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HISTOLOGY
Prof.Dr. Huda Al-khateeb
Lec. 3
ENDOCRINE SYSTEM
ADRENAL (SUPRARENAL) GLANDS
They are paired, flattened, triangular bodies that are located
superior to the superior pole of the kidney. Both glands are
weighing 8 gm. They are approximately 5x4x1 cm in
diameter.
Adrenal gland is enclosed by a dense connective tissue
capsule. Its stroma is composed of rich network of reticular
fibers that support the secretory cells.
Suprarenal gland has two parts that are of different
embryonic origin, these are:
1. Cortex (90%) – derived from the genital ridge of the
mesoderm.
2. Medulla (10%) – derived from neural crest cells.
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Adrenal cortex:
It is subdivided into three concentric layers, which are not
sharply defined (because they are derived from the same
embryonic origin). These are:
a) Zona glomerulosa
b) Zona fasciculata
c) Zona reticularis
Note: all cells of the adrenal cortex reveal ultrastructurall
features of steroid-hormone secreting cells.
Zona glomerulosa: characterized by being:
Thin outer layer (15%) that is located just under the
capsule
Light microscopical exam shows that its cells are
pyramidal and arranged in rounded or arched groups
that are surrounded by capillaries.
Their nuclei are rounded and central while cytoplasm
is lightly basophilic
These
cells
are
responsible
for
secretion
of
mineralocorticoids
mainly
aldosterone
(controls
electrolytes –Na
+
& K
+
- homeostasis and water
balance).
Zona fasciculata:
It is the thickest layer (65 – 80%) of the adrenal cortex
Cells are large polyhedral with rounded central
nucleus and pale foamy cytoplasm. These cells are
arranged in parallel columns of 1or 2 cells thickness.
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Columns usually run in right angle to the capsule.
Cells' columns are separated by sinusoidal capillaries.
The cytoplasm of zona fasciculata cells contains
numerous lipid droplets that contain neutral fats, fatty
acids, cholesterol and phospholipids. These substances
represent precursors for steroid hormones.
During slid preparation (by typical histological
procedures) lipid is extracted, thus gives vacuolated or
spongy appearance to these cells and that's why they
are called Spongyocytes.
Zona fasciculata cells secret the following hormones:
i. Glucocorticoids (mainly cortisol and cortisone),
which influence the carbohydrate, lipid and
protein metabolism.
ii. Gonadocorticoids (sex hormones - small amount
of androgens).
Zona reticularis:
Thin layer (10%) that lies between zona fasciculata and
medulla. It consists of small rounded cells that are arranged
in branching and anatomizing cords. Cells have rounded
central nucleus and deeply basophilic cytoplasm (
because
they contain fewer lipid droplets and more lipofuscin
pigment)
.
This
layer
secrets
the
weak
androgen
(
dehydroepiandrosterone - DHEA) which is converted to
testosterone in several other tissues.
MEDICAL APPLICATION
Because of the feedback mechanism controlling the adrenal
cortex, patients who are treated with corticoids for long
periods should never stop taking these hormones suddenly:
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because, secretion of ACTH in these patients is inhibited,
and thus the cortex will not be induced to produce
corticoids, causing severe drops in the levels of sodium and
potassium.
Fetal Adrenal Cortex
At birth in humans (but not most other mammals) the adrenal
gland is larger than that of the adult and produces up to 200
mg of corticosteroids per day, twice that of an adult. At this
age, a layer known as the fetal or provisional cortex,
comprising 80% of the total gland, is present between the thin
permanent cortex and an under-developed medulla. The fetal
cortex is thick and contains mostly cords of large, steroid-
secreting cells under the control of the fetal pituitary. The
principal function of the cells is secretion of sulfated DHEA
which is converted in the placenta to active estrogens (and
androgens), which mostly enter the maternal circulation. The
fetal adrenal cortex is an important part of a fetoplacental unit
which affects both endocrine systems during pregnancy but
whose physiological significance remains largely unclear.
After birth, the provisional cortex undergoes involution while
the permanent cortex organizes the three layers (zones)
described above.
