lamina propria and the closed ends
of uterine glands. It is supplied by straight arteries and
responsible for renewal of the functional layer.
Stratum functionalis which lies above the basalis and less
compact contains the rest of the glands, lamina propria and
the surface epithelium. It is supplied by the coiled (spiral)
arteries, and its thickness is controlled by ovarian hormones;
it exhibits cyclic changes like thickening and shedding
according to phases of the menstrual cycle.
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a. The surface epithelium is simple columnar epithelium ciliated


and simple columnar secretory non-ciliated.
b. The lamina propria is made of cellular connective tissue
(stroma) which is denser in the basalis. It is made of fibroblasts,
abundant ground substance, fine collagen (type III) and reticular
fibers; it contains capillaries and venules and coiled arteries in the
functional part of endometrium. Lamina propria also contains
simple tubular glands which extend along the whole thickness of
endometrium. The glands become branched at their deepest parts.
The glands are lined by simple columnar epithelium, some of
which show mitotic figures.
In the secretory phase of menstrual cycle:
The glands become tortuous giving the corkscrew appearance
throughout the functional zone. The nuclei of the lining cells
are basally located and the rest of the cell is full of secretory
material.
The functional zone becomes highly vascular.
The coiled or spiral arteries become larger in size.

2. The myometrium is a thick muscle layer of smooth muscles


and rich in blood supply and lymphatic drainage. It is composed
of four poorly defined layers. The inner (subvascular) and outer
(supravascular) layers tend to run longitudinally, while the middle
176

layer runs in circular and oblique directions. The middle


(vascular) layer is very rich in blood vessels and lymphatics; it
contains the arcuate arteries which send the straight and spiral
branches to the endometrium.
During pregnancy, the smooth muscle cells of myometrium
increase in number (hyperplasia) and increase in size
(hypertrophy), and increase their collagen synthesis. After the
pregnancy ends, reduction of muscle number as well as muscle
size and collagen degradation occurs.
3. The perimetrium (serosa) consists of mesothelium with
underlying loose connective tissue.

The uterine cervix


The cervix of the uterus and the Os cervix are lined with
simple columnar epithelium, mucus-secreting. The cervical
canal has numerous mucosal folds that resemble the glands.
The surface epithelium is continuous with lining of the
branched tubular mucus-secreting cervical glands which
proliferate and increase its mucous secretion during
pregnancy.
The simple columnar epithelium changes abruptly into
stratified squamous epithelium non-keratinized at the portio
177

vaginalis, the external aspect of the cervix that bulges into the
vagina.
Cervical mucosa does not exhibit cyclic changes during
menstruation.
The cervix is composed mainly of dense connective tissue
and few smooth muscle fibers.
Cervical secretion changes with phases of uterine cycle, it is
watery and thin during ovulation to allow passage of sperm
for fertilization, thick and viscous in luteal phase and during
pregnancy to prevent passage of germs and further sperms.
Cervical cancer is derived mainly from the stratified
squamous epithelium.

The uterine cycle (Menstrual cycle):


The menstrual cycle is the cyclic change occurring in the
endometrium every 28 days. It is under the control of the ovarian
hormones and the anterior lobe of pituitary gland (hypophysis
cerebri). The menstrual cycle is divided into 3 stages:
1. The menstrual phase: the fist 3-4 days of the cycle, during
which shedding and sloughing of the functional endometrial
layer occurs. The menstrual discharge contains epithelial
cells, connective tissue cells, blood and uterine secretion. By
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the end of this phase, the uterine mucosa is thin around 0.5
mm in thickness.
2. The proliferative phase occurs between the 5th and 14th day of
the cycle; it corresponds to the follicular phase of ovarian
cycle where the growing follicles secrete estrogen. Estrogen
stimulates the glandular cells in the basal layer to proliferate
and cover the shed area. The glands are long, straight and
narrow. By the end of this phase, the endometrium is about
23 mm thick.

3. The secretory phase or luteal phase occurs in 15th to 28th day


of the cycle; this corresponds to luteal ovarian phase. It starts
immediately after ovulation and depends on the formation of
progesterone producing corpus luteum. The epithelial cells
accumulate glycogen below their nuclei and the glands
become highly tortuous and full of secretion; the lamina
propria is edematous and the coiled arteries are elongated,
convoluted and extends to the superficial part of
endometrium. At this stage, the endometrium is 5 mm thick.
If fertilization takes place, the embryo is implanted to uterine
mucosa at this stage and the glandular secretion is used to
nourish the embryo.
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During pregnancy, the endometrium becomes thicker and the


embryonic trophoblasts secrete human chorionic
gonadotropin (HCG) which stimulates the corpus luteum to
continue progesterone progesterone secretion to inhibit the
contraction of myometrium.

If no fertilization occurs, corpus luteum degenerates and the


progesterone and estrogen blood level drops leading to constriction
of spiral arteries, ischemia, necrosis, liberation of
metalloproteinases, prostaglandin and nitric oxide, followed by
detachment of the functionalis. The blood vessels above the
constriction rupture and the bleeding starts as menstruation.
Summary of hormonal effects during uterine cycle
Stages of Pituitary Ovarian Dominant Endometrial
uterine cycle hormones events ovarian events
hormones
Proliferative FSH stimulates growth One of the Estrogen of Regeneration of
of a group of follicles growing follicles growing follicles uterine mucosa
reaches maturity affecting rest of
reproduct system
Secretory Estrogen LH surge Ovulation C Progesterone of C thickness of
Luteum formed Lut myom contr mucosa, gland
then degenerated secretion, coiling
Menstrual _ _ _ Shedding of zona
functionalis

Fertilization and implantation:


Fertilization is the fusion of male and female gametes producing
the zygote; it occurs in the lateral third (ampulla) of oviduct.
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The granulosa cells of corona radiata surrounding the newly


liberated mature ovum will be loosened by the acrosomal
enzymes of the sperm which also help the sperm head to
penetrate the zona pellucida.
The cell membrane surrounding the sperm head fuses with
the cell membrane of the ovum, and the sperm head enters
the ovum cytoplasm.
The process of fertilization stimulates the ovum to complete
its 2nd meiotic division and expel the 2nd polar body.
Fertilization is considered complete by intermingling of
ovum and sperm nuclear contents, the diploid number of
chromosomes is restored and the zygote is formed.
Successive mitotic divisions of the zygote lead to the
formation of the morula (compact collection of cells called
blastomeres); the morula covered by zona pellucid passes
passively to uterine cavity and will develop a central fluid-
filled cavity and reach the blastocyst stage.
The blastomeres in blastocyst are arranged into an inner cell
mass which will form the embryo and outer peripheral
trophoblasts which will form the fetal part of placenta.
On the 7th day after ovulation, the blastocyst reaches the
uterine cavity and implants itself on the dorsal or ventral part
of the body of the uterus by penetration through the uterine
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epithelium and lamina propria (interstitial implantation) in


the secretory phase of uterine cycle.
The trophoblasts multiply and differentiate into 2 layers: an
inner single layer of cuboidal cytotrophoblasts and an outer
thick layer of syncytiotrophoblasts where the cells fuse to
make multinucleated syncetium without cellular boundaries.
The trophoblasts become highly invasive; they erode the
endometrium at the site of implantation until the blastocyst is
completely embedded in the endometrium by the 9th day after
ovulation.
The inner cell mass forms the embryonic disc (ectoderm and
endoderm) which will form the embryo.
An extraembryonic mesoderm will appear covering the
embryonic disc and lining the inner surface of the
trophoblasts.
The future embryo is separated from the endometrium by the
chorion which is made of 3 cell layers: syncytiotrophoblasts,
cytotrophoblasts and the extraembryonic mesoderm.
If implantation occurs close to internal os, the placenta will
be formed between the fetus and the vagina and will be called
placenta previa. Delivery of the fetus will be by cesarean
section.
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Sometimes implantation occurs in uterine tube or


peritoneum; a condition will be called ectopic pregnancy.

The decidua:
Decidua is the term which describes the pregnant endometrium
where the fibroblasts of lamina propria increase in size, become
rounded and show the feature of protein-synthesizing cells.
Decidua is divided into 3 parts:
Decidua basalis is the part of endometrium lying between the
implanted blastocyst and the myometrium; it forms the
maternal part of placenta
Deciduas capsularis is the part of endometrium that covers
the blastocyst and separates it from the uterine cavity.
Decidua parietalis is the rest of the endometrium which is not
in direct contact with the embryo.

