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ANATOMY OF ENDOCRINE SYSTEM
FOR 2ND YEAR BSC NURSING
By:- Dr Temesgen Wirtu
ENDOCRINE SYSTEM
Comprises several
discrete ductless glands (the pituitary, pineal,
thyroid, parathyroids, and adrenal glands), which
secrete hormones directly into the blood or lymph
circulation.
clusters of endocrine cells located within certain
complex organs such as Islets of Langerhan’s of
pancreas, juxtaglomerular cells of the kidney, the
cells of the heart that produce the atrial natriuretic
factor, liver, lungs, and the cells of the placenta,
ovary and testes), and
isolated endocrine cells in the epithelial lining of the
gastrointestinal and respiratory system.
• characterized by the synthesis, storage and
secretion of chemical messengers or signals known
interacts closely with
 the nervous system (via the connection between
the adenohypophysis and the CNS) to modulate
and control all the physiological systems and
metabolic activities,
 the immune system.
-endocrine dysfunctions may affect the immune
response and vice versa.
-the hormones are liberated by specialized cells that are
called endocrine cells because they secrete
"inward,” as opposed to exocrine cells, which secrete
into a body cavity or toward the body surface.
 Endocrine cells usually aggregate as endocrine
glands, where they typically arrange themselves as
cords of cells.
 A notable exception is the thyroid gland, in which the
cells are organized as microspheres called follicles.
 Most hormones act at a distance from the site of their
secretion and hence,
-the endocrine cells lie very close to blood and lymph
capillaries, which receive the secreted hormones and
distribute them through out the body.
-The tissues and organs on which the hormones act are
called Target tissues or organs, because they have
receptors that specifically recognize and respond to
specific hormones.
Importance of Receptor Mechanism
1.Hormones in circulation do not indiscriminantly
influence all cells of the body.
2.When they are present in small amount in the blood,
target cells respond to this small concentration.
Hormones
-are chemical messengers that are carried via blood
stream to distant target cells.
-include low-molecular weight water soluble proteins and
polypeptides and lipid-soluble substances, principally
the steroid hormones.
A. Water-soluble hormones :hydrophilic
– are low-molecular weight proteins and polypeptides.
– interact with specific cell surface receptors on target cells.
– attach to the outer or inner surfaces (hydrophilic leaflet) of
plasma membrane.
1. G-protein-linked receptors
• are utilized by some hormones such as
epinephrine,
TRH, TSH, FSH, serotonin
• binding leads to production of a second messenger
that affects metabolic activity.
2. Catalytic protein receptors
-are utilized by insulin and growth hormone.
-binding activates protein kinases that phosphorylate
target proteins.
B. Lipid-soluble hormones
• are principally the steroid hormones.
• diffuse across the plasma membrane of target cells.
• bind to specific receptors in the cytosol or nucleus,
forming hormone-receptor complexes that regulate
transcription of DNA.
• include thyroxin, progesterone, estradiol,
Cells communication
 is vital for any multicellular organism to function
efficiently.
• at a local level, communicate is via cell surface
molecules and gap junctions,
• while remote communication is mediated by the
secretion of chemical messengers, which activate
cells by
interacting with specific receptors.
• such secretion may be one of four modes of
secretion:
1. Autocrine
2. Paracrine
3. Endocrine and
4. Synaptic secretion
1. Autocrine secretion
 occurs when a chemical messenger to act on its own
receptor.
• This is particularly evident in the local control of cell
growth by growth factors such as epidermal growth
factor.
2. Paracrine secretion
-describes the chemical messengers to act on adjacent
cells.
-this is also mainly concerned with the local control of
cell growth and is also a mode of action of many of the
cells of the diffuse neuroendocrine system.
3. Endocrine secretion
-is the secretion of chemical messengers (hormones)
into the blood stream to act on distant tissues.
4. Synaptic secretion
• refers to communication by direct structural targeting
from one cell to another via synapses, and
• is confined to the NS.
The chemical messengers and/or hormones belong to
four main molecular classes:
1. Amino acid derivatives
 Adrenaline or Epinephrine
 Noradrenaline or Norepinephrine
 Thyroxine
 Melatonin
 Serotonin
2. Small (short) Peptides
• Thyroid-releasing hormone (TRH)
• Anti-diuretic hormone (ADH) or Arginine-
vasopressin hormone (AVP)
• Oxytocin
3. Protein (Polypeptide) hormones
• Nerve growth factor (NGF)
• Epidermal growth factor (EGF)
• Insulin
• Growth hormone (GH)
• Thyroid-stimulating hormone (TSH)
• Calcitonin
• Parathormone (parathyroid hormone)
• Renin (proteolytic enzyme receptor)
4. Steroid hormones
• Cortisols e.g. Aldosterone
• Progesterone
• Testosterone
• oestradiol
Endocrine glands
• ductless glands (no duct system) in contrast to the
exocrine glands which have ducts.
• secrete hormones directly into the blood streams
• contain islands of secretory cells of epithelial origin, with
interlacing delicate supportive tissue rich in blood
and lymph capillaries.
• have rich vascular connective tissue stroma
Endocrine cells
• are usually characterized by prominent nuclei &
prolific
cytoplasmic organelles especially mitochondria, ER,
Golgi bodies and secretory vesicles.
• Liver: a mixed gland – secretes bile into the duct
system and passes secretions directly into the blood
vessel
• Pancreas: a mixed gland
Origin
• Ectoderm– hypophysis, adrenal medulla (chromaffin
bodies)
• Mesoderm– testes, ovaries, adrenal cortex
• Endoderm– thyroid, parathyroid, pancreatic islets
• 2 General Categories (based on the chemical nature
of secretions)
– Protein & polypeptide secreting : hypothesis,
thyroid, parathyroid, A & B cells of pancreas
– Steroid Secreting – gonads & adrenal cortex
PITUITARY GLAND (HYPOPHYSIS)
 Also called hypophysis cerebri
 Weighs about 0.5g (the size of a pea seed) and its normal
dimensions in humans are about 10 x 13 x 6mm
 Lies below the base of the brain, connected to the
hypothalamus to which it is structurally and functionally
related
 Situated in bony cavity of sphenoid bone named the
hypophyseal fossa(sella turcica)important radiological
landmark
 Consists of two major subdivisions- the adenohypophysis
and the neurohypophysis
 Each subdivision is derived from a distinct embryonic analog,
which is reflected in its unique cellular constituents and
functions.
Situated at the base of the brain
Is situated in the
hypophyseal
fossa (H) in the
body of sphenoid
bone, called sella
tursica
The pituitary gland is composed of an anterior part and a posterior
part, which is directly attached to the hypothalamus of the brain by a
stalk called the infundibulum. The gland occupies a fossa of the
sphenoid bone called the sella turcica (L. Turkish saddle)
1. Adenohypophysis
• constitutes the anterior portion of the pituitary
gland.
• originates from an ectodermal diverticulum of the
stomodeum (primitive oral cavity)
• is subdivided into the pars distalis, pars tuberalis,
and pars intermedia.
2. Neurohypophysis
• constitutes the posterior portion of the pituitary
gland.
• originates from an evagination of the hypothalamus.
• consists of a large portion, the pars nervosa, and the
smaller infundibulum, or the neural stalk
• the neural stalk is composed of the stem and
median eminence.
Parts of Pituitary gland
Parts of Adenohypophysis
1. Pars distalis
-External collagenous capsule and an internal supportive
reticular fiber network.
-It is highly vascular
-Consists of irregular cords of parenchymal cells lying
adjacent to fenestrated capillaries.
Cells of Pars distalis: Chromophils, Chromophobes
A. Chromophils
-are parenchymal cells that stain intensely
-are classified into two types, depending on the dyes they bind
using special histologic stains
Pituitary gland
 Synthesize, store, and release several hormones
 Regulated by an specific stimulatory and inhibitory
hormones that produced by neurosecretory cells in the
hypothalamus and conveyed to the pars distalis via portal
blood vessels in the median eminence
1.Acidophils
• bind acid dyes and often stain orange to red
• secrete direct action hormones
-most common in central and posterolateral regions
-are small, spherical cells (15-20µm in diameter) of
two subtypes: somatotrophs and mammotrophs
Somatotrophs
 Produce somatotropin (GH), w/c is contained intracellularly
within spherical, membrane-bounded granules (300-400nm)
 Are the most numerous cells making up almost half (50%)
of the bulk of the anterior pituitary
 Possess a centrally positioned nucleus, moderate-sized
Golgi complex, rod-shaped mitochondria, and abundant
rough endoplasmic reticulum (RER)
 Are stimulated by somatotropin-releasing hormone
(SRH) and are inhibited by somatostatin
 GH is generalized hormone b/c act not on specific target
organ, rather on several cells including epithelial cells,
fibroblasts, bone, cartillage, muscle, adipocytes, etc.
