HISTOLOGY

SHIFT 3
Endocrine System 06 FEB 2023 15
Nelson M. Maglinao, MD AY 2022-2023

TABLE OF CONTENTS Cells (Seen in EM)

Nuclei Organelles
1. Endocrine System ………………………………………1 Numerous (Mitochondria, ER, Golgi,
1.1. Chemicals that Can Act as Hormones Prominent
Secretory vesicles)
1.2. Anatomic Distributions
2. Pituitary Gland …………………………………………..1
2.1. Divisions
2.2. Pituitary Hormones 1.1. Chemicals That Can Act as Hormones (LWJ)
2.3. Pars Distalis
Proteins &
2.4. Pars Intermedia 1 Insulin, GH, PTH
2.5. Pars Nervosa Glycoproteins
2.6. Clinical Correlates Small
2 Vasopressin (ADH)
3. Thyroid Gland ……………………………………………5 Peptides
3.1. Thyroid Follicles Amino Acid Thyroxine, Adrenaline,
3.2. Thyroid C Cells 3
Derivatives Noradrenaline
3.3. Clinical Correlates
Parathyroid Glands ……………………………………..7 Steroids from Adrenal Cortical Hormones,
4. 4
4.1. Cells Cholesterol Ovarian and Testicular Hormones
4.2. Parathyroid Hormone
4.3. Clinical Correlates
5. Adrenal Glands ………………………………………….9 1.2. 3 Distinct Anatomic Distributions (LWJ)
5.1. Embryologic Development
5.2. Adrenal Cortex Definition Examples
5.3. Adrenal Medulla • Gathered together in a
6. Pancreas …………………………………………………12 specialized organ to
6.1. Islet of Langerhans Thyroid,
form an endocrine
7. Diffuse Neuroendocrine System …………………….13 Parathyroid,
Organ gland
8. Pineal Gland …………………………………………….14 Adrenal,
8.1. Cell Types • ✎ Function is for Pituitary, Pineal
8.2. Melatonin synthesis, storage and
9. Slide Review …………………………………………….15 secretion of hormones
9.1. Pituitary Gland • Formed into clusters in
9.2. Thyroid Gland another organ Pancreas,
Cluster
9.3. Parathyroid Glands • In association with Ovary, Testis
9.4. Adrenal Glands exocrine glands
9.5. Pancreas
9.6. Pineal Gland • Dispersed singly
among other cells in
epithelial tissues
Gut and
• “Diffuse neuroendocrine
LEGEND Diffuse Respiratory
system”
★ Take note / Important ☛ Prof verbatim Tract
• ✎ Major function of
✎ Textbook info ✂ Previous/Other trans info these cells is probably
paracrine
1. ENDOCRINE SYSTEM (LWJ)
Synthesis and secretion of chemical
Function 2. PITUITARY GLAND
messengers (hormones)
Coordinate and integrate functions of diff. aka Hypophysis Cerebri
Hormones physiological systems together with the • Small, slightly elongated, special
nervous system Definition
appendage of the brain
Composed Of • Buried in the sella turcica and covered
• (Microscopically) They are islands of Location by the diaphragm sella (extension of
Secretory dura)
secretory cells of epithelial origin
Cells Function • Secretes variety of hormones
• From any of the 3 primary germ layers
Endocrine • Ductless glands unlike exocrine
Glands glands
• Rich in blood and lymphatic capillaries
Supporting
for rapid absorption of hormones into
Tissues
the circulation

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2.1. Divisions (LWJ)

Pars Distalis (Anterior/Adenohypophysis)
Pars • Extension of adenohypophysis
Tuberalis surrounding the neural stalk
• ✎ An epithelial upgrowth from the roof of the primitive
1 oral cavity known as Rathke’s pouch
• Residual lumen of Rathke’s pouch
Vestigial • ✎ Divides the major part of the anterior
pituitary from a thin zone of tissue lying
Cleft
against the posterior pituitary known as
the pars intermedia Fig. 2.1.3. Pars tuberalis (red) encircling the infundibular stalk
Pars Intermedia (yellow)
2
• Thin zone lying against posterior pituitary
Pars Nervosa (Posterior/Neurohypophysis)
2.2. Pituitary Hormones (LWJ)
3 • ✎ Derived from a downgrowth of nervous tissue from
the hypothalamus, to which it remains joined by the • Mediate non neural mechanism where the CNS
pituitary stalk integrates and controls many bodily functions
2 Functional Groups
Act Directly on Non- Trophic Hormones
Endocrine Tissues (Modulate secretion of other
• Growth hormone endocrine glands)
• Prolactin • TSH
• ADH • ACTH
• Oxytocin • FSH
• MSH • LH
Pituitary-Dependent Endocrine Glands
• Thyroid
• Adrenal cortex
• Gonads

2.3.1. Control of Pituitary Secretions

Releasing Factors • By hypothalamus

Fig. 2.1.1. Divisions of the pituitary gland.
• From levels of circulating
Feedback
hormones produced by the
Mechanism
pituitary dependent glands

Fig. 2.1.2. Divisions of the pituitary gland.