The placenta
The placenta is not part of the female reproductive system, but it is
a temporary organ, closely related to the female reproductive
system, since the placenta is the interface between the mother and
the fetus. It is a disc-shaped temporary organ, consists of a fetal
part (chorionic plate and chorionic villi) and a maternal part (the
decidua basalis).
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Parts of the placenta:


1. The fetal part (chorionic plate and chorionic villi)
The chorionic plate consists of embryonic connective tissue. It is
covered on its lower surface by two layers of epithelial cells, the
cytotrophoblasts facing the connective tissue, and the syncytial
trophoblasts on the free surface facing the maternal blood spaces.
The chorionic villi are finger-like projections from the chorion;
they might be free or anchored. The anchored villi penetrate and
erode the endometrium (decidua basalis) causing rupture of
maternal blood vessels and filling the intervillous spaces with
maternal blood. The free villi do not reach the decidua basalis but
will be floating in the intervillous spaces.
Types of the villi:
The primary villus is a solid extension of the chorion with
an inner core of cytotrphoblasts and syncytiotrophoblasts.
The secondary villi develop by invasion of the
extraembryonic mesenchyme into the cytotrphic core of the
primary villi. Later on small fetal blood vessels appear in the
connective tissue core.
In the mature placenta, each villus is composed of a core of
embryonic connective tissue containing Hofbauer cells (large
macrophages), branches of fetal blood (umbilical) vessels, and an
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inner layer of cytotrophoblasts and a superficial layer of


syncytiotrophoblasts.
2. The maternal part of the placenta
The maternal part of placenta is the decidua basalis at the site of
zygote implantation; at this site the dicidua undergoes decidual
reactions.
In the decidual reactions, the endometrial blood vessels become
dilated engorged with blood, and the stromal cells of endometrium
(decidual cells) become polygonal, filled with glycogen and lipid
droplets, and have the characteristics of protein-synthesizing cells
(secrete placental prolactin).
Decidua basalis supplies the arterial blood to and receives the
venous blood from intervillous spaces.
Functions of placenta:
1. Gas exchange, nourishment and excretory function
2. Protection through the placental barrier which efficiently
separates the maternal from the fetal vascular system.
Placental barrier is made mostly of fetal tissues:
The endothelium of fetal chorionic blood vessels
The basement membrane of endothelium
The chorionic fetal connective tissue
Cytotrophoblasts basement membrane
Cytotrophoblasts to the 4th month of pregnancy
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Syncytiotrophoblasts
3. Placenta acts as an endocrine organ secreting many hormones to
maintain pregnancy. Syncytiotrophoblasts secrete human
chorionic gonadotropin, placental prolactin, estrogen and
progesterone.
The vagina
The vagina is a fibromuscular tube devoid of glands. Its thick wall
consists of folded mucosa, muscularis and a wide fibrosa.
1. The mucosa:
a. The epithelium is non-keratinized stratified squamous, 150 - 200
m thick. The cells appear empty although they are rich in
glycogen due to estrogen effect. The glycogen is released into the
vaginal lumen, where bacterial action produces lactic acid to
acidify the mucosa and protect it.
b. The lamina propria consists of loose connective tissue rich in
elastic fibers and blood vessels and nerves. Large number of
lymphocytes, neutrophils and plasma cells are present.
The mucosa has only few naked nerve endings for pain sensation.
2. The muscularis consists mainly of longitudinal bundles of
smooth muscle fibers interspersed with elastic fibers (outer layer).
Some circular bundles may be seen next to the mucosa which
might be considered as the inner layer. The blood vessels present
especially in the deep part of musculosa.
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3. The adventitia is made of dense connective tissue rich in thick


elastic fibers. Adventitia is very rich in nerve supply and has an
extensive venous plexus; it unites the vagina with the surrounding
connective tissue.

The vaginal smears:


Cells obtained from the vagina or the cervix for cytological
evaluation which is important for:
1. The smear indicates the hormonal balance of the woman.
2. Might indicate an early stage of cancer.

External genitalia
The female external genitalia, a highly innervated area, composed
of: clitoris, labia minora containing the vestibule, labia majora, and
some associated glands that open into the vestibule.
The clitoris is composed of two erectile bodies that end in glans
clitoris; clitoris corresponds to the penis in the male in embryonic
origin and histology. It is covered by stratified squamous
epithelium.
The labia minora are two hairless skin folds covered with thin
skin containing sweat and sebaceous glands on both sides of the
folds. The connective tissue core is spongy and very rich in elastic
fibers.
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The labia majora are skin folds with a core very rich in adipose
tissue and a thin layer of smooth muscles. The inner surface is
hairless and covered with stratified squamous epithelium with very
thin keratinized layer. The outer surface is covered with stratified
squamous keratinized with coarse thick hairs. Sweat and
sebaceous glands are present of both sides of the labia.
The vestibule present between the two labia minora at the entrance
of the vagina. The urethra and the ducts of vestibular glands open
in the vestibule. Bartholin glands are two mucus-secreting glands
open on both sides of the vestibule and correspond to bulbourethral
glands in the male; when inflamed form bartholin cysts. There are
numerous minor mucus-secreting vestibular present around the
urethra and the clitoris.

Umbilical cord
The cord consists of two umbilical arteries and one centrally
located umbilical vein. Umbilical cord carries the oxygenated
blood from the mother to the fetus through the umbilical vein and
deoxygenated blood is returned to placenta through the umbilical
arteries.
Structure:
1. The cord is covered with simple squamous or simple cuboidal
epithelium (part of the amnion).
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2. The stroma of the cord consists of mucus connective tissue with


mucoid ground substance (Wharton`s jelly) which contains fine
collagenous fibers and large branched fibroblasts.
3. Has two umbilical arteries and one centrally located umbilical
vein.
4. Umbilical arteries have atypical structure; they have a wide
inner layer of longitudinally oriented smooth muscle fibers and an
outer thick layer of circularly arranged smooth muscles. No
internal elastic membrane.
5. The diameter of umbilical vein is larger than that of the artery.
It has a thin layer of longitudinally arranged muscle fibers and a
thick circular layer. Fine reticular fibers are present between the
muscle fibers.
The mammary gland
The mammary glands are modified skin glands; they are
compound tubuloalveolar glands meant to secrete milk to nourish
the newborn babies.
Before puberty, in girls, the mammary glands are composed of
lactiferous sinuses and lactiferous ducts. At puberty due to
estrogen action, breast enlarges due to increase in adipose and
connective tissue and increased branching of lactiferous ducts.
General structure of breast in adult female:
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Each gland is covered with skin showing a central light pink


area called areola which becomes permanently pigmented
after the first pregnancy; areola contains modified sweat
glands of Montgomery.
The nipple is an elevation made of dense connective tissue
and smooth muscles and lying in the center of the areola; it
receives the lactiferous ducts.
Each mammary gland consists of 15 - 25 compound
tubuloalveolar glands also called lobes.
Each gland or lobe is composed of stroma and parenchyma.
The stroma is made of thick interlobar fibrous connective
tissue septa which divide the gland into lobes, interlobular
septa, adipose connective tissue and connective tissue cells.
The parenchyma is composed of the duct system, secretory
alveoli and their epithelial lining and myoepithelial cells.
The mammary glands exhibit cyclic changes according to
female age and hormonal status.

The resting (inactive) mammary gland:


1. The stroma starts proliferation under the effect of estrogen
secreted at puberty. The stroma is made of thick dense
collagenous connective tissue septa rich in adipose tissue which
separates the gland into 15-25 lobes.
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The connective tissue surrounding the parenchyma is more cellular


than the interlobar CT septa; it contains large number of
lymphocytes and plasma cells which secrete immunoglobulin IgA
necessary for the babys passive immunity.
2. The parenchyma consists of isolated groups of interlobular and
intralobular ducts.
In the resting mammary gland, there are no distinguished
secretory alveoli.
The intralobular ducts are lined with simple cuboidal or
simple columnar epithelium with myoepithelial cells located
between their bases and the basement membrane.
The terminal interlobular (intralobular) ducts join together to
form the larger lactiferous ducts which dilate before opening
on the nipple to form the lactiferous sinuses.
The lactiferous duct is lined with stratified columnar or
stratified cuboidal which changes to stratified squamous
epithelium at the end of lactiferous sinus near the duct
opening.
At the time of ovulation and high estrogen blood level, there
is slight proliferation of the duct system as well as slight
increase in vasculature and hydration of the connective tissue
leading to slight swelling and enlargement of the mammary
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glands. These symptoms disappear at the start of


menstruation.

B. The mammary gland during pregnancy:


The mammary glands exhibit great proliferation as a result of
several hormonal actions such as estrogen, progesterone, and
prolactin.
The stroma shows increased vascularity and reduced amount
of intralobular connective tissue.
The parenchyma shows proliferation and branching of the
duct system due to placental estrogen, and the appearance of
secretory alveoli lined with simple columnar epithelium and
myoepithelial cells. Alveolar cells show apical fat droplets
and secretory vacuoles containing dense milk protein
granules. The alveolar cells start secreting colostrums which
is serous fluid rich in protein contents and low in lipid
contents secreted during the first 2 days after labor.
Myoepithelial cells are stellate in shape and located between
the alveolar cells and the basal lamina.
Breast cancer (carcinoma) arises from the epithelial lining of
lactiferous ducts.

C. The lactating (active) mammary gland:


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The stroma shows increased vascularity of the connective


tissue septa, and the intralobular connective tissue is highly
reduced.
The parenchyma shows elaboration and branching of the duct
system, and the lobules appear packed with ducts and alveoli.
By LM, the secretory alveoli exhibit different phases of milk
secretion, some alveoli are full and others are empty.
Accordingly, the lining epithelium differs from simple low
cuboidal in full alveoli to simple columnar in the empty ones
with myoepithelial cells between the lining epithelium and
the basal lamina.
By EM, the alveolar cells show the features of protein-
synthesizing cells such as abundant RER, well-developed
supranuclear Golgi complex, ribosomes, lysosomes and
mitochondria.