Mammotrophs (Lactotrophs)
 Comprise up to 20% of the anterior pituitary,
increasing in number during pregnancy and lactation
 Produce prolactin, which is stored in small
membrane
bounded by granules (200nm in diameter)
 These granules are enlarge in pregnant and lactating
women, and after suckling is complete, they undergo
crinophagy
 Are stimulated by prolactin-releasing hormone (PRH)
and inhibited by prolactin-inhibiting hormone (PIH)
2. Basophils (Trophic hormones)
• bind to basic dyes and typically stain blue
• most common at the periphery region of pars distalis
• include three subtypes:
– Corticotrophs
– Thyrotrophs
– Gonadotrophs
Corticotrophs
 Produce adrenocorticotropic hormone (ACTH) and
lipotropic hormone (LPH)
 Both stored in granules that are 50-400 nm in
diameter
 constitute about 20% of anterior pituitary mass
 spherical to ovoid in shape with relatively few cells
 are stimulated by corticotropin-releasing hormone
Thyrotrophs
 Produce thyroid-stimulating hormone (TSH), which
is stored in small granules (150nm in diameter)
 usually located just beneath the plasma membrane
 stimulated by thyrotropin-releasing hormone (TRH)
makes only about 5%
Gonadotrophs
 Produce FSH and LH in sexes, although the latter is
often referred to as interstitial cell-stimulating
hormone
 Hormones are stored in large granules (200-400 nm)
 Make up only about 5% of the anterior pituitary
 stimulated by gonadotropin-releasing hormone (GnRH)
B.Chromophobes
 Are parenchyma cells that do not stain intensely
 Small cells, arranged close to each other in clusters,
that lack or have a few secretory granules
 They may also represent undifferentiated cells that
are capable of differentiating in to various types of
chromophils
2. Pars Intermedia
 lies b/n the pars distalis and pars nervosa
 characterized by the presence of numerous colloid-
containing cysts that are lined by cuboidal cells
 possesses basophilic cells, which sometimes extend
into the pars nervosa
 in some vertebrates, they secrete melanocyte-
stimulating hormone (MSH), endorphin etc.
Pituitary gland
PD
RP
PI
NH
• Pars intermedia PI- is
derived from Rathke’s
pouch, the cells are
basophilic and form
irregular clumps lying
between Pars ant:
(PA) and Pars post
(PP)
• Small cystic spaces
filled with
eosinophilic material
may be seen.
• It is poorly developed
in human but
relatively well
developed in animal.
P P
P A
P I
3. Pars Tuberalis
 surrounds cranial part of infundibulum(hypophyseal
stalk)
 composed of cuboidal basophilic cells, arranged in
cords along an abundant capillary network
 probably secretes FSH and LH
 highly PAS positive region due to high accumulation of
glycogen.
Folliculo-stellate cells
 supportive cells of the adenohypophysis
 maintain favorable fluid and electrolyte env’t for the
secretory cells of the adenohypophysis
B. Neurohypophysis
 constitutes the posterior portion of the pituitary gland
 originates from an envagination of the hypothalamus
 divided in to the infundibulum, w/c is continuous with
the hypothalamus and the pars nervosa, w/c is the
main body of neurohypophysis
1. Hypothalamohypophyseal tract
o contains unmyelinated elongated axons of
neurosecretory cells whose somata are located in
the supraoptic and paraventricular nuclei of the
hypothalamus
o transports oxytocin, vasoporessin, neurophysin (a
binding glycoprotein specific for each hormone)
and ATP to the pars nervosa
2. Pars Nervosa
 Contains distal ends of the hypothalamo-hypophyseal
axons and the site where the neurosecretory
granules in these axons are stored or site of
accumulation known as Herring bodies
 Releases oxytocin and vasopressin in to fenestrated
capillaries in response to nerve stimulation
Physiologic effects of pituitary hormones
1. Hormones of the pars distalis
a. Somatotropin (GH)
 increases metabolism in most cells
 indirectly stimulates epiphyseal plates and
the growth of long bones via production of
the somatomedins in the liver
b. prolactin
promotes dev’t of the mammary gland during
pregnancy
stimulates milk production during lactation
c. Adrenocorticotrophic hormone (ACTH)
 stimulate synthesis and release of adrenal cortex
hormones particularly glucocorticoids
d. Follicle-stimulating hormone (FSH)
 stimulates growth of secondary ovarian follicles and
estrogen secretion in women
 stimulates sterol cells, w/c are located in somniferous
tubules and function in species
e. Luteinizing hormone (LH)
 promotes ovulation, formation of corpus lutem and
progesterone secretion in women
 stimulates testosterone synthesis by Leydig cells in
the testes
f. Thyroid-stimulating hormone (TSH)
 stimulates synthesis and release of thyroid
hormones (T3 & T4) by thyroid follicular cells
2. Hormones released by the pars nervosa
a. Oxytocin (OT)
 induces smooth muscle contraction in the wall of the
uterus during copulation and at parturition
 induces contraction of epithelial cells of the mammary
gland during nursing
b. vasopressin, Argenine-vasopressin (AVP)
 also called antidiuretic hormone (ADH)
 renders cells of renal collecting tubules permeable to
water, reabsorbed to produce a concentrated urine
 acts as a powerful vasoconstrictor of smooth muscle
cell in the tunica media of arterioles.
D. Vascularization of the pituitary gland
1. Arterial supply
 From two pairs of BVs w/c derived from internal
carotid artery
a. The right and left superior hypophyseal arteries
This supply the pars tubelaris, infundibulum, and
median eminence
b. The right and left inferior hypophyseal arteries
This supply mostly the pars nervosa region
• Internal carotid gives
off superior and inferior
hypophyseal arteries
• Superior hypophyseal
arteries divide into
capillaries in the region
of median eminence
and neural stalk.
• These capp: are connected
to second set of capp: in
the adenohypophysis.
These 2 sets belong to
hypophyseal portal system
• The function of these cap:
is to convey the hormones
from hypothalamus to
adenohypophysis
Pituitary Gland
AdenoHypophysis
1. Pars Distalis
2. Pars Tuberalis
3. Pars Intermedia
Neurohypophysis
1. Pars Nervosa
2. Infundibulum
3. Median eminence
2. Hypophyseal portal system
a. Primary capillary plexus
 consists of fenestrated capillaries coming off to the
superior hypophyseal arteries.
 located in the median eminence where stored the
hypothalamic neurosecretory hormones enter to
the blood and drained by hypophyseal portal veins,
w/c descend through the infundibulum, into the
adenohypophysis
b. Secondary capillary plexus
• consists of fenestrated capillaries coming off to the
hypophyseal portal veins
• located in the pars distalis where neurosecretory
hormones leave the blood to stimulate or inhibit the
parenchymal cells
Regulation of the pars distalis
1. Neurosecretory cells in hypothalamus
synthesize
specific hormones that enter to the hypophyseal
portal system and stimulate or inhibit the
parenchymal cells of the pars distalis.
2.The hypothalamic neurosecretory cells in turn
are regulated by the level of hormones in the
blood (negative feedback) or by other
physiologic (or psychological) factors.
PINEAL GLAND
-is also known as the pineal body or epiphysis cerebri.
-is a flattened, conical structure that projects form the
roof of the diencephalon, measuring approximately 5-8
mm in length and 3-5mm at its greater width and
weighing about 150mg.
- has a capsule formed of the pia mater, from which
septa and trabeculae extend to subdivide the gland
into several incomplete lobules.
- the trabeculae convey vascular elements and
unmyelinated nerve fibers into the interior of the
gland.
- is developed as an evagination from the posterior
part of the roof of the 3rd ventricle in the midline
(i.e. the neural ectoderm of the hypothalamus)
- its size is greatest in infancy and childhood & stars to
involute towards puberty.
- it secretes melatonin at night and serotonin during
the day.
- regulates the daily rhythms of bodily activities
Pineal gland
Pineal gland
• It consists of pinealocyte and
neuroglial cells
• Pinealocytes (P) are clumps & cords
of modified neurons which have
rounded granular nuclei, prominent
nucleoli, highly branched processes &
poorly stained cytoplasm.
• Neuroglial (N) cells are similar to
astrocytes.
• In aging pineal gland, basophilic
extracellular bodies- pineal sand (S)
(copora arenacea) are present.
• These pineal sand are concentric
layers of calcium and magnesium
phosphate within an organic matrix.
Calcified pineal gland can be seen on
X- ray of the skull.
• It secretes melatonin which lightens
the skin and supresses the pituitary
gonadotrophin.
-is a neuroendocrine transducer which converts
nervous input into variations in hormone output
-its activity is influenced by daily cycle of light and dark
(circadian and seasonal biorhythms).
-the gland is active in young animals and children.
-influences reproductive system and gonadal activities.
-it is an unusual organ because there are no afferent or
efferent nerve connections with other parts of the brain.
-innervation is exclusively via sympathetic fibers from
superior cervical Gagnon
-contains calcified concretions of calcium and
magnesium salts known as copora arenacea (brain
sand) in its interstitium. The function of these is
unknown.
-is composed primarily of pinealocytes and neuroglial
cells
A. Pinealocytes
-synthesize and secrete serotonin (usually during day)
and melatonin (usually at night.
-may also produce Arginine vasotocin-peptide
hormone that may be an antagonist of luteinizing
hormone and follicle-stimulating hormone.
-are pale staining cells with numerous long processes,
which end in dilatations near capillaries.
-possess a large nucleus, well-developed smooth
endoplasmic reticulum some rough endoplasmic
reticulum, free ribosome's Golgi complex, and
numerous secretory granules.
-also contain microtubules, microfilaments, and
unusual structures called synaptic ribbons. The
latter are composed of dense tubular elements
surrounded by synaptic vesicle-like spheroids
whose function remains unclear.
B. Neuroglial (interstitial) cells
- resemble astrocytes, and called pineal astrocytes
- stain positively for glial fibrillary acidic protein
- have elongated nuclei more heavily stained than those of
pinealocytes, elongated processes and a small, densely
staining, oval RER, microtubulles, and many microfilaments,
and intermediate filaments:
- usually found in perivascular areas and between the groups
of pinealocytes.