PP – Posterior pituitary
AP – Anterior pituitary
P – Pituitary stalk
Fig. 2.3.1.1. Control of pituitary secretion

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2.3. Pars Distalis (Adenohypophysis) • Further classified according to the staining reaction
of their specific granules to eosin and hematoxylin
Makes up 75% of the pituitary gland
or with other combination of acid-basic dyes
o Acidophils
o Basophils
• Bigger than chromophobes
• Cytoplasm is crowded with secretory
granules
Somatotrophs
• Producing growth hormone (GH or
somatotrophin)
• Act on the epiphysis of the long bone
Acidophils and stimulates general body growth
Mammotrophs (Lactotrophs)
• Produce prolactin (leukotrophic
hormone)
• Initiates and maintains milk secretion
Parenchyma Is Made Of: after pregnancy
1 Anastomosing cords • Stimulates the corpus luteum of
2 Clusters of epithelial (secretory) cells ovaries to secrete progesterone
3 Reticular fibers • Larger than Acidophils
Small amount; separate cords and cells from
sinusoidal capillaries
• Smaller and less numerous granules
4 Numerous sinusoidal capillaries • Best identified with periodic acid
schiff reagent due to the high
concentration of glycoproteins in the
2.3.1. Cell Classification granules
Thyrotrophs
• Parenchymal cells are classified based on staining • Secrete and produce TSH
reaction (thyrotropin)
Corticotrophs
• Secrete and produce ACTH
(corticotropin)
o ✎ Polypeptide which becomes split
from a much larger peptide molecule
known as pro-opiomelanocortin
(POMC)
• ✎ Hyperpigmentation in excessive
ACTH secretion
o Lipotropins (involved in regulation of
Basophils lipid metabolism) endorphins
(endogenous opioids) and various
species of MSH can be derived from
POMC)
Gonadotrophs
• Females: LH and FSH
• Males: ICSH and FSH
• Luteinizing Hormone (Females)
o Converts ruptured ovarian follicle
Fig 2.3.1.1. Cell Classification into the corpus luteum
Chromophobes • Interstitial Cell Stimulating
Hormone (Males)
• Do NOT take up stains
o Stimulates the interstitial cells of
• Smallest cells type in the anterior pituitary
Leydig to produce testosterone
• With few cytoplasmic granules
• Follicle Stimulating Hormone
• Probably representing resting or degranulated o Females – stimulates the growth
chromophil cells of ovarian follicles
o Something referred to as gamma cells o Males – acts on the seminiferous
Chromophils epithelium to produce
• Take up stains spermatozoa

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Fig 2.4. Pars Intermedia

Fig 2.3.1.2. E/M of Chromophils
Acidophils and Basophils – Best identified with the characteristic and
predominance of secretory granules
2.5. Pars Nervosa/Neurohypophysis
• Includes the:
2.4. Pars Intermedia o Median eminence of tuber cinereum
• Located between the pars distalis and pars nervosa o Infundibular stalk
o Lies close to the residual lumen o Pars nervosa
o In man, this is poorly developed
• Composed of a thin layer of cells and vesicles
containing acidophilic colloidal substance
• Basophilic parenchymal cells of the
pars intermedia
• Produces melanocyte-
stimulating hormone (MSH) or
Melanotropes intermedin
o Initiates the production of
melanin → causes increase in
skin pigmentation (darkening
of the skin)
• Deterioration of the adrenal cortex Fig 2.5.1. Pars Nervosa
Addison’s causing an increase in pigmentation COMPOSITION
Disease due to excess production of ACTH and
Supraoptic and
MSH → increased melanin production • Terminal portion of their axons
Paraventricular
• Darkening of the skin as a result of from the hypothalamus
Pregnancy nuclei
ACTH and/or MSH
• Supporting cells resembling glial
Pituicytes
cells
• Distended termination of axons
Herring bodies containing accumulations of
neurosecretory granules
HORMONES PRODUCED
• Causes the following:
o Contraction of the uterus
Oxytocin during coitus and during delivery
o Milk ejection from the mammary
gland
Vasopressin • Antidiuretic hormone (ADH)