Adrenal Medulla
The adrenal medulla is composed of large, pale-staining
polyhedral cells arranged in cords or clumps and supported
by a reticular fiber network. A profuse supply of sinusoidal
capillaries intervenes between adjacent cords and a few
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parasympathetic ganglion cells are present. When medullary
cells are exposed to an oxidizing agent such as potassium
bichromate (K
2
Cr
2
O
2
), caticholamines (adrenalin and
noradrenalin) will be oxidized giving a brown coloration to
their cytoplasm, therefore these cells are called chromaffin
cells and the reaction is called Chromaffin reaction.
Chromaffin cells can be considered modified sympathetic
postganglionic neurons, lacking axons and dendrites and
specialized as secretory cells.
Unlike cells of the cortex, medullary chromaffin cells
contain many electron-dense granules, 150–350 nm in
diameter, for hormone storage and secretion. These granules
contain one or the other of the catecholamines, epinephrine
or norepinephrine. Ultrastructurally the granules of
epinephrine-secreting cells are less electron-dense and
generally smaller than those of norepinephrine-secreting
cells.
Norepinephrine-secreting cells are also found in paraganglia
(collections of catecholamine-secreting cells adjacent to the
autonomic ganglia) and in various viscera. The conversion of
norepinephrine to epinephrine (adrenalin) occurs only in
chromaffin cells of the adrenal medulla. About 80% of the
catecholamine secreted from the adrenal is epinephrine.
Medullary chromaffin cells are innervated by cholinergic
endings of preganglionic sympathetic neurons, from which
impulses trigger hormone release by exocytosis. Epinephrine
and norepinephrine are released to the blood in large
quantities during intense emotional reactions, such as fright,
and produce vasoconstriction, increased blood pressure,
changes in heart rate, and metabolic effects such as elevated
blood glucose. These effects facilitate various defensive
reactions to the stressor (the fight-or-flight response).
During normal activity, the adrenal medulla continuously
secretes small quantities of the hormones.
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MEDICAL APPLICATION
One disorder of the adrenal medulla is pheochromocytoma, a
tumor of its cells that causes hyperglycemia and transient
elevations of blood pressure.
Disorders of the adrenal cortex can be classified as
hyperfunctional or hypofunctional. Tumors of the adrenal
cortex can result in excessive production of glucocorticoids
(Cushing syndrome) or aldosterone (Conn syndrome).
Cushing syndrome is most often (90%) due to a pituitary
adenoma that results in excessive production of ACTH; it is
rarely caused by adrenal hyperplasia or an adrenal tumor.
Excessive production of adrenal androgens has little effect in
men, but precocious puberty (in boys) and hirsutism
(abnormal hair growth) and virilization (in girls) are
encountered in prepubertal children.
Adrenocortical insufficiency (Addison disease) is caused by
destruction of the adrenal cortex in some diseases. The signs
and symptoms suggest failure of secretion of both
glucocorticoids and mineralocorticoids by the adrenal cortex.
Blood supply
1. Superior suprarenal artery – from inf. phrenic artery
2. Middle suprarenal artery – from aorta
3. Inferior suprarenal artery – from renal artery
These arteries inter adrenals at various points of the capsule
to form subcapsular plexus, from which three groups of
arteries arise:
i. Arteries that supply the capsule
ii. Arteries of the cortex – branch repeatedly to form
capillaries that drain to medullary capillaries
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iii. Arteries of the medulla – they pass through the cortex
to reach the medulla then give rise to medullary
capillaries
All capillaries later drain to suprarenal veins.
Thyroid gland
Embryologically, it is derived from the cephalic portion
of the alimentary canal (endoderm)
It is located in the cervical region, anterior to larynx
and trachea
It has two lobes that are connected to each others by
the isthmus
It is covered by connective tissue capsule
Thyroid gland section is composed of thyroid follicles
that are filled with gelatinous substance called colloid
Follicular wall is composed of cells called follicular
cells which range from squamous to low columnar
epithelium, according to their secretory activity.
Follicular
cells
secret
both
Thyroxine
(tetraiodothyronin) (T
4
) and triiodothyronin (T
3
)
Between follicles, there is loose connective tissue that
contains Parafollicular cells (also called C-cells) which
are large, pale, polyhedral cells that secret calcitonin
(
suppress bone resorption by osteoclasts. Calcitonin
secretion is triggered by elevated blood Ca
2+
levels).
MEDICAL APPLICATION
A diet low in iodide hinders the synthesis of thyroid
hormones, causing increased secretion of TSH and
compensatory growth of the thyroid gland, a condition
known as iodine deficiency goiter. Goiters are endemic in
some regions of the world, where dietary iodide is scarce
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and addition of iodide to table salt is not required.