Milk secretion:
Milk is secreted by the lining cells of alveoli; it is a fluid that
contains the milk sugar (lactose) as well as the major milk proteins
caseins, -lactalbumin, immunoglobulin A, lipids, the monovalent
ions (sodium, potassium and chloride), citrate, calcium, and free
phosphate.
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The proteins and lactose are synthesized in Golgi complex then


secreted by exocytosis (merocrine); the milk lipids are neutral
triglycerides, membrane limited droplets secreted from the cell
apex by apocrine mode of secretion.
Hormonal control of milk secretion:
Prolactin stimulates the secretory alveoli to produce milk.
Prolactin release is stimulated by the babies sucking action.
Oxytocin stimulates the myoepithelial cell to contract and
expel the milk out of ducts and alveoli by stimulating the
milk-ejection reflex.
Sadness and disturbed psychological conditions of the mother
inhibits the milk-ejection reflex.

D. Mammary gland after menopause:


After menopause, due to absence of ovarian hormones, the
mammary glands undergo involution, reduction in size and atrophy
of secretory alveoli. Partial atrophy of the duct system and
interstitial connective tissue will take place.
194

The Special Sense Organs


195

The special sense organs


The eye
The eyes are the sense organs for sight, they are located in the
orbits; each eye consists of an anterior chamber, a small posterior
chamber, and a large vitreous chamber containing the vitreous
body.
The anterior chamber is separated from the posterior chamber by
the iris which regulates the size of pupillary aperture. The light
passes from the pupil to the retina through the refractive media:
the cornea, aqueous humor, lens and the vitreous body.
The eyeball is enclosed by three coats which are:
1. The outer fibrous protective coat including the cornea and the
sclera.
2. The middle vascular coat includes the choroid, ciliary body and
the iris.
3. The inner nervous coat includes the retina (inner nervous and
outer pigmented).

The outer fibrous coat


The cornea
The cornea forms the anterior transparent one sixth of the outer
fibrous coat.
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It is avascular and receives its nourishment by diffusion from the


aqueous humor in the anterior chamber and the adjacent blood
vessels in the sclera.
The cornea is composed of the following layers:
1. The epithelium is stratified squamous nonkeratinized and
consists of five to six layers of cells.
The basal layer rests on a straight basement membrane and shows
mitotic figures responsible for the high regenerative power of the
cornea after injuries. If the basal layer is destroyed, the epithelium
will heal by the underlying connective tissue leading to the
formation of corneal opacity.
The surface epithelium faces the external surface and has
microvilli extending into the protective tear film.
The epithelium is highly sensitive and very rich in free nerve
endings.
2. The corneal epithelium rests on the Bowman`s membrane
which is clear, thick (7-12 m), homogenous, acellular membrane,
made of collagen fibers. Its main function is to impart stability and
strength to cornea, and helps to protect against the spread of
bacterial invasion to the underlying tissue.
3. The substantia propria (the stroma) is the thickest layer of the
cornea. It is avascular and consists of about 60 layers of parallel
collagen bundles crossing each other at right angles, flattened
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fibroblast-like cells with cytoplasmic processes called keratocytes


and amorphous ground substance rich in the proteoglycan, lumican
containing keratan and chondroitin sulfates.
4. The Descemet`s membrane is a thick homogenous structure
composed of regularly arranged fine collagen fibrils in three
dimensional pattern. It is believed to be a basement membrane
produced by the corneal endothelium.
5. The endothelium consists of a simple squamous epithelium
covering the posterior surface of the cornea. Endothelial cells are
active in protein synthesis to maintain the basement membrane and
help pumping sodium ions into the anterior chamber thus helping
in corneal hydration for proper transparency and light refraction.
Keratoplasty: is the corneal transplant from one person to another.

The sclera
The sclera is the tough white opaque connective tissue coat
covering the posterior 5/6 of the eyeball. It is made of white
collagen fibers type I running in different directions, elastic fibers,
fibroblasts and few blood capillaries.
The sclera protects the internal delicate eye structures, helps
maintain the shape of the eyeball and provides insertions for the
eye muscles in its external surface (episclera) through the tenon`s
capsule.
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The part of the sclera perforated by the optic nerve fibers is called
lamina cribrosa; the connective tissue of the sclera fuses with the
epineurium covering the optic nerve.

The corneoscleral junction (Limbus):


It is an area of transition between the transparent cornea and the
opaque sclera; it is highly vascular and contains the canal of
schlemm which drains the fluid from the anterior chamber to the
episcleral veins. Limbus is considered as a stem cell reservoir for
the corneal epithelium. The following changes occur at the
corneoscleral junction:
At the junction the stratified squamous nonkeratinized
changes to stratified columnar of the bulbar conjunctiva.
The Bowman`s membrane of the cornea is replaced by
subcojunctival connective tissue.
The regular collagen bundles of the cornea are replaced by
the irregular bundles of sclera.
The Descemet membrane and the corneal endothelium stops.
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The middle vascular coat (Uvea)


It is the middle coat including the choroid, ciliary body and the iris.
1. Choroid:
The choroid is a highly vascular, pigmented connective tissue
which lies between the retina and sclera.
Choroid is attached to the sclera by a layer of loose connective
tissue called suprachoroidal lamina and is separated from the retina
by Bruch`s membrane.
Bruch`s membrane is a thin hyaline membrane separating the
choroid from the retina; it extends from the optic papilla to the ora
serrata. It is made of 5 layers: the basal lamina of
choriocapillaries, an outer layer of collagen fibers, network of
elastic fibers, an inner layer of collagen fibers and the basal lamina
of pigmented epithelium of the retina.
The main functions of choroid: to support and supply nourishment
to the retina, to absorb the excess light and to prevent the access of
harmful macromolecules to the retina.

2. The ciliary body:


The ciliary body is the thickened anterior expansion of choroid at
the level of the lens; at the corneoscleral junction, it makes a
continuous thick ring facing the inner surface of the anterior part of
the sclera.
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In transverse section, the ciliary body appears as a triangle; one


side facing the vitreous body, another side facing the sclera and the
third side faces the lens and the posterior chamber. Its apex is
continuous posteriorly with the choroid; its inner surface has
ciliary processes which give the zonule fibers to anchor the lens
capsule and keep it in place. Ciliary processes have loose
connective tissue cores with fenestrated capillaries and covered
with ciliary epithelium.
The LM examination reveals that ciliary body is composed:
The ciliary epithelium made of 2 layers of columnar cells:
deep pigmented layer continuous with the pigmented retina
and surface nonpigmented layer continuous with the nervous
retina. The lining cells secrete the aqueous humor in the
anterior chamber. The apices of nonpigmented epithelium
are bound together by tight junctions forming blood aqueous
barrier.
The stroma made of loose connective tissue rich in blood
vessels, elastic fibers and melanocytes.
The ciliary muscle formed of smooth muscles and arranged
in 3 directions: meridional, radial and circular. They are
inserted in the sclera, controlled by parasympathetic nerves
and important in visual accommodation.
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3. Iris:
Iris is a disc-shaped colored diaphragm with adjustable pupil
separating the anterior from the posterior chamber of the eye. It is
responsible for the eye color which depends on the number of
melanocytes in the stroma and the amount of melanin pigments in
melanocytes and in the pigment cells covering the posterior
surface.
Histology of the iris:
The anterior surface of the iris is irregular, rough with
grooves and ridges, more pigmented, and covered with a
discontinuous layer of fibroblasts and melanocytes.
The stroma is made of vascular pigmented connective tissue
and an underlying less vascularized
Its posterior surface is smooth, highly vascular and covered
by 2 layers of pigmented epithelium continuous with the
epithelium covering the ciliary processes; both layers are
heavily pigmented to prevent the passage of light into the
interior of the eye except through the pupil.
The iris has smooth muscles forming the sphincter and
myoepithelial cells forming the dilator pupillae muscles. The
fibers of the sphincter muscles are circular present at the
margin of the pupil and contract under the control of
parasympathetic nerve supply in response to bright light (the
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accommodation response). The cells of the dilator pupillae


are present at the periphery of the iris arranged radially and
contract in response to sympathetic stimulation if frightened
leading to dilatated pupils.

The lens:
The lens is highly elastic biconvex structure situated in the
posterior chamber, between the iris and the vitreous body and
encircled by the suspensory ligament and the ciliary processes.
The lens is highly flexible and able to change its curvature to focus
for near and far vision (accommodation), a feature that is lost by
the age progress due to hardening of the lens (presbiopia). The
lens has 3 elements: the capsule, the subcapsular epithelium and
the lens fibers.
The capsule is a thick homogenous, refractile, carbohydrate-
rich surrounding the whole capsule and coating the outer
surface of the epithelial cells. It is a very thick basement
membrane formed mainly of collagen type IV.
The lens epithelium is cuboidal epithelium covering the
anterior surface of the lens beneath the capsule; changes to
high columnar in the center or the equator of the lens, then
loose their nuclei and differentiate into lens fibers.
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The lens fibers are elongated, thin transparent fibers resulting


from differentiated lens epithelium.
At older age or in diabetics, the lens looses transparency and
become opaque (cataract), a condition where the lens should
be removed surgically and replaced by a plastic lens.

The vitreous humor (body):


The vitreous body is the gelatinous viscous transparent amorphous
material that fills the posterior compartment of the eyeball between
the lens and the retina. It consists mainly of water (99%),
hyaluronic acid, few fibers of type II collagen and the hyaloids
canal. Hyaloid canal indicates the site of the degenerated
embryonic hyaloids artery which used to run from the optic nerve
to posterior surface of the lens. It contains few cells which
synthesize collagen fibers and hyaluronic acid.
The main function of vitreous body is to transmit the light to retina
and stabilizes the lens and retina in place as well as helping in
retinal metabolism.