- represent only about 5% of the cells in the gland
 In humans and other mammals the cycle of light and
darkness is detected within the retinas and transmitted to
the pinealocytes via the retinohypothalamic tract, the
suprachiasmatic nucleus, and the tracts of sympathetic
fibers entering the pineal.
• Path of information transfer from eyes to
pineal is via
– retinohypothalamic tracts,
– to suprachiasmatic nucleus and then
– the tracts of sympathetic fibers entering the
pineal
THYROID GLAND
• lies deep to the sternothyroid and sternohyoid
muscles of anterior neck
• located anteriorly in the neck at the level of the
C5-T1 vertebrae
• consists primarily of right and left lobes,
anterolateral to the larynx and trachea.
• A thin isthmus unites the lobes over the trachea
anterior to the 2nd and 3rd tracheal rings.
• The gland surrounded by a thin fibrous capsule,
which sends septa deeply into the gland.
Arterial supply Venous drainage
Lymphatic drainage:
• Prelaryngeal
• Pretracheal
• paratracheal lymph nodes.
– The prelaryngeal nodes drain into the superior
cervical lymph nodes
– the pretracheal and para-tracheal lymph nodes
drain to the inferior deep cervical nodes
Nerves of thyroid gland.
• The nerves are derived from the superior, middle, and
inferior cervical (sympathetic) ganglia
• They reach the gland through cardiac and superior
and inferior thyroid periarterial plexuses that
accompany of the thyroid arteries
HISTOLOGY OF THYROID GLAND
 composed of two lobes connected by an isthmus
 in 50% additional median pyramidal lobe exists
 has a dense irregular collagenous CT capsule, in w/c the
parathyroid glands are embedded
 subdivided by capsular septa into lobules containing
follicles
 these septa also serve as conduits or blood vessels,
lymphatic vessels, and nerves
A. Thyroid follicles (diameter 0.2-0.9mm)
• spherical structures filled with colloid, a viscous gel
consisting mostly of iodinated thyroglobulin
• enveloped by a layer of epithelial cells, called follicular
cells, which in turn and surrounded by Parafollicular cells
• enclosed by a delicate network of reticular fibers and
plexus of capillaries, lymphatic vessels and nerves
Thyroid & Parathyroid Glands
Trachea, esophagus & thyroids
• Thyroid follicles are filled with
a glycoprotein complex called
thyroglobulin, also known as
colloid, which stores the thyroid
hormones (T3 and T4).
• In actively secreting gland,
follicles are small, very little
amount of colloid, the cuboidal
are relatively tall or columnar.
• When less active, the follicles
are distended with stored colloid
& lining cells appear flattened
(low cuboidal).
•The functional units of the
thyroid gland are the
thyroid follicles, lined by a
single layer of(1st type of
cells) cuboidal epithelial
cells or follicular cells
bounded by a basement
membrane.
•The follicles contain a
homogenous pinkish mass
of colloid material.
2nd type of cells are the
• Parafollicular cells or C cells
found singly or in small
clumps in the interfollicular
spaces. These are 2 to 3
times larger than follicular
cells.
• These cells secrete calcitonin
which lowers the blood
calcium level.
• Clinical correlation-Iodine
deficiency goiter
• Cretinism-in hypothyroid
children
Thyroid gland
Thyroid gland shows mostly rounded follicles containing
eosinophilic colloid & lined by a single layer of low
cuboidal epithelial cells
-these two parenchymal cell types rest on a basal
lamina,
which separates them from the abundant network of
fenestrated capillaries in the connective tissue.
-function as synthesis and storage sites for thyroid
hormones.
B. Follicular cells
-are normally cuboidal in shape but become columnar when
stimulated an squamous when inactive.
-possess a distended RER with many ribosome free regions, a
supranuclear Golgi complex, numerous lysosomes, and rod-
shaped mitochondria.
-nucleus is centrally located, spheroidal, poor in chromatin, and
contains one or more nucleoli.
-their cytoplasm is basophilic, the colloid is acidophilic
(eosinophilic)
-contain many small apical vesicles, which are involved in the
transport and release of thyroglobulin and enzymes.
-possess short, blunt micrivilli, which extend into the
colloid.
-synthesize and release thyroid hormones (T3 and T4)
by the sequence of events.
-is promoted by TSH, which binds to G-protein-linked
receptors on the basal surface of follicular cells.
c. Parafollicular cells
-are also called clear (C) cells because they stain less
intensely than thyroid follicular cells.
-are present singly or in small clusters of cells located
between the follicular cells and basal lamina.
-larger than follicular cells
-belong to the population of APUD cells (amine
precursor uptake and decarboxylation cells), which are
also known as entroendocrie cells of diffuse endocrine
cells.
-constitute only about 0.1% of the total epithelial mass of
the gland.
-possess eccentrically placed nucleus, elongated
mitochondria, substantial amounts of RER bounded
secretory granules (100-300nm in diameter).
-synthesize and release calcitonin, a polypeptide
hormone, which is also called thyrocalcitonin.
-release of calcitonin is stimulated by high blood calcium
levels.
Thyroid gland
Thyroid follicular cells
Parafollicular cells
Ultrastructure of thyroid follicular and parafollicular cells
Physiological effects of thyroid hormones
1. Thyroxine (T4) and Triiodotyrosine (T3)
-act on a variety of target cells.
-increase the basal metabolic rate and thus promote
heat production.
-have broad effects on gene expression and induction of
protein synthesis (i.e. why iodine deficiency results in
growth retardation particularly brain and mental
retardation and thus decreased learning ability).
2. Calcitonin
-functions primarily to lower blood calcium levels by
inhibiting bone resorption.
PARATHYROID GLANDS (Para, adjacent + thyroid)
-are usually four small glands (3 x 6mm, with a total
weight of about 0.4g)
-lie behind the thyroid gland, on its posterior surface at
the upper and lower poles of each lobe, embedded in
the capsule of the gland.
-sometimes they are embedded in the thyroid gland.
-they can also be found in the mediastinum, lying beside
the thymus as they originate from the same pharyngeal
pouches.
-are individually contained within a capsule composed of
slender strands of collagen.
Parathyroid gland
Parathyroid gland
-the parenchyma of the glands consists of two types of
cells: the chief cells and oxyphil cells.
-septa derived from the capsule penetrate each gland to
convey blood vessels into its interior and to support its
parenchymal cells.
-become infiltrated with fat cells in older persons : the
number of oxyphil cells also increases.
Chief or Principal Cells
-Smaller and more numerous
-possess a centrally located, spherical nucleus, a well
developed Golgi complex, abundant RER, small
mitochondria, glycogen, and secretory granules of
variable size (200-400nm in diameter).
Parathyroid gland
Parathyroid gland
Oxyphil or Acidophil
Cells
-bigger but fewer in number
-Occur singly or in small
groups
-Small, darkly staining
nucleus
-Strong, acidophilic
cytoplasm
Connective tissue Stroma
-delicate fibro-reticular
tissue containing blood
vessels and nerves
-Increase in age = increase
in number of fat cells
Oxyphil cells of parathyroid gland
Parathyroid gland
Parathyroid gland
The Chief (Principal) cells
-are small, basophilic cells, arranged in clusters forming
anastomosing cords, surrounded by a rich, fenestrated
capillary network.
-synthesize and secrete parathyroid hormone (PTH).
-high blood calcium levels inhibit production of PTH
-2 types: Dark staining (Actively secreting cells)
Light staining (Inactive cells)
The Oxyphil cells or Acidophil Cells
-are large eosinophilic cells that are present singly or in
small clusters within the parenchyma of the gland.
-possess small, darkly staining nucleus many large,
elongated mitochondria, a poorly developed Golgi
complex, and only a limited amount of RER.
Oxyphil cells
-Strong, acidophilic cytoplasm
-their number increases with age.
-have no known function.
C. Parathyroid hormone
-functions primarily to increase blood calcium levels by
stimulating bone resorption by osteoclasts.
-along with calcitonin provides a dual mechanism for
regulating blood calcium levels.
vi. Adrenal (suprarenal) Glands
-are glands that lie embedded in fat at the superior pole
of each kidney.
- about 4–6 cm long, 1–2 cm wide, and 4–6 mm thick in
adults
- Together they weigh about 8 g
-are derived from two embryonic sources: the ectodermic
neural crest, which gives rise to the adrenal medulla,
and mesoderm, which gives rise to the adrenal cortex.
-are invested by their own capsule of dense, irregular,
collagenous connective tissue.
-septa derived from the capsule penetrate each gland,
serving as conduits for a rich vascular supply.
Adrenal Glands
Adrenal Cortex:
1. Zona Glomerulosa
2. Zona Fasciculata
3. Zona Reticularis
Adrenal Medulla
1. Epinephrine secreting cells
2. Norepinephrine secreting
cells
Adrenal gland at low power. The cortex can be seen above & below with the
medulla sandiweched between
A. Adrenal cortex
-makes up 80-90% of the volume of the gland
-contains parenchymal cells that synthesize and secrete,
but do not store, various steroid hormones.
-is divided into three concentric histologically
recognizable regions:
zone glomerulosa,
zona fasciculata, and
zona reticularis.
Adrenal gland
Adrenal cortex
• Zona glomerulosa-is just
beneath the capsule, cells
are arranged in rounded or
ovoid clumps with delicate
trabeculae & wide
diameter cappillaries.
• Cells have strongly stained
nucleus & little cytoplasm.
Cytoplasm contains lipid
droplets.
• It secretes aldosterone
(mineralo- corticoid) which
stimulates the sodium
pump in the renal tubules
(DCT) & also acts on renin-
angiotensin-aldosterone
hormone system .