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• Promotes reabsorption of water in the
distal convoluted tubules of the
kidney (conserves water)
• Raises blood pressure
o By contraction of smooth
muscles in the walls of blood
vessels
• Diabetes insipidus
o Injury to hypothalamus causing a
decrease in ADH
o Loss of pure water in the kidneys
• Both hormones are produced by the
supraoptic and paraventricular
Other Info
nuclei (hypothalamus) and are
released from the nerve terminals
✂ PARS NERVOSA (Senior Trans)
• Produces 2 hormones:
o Vasopressin
o Oxytocin
o Act directly on non-endocrine tissues
• Both hormones are produced by the supraoptic and
paraventricular nuclei and are released from the
nerve terminals
o Vasopressin – supraoptic nucleus
o Oxytocin – paraventricular nucleus
• Bound to glycoproteins, the hormones pass down the
axons of the hypothalamopituitary tract through the
pituitary stalk to the posterior pituitary where they are
stored in the distended terminal parts of the axons.
• Neurosecretion – release of posterior pituitary
hormones controlled directly by nerves impulses
from the hypothalamus
2.6. Clinical Correlates
2.6.1. Pituitary Adenoma
• Condition affecting the pituitary gland
• ✎ Most common disease of the pituitary, which is benign
o Excessive, continuous production of hormone,
uncontrolled by any feedback mechanism
• ✎ Some pituitary adenomas produce no hormones but
grow locally so large that they grow upwards out of the sella
turcica to compress and damage the overlying optic
chiasma and nerves, leading to visual disturbance and
eventual blindness.
• ✎ Panhypopituitarism – necrosis of the cells and failure
of hormone output due to blockage of its arterial supply
Tumors of Somatotrophs
• Increased production of growth hormone
• In children
Gigantism
• The epiphysis are not yet fused
• In adults
Acromegaly
• The epiphysis are already fused
Tumors of Corticotrophs
Cushing’s • Excess ACTH → stimulates adrenals →
Disease increase corticosteroids
HISTOLOGY
2.6.2. Transphenoidal Surgery
• Way to approach the pituitary gland without opening
the skull
• Pituitary gland
o Sits on the sella turcica and is only separated
by a thin cortex of bone from the sphenoid sinus
(fairly accessible through the nose)
• Use endoscope to access pituitary gland and remove
tumor from it
Fig 2.6.2.1. Transphenoidal Surgery
3. THYROID GLAND (U10)
• A butterfly shaped endocrine gland lying in the
anterior neck in front of the upper part of the trachea
• Consists of two lateral lobes connected by a narrow
isthmus
• Divided into lobes and lobules by trabeculae and
septae that penetrate the gland
o ✎ The septa convey a rich blood supply, together with
lymphatics and nerves
• Gland is covered by 2 capsules
o Externally located capsule
(continuous with the deep cervical
Capsules
fascia)
o True capsule (adheres closely to
the gland)
• Tri-iodothyronine and Tetra-
iodothyronine (T3 and T4)
o ✎ T3 is much more potent than T4 and
appears to be the metabolically active
form of the hormone.
o ✎ Regulates the basal metabolic rate
and has an important influence on
growth and maturation, particularly of
nerve tissue
Hormones
• Calcitonin
o ✎ Lowers blood calcium levels by
inhibiting the rate of decalcification of
bone by osteoclastic resorption and by
stimulating osteoblastic activity
o ✎ Control of calcitonin secretion is
dependent only on blood calcium levels
and is independent of pituitary and
PTH levels
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Fig 3. Thyroid Gland

3.1. Thyroid Follicle (U10)

• Structural unit of the gland
Fig 3.1.2. Active Thyroid Follicle
o Compose the lobules
• Consists of a layer of simple epithelium enclosing a
cavity called the follicular cavity
o Filled with colloid, representing the stored 3.2. Thyroid C Cell (U10)
products of the follicular lining epithelium
• ✎ Store thyroglobulin, an iodinated glycoprotein, the
storage form of thyroxine (T4) and tri-iodothyronine (T3)
• ✎ The follicles are lined by epithelial cells which are
initially responsible for the synthesis of the glycoprotein
component of thyroglobulin and for the conversion of iodide
to iodine, the iodine linking to the glycoprotein in the follicle
lumen.
Epithelial Cells of the Follicle
Normal Gland Generally simple cuboidal
Hypoactive Low cuboidal or squamous
Hyperactive Tall columnar
• Important distinguishing feature of the gland:
o ★ Cuboidal epithelium with an orderly
arrangement of the nuclei around the follicles

Fig 3.2. Thyroid C Cell (Pointed with C)

• C cells or parafollicular cell
o 2nd type of endocrine cell
• Found in the thyroid gland, in the interstices between
the follicles
• Pale-staining cells with granular cytoplasm
• ★ Secretes calcitonin – lowers blood calcium
o Suppresses the osteoclastic resorption of bone

[space intentionally left blank]

