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HISTOLOGY OF THE ENDOCRINE
SYSTEM
ENDOCRINE SYSTEM
• The endocrine system is the system of glands,
each of which secretes different types
of hormones directly into the bloodstream
(some of which are transported along nerve
tracts) to maintain homeostasis. The endocrine
system in contrast to the exocrine system,
which secretes its chemicals using ducts. The
word endocrine derives from the Greek words
"endo" meaning inside, within, and "crinis" for
secrete.
Endocrine system
• Pituitary gland (hypophysis)
– Anterior pituitary
– Posterior pituitary
• Adrenal gland (suprarenal)
– Adrenal cortex
– Adrenal medulla
• Thyroid gland
– Follicles
– Parafollicular cells
• Parathyroid gland
THE PITUITARY GLAND
the pituitary gland, or hypophysis, is
an endocrine gland about the size of a
pea and weighing 5 grams (0.18 oz) in
humans. It is a protrusion off the bottom of
the hypothalamus at the base of the brain,
and rests in a small, bony cavity (sella
turcica) covered by a dural fold
(diaphragma sellae). The pituitary is
functionally connected to
the hypothalamus by the median
eminence via a small tube called the
infundibular stem (Pituitary stalk). The
pituitary fossa, in which the pituitary gland
sits, is situated in the sphenoid bone in
the middle cranial fossa at the base of the
brain. The pituitary gland secretes
nine hormones that regulate homeostasis.
EMBRYOLOGICAL DEVELOPMENT
Structurally &
functionally
divided into 2
lobes:
1) Anterior
lobe/Adenohypop
hysis (2/3(
2) Posterior
lobe/neurohypoph
ysis )1/3(.
The anterior pituitary lobe
(adenohypophysis)
•
•
Master gland (adenohypophysis).
Consists of 2 parts in adults:
1. Pars distalis … known as the anterior pituitary.
rounded portion & the major endocrine part of the gland.
2. Pars tuberalis …
thin extension in contact with the infundibulum.
Pars intermedia…
Avascular tissue b/w anterior & posterior lobes, exists in fetus
(no longer present in adults). Much more functional in some
lower animals, such as fish, amphibians, & reptiles.
The bulk of the adenohypophysis is pars
distalis. That tissue is composed of winding cords of
epithelial cells flanked by vascular sinusoids. In
sections stained with dyes such as hematoxylin and
eosin, three distinct cell types are seen among
epithelial cells:
•Acidophils have cytoplasm that stains red or
orange
•Basophils have cytoplasm that stains a bluish color
•Chromophobes have cytoplasm that stains very
poorly
Acidophils
Cells that contain the polypeptide
hormones:
•Somatotropes which produce growth hormone
•Lactotropes which produce prolactin
Basophils
Cells that contain the glycoprotein
hormones:
•Thyrotropes which produce thyroid stimulating
hormone
•Gonadotropes which produce luteinizing
hormone or follicle-stimulating hormone
•Corticotropes which
produce adrenocorticotrophic hormone
Due the high carbohydrate content of the
hormones within acidophils, they also stain
bright purple with PAS stains.
Chromophobes
These are cells that have minimal or no
hormonal content. Many of the
chromophobes may be acidophils or
basophils that have degranulated and
thereby are depleted of hormone. Some
chromophobes may also represent stem
cells that have not yet differentiated into
hormone-producing cells.
The pars intermedia is closely associated with pars nervosa and separated
from the pars distalis by the hypophyseal cleft. This lobe of the pituitary
shows considerable variation in size among species. It is small in man, but
much larger in species such as amphibians. The pars intermedia contains
large pale cells that often surround follicles filled with ill-defined "colloid".
Melanocyte-stimulating hormone is the predominant hormone secreted by
the pars intermedia
The neurohypophysis is known also as the pars nervosa.
Anatomists distinguish between three areas of this organ,
starting closest to the hypothalamus:
•the median eminence
•infundibular stalk
•infundibular process
The infundibular process froms the bulk of the neurohypophysis
is what is usually referred to as the posterior pituitary.
The bulk of the neurohypophysis is composed on largely
unmyelinated axons from hypothalamic neurosecretory
neurons. These axons have their cell bodies in the
paraventricular and supraoptic nuclei of the hypothalamus.