Note that:
The anterior chamber of the eye is bounded anteriorly by the
cornea and posteriorly by the ciliary body and iris, and
laterally on both sides by the limbus.
204

The posterior chamber is bounded anteriorly by the iris and


posteriorly by the lens and ciliary processes.
The aqueous humor passes from the posterior chamber to the
anterior chamber and drained through the canal of schlemm
which empties into the sclera veins. Obstruction of the
aqueous fluid leads to increased intra-ocular pressure
(glaucoma) which results in blindness if not treated.

The inner nervous coat (Retina)


Retina is the innermost layer lining the eyeball; it consists of 2
parts, posterior photosensitive and an anterior non-photosensitive
forming the inner lining of ciliary body and the posterior part of
the iris.
The neural part of the retina develops from the inner layer of the
optic cup, while the outer layer gives rise to the pigmented
epithelium.
The retina is composed of ten layers numbered from outside
inward:
1. The pigmented epithelium layer is a simple layer of cells with
basal nuclei and their cytoplasm is rich in melanin granules; it is
separated from the choroid by Bruch`s membrane. By EM, the
apices of cells have microvilli which project between rods and
205

cones, rich in mitochondria, RER, Golgi complex, lysosmes,


melanin pigments and residual bodies.
2. The rods and cones layer consists of thin elongated cells (rods)
and shorter but elongated neurons, the cones.
3. The outer (external) limiting membrane is not a true
membrane, but a narrow area formed by cellular contact and
junctional complexes between Muller cells (neuroglia) and rods
and cones.
4. The outer nuclear layer contains the cell bodies and nuclei of
rods and cones; their processes form
5. The outer plexiform layer is a synaptic layer containing nerve
processes and the synapses between the axons of rods and cones,
and the dendrites of the bipolar cells. It also contains the synapses
of short horizontal neurons.
6. The inner nuclear layer contains the bipolar cells that connect
the rods and cones to the ganglion cell layer. (Cell bodies of
horizontal, bipolar, amacrine and Muller)
7. The inner plexiform layer contains the synapses between the
bipolar cells and the ganglion cells. The processes of the inner
nuclear layer which convey the impulses to the ganglion cell layer
8. The ganglion cell layer consists of large ganglion cells whose
dendrites synapse with the bipolar cells (3rd order neurons).
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9. The nerve fiber layer consists of the unmyelinated axons of the


ganglion cells which form the optic nerve.
10. The internal limiting membrane is the most anterior layer of
the retina. It is made of the end processes of the Muller neuroglial
cells.

The rod cells:


The rod cells are thin elongated, rod-shaped cells which lie
perpendicular to retinal epithelium; the rod cell is composed of an
inner (basal) extension (an axon synapses with the bipolar cells),
cell body (containing the nucleus), and an outer (apical) elongated
cylindrical protrusion. Each apical protrusion is made of inner and
outer segment; the base of the outer segment is separated from the
top of inner segment by a constriction which contains a modified
cilium (9 peripheral doublets with no central singlets).
The outer segment is photosensitive and composed of stacked
membranous flattened disks which contain the visual purple
pigment or rhodopsin.
The inner segment is very rich in glycogen, RER, ribosomes and
numerous mitochondria lying just below the constriction. The
inner segment actively synthesizes proteins, some of which is sent
and incorporated into the newly assembled flattened disks of the
outer segment.
207

The cone cells:


The cone cells are elongated but shorter than the rod cells; there
are about 6 million cone cells in the human retina. Like rod cells,
the cone cell is composed of basal extension (an axon), cell body
and apical protrusion composed of an inner and an outer segment.
The outer segments contain flattened membranous disks which
uniformly contain the newly synthesized proteins.
The cone cells contain the cone pigment called iodopsin; according
to iodopsin content, the rod cells are classified functionally into 3
types depending upon the presence of different pigments in the
cone absorbing the light most efficient at red, blue or green
wavelength. No morphological differences.
The fovea centralis is an area of the retina surrounding the optic
disc and provides the highest visual acuity; it is made of cone cells
only.
The basal segments of rods (rod spherule) and cones (cone pedicle)
synapse with the bipolar cells in the outer plexiform layer.

The cell types of the retina:


There are three main cell types in the retina which are: the
photoreceptors, the bipolar and the ganglion cells. In addition to
the three main types of cells, there are other cells such as:
208

Horizontal cells are large branched cells which synapse with


rods and cones.
Amacrine cells are small neurons which synapse with the
ganglion cells and the bipolar cells.
Supporting cells are neuroglial cells such as astrocytes,
microglia and Muller cells which are branched cells whose
processes extend from inner to outer limiting membrane.

The accessory structures of the eye


The conjunctiva:
The eyelid
The lacrimal gland
The conjunctiva:
The conjunctiva is a transparent mucous membrane which lines the
eyelid and the anterior part of the up to the cornea. The lining
epithelium is stratified columnar and the lamina propria is loose
connective tissue. Its main function is lubrication and antibacterial
protection.

The eyelid:
For each eye, there are two movable folds of connective tissue
covered by skin, the upper and lower eyelids.
Structure of the eyelid:
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1. The inner surface is lined with stratified columnar epithelium


(palpebral conjunctiva). The outer surface is covered with thin
skin (stratified squamous keratinized) with few fine hairs; its
hypodermis is devoid of fat.
2. The eyelid contains eyelashes (modified hair follicles), modified
long sebaceous glands (meibomian or tarsal glands), sweat glands
and bundles of orbicularis oculi muscle and levator palpebrae
superioris (skeletal muscles).
3. The tarsal plate is made of dense collagen connective tissue
containing meibomian glands which are not connected to the hair
follicles. They secrete oily secretion.
4. The glands of Moll are modified sweat glands present posterior
to the eyelashes.
5. Zeis glands are small modified sebaceous glands connected to
the follicles of eyelashes.

The lacrimal gland:


It is the tear-secreting gland, located in the anterior superior part of
the orbit. It is a compound tubuloalveolar gland, and consists of
pure serous acini lined by simple cuboidal epithelium with
myoepithelial cells. The glands secrete tears which moisten the
cornea and conjunctiva; tears are rich in lysozymes which have
strong antibacterial effect. Tears are drained into the lacrimal
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canaliculi to lacrimal sac then to nasolacrimal duct which opens


into nasal cavity.

The ear
The ear is the organ of hearing and equilibrium; it is composed of
external, middle and internal parts.
The external ear:
The external ear is composed of auricle, external auditory meatus
and tympanic membrane.
The auricle receives the sound waves to be transmitted to external
auditory meatus. The auricle is composed of elastic cartilage
covered on both sides by thin skin containing hair, sebaceous and
sweat glands.
The external auditory meatus is a canal that extends from the
surface to the tympanic membrane; its outer one third is made of
elastic cartilage and its inner two thirds are made of bone. It is
lined with skin; in the outer third the skin has hairs with sebaceous
and modified sweat glands called ceruminous glands which secrete
the protective wax (cerumen).
The tympanic membrane or ear drum is an oval membrane that
separates the external from the middle ear. It is composed of:
An external surface covered with stratified squamous
keratinized epithelium.
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A middle layer (tonica propria) composed of dense


connective tissue.
An internal surface covered with simple squamous or low
cuboidal epithelium.

The middle ear:


The middle ear lies in the tympanic cavity of the temporal bone.
The tympanic membrane forms its lateral wall and it is separated
from the inner ear by a bony wall which has two openings, the oval
and the round windows. It communicates with the nasopharynx by
the Eustachian tube which might be occluded by enlarged lymph
nodes in nasal infection causing temporary hearing loss.
The middle ear and its contents are lined with simple squamous
cuboidal epithelium. The lamina propria is adherent to the
underlying periosteum.
The middle ear contains 3 bony ossicles (malleus, incus, and
stapes), 2 muscles (tensor tympani and stapedius) and the chorda
tympani nerve which traverse the tympanic cavity.
The bony ossicles are small tiny bones that transmit the vibration
of tympanic membrane to perilymph of internal ear.
The malleus is the largest auditary bone, its handle articulates
with tympanic membrane on one side and with the incus on
the other side.
212

The incus is the middle bone; it articulates with malleus and


stapes.
The stapes articulates with the incus and inserts its base into
the membrane of the oval window.
The tensor tympani muscle is attached to the malleus and stapedius
muscle is attached to stapes. Both muscles are striated and
contract on hearing loud sounds.

The inner ear (Labyrinth)


The inner ear or labyrinth is composed of bony labyrinth and a
membranous labyrinth; it lies in the temporal bone. The
membranous labyrinth is a delicate closed system of membranes,
protected and located within the bony labyrinth. The space
between the bony and membranous labyrinth is filled with
perilymph and the membranous labyrinth is filled with endolymph.
Perilymph is tissue fluid similar to CSF, while endolymph has a
high potassium and low sodium content.
The inner ear has the auditory and the vestibular receptors; each
one is located in bony and membranous labyrinth forming the
auditory and vestibular systems. The auditory system is
responsible for hearing while the vestibular system is responsible
for equilibrium functions.
213

The bony labyrinth is filled with perilymph and contains the


membranous labyrinth; it includes cochlea, vestibule and 3
semicircular canals.
The membranous labyrinth is composed of series of
membranous sacs and tubes filled with endolymph; it
includes cochlear duct (in cochlea), utercle and saccule (in
the vestibule) and 3 membranous semicircular canals in the 3
bony semicircular canals.