1. Zone glomerulosa
-is located just beneath the adrenal capsule and
constitutes abut 13% of the total cortical volume.
-synthesizes and secretes mineralocorticoids, mostly
aldosterone and some deoxycorticosterone.
-hormone production is stimulated by angiotensin II
and ACTH. is composed of small cells arranged in
arch-like cords and spherical clusters. These cells
possess few small lipid droplets: a dense, round
nucleus with one or two nucleoli; an extensive
network of smooth endoplasmic retinue (SER);
short mitochondria with shelf-like cristae;
- A well-developed Golgi complex; RER and free
ribosomes.
Adrenal gland cortex – zona glomerulosa
2. Zona fasciculata
-is the largest region of the adrenal cortex ting up to
80% of its volume.
is composed of cells that are larger than those in the
zona glomerulosa and are arranged in columns, one
or two cells thick, oriented perpendicularly to the
capsule.
-contains longitudinally oriented sinusoidal capillaries
running between neighboring columns of cells.
-synthesizes and secretes glucocorticoids, namely
cortisol and corticosterone, hormone production is
stimulated by ACTH.
Zona fasciculata
-is composed of cells that are lager than those in the zona
glomerulosa and are arranged in columns, one or two
cells thick, oriented perpendicularly to the capsule.
-contains longitudinally oriented sinusoidal capillaries running
between neighboring columns of cells.
-cells contain many lipid droplets, which are lost during
histological processing; hence the cells appear vacuolated
and are referred to as spongiocytes.
-These cells also possess spherical mitochondria with tubular
and vesicular crystal, a network of smooth endoplasmic
reticulum. Some rough endoplasmic
reticulum,lysosomes,and lipofuscin pigment granules.
3. Zona reticularis
-is the deepest layer of the cortex and constitutes
about 7% of its total volume.
-synthesize and secretes androgens (mostly
dehydroepiandrosterone and some
androstenedione) and perhaps small amounts of
glucocorticoids.
-hormone production is stimulated by ACTH.
-is composed of cells, arranged in anastomosing
cords, that are smaller in size and contain fewer lipid
droplets than spongiocytes; numerous, large
lipofuscin pigment granules are common in these
cells.
-also contains some cells with pyknotic nuclei.
Adrenal gland cortex
4. physiologic effects of adrenocortical hormones
a. Mineralocorticoids
-regulate electrolyte and water balance vital effect on
epithelial cells of the renal tubules.
b. Glucocorticoids
-primarily regulate carbohydrate metabolism by
promoting gluconeogenesis, deposition of liver
glycogen, and elevation of blood glucose levels.
-also influence fat and protein metabolism and have
diverse other effects.
c. Dehydroepiandrosterone
-has typical androgenic effects, promoting masculine
characteristics.
Fetal, or Provisional Cortex
-in humans and some other animals, the adrenal gland
of the newborn is proportionately larger than that of
the adult.
-at this early age, a layer known as the fetal, or
provisional cortex is present between the medulla and
the thin permanent cortex.
-is fairly thick, and its cells are disposed in cords.
-after birth, it undergoes involution, while the permanent
cortex—the initially thin layer- develops, differentiating
into the three layers.
-its function is secretion of sulfate conjugates of
androgens, which are converted to the placenta to
active androgens and estrogens that enter the maternal
circulation.
.
Adrenal Medulla
-is completely invested by the adrenal cortex.
-contains two populations of parenchymal cells,
called chromaffin cells, which synthesize, store,
and secrete the catecholamine epinephrine and
norepinephrine (but not both in the same cell).
-also contains sympathetic ganglion cells
scattered in the connective tissue.
Chromaffin cells
-are large, polyhedral cells containing secretory
granules that stain in tensely with chromium salts
(chromaffin reacting).
-are arranged in short, irregular cords surrounded
by an extensive capillary network.
Adrenal Medulla
-Cells have larger, vesicular nuclei
-Cytoplasm contains fine granules
(chromaffin) which results in a brown
coloration when treated with chromium
salts – (Chromaffin of Pheocrome
Reaction)
-2 kinds of cells:
-Epinephrine secreting
- (+) Azocarmine & acid phosphatase (-)
iodate or silver reaction
-Norepinephrine secreting
- (+) Argentaffin and Potassium Iodate
(-) Azocarmine & acid phosphatase
-Center of Medulla:
- Several large veins with a prominent
tunica media & longitudinally disposed
smooth muscle
-Cells of Adrenal Medulla
-Chromaffin Cells (Brown)
-Ganglion Cells (Occur singly or in
groups)
Adrenal gland medulla
Adrenal gland medulla
Adrenal gland medulla
-are innervated by preganglionic sympathetic
(cholinergic) fibers, making these cells analogous in
function to postganglionic sympathetic neurons.
-possess a well developed Golgi complex, isolated
regions of RER, and numerous mitochondria.
-also contain large numbers of membrane-bounded
granules (100-300nm in diameter) containing one of the
catecholamines,
ATP,enkephalins, and cnromogranins, which may
function as binding proems for epinephrine and
norepinephrine.
a. Epinephrine-producing cells contain
homogeneous, electron-dense granules that are
smaller than granules in norepinephrine producing
cells.
b. Norepinephrine-producing cells contain heterogeneous
granules that have an extremely electron-dense core
surrounded by an electron-lucent
• the adrenal medulla is composed of polyhedral
parenchymal cells arranged in cords or clumps and
supported by a reticular fiber network.
• Profuse capillary supply intervenes between adjacent
cords, and there are a few parasympathetic ganglion
cells.
• Medullar parenchymal cells arise from neural crest cells,
as do the postganglionic neurons of sympathetic and
parasympathetic ganglia.
Adrenal gland. The medulla is highly vascular
• Parenchymal cells of the adrenal medulla can be
regarded as modified sympathetic postganglionic
neurons that have lost their axons and dendrites
during embryonic development and become
secretory cells.
• Medullary parenchymal cells have abundant
membrane-limited electron dense secretory
granules,15-350nm in diameter.
medullary cells are also found in the paraganglia
(collections of catecholamine secreting cells adjacent to
autonomic ganglia) as well as in various viscera.
-paraganglia are a diffuse source of catecholamines.
Catecholamines Release
-occurs in response to intense emotional reactions.
-is mediated by the preganglionic sympathetic fibers that
inneryate chromaffin cells.
Physiologic effects of adrenal Catecholamines
-contrite the fight-or-flight” response.
-include increased blood pressure, faster heat rate,
faster berthing and elevated blood glucose levees.
Blood supply to the adrenal glands
-is derived from the superior, middle, and inferior
adrenal arteries, which form three groups of
vessels: to the capsule, to parenchymal cells of the
cortex, and directly to the medulla.
1. Cortical blood supply: the cortical arterioles,
which quickly form capillaries and sinusoids that irrigate all
cells of the cortex and eventually join the medullary
capillaries
a. A fenestrated capillary network bathes cells of the
zona glomerulosa.
b. Straight discontinuous fenestrated capillaries
(sinusoids) supply the zona fasciculata and zona
reticularis.
2. Medullary blood supply
a. Venous blood rich in hormones reaches the
medulla via the discontinuous fenenestrated
capillaries that pass through the cortex.
b. Arterial blood: Medullary arterioles
• pass directly through the cortex and form an
extensive capillary network in the medulla.
• direct branches of capsular arteries
• form an extensive fenestrated capillary network
among the chromaffin cells of the medulla.
c. Medullary veins join to form the suprarenal vein
which exits the gland
Pancreatic Islets
• The pancreatic islets (islets of Langerhans) are compact
spherical or egg-shaped masses of endocrine tissue embedded
within the acinar exocrine tissue of the pancreas
• Most islets are 100–200 m in diameter and contain several
hundred cells, but some are much smaller with only a few cells.
• There are more than 1 million islets in the human pancreas,
with the gland's narrow tail region most enriched for islets, but
they only constitute 1–2% of the organ's volume.
• A very thin capsule of reticular fibers surrounds each islet,
separating it from the adjacent acinar tissue.
• Pancreatic islets have the same embryonic origin as the
pancreatic acinar tissue: masses of cells in epithelial
outgrowths from the intestinal lining (endoderm) near the
common bile duct
• Endocrine portion, the islets of
Langerhans is developed
together with the exocrine
portion. They are most
numerous in the tail of the
pancreas.
• It consists of clumps or cords of
secretory cells, supported by
fine collagenous net work with
numerous fenestrated
cappillaries. Cells are poorly
stained and has granular
cytoplasm.
• Cells types are indistinguishable
in H and E stain.
• Under special stain, 3
types of cells can be
seen. They are alpha
(glucagon secreting
cells), beta (insulin
secreting cells) and
delta cells(
somatostatin
secreting cells). Beta
cells are situated
more peripherally.
• PP cells secrete
pancreatic
polypeptide.
Pancreas
-With thin, fibroelastic capsule that divides the organ into
lobules
-Intercalary type of intralobular ducts
-Loose interlobular connective tissue
-Thick walled Interlobular ducts
-Pancreatic Islets of Langerhans
-richly vascularized, spheroidal masses of pale
staining cells, arranged in the form of irregular
anastomosing cords
- all serous acini
- presence of centro-acinar cells inside the
lumen of the acini
Four types of granular cells
- cells (Glucagon)
- insolube in alcohol and relatively large and
colored brilliant red
-Accumulate in the periphery of the islet
-Abundant dense granules
- cells (Insulin)
-Contain fine granules that are soluble in
alcohol
-Located in the interior of the islet
-60-90% of the islet cells
- cells (Somatostatin)
-Larger & less dense than alpha cells
-Contains small blue staining granules
• Endocrine tissue (E) scattered in
the GI tract also known as DNES
cells( diffuse neuroendocrine
system cells)
• They are peptide & amine
secreting endocrine cells found at
any level in the mucosa from the
base of the gland to the tip of villi.