Fig 3.1.1. Inactive Thyroid Follicle

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3.3. Clinical Correlates (U10) 3.3.3. Cretinism (U10)

3.3.1. Hyperthyroidism (U10) • Hypothyroidism in infants.

• Characterized by:
• Disease characterized by the overproduction of o Severe mental retardation
thyroid hormones. o Stunting of growth
• Clinically manifests as: • Can be easily remedied by replacement of the thyroid
o Tremors hormones once it is diagnosed.
o Tachycardia o This is the reason why thyroid hormone is part of
o Hypertension newborn screening.
o Hyperglycemia
o Muscle Atrophy
• More commonly observed as Graves’ Disease
An immune system disorder that results in
Graves’
the overproduction of thyroid hormones.
Disease
[Internet]

Fig 3.3.3. Cretinism

4. PARATHYROID GLANDS (U10)

• Small, oval endocrine glands found on the posterior
Fig 3.3.1. Graves’ Disease surface of the thyroid gland.
• Covered by a capsule, separating it from the thyroid
gland.
3.3.2. Hypothyroidism (U10) o A delicate septa from the capsule passes
inwards into the gland.
• Disease characterized by the underproduction of
thyroid hormones. • Regulates serum and calcium
• Clinically manifests as: Parathyroid phosphate levels.
o Lethargy Hormone (PTH) • Secretion is stimulated by a
o Lethargic facies decrease in calcium levels.
o Low, deep voice
o Large tongue
o Coarse skin
o Cold Intolerance
A term used to denote severe
hypothyroidism, used to describe the
Myxedema
dermatologic changes that occur in
hypothyroid patients. [Internet]

Fig 4.0.0 – Parathyroid Glands

Fig 3.3.1. Myxedema

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Fig 4.1.2. Oxyphil Cells

4.2. Parathyroid Hormone (U10)

PTH raises serum calcium levels in three ways:
• Direct action of PTH on the Bone
Fig 4.1 Micrograph of the parathyroid gland embedded under the Osteoclastic • Promotes breakdown of the bone
capsule of the thyroid gland. Resorption matrix, releasing calcium into the
circulation.
• Direct action of PTH on the
4.1. Cells (U10) Kidneys
• Arranged in clusters or ribbons • Promotes renal tubular
Renal Tubular
Principal • Small with round central, vesicular Reabsorption
reabsorption of calcium ions and
(Chief) nucleus and pale eosinophilic inhibition of reabsorption of
Cells cytoplasm phosphate ions from the
• ★ Synthesize and secrete PTH glomerular filtrate.
• Occur in nodules Intestinal • Promotes calcium reabsorption in
Oxyphil • Have copious eosinophilic cytoplasm Absorption of the small intestine
Calcium • Involves Vitamin D
Cells • Increases in number with age
• ★ Does not secrete PTH
4.3. Clinical Correlates (U10)

4.3.1. Hypocalcemia
• Results from a decrease in serum calcium levels.
• Commonly occurs in patients who obtained a total
thyroidectomy.
o Due to the anatomic proximity of the parathyroids
in its location posterior to the thyroids, total
thyroidectomy may have caused the removal of
parathyroids as well.
Clinical Manifestations
Trousseau’s • Applying a tourniquet to the upper
Sign arm causes finger spasms.
Chvostek’s • Tapping the face of the patient
Sign results to facial muscle spasms.
• Hyperreflexia
Other Signs • Laryngeal Spasms
Fig 4.1.1. Principal/Chief Cells • Convulsions

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• ECG Changes 5.1. Embryologic Divisions (U10)

• Retinal Changes
✎ DISORDERS OF THE PARATHYROID GLAND (pp. 327)
• The parathyroid glands may either overwork, producing
excessive PTH (hyperparathyroidism) or underwork,
producing little or no hormone (hypoparathyroidism).
PRIMARY HYPERPARATHYROIDISM
• The commonest cause of hyperparathyroidism is a
benign tumour of one of the parathyroid glands
(parathyroid adenoma) which constantly produces
excessive PTH, unresponsive to normal feedback
mechanisms related to the blood calcium levels.
• The excess parathormone stimulates excessive
osteoclastic erosion of bone, with the release of bone
calcium into the blood to produce hypercalcemia. The Fig 5.1.1. Adrenal Gland showing Cortex (C) and Medulla (M) as
results include bone pain with X-ray abnormalities and an its divisions
increased risk of kidney stones. • Also called inter-renal tissue
SECONDARY HYPERPARATHYROIDISM • Outer bright yellow in color
Cortex
• Secondary response of all the parathyroid glands to a • Rich in cholesterol
persistent low serum calcium level in patients with kidney • Mesodermal in origin
failure who are constantly losing calcium in their urine. • Also called chromaffin tissue
• The feedback mechanism is triggered and all of the • Inner reddish in color
parathyroids become enlarged (parathyroid hyperplasia)
and secrete excess PTH in an attempt to bring the serum Medulla • Rich in vascular supply
calcium level back to normal • Has chromaffin granules in the cell
TERTIARY HYPERPARATHYROIDISM • Ectodermal in origin
• Occurs when the hyperplastic glands of secondary
hyperparathyroidism cease to respond to serum calcium
levels 5.2. Zones of the Adrenal Cortex (U10)
• The glands secrete high levels of PTH autonomously.
HYPOPARATHYROIDISM
• Rare and is usually due to inadvertent surgical removal of
all parathyroid glands during total thyroidectomy