These neurons secrete oxytocin or antidiuretic hormone.
Roughly 100,000 axons participate in this process to form the
posterior pituitary. In addition to axons, the neurohypophysis
contains glial cells and other poorly-defined cells called called
pituicytes.
An interesting histologic feature of the neurohypophysis is the presence
of Herring bodies. When viewed with an electron microscope, these are
dilated areas or bulges in the terminal portion of axons that contain clusters
of neurosecretory granules. The granules contain oxytocin or antidiuretic
hormone, along with their associated neurophysins. Herring bodies often
are seen in association with capillaries. They are somewhat difficult to
identify unambiguously by light microscopy; in the image to the right, the
label might better say "probable Herring bodies".
THYROID AND PARATHYROID
GLAND
System
Endocrine
Artery
superior thyroid artery, inferior thyroid
artery,
Vein
superior thyroid vein, middle thyroid
vein, inferior thyroid vein,
Nerve
middle cervical ganglion, inferior cervical
ganglion
Lymph
pretracheal, prelaryngeal, jugulodiagastric,and lympahtics of thymus
Precursor
neural crest mesenchyme and third and
fourth pharyngeal pouchendoderm
THYROID GLAND
•located anteriorly in
cervical region, just
inferior to thyroid
cartilage; two lobes
connected by thin
isthmus
•largest purely
endocrine gland in
body
The thyroid gland is composed of many
spherical hollow sacs called thyroid follicles. In
this tissue section, each follicle (A) appears as
an irregular circle of cells. The principal cells,
which surround the follicle are simple cuboidal
epithelium. These follicles are filled with
a colloid (B), which usually stains pink. The
principal cells use the thyroglobulin and iodide
stored in the colloid to produce the primary
thyroid hormones - including thyroxine.
Between these follicles are the parafollicular
cells (C) which produce calcitonin.
Disorders of the thyroid gland:
Hyperthyroidism
• Increased metabolic rate (thyrotoxicosis)
• Causes
– overmedication in thyroid gland failure
– increased hormone due to thyroid gland diseases
– primary
– increased hormone due to TSH - secondary
Graves Disease
• 80-90% of all hyperthyroidism
• One of most common autoimmune diseases in
US
• Mostly women
• Antibody that acts like TSH
• Gland is diffusely enlarged & smooth
Thyroiditis
• Inflammation of thyroid
• Mostly chronic
– autoimmune
• Presents as goiter
Hasimoto Thyroiditis
• Most common type in
US
• One of most common
causes of goiter &
hypothyroidism
• Antibodies that block
TSH
Neoplasms of Thyroid Gland
• Not common
• Neoplastic masses are more likely to
– be solitary masses
– “cold”
– in younger patients
– in males
• Most are from nodular goiter
• Adenomas
– Bbnign
– epithelial cells of follicles
• Carcinomas
– from follicular epithelium
– uncommon
– papillary
• most common
• > 90% survive 5 yrs
– follicular
• more aggressive
– medullary
• from specialized nonepithelial cells that secrete calcitonin
• aggressive
– anaplastic
• most aggressive
• most fatal within a year
PARATHYROID GLAND
4 glands in 2 pairs usually close to upper
and lower poles of thyroid lobe
● May be found anywhere along pathway
of descent of branchial pouches
● 10% have 2-3 glands; 5% have 5 glands,
0.2% have 6 glands
● Upper pair arises from fourth branchial
cleft and descends with thyroid gland;
usually at cricothyroid junction
● Lower pair arises from third branchial
cleft and descends with thymus; usually
near inferior thyroid
● Other locations: carotid sheath, anterior
mediastinum, intrathyroidal; glands tend to
be bilaterally symmetrical
● Stromal fat increases to 30% at age 25;
percent fat is related to constitutional
percent fat, but reduced in dying
individuals; mean is 17% with wide
variation
● Composed primarily of chief cells and fat with thin fibrous capsule dividing gland
into lobules
● May have a pseudofollicle pattern resembling thyroid follicles (pink material is
PAS positive)
Chief cells:
● 6-8 microns, polygonal, central round nuclei, contain granules of parathyroid
hormone (PTH)
● Basic cell type, other cell types are due to differences in physiologic activity
● 80% of chief cells have intracellular fat
● Chief cell is most sensitive to changes in ionized calcium
Oxyphil cells:
● Slightly larger than chief cell (12 microns), acidophilic cytoplasm due to
mitochondria
● No secretory granules
● First appear at puberty as single cells, then pairs, then nodules at age 40
Water clear cell:
● Abundant optically clear cytoplasm and sharply defined cell membranes
● Chief cells with excessive cytoplasmic glycogen
Because the parathyroids (A) are embedded in the thyroid tissue,
their tissues are often found with the thyroid tissue. The chief
cells that make up this gland are smaller and darker staining than
those of the thyroid. At higher magnifications, we could see that
the chief cells appeared in "ribbons" or "cords." These cells
secrete parathyroid hormone (PTH) Recall that you are only
responsible for recognizing this tissue when it appears with the
thyroid gland.