• These cells secrete gastrin,
secretin, serotonin,
enteroglucagon, somatostatin etc.
• These hormones constitute a
balanced system of agonists &
antagonists which collectively
regulate & coordinate most aspects
of GI activity in concert with ANS
THANK YOU!

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Endocrine System.ppt

  • 1. ANATOMY OF ENDOCRINE SYSTEM FOR 2ND YEAR BSC NURSING By:- Dr Temesgen Wirtu
  • 2. ENDOCRINE SYSTEM Comprises several discrete ductless glands (the pituitary, pineal, thyroid, parathyroids, and adrenal glands), which secrete hormones directly into the blood or lymph circulation. clusters of endocrine cells located within certain complex organs such as Islets of Langerhan’s of pancreas, juxtaglomerular cells of the kidney, the cells of the heart that produce the atrial natriuretic factor, liver, lungs, and the cells of the placenta, ovary and testes), and isolated endocrine cells in the epithelial lining of the gastrointestinal and respiratory system. • characterized by the synthesis, storage and secretion of chemical messengers or signals known
  • 3.
  • 4. interacts closely with  the nervous system (via the connection between the adenohypophysis and the CNS) to modulate and control all the physiological systems and metabolic activities,  the immune system. -endocrine dysfunctions may affect the immune response and vice versa. -the hormones are liberated by specialized cells that are called endocrine cells because they secrete "inward,” as opposed to exocrine cells, which secrete into a body cavity or toward the body surface.  Endocrine cells usually aggregate as endocrine glands, where they typically arrange themselves as cords of cells.
  • 5.  A notable exception is the thyroid gland, in which the cells are organized as microspheres called follicles.  Most hormones act at a distance from the site of their secretion and hence, -the endocrine cells lie very close to blood and lymph capillaries, which receive the secreted hormones and distribute them through out the body. -The tissues and organs on which the hormones act are called Target tissues or organs, because they have receptors that specifically recognize and respond to specific hormones. Importance of Receptor Mechanism 1.Hormones in circulation do not indiscriminantly influence all cells of the body. 2.When they are present in small amount in the blood, target cells respond to this small concentration.
  • 6. Hormones -are chemical messengers that are carried via blood stream to distant target cells. -include low-molecular weight water soluble proteins and polypeptides and lipid-soluble substances, principally the steroid hormones. A. Water-soluble hormones :hydrophilic – are low-molecular weight proteins and polypeptides. – interact with specific cell surface receptors on target cells. – attach to the outer or inner surfaces (hydrophilic leaflet) of plasma membrane.
  • 7. 1. G-protein-linked receptors • are utilized by some hormones such as epinephrine, TRH, TSH, FSH, serotonin • binding leads to production of a second messenger that affects metabolic activity. 2. Catalytic protein receptors -are utilized by insulin and growth hormone. -binding activates protein kinases that phosphorylate target proteins. B. Lipid-soluble hormones • are principally the steroid hormones. • diffuse across the plasma membrane of target cells. • bind to specific receptors in the cytosol or nucleus, forming hormone-receptor complexes that regulate transcription of DNA. • include thyroxin, progesterone, estradiol,
  • 8. Cells communication  is vital for any multicellular organism to function efficiently. • at a local level, communicate is via cell surface molecules and gap junctions, • while remote communication is mediated by the secretion of chemical messengers, which activate cells by interacting with specific receptors. • such secretion may be one of four modes of secretion: 1. Autocrine 2. Paracrine 3. Endocrine and 4. Synaptic secretion
  • 9. 1. Autocrine secretion  occurs when a chemical messenger to act on its own receptor. • This is particularly evident in the local control of cell growth by growth factors such as epidermal growth factor. 2. Paracrine secretion -describes the chemical messengers to act on adjacent cells. -this is also mainly concerned with the local control of cell growth and is also a mode of action of many of the cells of the diffuse neuroendocrine system. 3. Endocrine secretion -is the secretion of chemical messengers (hormones) into the blood stream to act on distant tissues.
  • 10. 4. Synaptic secretion • refers to communication by direct structural targeting from one cell to another via synapses, and • is confined to the NS. The chemical messengers and/or hormones belong to four main molecular classes: 1. Amino acid derivatives  Adrenaline or Epinephrine  Noradrenaline or Norepinephrine  Thyroxine  Melatonin  Serotonin
  • 11. 2. Small (short) Peptides • Thyroid-releasing hormone (TRH) • Anti-diuretic hormone (ADH) or Arginine- vasopressin hormone (AVP) • Oxytocin 3. Protein (Polypeptide) hormones • Nerve growth factor (NGF) • Epidermal growth factor (EGF) • Insulin • Growth hormone (GH) • Thyroid-stimulating hormone (TSH) • Calcitonin • Parathormone (parathyroid hormone) • Renin (proteolytic enzyme receptor)
  • 12. 4. Steroid hormones • Cortisols e.g. Aldosterone • Progesterone • Testosterone • oestradiol Endocrine glands • ductless glands (no duct system) in contrast to the exocrine glands which have ducts. • secrete hormones directly into the blood streams • contain islands of secretory cells of epithelial origin, with interlacing delicate supportive tissue rich in blood and lymph capillaries. • have rich vascular connective tissue stroma
  • 13. Endocrine cells • are usually characterized by prominent nuclei & prolific cytoplasmic organelles especially mitochondria, ER, Golgi bodies and secretory vesicles. • Liver: a mixed gland – secretes bile into the duct system and passes secretions directly into the blood vessel • Pancreas: a mixed gland
  • 14. Origin • Ectoderm– hypophysis, adrenal medulla (chromaffin bodies) • Mesoderm– testes, ovaries, adrenal cortex • Endoderm– thyroid, parathyroid, pancreatic islets • 2 General Categories (based on the chemical nature of secretions) – Protein & polypeptide secreting : hypothesis, thyroid, parathyroid, A & B cells of pancreas – Steroid Secreting – gonads & adrenal cortex
  • 15. PITUITARY GLAND (HYPOPHYSIS)  Also called hypophysis cerebri  Weighs about 0.5g (the size of a pea seed) and its normal dimensions in humans are about 10 x 13 x 6mm  Lies below the base of the brain, connected to the hypothalamus to which it is structurally and functionally related  Situated in bony cavity of sphenoid bone named the hypophyseal fossa(sella turcica)important radiological landmark  Consists of two major subdivisions- the adenohypophysis and the neurohypophysis  Each subdivision is derived from a distinct embryonic analog, which is reflected in its unique cellular constituents and functions.
  • 16. Situated at the base of the brain
  • 17.
  • 18. Is situated in the hypophyseal fossa (H) in the body of sphenoid bone, called sella tursica
  • 19. The pituitary gland is composed of an anterior part and a posterior part, which is directly attached to the hypothalamus of the brain by a stalk called the infundibulum. The gland occupies a fossa of the sphenoid bone called the sella turcica (L. Turkish saddle)
  • 20.
  • 21. 1. Adenohypophysis • constitutes the anterior portion of the pituitary gland. • originates from an ectodermal diverticulum of the stomodeum (primitive oral cavity) • is subdivided into the pars distalis, pars tuberalis, and pars intermedia. 2. Neurohypophysis • constitutes the posterior portion of the pituitary gland. • originates from an evagination of the hypothalamus. • consists of a large portion, the pars nervosa, and the smaller infundibulum, or the neural stalk • the neural stalk is composed of the stem and median eminence.
  • 23. Parts of Adenohypophysis 1. Pars distalis -External collagenous capsule and an internal supportive reticular fiber network. -It is highly vascular -Consists of irregular cords of parenchymal cells lying adjacent to fenestrated capillaries. Cells of Pars distalis: Chromophils, Chromophobes A. Chromophils -are parenchymal cells that stain intensely -are classified into two types, depending on the dyes they bind using special histologic stains
  • 25.  Synthesize, store, and release several hormones  Regulated by an specific stimulatory and inhibitory hormones that produced by neurosecretory cells in the hypothalamus and conveyed to the pars distalis via portal blood vessels in the median eminence 1.Acidophils • bind acid dyes and often stain orange to red • secrete direct action hormones -most common in central and posterolateral regions -are small, spherical cells (15-20µm in diameter) of two subtypes: somatotrophs and mammotrophs
  • 26.
  • 27. Somatotrophs  Produce somatotropin (GH), w/c is contained intracellularly within spherical, membrane-bounded granules (300-400nm)  Are the most numerous cells making up almost half (50%) of the bulk of the anterior pituitary  Possess a centrally positioned nucleus, moderate-sized Golgi complex, rod-shaped mitochondria, and abundant rough endoplasmic reticulum (RER)  Are stimulated by somatotropin-releasing hormone (SRH) and are inhibited by somatostatin  GH is generalized hormone b/c act not on specific target organ, rather on several cells including epithelial cells, fibroblasts, bone, cartillage, muscle, adipocytes, etc.