The auditory system


The auditory apparatus is composed of the bony labyrinth, cochlea
and the membranous labyrinth, cochlear duct.
The cochlea or bony labyrinth
The cochlea looks like a snail shell, it is a spiral bony canal that
makes 2 turns around a central axis called modulus; the lower
turns are wider than the apical turns. It contains and protects the
membranous labyrinth cochlear duct.

The membranous labyrinth


The lumen of the cochlear canal is formed of 3 chambers, scala
vestibuli, scala media (cochlear duct) and scala tympani. The scala
vestibuli and scala tympani contain perilymph, while the scala
media contains endolymph and the organ of Corti.
214

The cochlear duct


The cochlear duct is the membranous labyrinth, triangular in cross
section, containing organ of Corti , filled with endolymph and is
surrounded by perilymph in scala vestibule and scala tympani.
Vestibular membrane lies between the cochlear duct and scala
vestibule, and the basilar membrane separates the cochlear duct
from scala tympani. The vestibular membrane (Reissners
membrane) forms the roof of cochlear duct; it is lined with 2 layers
of simple squamous epithelium with the basal lamina in between.
The basilar membrane forms the floor of the cochlear duct and is
lined by one layer of simple squamous epithelium; it extends from
the bony spiral lamina to the spiral ligament. The outer border of
the cochlear duct is made by the stria vascularis (unuasually
vascularized cuboidal epithelium of spiral ligament).

The organ of Corti

The organ of hearing (the organ of Corti) is located in the scala


media of the inner ear resting on the basilar membrane which is a
thick layer of amorphous substance which separates it from the
underlying scala tympani. It is composed of hair and receptor
cells.

1. Inner and outer pillar cells are supporting cells found on


either sides of the tunnel of Corti.
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2. Inner and outer phalangeal cells are columnar cells present on


both sides of pillar cells. They rest on the basilar membrane
and have apical indentation
3. Inner hair cells are neuroepithelial cells present as a single
layer of goblet-shaped columnar cells lining the inner side of
tunnel of Corti. They have basal nuclei and apical stereocilia
which are embedded in the tectorial membrane.
4. Outer hair cells are arranged as 5 layers of specialized
neuroepithelial goblet-shaped (cupshape) cells with basal
nuclei and stereocilia embedded in the tectorial membrane.
They line the outer border of tunnel of Corti.
5. The tectorial membrane is a glycoprotein-rich non-cellular
structure secreted by the cells of spiral limbus where the
stereocilia of the outer hair cells are embedded.
6. Nerve fibers of the auditory components of 8th cranial nerve
make synaptic contacts with the hair cells.

Mechanism of hearing

Sound waves are collected by the auricle, reach the tympanic


membrane and initiate vibrations that are transmitted through
the bony ossicles of the middle ear to the oval window.
Vibrations of the oval window are transmitted to the
perilymph in the scala vestibuli and across the vestibular
membrane to the endolymph of the cochlear duct. Such
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induced pulsations in the endolymph will displace the basilar


membrane on which the organ of Corti lies and alter the
relationship of the tectorial membrane, which overlies the
organ of Corti, to the hairs of the hair cells.
Thus, bending or stretching of the hairs acts as a stimulus to
the hair cells, causing release of a chemical neurotransmitter,
generation of a receptor potential, and subsequent
development of an action potential in the peripheral
processes of bipolar neurons of the spiral ganglion. The
central processes of bipolar neurons constitute the auditory
component of the eighth cranial nerve, which projects
centrally to the cochlear nuclei. In man, the cochlea and the
organ of Corti follow a spiral course of two and one half
turns.
It is believed that the hair cells in the lower turns respond
best to high frequency sounds, whereas those of the upper
turns respond best to low-frequency sounds. Exposure to
excessively loud sound as occurs in discos and around jet
engines results in damage to hair cells in the lower turns of
the cochlea (high-tone deafness).

The vestibular system (apparatus)

The vestibular apparatus is composed of bony labyrinth and


membranous labyrinth.
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The bony labyrinth is composed of:

A central part lying in the posterior part of the cochlea,


anterior to semicircular canals, called the vestibule. On the
lateral wall of the vestibule, there are oval and round
windows.
Semicircular canals are 3 canals oriented in 3 planes
perpendicular to each other, lateral, superior and posterior;
they open into the posterior part of the vestibule.

The membranous labyrinth

The membranous labyrinth lies in the bony labyrinth, composed of


utricle and saccule, connected by a Y-shaped endolymphatic duct,
and the semicircular ducts lying in semicircular canals. It is filled
with endolymph and surrounded with perilymph; it is lined with
simple squamous epithelium and neuroepithelium (macula for
equilibrium).

Macula

Macula is made of specialized neuroepithelial cells responsible for


equilibrium; it is made of hair cells (receptors), supporting cells
and otolithic membrane.

Type I hair cells which are goblet or flask-shaped with


stereocilia and kinocilium (a true cilium) on their free
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surfaces; their bases are surrounded by afferent nerve endings


of the vestibular division of 8th cranial nerve.
Type II hair cells are receptor columnar cells with apical
stereocilia and a kinocilium which are embedded in otolithic
membrane. Their bases are surrounded by afferent and
efferent nerve endings of the vestibular part of 8th cranial
nerve.
Supporting cells are columnar cells located between the hair
cells; they have short apical microvilli.
Otolithic membrane is a thick gelatinous membrane
composed mainly of calcium carbonates (and proteins)
crystalline bodies (otoliths or otoconia); it serves as an
embedding site for stereocilia and kinocilia of hair cells.

Semicircular ducts

The semicircular ducts are 3 membranous ducts located in the 3


bony semicircular canals (lateral, superior and posterior) located
perpendicular on each other. They are lined with simple squamous
epithelium and neuroepithelium (crista ampullaris).

Crista ampullaris

Crista ampullares are present in the ampullae of each semicircular


basal dilatation. Their structure resembles that of macula; they are
composed of 2 types of receptor hair cells and supporting cells.
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Stereocilia and kinocilia are embedded in a gelatinous protein-


polysaccharide mass called cupula. The main function of cupula is
equilibrium in rotational and angular movements.

Position and Movement (Vestibular Sensations)

The neuroepithelial component of the utricle and saccule


provides information regarding static equilibrium and
position of the head in space.
Gravitational pull acts on the otoconia on the surface of the
macula, and the hair tufts of underlying neuroepithelial hair
cells are thus stimulated.
The apical processes of receptor cells of crista ampullares are
embedded in a dome-shaped, gelatinous protein-
polysaccharide mass, the cupula.
The cupula swings from side to side in response to currents in
the endolymph bathing it.
Movement of the cupula bends or deforms the hairs of
receptor cells which are embedded within it and thus
modifies the rate of impulse discharge from these receptor
cells.
Each crista is stimulated by movements occurring in the
plane of its semicircular canal.
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Stimuli from the vestibular sense organs travel by way of the


peripheral processes of the bipolar neurons of the ganglion of
Scarpa.
The central processes form the vestibular component of the
eighth nerve. Although we are normally not aware of the
vestibular component of our sensory experience, this
component is essential for the coordination of motor
responses, eye movements, and posture.
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The Central Nervous System


(CNS)
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The central nervous system (CNS)


The nervous system is divided into central nervous system (CNS),
composed of brain and spinal cord, and peripheral nervous system
(PNS), composed of nerves and ganglia outside the CNS.
The distant parts of the nervous system are linked together via
tracts of nerve fibers. These tracts might be ascending (sensory)
or descending (motor) pathways. Both ascending and descending
pathways decussate during their course, thus carrying information
from or to the contralateral side of the body.
The brain is divided into:
Forebrain (prosencephalon)
Midbrain (mesencephalon)
Hind brain (rhombencephalon).

The prosencephalon is further subdivided into, telencephalon


(cerebral hemispheres) and diencephalon (mainly thalamus and
hypothalamus).

The rhombencephalon includes metencephalon (pons and


cerebellum) and myelencephalon (medulla oblongata).

The brain stem consists of medulla oblongata, pons and


midbrain.
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The brain stem is very important because it contains the fiber


tracts (sensory and motor) linking brain and spinal cord,
centers controlling respiratory and cardiovascular systems,
and origin or termination of cranial nerves.
Anatomically, the telencephalon consists of two cerebral
hemispheres linked by a heavy bundle of association fibers called
corpus callosum. Each cerebral hemisphere is divided into four
lobes and its surface is highly folded or convoluted forming gyri,
sulci and fissures.
Histologically, the cerebrum is composed of:
A surface layer of grey matter forming the cortex,
A deep layer of subcortical white matter containing fiber
bundles (projection, association, commissural),
Several grey matter nuclei embedded deeply in the white
matter (the basal ganglia).

Cerebellum is the largest part of hindbrain; it lies on the dorsal


aspect of the hindbrain overlying the fourth ventricle.
Histologically, the cerebellum consists of:
Superficial layer of grey matter, the cortex
A deeper layer of white matter
The cerebellar nuclei which are embedded deeply in the
white matter.
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Function of cerebellum:
Maintenance of equilibrium
Motor coordination
Regulation of muscle tone and activity.

Spinal cord
The spinal cord is a long cylindrical column of nervous tissue,
encased in the vertebral column; it extends from foramen magnum
of skull to the intervertebral disc between L1 and L2. The spinal
cord is composed of two main parts:
An inner core of grey matter made of an H-shaped central
core surrounded by an outer layer of white matter.
An outer layer of white matter containing the fiber tracts of
both ascending and descending pathways.
The cord bears thirty-one pairs of spinal nerves formed of sensory
(dorsal) and motor (ventral) roots, and is covered by meninges.
The proportion of grey to white matter differs according to the
segment level of spinal cord and the number of muscles innervated
by that segment.
In cross section, the spinal cord appears oval in shape, composed
of 2 symmetrical halves separated posteriorly, partially by the
posterior (dorsal) median septum and anteriorly by the deep
median anterior (ventral) fissure. The marginal glial membrane is
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the most peripheral part of spinal cord; it is formed of processes of


astrocytes and lacks the nerve fibers.