Chief cells
Oxyphilic nodule
Clear cells
THE ADRENAL GLANDS
Outline
•
•
•
•
•
Introduction
Adrenal cortex
Cortical hormones
Adrenal Medulla
Medical application.
Introduction
• The adrenal glands are paired organs that lie
near the superior poles of the kidneys,
embedded in adipose tissue .
• They are flattened structures with a halfmoon shape; in the human, they are about 4–
6 cm long, 1–2 cm wide, and 4–6 mm thick.
…………….
• Together they weigh about 8 g, but their
weight and size vary with the age and
physiological condition of the individual.
• Examination of a fresh section of adrenal
gland shows that it is formed by two
concentric layers: a yellow peripheral layer,
the adrenal cortex; and a reddish-brown
central layer, the adrenal medulla
……
• The adrenal cortex and the adrenal medulla can
be considered two organs with distinct origins,
functions, and morphological characteristics that
became united during embryonic development.
• They arise from different germ layers. The cortex
arises from the coelomic epithelium, whereas the
cells of the medulla derive from the neural crest,
from which sympathetic ganglion cells also
originate.
……
• The general histological appearance of the
adrenal gland is typical of an endocrine gland in
which cells of both cortex and medulla are
grouped in cords along capillaries.
• The dense connective tissue capsule that covers
the adrenal gland sends thin septa to the interior
of the gland as trabeculae.
• The stroma consists mainly of a rich network of
reticular fibers that supports the secretory cells.
……
Blood Supply
• The adrenal glands are supplied by several
arteries that enter at various points around their
periphery.
• The branches of these arteries can be divided into
three groups: arteries that irrigate the capsule;
cortical arteries, branching into capillaries that
irrigate the gland cells of the cortex and that
eventually reach the medullary capillaries;
• and medullary arteries, which pass through the
cortex and form an extensive capillary network in
the medulla.
………..
• The cells of the medulla are, thus, bathed with
both arterial blood from the medullary
arteries and venous blood originating from
the capillaries of the cortex.
• The capillary endothelium is extremely
attenuated and interrupted by small fenestrae
that are closed by thin diaphragms.
......
• A continuous basal lamina is present beneath
the endothelium.
• Capillaries of the medulla, together with
capillaries that supply the cortex, form the
medullary veins, which join to constitute the
adrenal or suprarenal vein
Adrenal Cortex
• The cells of the adrenal cortex , which have
the typical ultrastructure of steroid-secreting
cells, do not store their secretory products in
granules;
• rather, they synthesize and secrete steroid
hormones upon demand.
……
• Steroids, being low-molecular-weight lipidsoluble molecules, diffuse through the plasma
membrane and do not require the specialized
process of exocytosis for their release.
……
• Because of the differences in disposition and
appearance of its cells, the adrenal cortex can be
subdivided into three concentric layers whose
limits are usually not sharply defined in humans :
• the zona glomerulosa, the zona fasciculata, and
the zona reticularis.
• These layers occupy 15%, 65%, and 7%,
respectively, of the total volume of the adrenal
glands.
……
• The layer immediately beneath the connective
tissue capsule is the zona glomerulosa, in
which columnar or pyramidal cells are
arranged in closely packed, rounded, or
arched cords surrounded by capillaries
……
• The next layer of cells is known as the zona
fasciculata because of the arrangement of the
cells in one- or two-cell thick straight cords
that run at right angles to the surface of the
organ and have capillaries between them .