  • 28. Mammotrophs (Lactotrophs)  Comprise up to 20% of the anterior pituitary, increasing in number during pregnancy and lactation  Produce prolactin, which is stored in small membrane bounded by granules (200nm in diameter)  These granules are enlarge in pregnant and lactating women, and after suckling is complete, they undergo crinophagy  Are stimulated by prolactin-releasing hormone (PRH) and inhibited by prolactin-inhibiting hormone (PIH)
  • 29. 2. Basophils (Trophic hormones) • bind to basic dyes and typically stain blue • most common at the periphery region of pars distalis • include three subtypes: – Corticotrophs – Thyrotrophs – Gonadotrophs
  • 30. Corticotrophs  Produce adrenocorticotropic hormone (ACTH) and lipotropic hormone (LPH)  Both stored in granules that are 50-400 nm in diameter  constitute about 20% of anterior pituitary mass  spherical to ovoid in shape with relatively few cells  are stimulated by corticotropin-releasing hormone Thyrotrophs  Produce thyroid-stimulating hormone (TSH), which is stored in small granules (150nm in diameter)  usually located just beneath the plasma membrane  stimulated by thyrotropin-releasing hormone (TRH) makes only about 5%
  • 31. Gonadotrophs  Produce FSH and LH in sexes, although the latter is often referred to as interstitial cell-stimulating hormone  Hormones are stored in large granules (200-400 nm)  Make up only about 5% of the anterior pituitary  stimulated by gonadotropin-releasing hormone (GnRH)
  • 32. B.Chromophobes  Are parenchyma cells that do not stain intensely  Small cells, arranged close to each other in clusters, that lack or have a few secretory granules  They may also represent undifferentiated cells that are capable of differentiating in to various types of chromophils
  • 33. 2. Pars Intermedia  lies b/n the pars distalis and pars nervosa  characterized by the presence of numerous colloid- containing cysts that are lined by cuboidal cells  possesses basophilic cells, which sometimes extend into the pars nervosa  in some vertebrates, they secrete melanocyte- stimulating hormone (MSH), endorphin etc.
  • 35. • Pars intermedia PI- is derived from Rathke’s pouch, the cells are basophilic and form irregular clumps lying between Pars ant: (PA) and Pars post (PP) • Small cystic spaces filled with eosinophilic material may be seen. • It is poorly developed in human but relatively well developed in animal. P P P A P I
  • 36. 3. Pars Tuberalis  surrounds cranial part of infundibulum(hypophyseal stalk)  composed of cuboidal basophilic cells, arranged in cords along an abundant capillary network  probably secretes FSH and LH  highly PAS positive region due to high accumulation of glycogen. Folliculo-stellate cells  supportive cells of the adenohypophysis  maintain favorable fluid and electrolyte env’t for the secretory cells of the adenohypophysis
  • 37.
  • 38. B. Neurohypophysis  constitutes the posterior portion of the pituitary gland  originates from an envagination of the hypothalamus  divided in to the infundibulum, w/c is continuous with the hypothalamus and the pars nervosa, w/c is the main body of neurohypophysis 1. Hypothalamohypophyseal tract o contains unmyelinated elongated axons of neurosecretory cells whose somata are located in the supraoptic and paraventricular nuclei of the hypothalamus o transports oxytocin, vasoporessin, neurophysin (a binding glycoprotein specific for each hormone) and ATP to the pars nervosa
  • 39. 2. Pars Nervosa  Contains distal ends of the hypothalamo-hypophyseal axons and the site where the neurosecretory granules in these axons are stored or site of accumulation known as Herring bodies  Releases oxytocin and vasopressin in to fenestrated capillaries in response to nerve stimulation
  • 40.
  • 41. Physiologic effects of pituitary hormones 1. Hormones of the pars distalis a. Somatotropin (GH)  increases metabolism in most cells  indirectly stimulates epiphyseal plates and the growth of long bones via production of the somatomedins in the liver b. prolactin promotes dev’t of the mammary gland during pregnancy stimulates milk production during lactation
  • 42. c. Adrenocorticotrophic hormone (ACTH)  stimulate synthesis and release of adrenal cortex hormones particularly glucocorticoids d. Follicle-stimulating hormone (FSH)  stimulates growth of secondary ovarian follicles and estrogen secretion in women  stimulates sterol cells, w/c are located in somniferous tubules and function in species e. Luteinizing hormone (LH)  promotes ovulation, formation of corpus lutem and progesterone secretion in women  stimulates testosterone synthesis by Leydig cells in the testes
  • 43.
  • 44. f. Thyroid-stimulating hormone (TSH)  stimulates synthesis and release of thyroid hormones (T3 & T4) by thyroid follicular cells 2. Hormones released by the pars nervosa a. Oxytocin (OT)  induces smooth muscle contraction in the wall of the uterus during copulation and at parturition  induces contraction of epithelial cells of the mammary gland during nursing b. vasopressin, Argenine-vasopressin (AVP)  also called antidiuretic hormone (ADH)  renders cells of renal collecting tubules permeable to water, reabsorbed to produce a concentrated urine  acts as a powerful vasoconstrictor of smooth muscle cell in the tunica media of arterioles.
  • 45. D. Vascularization of the pituitary gland 1. Arterial supply  From two pairs of BVs w/c derived from internal carotid artery a. The right and left superior hypophyseal arteries This supply the pars tubelaris, infundibulum, and median eminence b. The right and left inferior hypophyseal arteries This supply mostly the pars nervosa region
  • 46. • Internal carotid gives off superior and inferior hypophyseal arteries • Superior hypophyseal arteries divide into capillaries in the region of median eminence and neural stalk. • These capp: are connected to second set of capp: in the adenohypophysis. These 2 sets belong to hypophyseal portal system • The function of these cap: is to convey the hormones from hypothalamus to adenohypophysis
  • 47. Pituitary Gland AdenoHypophysis 1. Pars Distalis 2. Pars Tuberalis 3. Pars Intermedia Neurohypophysis 1. Pars Nervosa 2. Infundibulum 3. Median eminence
  • 48. 2. Hypophyseal portal system a. Primary capillary plexus  consists of fenestrated capillaries coming off to the superior hypophyseal arteries.  located in the median eminence where stored the hypothalamic neurosecretory hormones enter to the blood and drained by hypophyseal portal veins, w/c descend through the infundibulum, into the adenohypophysis b. Secondary capillary plexus • consists of fenestrated capillaries coming off to the hypophyseal portal veins • located in the pars distalis where neurosecretory hormones leave the blood to stimulate or inhibit the parenchymal cells
  • 49. Regulation of the pars distalis 1. Neurosecretory cells in hypothalamus synthesize specific hormones that enter to the hypophyseal portal system and stimulate or inhibit the parenchymal cells of the pars distalis. 2.The hypothalamic neurosecretory cells in turn are regulated by the level of hormones in the blood (negative feedback) or by other physiologic (or psychological) factors.
  • 50. PINEAL GLAND -is also known as the pineal body or epiphysis cerebri. -is a flattened, conical structure that projects form the roof of the diencephalon, measuring approximately 5-8 mm in length and 3-5mm at its greater width and weighing about 150mg.
  • 51. - has a capsule formed of the pia mater, from which septa and trabeculae extend to subdivide the gland into several incomplete lobules. - the trabeculae convey vascular elements and unmyelinated nerve fibers into the interior of the gland. - is developed as an evagination from the posterior part of the roof of the 3rd ventricle in the midline (i.e. the neural ectoderm of the hypothalamus) - its size is greatest in infancy and childhood & stars to involute towards puberty. - it secretes melatonin at night and serotonin during the day. - regulates the daily rhythms of bodily activities
  • 54. • It consists of pinealocyte and neuroglial cells • Pinealocytes (P) are clumps & cords of modified neurons which have rounded granular nuclei, prominent nucleoli, highly branched processes & poorly stained cytoplasm. • Neuroglial (N) cells are similar to astrocytes. • In aging pineal gland, basophilic extracellular bodies- pineal sand (S) (copora arenacea) are present. • These pineal sand are concentric layers of calcium and magnesium phosphate within an organic matrix. Calcified pineal gland can be seen on X- ray of the skull. • It secretes melatonin which lightens the skin and supresses the pituitary gonadotrophin.
  • 55. -is a neuroendocrine transducer which converts nervous input into variations in hormone output -its activity is influenced by daily cycle of light and dark (circadian and seasonal biorhythms). -the gland is active in young animals and children. -influences reproductive system and gonadal activities. -it is an unusual organ because there are no afferent or efferent nerve connections with other parts of the brain. -innervation is exclusively via sympathetic fibers from superior cervical Gagnon
  • 56. -contains calcified concretions of calcium and magnesium salts known as copora arenacea (brain sand) in its interstitium. The function of these is unknown. -is composed primarily of pinealocytes and neuroglial cells A. Pinealocytes -synthesize and secrete serotonin (usually during day) and melatonin (usually at night. -may also produce Arginine vasotocin-peptide hormone that may be an antagonist of luteinizing hormone and follicle-stimulating hormone.
  • 57.
  • 58. -are pale staining cells with numerous long processes, which end in dilatations near capillaries. -possess a large nucleus, well-developed smooth endoplasmic reticulum some rough endoplasmic reticulum, free ribosome's Golgi complex, and numerous secretory granules. -also contain microtubules, microfilaments, and unusual structures called synaptic ribbons. The latter are composed of dense tubular elements surrounded by synaptic vesicle-like spheroids whose function remains unclear.