5. ADRENAL GLANDS (U10)

• Also called suprarenal gland.
• Small, flattened endocrine glands which are closely
applied to the upper pole of each kidney.
• Pair of triangular, flattened, yellowish organ
embedded in the retroperitoneal adipose tissue
• Encapsulated and gives trabeculae into the cortex.
• Epithelial parenchyma is supported by reticular
connective tissue richly perfused by capillaries and
sinusoids.

Fig 5.2.1. Zones of the Adrenal Cortex: Capsule (Cap), Zona

Glomerulosa (G), Zona Fasciculata (F), Zona Reticularis (R),
Medulla (M)

Fig 5.1. Adrenal Gland in Situ

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ZONA GLOMERULOSA • Thick middle layer zone

• Cells running parallel to one another, in
radial direction towards the medulla
• ✂ Consists of narrow columns and cell
cords, one cell thick, separated by fine
strands of collagen and longitudinally
arranged sinusoidal capillaries
• ✂ Secretory cells contain vesicular nucleus
and abundant pale staining cytoplasm due to
large number of lipid droplets present
• ✂ During slide preparation, lipid content is
removed and cells appear vacuolated and
spongy. Therefore cells are called
spongiocytes
Histology ★ Secretes Glucocorticoids (Cortisol)
Function
and Androgenic Sex Hormones
ZONA RETICULARIS

Fig 5.2.2. Zona Glomerulosa (G), Capsule (C),

Trabeculae (T)
• Outermost zone
• Lies beneath the capsule
• Cells arranged in irregular ovoid
clusters separated by delicate fibrous
trabeculae (T)
• Round, highly stained nuclei
• Acidophilic cytoplasm
• ★ Secretes Aldosterone, a
mineralocorticoid hormone.
• Aldosterone functions to:
o Increase sodium and water Histology
retention via renal tubules
o Increase extracellular fluid
volume
Function
o Increase arterial blood pressure
• Secretion control is from Renin-
Fig 5.2.4. Zona Reticularis (R), Adrenal Medulla (M)
Angiotensin System (RAAS), which in
• Thin innermost layer.
turn is controlled by the Macula Densa
• Has anastomosing network of branching
of the renal tubules.
cords and clusters of glandular cells
★ Aldosterone secretion is independent separated by wide diameter capillaries.
of ACTH control • Smaller than the adjacent zona
ZONA FASCICULATA fasciculata, has less cytoplasm,
cytoplasm is darker staining (contains
fewer lipid droplets)
★ Secretes small amounts of androgens
Function
and glucocorticoids

5.3. Clinical Correlates (M47)

CUSHING’S DISEASE
Histology
• A condition affecting the adrenal cortex
Definition • Caused by an increase in amount of
glucocorticoids in the body
• Exogenously given steroid
• Steroid produced by a functioning
Causes
pituitary adenoma
• Tumors in the adrenal cortex
Clinical • Moon facies
Fig 5.2.3. Zona Fasciculata features • Buffalo hump

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• Skin striae 5.4. Adrenal Medulla (M47)

• Thin arms and legs
• Composed of clusters (closely-packed clumps) of
• Red cheeks
secretory cells with numerous wide diameter
• Hypertension capillaries in their fine supporting stroma.
• Diabetes • Adrenal medulla secretes the catecholamines,
• Osteoporosis adrenaline and noradrenaline, under the direct
control of sympathetic nervous system (SNS)
• On E/M, the most characteristic feature is the
presence of numerous membrane-bound granules
• Have large vesicular nuclei and
faintly basophilic cytoplasm with
Secretory chromaffin granules
cells • Granules become brown when fixed
(Chromaffin with potassium dichromate
cells) (Zenker’s fixative)
o Hence, the name chromaffin cells,
was often applied to secretory cells
of the adrenal medulla
• Brown coloration of the granules
when exposed to chromium salts
• Due to the oxidation of
Chromaffin / epinephrine and norepinephrine
within the granules of the cells.
Pheochrome
• Cells containing noradrenaline
reaction
(norepinephrocytes) exhibit a
stronger positive chromaffin
reaction than adrenalin containing
cells (epinephrocytes)