Hypothyroidism in the fetus may present at birth as
cretinism, characterized by arrested or retarded physical
and mental development
Parathyroid glands
they are four small glands, their total weight = 0.4 gm
(0.1 each)
they lie within the capsule of thyroid gland one at each
end of the upper and lower poles
Embryologically,
they are derived from pharyngeal
pouches; the two superior parathyroid glands are
derived from the fourth pouch, while the two inferiors
from the third one. each parathyroid gland is covered
by connective tissue capsule
Two types of cells are present in parathyroid glands:
chief (or principal) cells and oxyphil cells. The chief
cells are small polygonal cells with round nuclei and
pale-staining,
slightly
acidophilic
cytoplasm.
Ultrastructurally the cytoplasm is seen to be filled with
irregularly shaped granules 200–400 nm in diameter.
These
are
secretory
granules
containing
the
polypeptide parathyroid hormone (PTH), a major
regulator of blood calcium levels. Much less, often
clustered, populations of oxyphil cells are sometimes
present, more commonly in older individuals. These
are much larger than the principal cells and are
characterized by acidophilic cytoplasm filled with
abnormally shaped mitochondria. Some oxyphil cells
show low levels of PTH synthesis, suggesting these cells
are
transitional
derivatives
from
chief
cells.
Parathyroid hormone targets osteoblasts, which
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respond by producing an osteoclast-stimulating factor
to increase the number and activity of osteoclasts. This
promotes resorption of the calcified bone matrix and
the release of Ca
2+
, increasing the concentration of Ca
2+
in the blood, which suppresses parathyroid hormone
production. Calcitonin from the thyroid gland inhibits
osteoclast
activity,
lowering
the
blood
Ca
2+
concentration and promoting osteogenesis. Parathyroid
hormone and calcitonin thus have opposing effects and
constitute a dual mechanism to regulate blood levels of
Ca
2+
, an important factor in homeostasis. Parathyroid
hormone also indirectly increases the absorption of
Ca
2+
from the gastrointestinal tract by stimulating the
synthesis of vitamin D, which is necessary for this
absorption.
Pineal body (gland) (Epiphysis cerebri)
It regulates the daily rhythms of bodily activities.
It is a very small, pine cone-shaped organ in the brain
measuring approximately 5–8 mm in length and 3–5
mm at its greatest width and weighing about 150 mg.
The
pineal
develops
with
the
brain
from
neuroectoderm in the roof of the diencephalon and is
found in the posterior of the third ventricle, attached to
the brain by a short stalk.
The pineal gland is covered by connective tissue of the
pia mater, from which emerge septa containing small
blood vessels and subdividing various sized groups of
secretory cells as lobules.
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The prominent and abundant secretory cells are the
pinealocytes, which have slightly basophilic cytoplasm
and large, lobulated nuclei and prominent nucleoli.
Ultrastructurally pinealocytes are seen to have
secretory vesicles, many mitochondria, and long
cytoplasmic processes extending to the vascularized
septa, where they end in dilatations near capillaries,
indicating an endocrine function. These cells produce
melatonin,
a
low
molecular-weight
tryptophan
derivative. Unmyelinated sympathetic nerve fibers
enter the pineal gland and end among pinealocytes,
with some forming synapses.
Interstitial glial cells resemble astrocytes. They have
elongated nuclei more heavily stained than those of
pinealocytes, long cytoplasmic processes, and are
usually found in perivascular areas and between the
groups of pinealocytes. Pineal astrocytes represent only
about 5% of the cells in the gland.
A characteristic feature of the pineal gland is the
presence of variously sized concretions of calcium and
magnesium salts called brain sand, which form by
precipitation around extracellular protein deposits.
Accumulations of brain sand are opaque to x-rays and
allow the pineal to serve as a good midline marker in
radiological and computer-assisted tomography studies
of the brain.
Melatonin release from pinealocytes is promoted by
darkness and inhibited by daylight and the resulting
diurnal fluctuation in blood melatonin levels induces
rhythmic changes in the activity of the hypothalamus,
pituitary gland, and other endocrine tissues that
characterize the circadian (24 hours, day/night)
rhythm of physiological functions and behaviors.
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