  • 59. B. Neuroglial (interstitial) cells - resemble astrocytes, and called pineal astrocytes - stain positively for glial fibrillary acidic protein - have elongated nuclei more heavily stained than those of pinealocytes, elongated processes and a small, densely staining, oval RER, microtubulles, and many microfilaments, and intermediate filaments: - usually found in perivascular areas and between the groups of pinealocytes. - represent only about 5% of the cells in the gland  In humans and other mammals the cycle of light and darkness is detected within the retinas and transmitted to the pinealocytes via the retinohypothalamic tract, the suprachiasmatic nucleus, and the tracts of sympathetic fibers entering the pineal.
  • 60. • Path of information transfer from eyes to pineal is via – retinohypothalamic tracts, – to suprachiasmatic nucleus and then – the tracts of sympathetic fibers entering the pineal
  • 61. THYROID GLAND • lies deep to the sternothyroid and sternohyoid muscles of anterior neck • located anteriorly in the neck at the level of the C5-T1 vertebrae • consists primarily of right and left lobes, anterolateral to the larynx and trachea. • A thin isthmus unites the lobes over the trachea anterior to the 2nd and 3rd tracheal rings. • The gland surrounded by a thin fibrous capsule, which sends septa deeply into the gland.
  • 62.
  • 64. Lymphatic drainage: • Prelaryngeal • Pretracheal • paratracheal lymph nodes. – The prelaryngeal nodes drain into the superior cervical lymph nodes – the pretracheal and para-tracheal lymph nodes drain to the inferior deep cervical nodes Nerves of thyroid gland. • The nerves are derived from the superior, middle, and inferior cervical (sympathetic) ganglia • They reach the gland through cardiac and superior and inferior thyroid periarterial plexuses that accompany of the thyroid arteries
  • 65.
  • 66. HISTOLOGY OF THYROID GLAND  composed of two lobes connected by an isthmus  in 50% additional median pyramidal lobe exists  has a dense irregular collagenous CT capsule, in w/c the parathyroid glands are embedded  subdivided by capsular septa into lobules containing follicles  these septa also serve as conduits or blood vessels, lymphatic vessels, and nerves A. Thyroid follicles (diameter 0.2-0.9mm) • spherical structures filled with colloid, a viscous gel consisting mostly of iodinated thyroglobulin • enveloped by a layer of epithelial cells, called follicular cells, which in turn and surrounded by Parafollicular cells • enclosed by a delicate network of reticular fibers and plexus of capillaries, lymphatic vessels and nerves
  • 68.
  • 70. • Thyroid follicles are filled with a glycoprotein complex called thyroglobulin, also known as colloid, which stores the thyroid hormones (T3 and T4). • In actively secreting gland, follicles are small, very little amount of colloid, the cuboidal are relatively tall or columnar. • When less active, the follicles are distended with stored colloid & lining cells appear flattened (low cuboidal).
  • 71. •The functional units of the thyroid gland are the thyroid follicles, lined by a single layer of(1st type of cells) cuboidal epithelial cells or follicular cells bounded by a basement membrane. •The follicles contain a homogenous pinkish mass of colloid material.
  • 72. 2nd type of cells are the • Parafollicular cells or C cells found singly or in small clumps in the interfollicular spaces. These are 2 to 3 times larger than follicular cells. • These cells secrete calcitonin which lowers the blood calcium level. • Clinical correlation-Iodine deficiency goiter • Cretinism-in hypothyroid children
  • 74. Thyroid gland shows mostly rounded follicles containing eosinophilic colloid & lined by a single layer of low cuboidal epithelial cells
  • 75. -these two parenchymal cell types rest on a basal lamina, which separates them from the abundant network of fenestrated capillaries in the connective tissue. -function as synthesis and storage sites for thyroid hormones. B. Follicular cells -are normally cuboidal in shape but become columnar when stimulated an squamous when inactive. -possess a distended RER with many ribosome free regions, a supranuclear Golgi complex, numerous lysosomes, and rod- shaped mitochondria. -nucleus is centrally located, spheroidal, poor in chromatin, and contains one or more nucleoli. -their cytoplasm is basophilic, the colloid is acidophilic (eosinophilic) -contain many small apical vesicles, which are involved in the transport and release of thyroglobulin and enzymes.
  • 76. -possess short, blunt micrivilli, which extend into the colloid. -synthesize and release thyroid hormones (T3 and T4) by the sequence of events. -is promoted by TSH, which binds to G-protein-linked receptors on the basal surface of follicular cells. c. Parafollicular cells -are also called clear (C) cells because they stain less intensely than thyroid follicular cells. -are present singly or in small clusters of cells located between the follicular cells and basal lamina. -larger than follicular cells
  • 77. -belong to the population of APUD cells (amine precursor uptake and decarboxylation cells), which are also known as entroendocrie cells of diffuse endocrine cells. -constitute only about 0.1% of the total epithelial mass of the gland. -possess eccentrically placed nucleus, elongated mitochondria, substantial amounts of RER bounded secretory granules (100-300nm in diameter). -synthesize and release calcitonin, a polypeptide hormone, which is also called thyrocalcitonin. -release of calcitonin is stimulated by high blood calcium levels.
  • 81. Ultrastructure of thyroid follicular and parafollicular cells
  • 82. Physiological effects of thyroid hormones 1. Thyroxine (T4) and Triiodotyrosine (T3) -act on a variety of target cells. -increase the basal metabolic rate and thus promote heat production. -have broad effects on gene expression and induction of protein synthesis (i.e. why iodine deficiency results in growth retardation particularly brain and mental retardation and thus decreased learning ability). 2. Calcitonin -functions primarily to lower blood calcium levels by inhibiting bone resorption.
  • 83. PARATHYROID GLANDS (Para, adjacent + thyroid) -are usually four small glands (3 x 6mm, with a total weight of about 0.4g) -lie behind the thyroid gland, on its posterior surface at the upper and lower poles of each lobe, embedded in the capsule of the gland. -sometimes they are embedded in the thyroid gland. -they can also be found in the mediastinum, lying beside the thymus as they originate from the same pharyngeal pouches. -are individually contained within a capsule composed of slender strands of collagen.
  • 84.
  • 87. -the parenchyma of the glands consists of two types of cells: the chief cells and oxyphil cells. -septa derived from the capsule penetrate each gland to convey blood vessels into its interior and to support its parenchymal cells. -become infiltrated with fat cells in older persons : the number of oxyphil cells also increases. Chief or Principal Cells -Smaller and more numerous -possess a centrally located, spherical nucleus, a well developed Golgi complex, abundant RER, small mitochondria, glycogen, and secretory granules of variable size (200-400nm in diameter).
  • 90. Oxyphil or Acidophil Cells -bigger but fewer in number -Occur singly or in small groups -Small, darkly staining nucleus -Strong, acidophilic cytoplasm Connective tissue Stroma -delicate fibro-reticular tissue containing blood vessels and nerves -Increase in age = increase in number of fat cells
  • 91. Oxyphil cells of parathyroid gland
  • 94. The Chief (Principal) cells -are small, basophilic cells, arranged in clusters forming anastomosing cords, surrounded by a rich, fenestrated capillary network. -synthesize and secrete parathyroid hormone (PTH). -high blood calcium levels inhibit production of PTH -2 types: Dark staining (Actively secreting cells) Light staining (Inactive cells) The Oxyphil cells or Acidophil Cells -are large eosinophilic cells that are present singly or in small clusters within the parenchyma of the gland. -possess small, darkly staining nucleus many large, elongated mitochondria, a poorly developed Golgi complex, and only a limited amount of RER.
  • 95. Oxyphil cells -Strong, acidophilic cytoplasm -their number increases with age. -have no known function. C. Parathyroid hormone -functions primarily to increase blood calcium levels by stimulating bone resorption by osteoclasts. -along with calcitonin provides a dual mechanism for regulating blood calcium levels.
  • 96. vi. Adrenal (suprarenal) Glands -are glands that lie embedded in fat at the superior pole of each kidney. - about 4–6 cm long, 1–2 cm wide, and 4–6 mm thick in adults - Together they weigh about 8 g -are derived from two embryonic sources: the ectodermic neural crest, which gives rise to the adrenal medulla, and mesoderm, which gives rise to the adrenal cortex. -are invested by their own capsule of dense, irregular, collagenous connective tissue. -septa derived from the capsule penetrate each gland, serving as conduits for a rich vascular supply.
  • 97.
  • 98. Adrenal Glands Adrenal Cortex: 1. Zona Glomerulosa 2. Zona Fasciculata 3. Zona Reticularis Adrenal Medulla 1. Epinephrine secreting cells 2. Norepinephrine secreting cells
  • 99. Adrenal gland at low power. The cortex can be seen above & below with the medulla sandiweched between
  • 100. A. Adrenal cortex -makes up 80-90% of the volume of the gland -contains parenchymal cells that synthesize and secrete, but do not store, various steroid hormones. -is divided into three concentric histologically recognizable regions: zone glomerulosa, zona fasciculata, and zona reticularis.
  • 101.
  • 104.
  • 105.
  • 106. • Zona glomerulosa-is just beneath the capsule, cells are arranged in rounded or ovoid clumps with delicate trabeculae & wide diameter cappillaries. • Cells have strongly stained nucleus & little cytoplasm. Cytoplasm contains lipid droplets. • It secretes aldosterone (mineralo- corticoid) which stimulates the sodium pump in the renal tubules (DCT) & also acts on renin- angiotensin-aldosterone hormone system .