Fig 5.3.1. Cushing’s Disease

✎ DISORDERS OF THE ADRENAL CORTEX (Wheater’s, p. 329)

HYPOADRENALISM: ADDISON’S DISEASE
• Clinical syndrome wherein there is failure of secretion of all
adrenal cortical hormones due to the destruction of both
adrenals (e.g.) by autoimmune adrenalitis, or in former
years, by tuberculosis
HYPERADRENALISM: CUSHING’S OR CONN’S
• More common, when there is excess secretion of one or
more cortical hormones mainly:
o Glucocorticoids – producing Cushing’s disease;
o Mineralocorticoids – producing Conn’s syndrome
• The excess hormone may be produced by a benign tumor
(adrenal cortical adenoma) or a malignant tumor
(adrenal cortical carcinoma) or by diffuse hyperplasia of
the adrenal cortex.
• In adrenal cortical carcinoma, the excessive output may
affect all three types of cortical hormone, including
androgens, and hirsutism or virilization are sometimes
present
ECTOPIC ACTH SYNDROME
• Occurs when some types of tumor elsewhere in the body
(e.g. neuroendocrine carcinomas in the lung) secrete
excessive amounts of an ACTH-like substance which Fig 5.4.1. Adrenal medulla (Chrome salt fixation, H&E)
stimulates zona fasciculata to produce excess When fixed in chrome salts, stored catecholamine granules of
glucocorticoids adrenal medullary cells are oxidized to a brown color. Those
cells containing noradrenaline (Na) exhibit a much more
strongly positive chromaffin reaction than adrenaline-secreting
cells (A).

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Fig 5.4.2. Adrenal medulla (E/M)

Take note of the presence of numerous membrane-bound granules

✎ Secretion of catecholamines (Wheater’s, p. 331)

• Acute physical and psychological stresses initiate release
of adrenal medullary hormones Fig 6.1.2. Islet of Langerhans
• The released catecholamines act on adrenergic receptors
throughout the body, particularly in the heart and blood
vessels, bronchioles, visceral muscle and smooth muscle, 6.2. Secretory Cells of Endocrine Pancreas(M47)
producing physiological effects.
• Adrenaline also has potent metabolic effects, such as the • The endocrine pancreas contains different types of
promotion of glycogenesis in liver and skeletal muscles, secretory cells when stained with Mallory Azan
thus releasing a readily available energy source during Stain
stress situations. • Stained brown
• Smaller cells located at the interior of the
Beta islet
6. PANCREAS cells • 60-90% of cells
6.1. Islet of Langerhans (M47) • Produce insulin: lowers blood sugar
levels
• Endocrine portion of the pancreas
• Large granules
• Scattered, richly-vascularized, small endocrine cells
• Located in the periphery of the islet
• On H&E the islets appear as round masses of pale Alpha
• Less numerous (25% of total)
staining cells supported by a fine collagenous cells
network containing numerous capillaries • Produce glucagon: increases blood
• The islet cells are paler staining than the calcium level
• Secrete somatostatin: effects on GI
surrounding acinar cells and they vary in sizes Delta
• function, may inhibit insulin and glucagon
Most numerous in the tail of the pancreas cells
secretion

Fig 6.1.1. Pancreas

Fig 6.2.1. Immunohistochemical stain for insulin

Shows the presence of Beta cells (stained brown)

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7. DIFFUSE NEUROENDOCRINE SYSTEM (M47)

• Scattered system of neuroendocrine cells which
secrete hormones and active peptides
• On EM, characteristic membrane-bound
neurosecretory vesicles
o Usually spherical, with an electron-dense central
core (dense core vesicles)
• The gastrointestinal neuroendocrine cells are
seen in GIT and respiratory system
• Cells of the neuroendocrine system are not easily
identifiable with ordinary H&E stain
o Reason we use immunohistochemical stains for
Chromogranin A
Fig 6.2.2. Immunohistochemical stain for glucagon
Shows the presence of Alpha cells (stained brown) Chromogranin A
• Component of all neurosecretory granules
• Identify the cells as neuroendocrine cells without
giving any clue as to their secretory product
Neuroendocrine cells
• Pyramidal shaped with broad base sitting on the
basement membrane
• Secretes numerous hormones which collectively
regulate GI activity together with the ANS
• Neuroendocrine cell of respiratory system which
secrete hormones (serotonin & bombesin) regulate
muscle tone in bronchial and vessel walls

Fig 6.2.3. Blood supply of endocrine pancreas

Was initially perfused with Carmine before fixation showing the rich
blood supply of the islet

✎ Disorders of the endocrine pancreas (p. 333)