The meninges
The spinal cord is covered by meninges; dura matter is the
outermost, followed by the arachnoid then the pia matter
which is the innermost.
The dura matter which is the thick outermost layer of the
meninges. It is made of dense fibrous connective tissue.
Pia matter is a fibrous membrane attached to spinal cord,
from which connective tissue septa carrying blood vessels
penetrate the white and grey matter.
When the dorsal root fibers enter the cord and the ventral root
fibers leave the cord, they lie in the subarachnoid space.
When the root fibers exit through the intervertebral foramina,
the arachnoid matter disappears quickly, while the dura
matter continues over them as epineurium.

The grey matter


The grey matter is composed of two large lateral masses
connected by the grey commissure, in which lies the central
canal which is largely obliterated in adults.
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Each lateral grey mass has a dorsal grey horn or column, a


ventral grey horn or column and an intermediate grey area (in
thoracic segments).
The shape of grey matter varies in different parts; the ventral
horns are widest in the cervical and lumbar enlargements
where the anterior horn cells innervating the muscles of the
upper and lower limbs are located.
The ventral horns are narrowest in thoracic segments.
The grey matter (neuropil) contains neuron cell bodies with
their dendrites and the initial segments of their axons,
unmyelinated nerve fibers, the termination of myelinated
nerve fiber tracts and numerous blood vessels. The grey
matter also contains groups of nerve cell bodies having the
same function called nuclei.

Motor nuclei of dorsal horn


The dorsal horn is made of small multipolar sensory neurons which
receive and process the incoming sensory input.
1. The substantia gelatinosa is the uppermost large pale area which
lies at the tip of dorsal grey column; it is an important relay station
for impulses of pain and temperature carried by the lateral
spinothalamic tracts. It is present in all segments of spinal cord.
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2. The nucleus proprius or the main sensory nucleus contains the


nerve cell bodies of the second order neurons for the sensory
pathway of crude or simple touch. It is present in all segments of
spinal cord.
3. Clark`s nucleus dorsalis contains the nerve cell bodies for the
second order neurons for the proprioceptive sensory pathway to the
cerebellum. It lies at the lower medial part of the dorsal horn of T1
to L2 segments (in some books C8 to L3).

Motor nuclei of the ventral horn


The ventral horn of the cervical and lumbar segments is broad to
supply the muscles of the upper and lower limbs, while it is narrow
and slender in thoracic segments. The ventral horn nuclei contain
large multipolar neurons which have Nissl bodies in the soma and
dendrites, large nucleus and prominent nucleolus. The axons of
these anterior horn cells emerge in groups from the anterior horn
cells to form the ventral roots.
There are motor nuclei which present in all segments, while other
nuclei are present only in cervical and lumbar levels. The nuclei of
ventral horn contain large-sized multipolar lower motor neurons
which form the second order neurons of somatic motor pathways.
Nuclei present in all levels such as: postero-medial, antero-
medial and antero-lateral.
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Nuclei present in cervical and lumbar segments only such as:


central and postero-lateral.

Motor Nuclei of the lateral horn


The lateral horn is present as a lateral extension between the
anterior and posterior horns in thoracic and upper lumbar 2
segments of spinal cord; it contains small multipolar motor
sympathetic neurons whose axons constitute preganglionic
sympathetic nerve fibers.

Associative nuclei
The associative nuclei are small multipolar neurons with short
axons; they are present in the grey matter of all segments of spinal
cord. They are important in local spinal cord reflex arcs and in
forming the short associative tracts; the associative nuclei are of
two types:
Commissural neurons which are present around the central
nuclei and their axons cross to the opposite side.
Intersegmental neurons which are also located around the
central canal and their axons ascend or descend several
segments in the same side.
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The white matter


The white matter appears white in fresh state; it is composed
of bundles of myelinated and few unmyelinated nerve fibers,
neuroglia (mostly oligodendrocytes which produce myelin in
CNS), and connective tissue septa containing blood vessels
coming from the pia matter.
Dorsal roots (incoming sensory fibers) are attached to the
dorsolateral surface of the cord (dorsolateral sulcus), while
the ventral roots are attached to the ventrolateral surface
(ventrolateral sulcus).
In relation to these sulci, the white matter is divided into
dorsal white columns, lateral white columns, and ventral
white columns.
A group of the nerve fibers in the white matter is called a
tract. Each tract has a definite origin and termination and a
specific function.

Fiber tracts of the spinal cord


A tract is formed of axons of neurons serving a common function.
It is named according to the site of origin, termination, general
location or according to distinctive characteristics e.g. lateral
spinothalamic tract. The ascending tracts serve sensory functions
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while the descending tracts serve motor functions. The spinal cord
tracts are classified into short and long tracts.
Short tracts:
The short tracts begin and terminate in the spinal cord whether
ascending or descending and function as associative and
coordinating tracts; they are:
1. Fasiculus proprius: lies just outside the gery matter surrounding
it like a ring, ascends or descends for few segments and
coordinates the functions of different segments of the spinal cord.
2. Comma-shaped tract lies in the posterior white column between
the gracile and cuneate tracts of the cervical and upper 6 thoracic
segments. This tract carries the prorioceptive fibers to the anterior
horn cells in the upper half of the body.
3. The septo-marginal tract is found in the posterior column along
the posterior median septum of the lower 6 thoracic, lumbar and
sacral segments. It carries prorioceptive fibers to the anterior horn
cells of the lower half of the body.
4. Lissauer`s tract fibers arise from small cells in the dorsal root
ganglia and pass through the posterior root to the spinal cord.
They carry pain and temperature sensation and relay in substantia
gelatinosa.
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Long tracts
The long tracts of spinal cord might be ascending or descending.
A. Ascending tracts:
1. Posterior column system composed of fasiculus gracilis
(medially) carrying impulses from the lower parts of the body
(lower limbs), fasiculus cuneatus (laterally) carrying impulses from
the upper parts of the body (upper limbs).
They mediate fine tactile discrimination (2-point tactile), vibration
sense, and conscious recognition or position sense (joint and
muscle sense).
They receive input from the nerve endings: Pacinian`s and
Meissner`s corpuscles, joint receptors, muscle spindles and Golgi
tendon organs.
Their first order neurons are located within the dorsal root
ganglia; the fibers enter the dorsal funiculus and ascend through
the entire length of the cord without interruption. These fibers end
in lower medulla at the corresponding nuclei (nucleus gracilis and
nucleus cuneatus).
Second order neurons arise from these nuclei, cross the midline
and form the medial lemniscus whose fibers terminate in the
ventralis posterolateralis (VPL) nucleus of thalamus. From the
latter nucleus, third order neurons project to the postcentral gyrus
of the cerebrum.
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In pernicious anemia and tabes dorsalis, the posterior column


funiculus is affected and the patient cannot perceive the vibration
of a tuning fork and cannot determine the position of toes and
fingers with closed eyes.
2. The spinothalamic tracts: They run in the ventral (ventral
spinothalamic tract) and lateral white column (lateral
spinothalamic tract). They mediate the light or crude touch
(ventral), pain and temperature (lateral) sensation. The first order
neurons are located in the dorsal root ganglia, which are projected
to the dorsal horn of spinal cord and then to VPL of thalamus.
From thalamus a third order neuron is projected to postcentral
gyrus of the cerebrum.
3. Spinocerebellar tracts: consist of dorsal and ventral
spinocerebellar tracts, they receive information through the nerve
endings muscle spindle, Golgi tendon organ and pressure
receptors. They are located in the dorsolateral and dorsoventral
surface of the cord; they consist of a two-order neuron pathway.
Some fibers of the posterior column synapse on the cells of dorsal
nucleus of Clarke in the same side (ipsilateral) of the cord, then to
the cerebellum.
Dorsal spinocerebellar tract reaches the cerebellum via the inferior
cerebellar peduncle (restiform body). The ventral spinocerebellar
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tract enters the cerebellum via the brachium conjuctivum (superior


cerebellum peduncle).

** Proprioceptive impulses from the cervical levels (upper limbs)


ascend in the fasiculus cuneatus to terminate in the accessory
cuneate nucleus just lateral to the main cuneate nucleus. Then
proprioceptive impulses are projected to the cerebellum via the
direct arcuate fibers via the ipsilateral restiform body. This
cuneatocerebellar tract is equivalent to dorsal spinocerebellar tract.
4. Spino-olivary tracts
These tracts carry proprioceptive impulses to cerebellum. The
axons from dorsal root ganglia enter the spinal cord and synapse
on 2nd order neurons in gracile and cuneate nuclei. Axons of
second order neurons cross the midline and ascend as spino-olivary
to synapse on 3rd order neurons in inferior olive of medulla. Axons
of 3rd order neurons cross the midline and enter the cerebellum
through the inferior cerebellar peduncle.
5. Spino-tectal tract is composed of fibers projecting from the
spinal cord as a crossed tract adjacent to the lateral spinothalamic
tract and terminating in the deep layers of superior colliculus. This
tract may have a role in transmission of tactile, thermal and pain
sensation.
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6. Spino-vestibular tract is composed of few uncrossed fibers


ascending from the grey matter of spinal cord and terminating in
the lateral and inferior vestibular nuclei.