  • 107. 1. Zone glomerulosa -is located just beneath the adrenal capsule and constitutes abut 13% of the total cortical volume. -synthesizes and secretes mineralocorticoids, mostly aldosterone and some deoxycorticosterone. -hormone production is stimulated by angiotensin II and ACTH. is composed of small cells arranged in arch-like cords and spherical clusters. These cells possess few small lipid droplets: a dense, round nucleus with one or two nucleoli; an extensive network of smooth endoplasmic retinue (SER); short mitochondria with shelf-like cristae; - A well-developed Golgi complex; RER and free ribosomes.
  • 108.
  • 109. Adrenal gland cortex – zona glomerulosa
  • 110. 2. Zona fasciculata -is the largest region of the adrenal cortex ting up to 80% of its volume. is composed of cells that are larger than those in the zona glomerulosa and are arranged in columns, one or two cells thick, oriented perpendicularly to the capsule. -contains longitudinally oriented sinusoidal capillaries running between neighboring columns of cells. -synthesizes and secretes glucocorticoids, namely cortisol and corticosterone, hormone production is stimulated by ACTH.
  • 112. -is composed of cells that are lager than those in the zona glomerulosa and are arranged in columns, one or two cells thick, oriented perpendicularly to the capsule. -contains longitudinally oriented sinusoidal capillaries running between neighboring columns of cells. -cells contain many lipid droplets, which are lost during histological processing; hence the cells appear vacuolated and are referred to as spongiocytes. -These cells also possess spherical mitochondria with tubular and vesicular crystal, a network of smooth endoplasmic reticulum. Some rough endoplasmic reticulum,lysosomes,and lipofuscin pigment granules.
  • 113. 3. Zona reticularis -is the deepest layer of the cortex and constitutes about 7% of its total volume. -synthesize and secretes androgens (mostly dehydroepiandrosterone and some androstenedione) and perhaps small amounts of glucocorticoids. -hormone production is stimulated by ACTH. -is composed of cells, arranged in anastomosing cords, that are smaller in size and contain fewer lipid droplets than spongiocytes; numerous, large lipofuscin pigment granules are common in these cells. -also contains some cells with pyknotic nuclei.
  • 114.
  • 116. 4. physiologic effects of adrenocortical hormones a. Mineralocorticoids -regulate electrolyte and water balance vital effect on epithelial cells of the renal tubules. b. Glucocorticoids -primarily regulate carbohydrate metabolism by promoting gluconeogenesis, deposition of liver glycogen, and elevation of blood glucose levels. -also influence fat and protein metabolism and have diverse other effects. c. Dehydroepiandrosterone -has typical androgenic effects, promoting masculine characteristics.
  • 117. Fetal, or Provisional Cortex -in humans and some other animals, the adrenal gland of the newborn is proportionately larger than that of the adult. -at this early age, a layer known as the fetal, or provisional cortex is present between the medulla and the thin permanent cortex. -is fairly thick, and its cells are disposed in cords. -after birth, it undergoes involution, while the permanent cortex—the initially thin layer- develops, differentiating into the three layers. -its function is secretion of sulfate conjugates of androgens, which are converted to the placenta to active androgens and estrogens that enter the maternal circulation. .
  • 118. Adrenal Medulla -is completely invested by the adrenal cortex. -contains two populations of parenchymal cells, called chromaffin cells, which synthesize, store, and secrete the catecholamine epinephrine and norepinephrine (but not both in the same cell). -also contains sympathetic ganglion cells scattered in the connective tissue. Chromaffin cells -are large, polyhedral cells containing secretory granules that stain in tensely with chromium salts (chromaffin reacting). -are arranged in short, irregular cords surrounded by an extensive capillary network.
  • 119. Adrenal Medulla -Cells have larger, vesicular nuclei -Cytoplasm contains fine granules (chromaffin) which results in a brown coloration when treated with chromium salts – (Chromaffin of Pheocrome Reaction) -2 kinds of cells: -Epinephrine secreting - (+) Azocarmine & acid phosphatase (-) iodate or silver reaction -Norepinephrine secreting - (+) Argentaffin and Potassium Iodate (-) Azocarmine & acid phosphatase -Center of Medulla: - Several large veins with a prominent tunica media & longitudinally disposed smooth muscle -Cells of Adrenal Medulla -Chromaffin Cells (Brown) -Ganglion Cells (Occur singly or in groups)
  • 123. -are innervated by preganglionic sympathetic (cholinergic) fibers, making these cells analogous in function to postganglionic sympathetic neurons. -possess a well developed Golgi complex, isolated regions of RER, and numerous mitochondria. -also contain large numbers of membrane-bounded granules (100-300nm in diameter) containing one of the catecholamines, ATP,enkephalins, and cnromogranins, which may function as binding proems for epinephrine and norepinephrine. a. Epinephrine-producing cells contain homogeneous, electron-dense granules that are smaller than granules in norepinephrine producing cells.
  • 124. b. Norepinephrine-producing cells contain heterogeneous granules that have an extremely electron-dense core surrounded by an electron-lucent • the adrenal medulla is composed of polyhedral parenchymal cells arranged in cords or clumps and supported by a reticular fiber network. • Profuse capillary supply intervenes between adjacent cords, and there are a few parasympathetic ganglion cells. • Medullar parenchymal cells arise from neural crest cells, as do the postganglionic neurons of sympathetic and parasympathetic ganglia.
  • 125. Adrenal gland. The medulla is highly vascular
  • 126. • Parenchymal cells of the adrenal medulla can be regarded as modified sympathetic postganglionic neurons that have lost their axons and dendrites during embryonic development and become secretory cells. • Medullary parenchymal cells have abundant membrane-limited electron dense secretory granules,15-350nm in diameter.
  • 127. medullary cells are also found in the paraganglia (collections of catecholamine secreting cells adjacent to autonomic ganglia) as well as in various viscera. -paraganglia are a diffuse source of catecholamines. Catecholamines Release -occurs in response to intense emotional reactions. -is mediated by the preganglionic sympathetic fibers that inneryate chromaffin cells. Physiologic effects of adrenal Catecholamines -contrite the fight-or-flight” response. -include increased blood pressure, faster heat rate, faster berthing and elevated blood glucose levees.
  • 128. Blood supply to the adrenal glands -is derived from the superior, middle, and inferior adrenal arteries, which form three groups of vessels: to the capsule, to parenchymal cells of the cortex, and directly to the medulla. 1. Cortical blood supply: the cortical arterioles, which quickly form capillaries and sinusoids that irrigate all cells of the cortex and eventually join the medullary capillaries a. A fenestrated capillary network bathes cells of the zona glomerulosa. b. Straight discontinuous fenestrated capillaries (sinusoids) supply the zona fasciculata and zona reticularis.
  • 129. 2. Medullary blood supply a. Venous blood rich in hormones reaches the medulla via the discontinuous fenenestrated capillaries that pass through the cortex. b. Arterial blood: Medullary arterioles • pass directly through the cortex and form an extensive capillary network in the medulla. • direct branches of capsular arteries • form an extensive fenestrated capillary network among the chromaffin cells of the medulla. c. Medullary veins join to form the suprarenal vein which exits the gland
  • 130. Pancreatic Islets • The pancreatic islets (islets of Langerhans) are compact spherical or egg-shaped masses of endocrine tissue embedded within the acinar exocrine tissue of the pancreas • Most islets are 100–200 m in diameter and contain several hundred cells, but some are much smaller with only a few cells. • There are more than 1 million islets in the human pancreas, with the gland's narrow tail region most enriched for islets, but they only constitute 1–2% of the organ's volume. • A very thin capsule of reticular fibers surrounds each islet, separating it from the adjacent acinar tissue. • Pancreatic islets have the same embryonic origin as the pancreatic acinar tissue: masses of cells in epithelial outgrowths from the intestinal lining (endoderm) near the common bile duct
  • 131. • Endocrine portion, the islets of Langerhans is developed together with the exocrine portion. They are most numerous in the tail of the pancreas. • It consists of clumps or cords of secretory cells, supported by fine collagenous net work with numerous fenestrated cappillaries. Cells are poorly stained and has granular cytoplasm. • Cells types are indistinguishable in H and E stain.
  • 132. • Under special stain, 3 types of cells can be seen. They are alpha (glucagon secreting cells), beta (insulin secreting cells) and delta cells( somatostatin secreting cells). Beta cells are situated more peripherally. • PP cells secrete pancreatic polypeptide.
  • 133. Pancreas -With thin, fibroelastic capsule that divides the organ into lobules -Intercalary type of intralobular ducts -Loose interlobular connective tissue -Thick walled Interlobular ducts -Pancreatic Islets of Langerhans -richly vascularized, spheroidal masses of pale staining cells, arranged in the form of irregular anastomosing cords - all serous acini - presence of centro-acinar cells inside the lumen of the acini Four types of granular cells - cells (Glucagon) - insolube in alcohol and relatively large and colored brilliant red -Accumulate in the periphery of the islet -Abundant dense granules - cells (Insulin) -Contain fine granules that are soluble in alcohol -Located in the interior of the islet -60-90% of the islet cells - cells (Somatostatin) -Larger & less dense than alpha cells -Contains small blue staining granules
  • 134.
  • 135. • Endocrine tissue (E) scattered in the GI tract also known as DNES cells( diffuse neuroendocrine system cells) • They are peptide & amine secreting endocrine cells found at any level in the mucosa from the base of the gland to the tip of villi. • These cells secrete gastrin, secretin, serotonin, enteroglucagon, somatostatin etc. • These hormones constitute a balanced system of agonists & antagonists which collectively regulate & coordinate most aspects of GI activity in concert with ANS

Editor's Notes

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  3. 54
  4. 70
  5. 71
  6. 72
  7. 106
  8. 131
  9. 132
  10. 135