DIABETES MELLITUS
• Diabetes mellitus is a common and important disease of
insulin metabolism, resulting in hyperglycemia
• Usually begins in childhood or adolescence
• Caused by the loss of endocrine cells in the
pancreatic islets, including those which
secrete insulin.
• The islet cell destruction is thought to be due
Type I to an abnormal autoimmune response,
possibly triggered by a viral infection, and
results in insulin deficiency.
• This has widespread metabolic effects on
carbohydrate, protein, and fat metabolism,
leading to complex metabolic and structural
effects Fig 7.1 Neuroendocrine system
Type II • Begins in late adult life (maturity onset)
• Result of the resistance of target cells to the
effect of insulin, rather than a failure of insulin
production by the pancreatic islets
PANCREATIC TUMORS
• Rarely, tumors of the islets of Langerhans may produce
disease as a result of excessive secretion of one of the islet
hormones, for example, an insulin-secreting tumor
produces hyperinsulinism with hypoglycemic symptoms

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• Among the most frequent and most important of

neuroendocrine tumors
• Grows very rapidly and infiltrates and destroys nearby
tissues, but also spreads to distant sites such as bones,
liver, and brain (metastasis)
• Often secretes an ACTH-like substance which stimulates
excessive and uncontrolled secretion of hormones from the
adrenal cortex
CARCINOID TUMOR
• Most common tumor of the neuroendocrine cells in the
alimentary tract
• Most common in the small intestine and appendix, and
grow slowly
• Secrete 5-HT
o Usually has no systemic effect because it passes from
the tumor in the gut via the hepatic portal vein to the
liver where it is broken down into inactive products
• Although they are slow-growing, they are potentially
malignant and can spread to secondary sites away from
the gut.
• In this case, 5-HT can enter the systemic blood circulation
and produce metabolic effects; this is called carcinoid
syndrome

8. PINEAL GLAND (M47)

• Small roughly spherical gland lies midline of the
brain, below the posterior end of the corpus
Fig 7.2 Neuroendocrine cells of the GI tract
Shows duodenal mucosa with crypts (C) and lower segment of villi (V) callosum
stained by immunohistochemical method for chromogranin A. • Produces melatonin
Neuroendocrine cells appear as pyramidal shaped cells with broad
base, sitting on the basement membrane.

Fig. 8.1 Pineal Gland

8.1. Main Cell Types (M47)

• Highly modified neurons arranged in
clusters and cords
Fig 7.3 Bronchiole, immunohistochemical staining for • Surrounded by a rich network of
chromogranin A fenestrated capillaries
Pinealoyctes
✎ Tumors of the Diffuse Neuroendocrine System (p. 346)
• Cytoplasm contains granules with
SMALL CELL (OAT CELL) CARCINOMA
melatonin and its precursor 5HT
• Highly malignant tumor of neuroendocrine cells of the • ✎ Round nuclei with prominent nucleoli
bronchial tree and granular cytoplasm and many highly

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branched processes, some of which 8.2. Melatonin (M47)
terminate near or upon blood vessels
• Hormone produced by pineal gland
• Similar to the astrocytes of the CNS
Neuroglial • An endocrine transducer
• Seen in between clusters of
cells • Production is induced by darkness & inhibited by
pinealocytes
light
• Also known as psammoma bodies o Inducing rhythmical changes in the endocrine
• Characteristic features of aging activity of the hypothalamus, pituitary gland,
pineal glands
Pineal Sand ovaries and testes in response to changes in light
• Basophilic
(Corpora perceived by the retina
• Extracellular bodies consisting of •
Arenacea) Has influence on the onset of puberty and body
concentric layers of calcium and biorhythms
magnesium phosphate in an • As treatment for sleep disturbance and depression
organic matrix

Fig. 8.1.1 Pineal Gland

Pinealocytes (P), Neuoglial cells (N), Pineal sand (S)

9. SLIDE REVIEW (RBK)

9.1. Pituitary Gland

Fig. 9.1 Pituitary Gland

• AKA Hypophysis Cerebri

• Small appendage of the brain in the sella turcica
• Divided into anterior adenohypophysis/pars distalis and neurohypophysis/pars nervosa by a cleft which is a
residual lumen of the Rathke’s pouch.