B. Descending tracts:
1. Corticospinal tracts are concerned with the control of the
voluntary skilled motor movements especially of the limbs. They
originate from pyramidal neurons located in the primary motor
cortex (area 4), premotor cortex (area 6) and the postcentral cortex.
Betz cells (giant pyramidal cells present in the primary motor area
of frontal lobe) give rise to the largest diameter axons of
corticospinal fibers. They become fully myelinated by the end of
second year. The lateral corticospinal tract (80%) is larger and
more important than the smaller ventral corticospinal tract (20%).
Their fibers leave the cerebral cortex through the corona radiata,
then the internal capsule, the crus cerebri then through the pons to
the ventral surface of medulla where they form large masses called
pyramids. The lateral corticospinal tract crosses at motor or
pyramidal decussation at the caudal medulla, while the fibers of
the ventral tract cross at the level of their termination. In spinal
cord, the lateral corticospinal tract lies in the dorsal quadrant of the
lateral funiculus, while the ventral lies in the ventral funiculus,
lateral to the ventral median fissure. Both tracts terminate on the
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interneurons which synapse upon the motor neurons of the anterior


horn cells, but the ventral corticospinal tract ends at the
midthoracic segment.
2. Rubrospinal tract lies ventral to the lateral corticospinal tract
and arises from the contralateral red nucleus of midbrain
tegmentum. It controls the spinal motor activity, the flexor tone.

3. Tectospinal tract arises from the midbrain superior colliculus,


passes to spinal cord and lies near the ventral median fissure. It is
crossed, and ends in the cervical segments. This tract controls the
head and eye movements through the reflex movements in
response to visual stimuli.

4. Vestibulospinal tract arises from the ipsilateral vestibular


nuclei in pons and medulla, descends to spinal cord and lies in the
ventral funiculus. It controls the posture and balance and the
extensor muscle tone.

5. Reticulospinal tracts are two types: medullary and pontine


reticulospinal. The medullary reticulospinal tract descends in the
anterolateral column; they inhibit extensor and facilitate the flexor
motor neurons.
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The pontine reticulospinal tract descends in medial to medullary


tract; they facilitate extensor and inhibit flexor motor neurons.
Both tracts receive strong sensory and descending excitatory
cortical input, but the excitatory cortical input predominates in the
medullary nuclei.

6. Sulcomarginal tract is the continuation of the medial


longitudinal into spinal cord of all segments.

Cerebellum
Cerebellum (hind brain) does not make part of the brain stem from
which it is separated by the 4th ventricle and connected to brain
stem by 3 pairs of cerebellar peduncles. Its main function is to
regulate and subconscious fine tuning of the motor movements and
to coordinate the contraction movement of the different muscle
groups.
The cerebellum lies in the occipital region and is covered by
tentorial cerebelli.
Cerebellum is a highly folded structure with pia matter extending
down between the folds.
Each fold or folium has an outer cortex of grey matter and an inner
central layer of white matter made of nerve fibers.
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The layers of grey matter:


1. The outer molecular layer which is the most superficial and is
largely made of unmyelinated nerve fibers with scattered small
neuron cell bodies and neuroglial cells. The neurons of this layer
are small stellate association neurons and basket cells with short
dendrites and long axons with basket-like arborizations around the
Purkinje cells.
2. The Purkinje cell layer lies in the middle between the outer
molecular layer and the inner granular layer.
The Purkinje cells are large multipolar, Golgi type I neurons,
pyriform or flask-shape and arranged as a single layer.
The dendrites of Purkinje cells extend into the external molecular
layer where they synapse with axons of molecular layer, the
climbing fibers and the association neurons of the molecular layer.
Their axons extend down through the granular layer to the white
matter to the deep cerebellar nuclei and vestibular nuclei. These
are the efferent fibers of the cerebellum.
Note that all the incoming fibers to cerebellar cortex synapse
indirectly on Purkinji cells.
3. The inner granular layer is formed of darkly-stained cells,
atypical small multipolar neurons with dark nuclei and very little
cytoplasm. They have few short dendrites and long axons which
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pass perpendicular into the molecular layer, send collaterals and


synapse with the dendrites of Purkinje cells in the molecular layer.

The white matter:


The white matter of cerebellum include commissural, association,
efferent and afferent fibers.
The efferent fibers are the axons of Purkinje cell layer
The afferent fibers are: the mossy fibers which end on the
granular cell layer, the climbing fibers arising from the
inferior olive and end on dendrites of Purkinje cells.
Recurrent collaterals arise from the axons of Purkinje cells.
The deep cerebellar nuclei:
1. Dentate nucleus
2. Emboliform nucleus
3. Globose nucleus
4. Fastigial nucleus

The cerebellar peduncles:


There are three cerebellar peduncles connecting the cerebellum to
the brain stem; each peduncle has both afferent and efferent fibers.
The superior cerebellar peduncle has afferent fibers in the
ventral spinocerebellar tract and tectocerebellar tract, and
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efferent fibers in the dentatorubrothalamic tract and


fastigiobulbar fibers.
The middle cerebellar peduncle which contains afferent
fibers in the pontocerebellar tract and efferent fibers in the
cerebellopontine tract.
The inferior cerebellar peduncle contains efferent fibers in
the fastigiobulbar tract and direct cerebellovestibular fibers.
Its afferent fibers are coming through: dorsal spinocerebellar
tract, ventral external arcuate fibers, dorsal external arcuate
fibers, reticulocerebellar fibers, olivo-cerebellar and
vestibulocerebellar fibers.

Cerebrum
The cerebrum is composed of two cerebral hemispheres connected
together by the corpus callosum. Each hemisphere consists of
outer convoluted cortex of grey matter and an inner white matter
composed of fibers and neuroglia.
The grey matter of the cerebral cortex consists of a number of
layers of neuron cell bodies of different shape and sizes. These
layers are named according to the appearance of the cells. Most of
these are association cells, they receive fibers from various parts of
the cortex and their axons pass to other parts of the cortex. Axons
of the large pyramidal cells of the motor cortex (upper motor
240

neurons) terminate indirectly on the motor neurons of the brain


stem and on the anterior horn cells in the spinal cord.
The layers of cerebral cortex are from superficial to deep layers:
I. Molecular layer made of small horizontal cells of Cajal and the
dendrites of stellate and horizontal neurons and axons of granular
cells. The fibers run parallel to the surface as well as in other
directions.
II. Outer granular made of densely-packed small pyramidal cells.
III. Outer pyramidal layer made of medium-sized pyramidal cells
which increase in size in the deep part of the layer.
IV. Inner granular layer made of small stellate cells.
V. Inner pyramidal layer made of large pyramidal cells with long
dendrites running towards the molecular layer and their axons
towards the pyramidal tract. Betz cells are giant pyramidal cells;
they are a landmark for the precentral motor area.
VI. Polymorph layer is made of irregularly shaped neurons.
The areas of cerebral cortex:
1. The precentral motor area
2. The sensory (poscentral) area
3. The visual area
4. The olfactory area
The fiber design of cerebral cortex:
1. Radial fibers
241

2. Horizontal fibers
3. Efferent fibers: pyramidal tract, corticopontine,
corticothalamic, fibers to basal ganglia, red
nucleus, substantia nigra, inferior olive and
gracile and cuneate nuclei.
4. Thalamocortical afferent fibers
5. Association fibers.

The basal ganglia:


These ganglia are groups of cells located in the white matter of
cerebral hemispheres. They include corpus striatum (caudate and
lentiform), amygdaloid nuclei and claustrum.

The ventricles:
The ventricles include the lateral ventricles in cerebral
hemispheres, third ventricle in midbrain and 4th ventricle in
medulla and pons. These ventricles are continuous with the central
canal of spinal cord and contain cerebro-spinal fluid (CSF).

Choroid plexus
The central canal and the ventricles of the CNS are lined with
ependymal cells. These cells are covered externally with pia
matter and constitute the vascular tela choroidae. From the tela
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choroidae, complex evaginations project into the lumen of the


ventricles forming the choroid plexus.
The core of the evagination is highly vascularized connective
tissue containing many capillaries and small blood vessels. The
covering epithelium is cuboidal or low columnar cells with very
granular cytoplasm; these are modified ependymal cells. The
choroid plexus and the ventricular ependyma secrete the
cerebrospinal fluid (CSF).

The cerebrospinal fluid:


The cerebrospinal fluid is a colorless, clear fluid containing small
amount of proteins, few cells, glucose and sodium and potassium
chloride. CSF circulates through the ventricular system to
subarachnoid space. Impairment of CSF normal flow leads to its
accumulation and hence hydrocephalus.
The blood-brain barrier:
It is meant to restrict the passage of circulating substances to brain
and spinal cord for protection. By EM, the blood-brain barrier is
composed of:
The basal lamina of capillary endothelium within the brain
The tight junction between the capillary endothelial cells and
the perivascular end-feet of astrocytes.
Blood-brain barrier is lacking in some areas of the brain.
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Brain stem
It is composed of medulla, pons and midbrain containing the main
sensory and motor tracts entering and leaving the brain and most of
the cranial nerve nuclei.