• The cells of the zona fasciculata are
polyhedral, with a great number of lipid
droplets in their cytoplasm.
……
• As a result of the dissolution of the lipids
during tissue preparation, the fasciculata cells
appear vacuolated in common histological
preparations.
• Because of their vacuolization, the cells of the
fasciculata are also called spongyocytes
……
• The zona reticularis , the innermost layer of the
cortex, lies between the zona fasciculata and the
medulla; it contains cells disposed in irregular
cords that form an anastomosing network.
• These cells are smaller than those of the other
two layers.
• Lipofuscin pigment granules in the cells are large
and quite numerous. Irregularly shaped cells with
pyknotic nuclei—suggesting cell death—are often
found in this layer.
Cortical hormones
• The steroids secreted by the cortex can be
divided into three groups, according to their main
physiological action: mineralocorticoids,
glucocorticoids, and androgens .
• The main product of the zona glomerulosa is a
mineralocorticoid called aldosterone;
• the zona fasciculata and possibly the zona
reticularis secrete glucocorticoids, especially
cortisol; the zona reticularis produces
dehydroepiandrosterone, a weak androgen
Control of the Adrenal Cortex
• The secretion of glucocorticoids is controlled
initially through the release of corticotropinreleasing hormone in the median eminence,
followed by secretion of adrenocorticotropic
hormone (ACTH, corticotropin) by the pars
distalis of the hypophysis
……
• Free glucocorticoids may then inhibit ACTH
secretion. The degree of pituitary inhibition is
proportionate to the concentration of
circulating glucocorticoids; inhibition is
exerted at both the pituitary and
hypothalamic levels .
• Aldosterone secretion is controlled primarily
by renin-angiotensin and secondarily by ACTH.
MEDICAL APPLICATION
• Because of the feedback mechanism of
adrenal cortex control, patients who are
treated with corticoids for long periods should
never stop taking these hormones suddenly:
• secretion of ACTH in these patients is
inhibited, and thus the cortex will not be
induced to produce corticoids, causing a
severe misbalance in the levels of sodium and
potassium.
Adrenal Medulla
• The adrenal medulla is composed of
polyhedral cells arranged in cords or clumps
and supported by a reticular fiber network.
• A profuse capillary supply intervenes between
adjacent cords, and there are a few
parasympathetic ganglion cells.
……
• The medullary cells arise from neural crest
cells, as do the postganglionic neurons of
sympathetic and parasympathetic ganglia.
• Thus, the cells of the adrenal medulla can be
considered modified sympathetic
postganglionic neurons that have lost their
axons and dendrites during embryonic
development and have become secretory
cells.
……
• Medullary cells have abundant membranelimited electron-dense secretory granules, 150–
350 nm in diameter.
• These granules contain one or the other of the
catecholamines, epinephrine or norepinephrine.
• The secretory granules also contain adenosine
triphosphate (ATP), proteins called
chromogranins (which may serve as binding
proteins for catecholamines),
……
• dopamine -hydroxylase (which converts
dopamine to norepinephrine), and opiatelike
peptides (enkephalins)
…….
• A large body of evidence shows that
epinephrine and norepinephrine are secreted
by two different types of cells in the medulla.
• When observed with the transmission
electron microscope epinephrine-secreting
cells show smaller and less electron-dense
granules, whose contents fill the granule.
• Norepinephrine-secreting cells have larger,
more electron-dense granules. Their content is
irregular in shape, and there is an electronlucent layer beneath the surrounding
membrane. About 80% of the catecholamine
output of the adrenal vein is epinephrine.
……
• Unlike the cortex, which does not store steroids,
cells of the medulla accumulate and store their
hormones in granules.
• The adrenal medullary cells are innervated by
cholinergic endings of preganglionic sympathetic
neurons.
• Glucocorticoids produced in the cortex, which
reach the medulla through capillaries that bathe
cells of the cortex, constitute another mechanism
of control.
MEDICAL APPLICATION
• Epinephrine and norepinephrine are secreted
in large quantities in response to intense
emotional reactions, such as fright, that are
part of an alarm reaction (the fight-or-flight
response).