Medulla oblongata
The medulla is the lowest part of the brain stem; it is continuous
inferiorly at the foramen magnum with the spinal cord and
superiorly with the pons; the central canal of spinal cord is
continuous in the medulla (closed medulla) to open in the 4 th
ventricle (open medulla).
The medulla has four important levels, pyramidal decussation (in
lower medulla), sensory decussation (in upper level), inferior olive
and the cochlear nuclei levels.
A. Pyramidal decussation level (closed medulla):
This level is the lowest level of the medulla, where it resembles the
cervical segments with centrally located central canal surrounded
by the central grey matter. Pyramidal decussation of the
corticospinal tracts is the most characteristic feature of the
following:
1. The pyramidal decussation consists of crossing corticospinal
fibers, and the prominent fiber tract masses (pyramids) of
corticospinal tracts. The crossed fibers descend in the spinal cord
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as the lateral corticospinal tract, while the remaining uncrossed


fibers descend on the same side as ventral corticospinal tracts.
2. Nucleus gracilis medially and nucleus cuneatus laterally with
their corresponding larger tracts overlying the nuclei.
3. The central canal is centrally located.
4. The spinal tract and nucleus of trigeminal nerve carrying pain
and temperature from the face, replacing the Lissauer`s tract and
substantia gelatinosa of Rolandi of spinal cord which carry pain
and temperature from the trunk.
5. The ventral and dorsal spinocerebellar tract.
6. The spinal nucleus of accessory nerve.

B. Sensory decussation level (of medial lemniscus, closed upper


medulla):
The medulla level is higher but still closed medulla; its general
outline is very much the same like the lower level. Sensory
decussation is the most striking feature of this level in addition to
the following:
1. The central canal position moved more dorsally.
2. Well-developed corticospinal tracts in ventral aspect.
3. The presence of the medial lemnisci (continuation of gracile and
cuneate tracts) and their decussation on top of corticospinal tracts
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in the midline, and the medial longitudinal fasiculus (MLF = MLB


= medial longitudinal bundle) on top of the medial lemnisci.
4. The presence of fasiculus and nucleus gracilis, fasiculus and
nucleus cuneatus and accessory cuneate nucleus just lateral to it.
5. The dorsal and ventral spinocerebellar tracts, the spinal tract and
nucleus of trigeminal nerve.
6. Appearance of inferior olivary nucleus.
7. The hypoglossal nuclei, nucleus ambiguus (of IX, X, XI), the
solitary tract and nucleus and the dorsal nucleus of vagus nerve.

C. Open medulla at midolivary level:


The outline of the medulla at midolivary nucleus is completely
different from the previous levels due to presence of 4 th ventricle
and the inferior cerebellar peduncles. At this level, the medulla
contains all the tracts and nuclei present in closed upper medulla
with the following differences:
1. Loss of the central canal and the appearance of 4th ventricle
2. The appearance of the inferior cerebellar peduncles (previously
the dorsal spinocerebellar tract) on both sides.
3. The appearance of inferior and medial vestibular nuclei.
4. Well-developed inferior olivary nucleus and the appearance of
medial and dorsal accessory olivary nuclei.
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5. The hypoglossal nucleus lies beneath the floor of the fourth


ventricle and the hypoglossal nerve emerging from the medulla
lateral to the corticospinal tracts.

D. Rostral medulla (open) at cochlear nuclei level:


The medulla at the rostral level contains most of the structures
mentioned in the previous level with some differences:
1. The appearance of dorsal and ventral cochlear nuclei of cranial
nerve VIII.
2. Well-developed medial and inferior vestibular nuclei.
3. The appearance of inferior salivatory nucleus of cranial nerve
IX.
4. The hypoglossal nerve is replaced by the nucleus prepositus.

The Pons
The pons lies between the midbrain superiorly and the medulla
inferiorly; it is connected to cerebellum by the middle cerebellar
peduncles. It consists of two parts:
A base or basis pontis containing the corticobulbar,
corticospinal, and corticopontine tracts and pontine nuclei
The tegmentum containing the cranial nerve nuclei, reticular
nuclei and the major ascending sensory pathways.
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It has three important levels, caudal or inferior level, midpons level


and superior level.

A. The pons at the inferior level (facial colliculus):


A cross section of the pons at the inferior level will show the
following:
1. Small separate longitudinal bundles of corticospinal tracts
moved more dorsally and transverse pontine fibers appear ventrally
and scattered pontine nuclei.
2. The medial lemnisci assumed horizontal position.
3. The appearance of trapezoid body (decussating fibers of ventral
cochlear nuclei).
4. Inferior cerebellar peduncle is still being seen on the lateral
sides.
5. The appearance of the roof of the fourth ventricle with the
appearance of the deep cerebellar nuclei (dentate, emboliform,
globose and fastigial).
6. The presence of superior, lateral and medial vestibular nuclei.
7. Dorsal and ventral cochlear nuclei are present.
8. Spinal tract and nucleus of trigeminal nerve.
9. Abducent nucleus
10. The facial nerve nuclei, motor nucleus, superior salivatory
nucleus and solitary nucleus.
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B. The mid-pons level (trigeminal):


At the midpons level, the 4th ventricle attains a roof besides the
following characteristic features:
1. The transverse pontocerebellar fibers which arise from the
pontine nuclei and pass to the contralateral side of cerebellum via
middle cerebellar peduncle (brachium pontis).
2. Scattered small longitudinal bundles of corticospinal moved
more dorsally.
3. The trigeminal nuclei are seen as well as the origin of trigeminal
nerve itself. The trigeminal nuclei are: the main (principal)
sensory nucleus for discriminative touch and pressure in the face,
the motor nucleus for muscles of mastication and the
mesencephalic nucleus extending to the upper midbrain level for
the proprioception from muscles of mastication and extra-ocular
muscles.
4. The medial lemnisci, medial longitudinal fasiculi, superior
cerebellar peduncles and the fourth ventricle are seen.

C. Superior or rostral level of the pons:


At this level, the 4th ventricle and tegmentum become smaller and
the basis pontis becomes larger in addition to the following
features:
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1. The basis pontis contains transverse pontocerebellar fibers,


pontine nuclei, small scattered bundles of corticospinal and
corticobulbar tracts and the massive brachium conjuctivum on both
sides.
2. The medial lemniscus as a continuation of the gracile and
cuneate tracts.
3. The trigeminal lemniscus made by fibers arising from the four
trigeminal nuclei.
3. Spinal lemniscus (continuation of the lateral and ventral
spinothalamic tracts) lies laterally to the medial lemniscus; the
lateral lemniscus containing the ascending cochlear fibers lies
more laterally and dorsally, and the superior cerebellar peduncles
lie more medially.
4. Medial longitudinal fasiculus and medial tectospinal tracts are
located at the sides of the midline.
5. The fourth ventricle is smaller.

The Midbrain
The midbrain or mesencephalon is the smallest part of brain stem;
it lies superior to the pons and contains the cerebral aqueduct of
Sylvius and the nuclei for the cranial nerves III and IV.
It connects the pons and cerebellum to thalamic and subthalamic
regions.
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It consists of:
The tectum dorsally
The tegmentum ventrally
The cerebral peduncles (basis pedunculi or crus cerebri).
The tectum or roof of the midbrain consists of four nuclei lying on
the dorsal surface and are called corpora quadrigemina.
The corpora quadrigemina are made of 2 superior colliculi (centers
for visual reflexes), and 2 inferior colliculi (centers for auditory
reflexes).
Each colliculus is formed of a central nucleus of neurons
surrounded by white matter of afferent and efferent fibers.
The inferior colliculi receive afferent fibers from lateral lemniscus
and temporal lobe of cerebral cortex. They give afferent fibers to
each other, to medial geniculate bodies, tectospinal and tectobulbar
tracts.
The superior colliculi receive afferent fibers from retina, visual
cortex and inferior colliculi; they give afferent fibers to each other,
MLF and tectospinal and tectobulbar tracts
The tegmentum or the floor of the midbrain is made of ascending
spinal tracts to the brain and two red nuclei which are rich in blood
supply and appear pinkish in fresh state.
The cerebral peduncles lie inferior to the tegmentum and contain
the descending corticobulbar, corticopontine and corticospinal
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tracts. The cerebral peduncles are separated from the tegmentum


by substantia nigra.
Substantia nigra is a dark gray pigmented nuclear mass of grey
matter, rich in melanin pigments and belongs to extrapyramidal
system.
Midbrain is studied in two levels, a lower inferior and an upper
superior level.

A. Midbrain inferior level (lower) at the inferior colliculi


At this level, the following structures will be seen:
1. Cerebral peduncles contain the CNS major motor pathways. Its
medial 1/5 contains medial corticobulbar and medial
corticopontine fibers, its middle 3/5 contain corticospinal fibers
and its lateral 1/5 contains lateral corticobulbar and lateral
corticopontine fibers.
2. The medial longitudinal fasiculus and medial tectospinal tract.
3. Decussation of superior cerebellar peduncles.
4. Trochlear nerve nucleus and mesencephalic nucleus of
trigeminal nerve.
5. The cerebral aqueduct.
6. Lateral lemniscus and spinal lemniscus
7. Medial lemniscus and trigeminal lemniscus
8. Rubrospinal tract.
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B. Midbrain at the superior collicular level:


1. MLF, medial lemniscus, trigeminal lemniscus, and spinal
lemniscus.
2. Dorsal tegmental decussation of tectospinal tract.
3. Ventral tegmental decussation of rubrospinal tracts
4. Red nucleus (extrapyramidal center).
5. Oculomotor nucleus and mesencephalic nucleus of trigeminal
nerve.