• Secretion of these substances is mediated by
the preganglionic fibers that innervate
medullary cells.
……
• Vasoconstriction, hypertension, changes in
heart rate, and metabolic effects such as
elevated blood glucose result from the
secretion and release of catecholamines into
the bloodstream.
• During normal activity, the medulla
continuously secretes small quantities of
these hormones.
……
• Medullary cells are also found in the
paraganglia (collections of catecholaminesecreting cells adjacent to the autonomic
ganglia) as well as in various viscera.
• Paraganglia are, thus, a diffuse source of
catecholamines.
Adrenal Dysfunction
MEDICAL APPLICATION
• One disorder of the adrenal medulla is
pheochromocytoma, a tumor of its cells that
causes transient elevations of blood pressure.
These tumors can also develop in
extramedullary sites.
continues
•
•
•
•
•
Rare catecholamines producing tumors
Prevalence is 1- 2% in hypertensives
It can be fatal
No sex predilection
Maximum incidence between the ages of 20
and 50 years, though they can occur at any
age.
• In general, it is said that 10% are bilateral, 10%
are extra-adrenal, 10% occur in childhood and
that 10% are malignant.
The clinical features
• An important clinical feature is hypertension
• Sustained in about 50% of cases
• 50% have paroxysmal HT lasting for minutes to
1 hour (usualy 15 minutes)
• HT due to Pheo. has a triad of characteristics
(sweating attacks, tachycardia and headache)
• Orthostatic HT (60%)
• Crises may be precipitated (infections, stress,
anxiety etc)
Diagnosis (basal levels)
• Demonstration of increased levels of
- Plasma catecholamines (95% sensitivity)
- Urinary vanilyl mandelic acid (VMA- 90%
sensitivity
- Urinary matanephrines (95% sensitivity)
……
• 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 produces excessive ACTH;
it is rarely caused by adrenal hyperplasia or an
adrenal tumor.
……
• Excessive production of adrenal androgens has
little effect in men. However, hirsutism (abnormal
hair growth) is seen in women, and precocious
puberty (in boys) and virilization (in girls) are
encountered in prepubertal children.
• These adrenogenital syndromes are the result of
several enzymatic defects in steroid metabolism
that cause increased biosynthesis of androgens
by the adrenal cortex.
……
• Adrenocortical insufficiency (Addison disease)
is caused by destruction of the adrenal cortex
in some diseases.
• The signs and symptoms result from failure of
secretion of both glucocorticoids and
mineralocorticoids by the adrenal cortex.
The endocrine pancreas
• The islets of langerhans appears as circular or
oval areas containing pale staining cells with H
‘n’ E stain.
• The endocrine portion is associated with
numerous small blood vessels and capillaries.
• The cells are polyhedral, the use of special
stains identifies three major types of cells;
these are alpha, beta, delta and PP cells.
Alpha cells (A-cells)
• The alpha cells occupy the central part of the
islets and they form 20% of the islet cells.
• These cells secrets glucagon, a hormone which
increases the blood levels of glucose.
Beta cells (B cells)
• The beta cells occupy a peripheral position in the
islets. These cells constitute 75%-80% of the islets
cells and they are important in the body because
they secret insulin.
• Insulin when secreted it enters the blood stream and
become available to cells of the body. It allows
glucose to be utilized by the cells, without insulin
glucose will not be utilized.
slide
Delta cells (D- cells)
• The delta cells occupy a central position in the
islets and form only about 5% of the islets cell
population.
• It is thought that the delta cells secret either
serotonin or pancreatic gastrin.
PP cells
• These are very rare cells in man but well
demonstrated in guinea pigs, rats and rabbits. The PP
cells secret the pancreatic polypeptide, a hormone
which stimulates the chief cells of the stomach to
produce more pepsinogen. Pepsinogen is the
precursor of the enzyme pepsin.
• Islets of langerhans are most numerous in the tail of
the pancreas and they become less in number at the
head.
The end.
References
• Human Anatomy and Physiology (3rd ed.).
Benjamin/Cummings.
• Janqueira, Carneiro-Basic Histology-Text and
Atlas 11 edition
• Platzer, Werner (2008). Color atlas of human
anatomy:
Ganyaka,Sebastian,2012