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o Vestigial cleft divides the anterior pituitary from the pars intermedia which is a thin zone lying against the pars
nervosa
ANDENOHYPOPHYSIS/PARS DISTALIS
• Made of clusters of secretory cells w/ numerous sinosoidal capillaries
• Classified according to their staining characteristics
Chromophobes
• Do not take up stains
• Smallest cell type
• Few or degranulated chromophil cells
Chromophils
• Take up stains
• Divided into acidophils or basophils according to staining reaction of their specific granules to eosin or hematoxylin
or to any acid-base dye stain combination
Acidophils Basophils
Somatotrophs – Growth hormone Thyrotrophs – TSH
Mammotrophs – Prolactin Corticotrophs – ACTH
Gonadotrophs – Females: LH, FSH Males: ICSH, FSH
NEUROHYPOPHYSIS/PARS NERVOSA
• Fibrous in character
• Composed of terminal portions of supraoptic and paraventricular nuclei of the hypothalamus
• Supporting cells known as pituicytes
• Oxytocin – causes contraction of the uterus during delivery & milk ejection in mammary glands
• Vasopressin – promotes reabsorption of water in the distal tubules of the kidney, producing water
PARS INTERMEDIA
• Between pars distalis and pars nervosa
• Composed of a thin layer of cells and vesicles containing acidophilic colloidal substance
• Parenchymal cells are basophils known as melanotrophs
o Produces melanocyte-stimulating hormone
o Causes increase in skin pigmentation

9.2. Thyroid Gland

Thyroid gland showing parafollicular cells and thyroid follicle

• Functional unit of the thyroid gland
• Spheroidal structure lined by a
Thyroid
single layer of cuboidal cells w/ an
Follicle
acidophilic colloidal material
• Produces T3 & T4
--space intentionally left blank--
• Individual scattered cells
• Pale-staining with granular
C Cells / cytoplasm
Parafollicular • Synthesize calcitonin
Cells o Lowers blood calcium level by
inhibiting osteoclastic
resorption of bone

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9.3. Parathyroid Gland • Pair of triangular flattened yellowish organ located in

the retroperitoneal area above the kidneys
• Divided into 2 components which are functionally and
embryologically distinct from one another
o Adrenal cortex – mesodermal
o Adrenal medulla – ectodermal
ADRENAL CORTEX
• Divided into 3 zones
o Outer zona glomerulosa
o Middle zona fasciculata
o Inner zona reticularis
• Composed of irregular ovoid
clusters of cells that secrete the
Zona mineralocorticoid aldosterone
Glomerulosa o Acts on the renal tubules to
increase sodium & water
Parathyroid gland in relation to thyroid gland
absorption
• Oval endocrine gland on the posterior surface of the
thyroid gland • Made of narrow columns and cell
cords one cell thick separated by
strands of collagen and
sinusoidal capillaries
• Cells have vesicular nucleus and
abundant pale-staining
cytoplasm giving them a sponge-
like appearance
o Spongiocytes
• Secrete mostly glucocorticoids,
cortisol, and a small amount of
androgenic sex hormone.

Zona
• Arranged in Clusters Fasciculata
• Small cells with round central nucleus
Principal and pale eosinophilic cytoplasm
or Chief • Secrete parathyroid hormone
cells o Increases serum calcium level by
increasing osteoclastic resorption
of the bone matrix
• Copious eosinophilic cytoplasm
Oxyphils • Increase in numbers as you age
• Do not secrete parathyroid hormone

9.4. Adrenal Gland

Zona fasciculata
• Thin innermost layer
• Adjacent to adrenal medulla
Zona • Consist of irregular anastomosis
Reticularis of branching cords and clusters
of glandular cells
• Secrete small amount of androgens
and glucocorticoids

Fig. 9.4-1 Adrenal gland

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9.6. Pineal Gland

Zona reticularis Pineal Gland

• Spherical gland lies midline of the brain, below the
ADRENAL MEDULLA
posterior end of the corpus callosum
• Composed of clusters of chromaffin cells with
• Produces melatonin
numerous capillaries
o Hormone produced by pineal gland
• Presence of numerous membrane-bound dense
o An endocrine transducer
granules
o Production is induced by darkness & inhibited by
• Produces epinephrine and norepinephrine light
o Has influence on the onset of puberty and body
biorhythms
• Highly modified neurons arranged in
clusters and cords with rich network
Pinealocytes of fenestrated capillaries
• Cytoplasm contains granules with
melatonin and its precursor 5HT
• Similar to the astrocytes of the CNS
Neuroglial
• Scattered between clusters of
Cells
pinealocytes
• Characteristic features of aging
pineal glands
Pineal Sand • Basophilic
Fig. 9.4-5 Adrenal medulla (Corpora • Extracellular bodies consisting of
Arenacea) concentric layers of Calcium and
Magnesium Phosphate in an
9.5. Pancreas organic matrix

REFERENCES
• Young, B., Woodford, P., & O’Dowd, G. (2013). Wheater’s
functional histology (6th ed.). Churchill Livingstone.
• Lecture recording of Dr. Maglinao
• Upper batch trans

TL: HCZ (1B)

FREEDOM WALL

Pancreas
• Endocrine portion – Islet of Langerhans
o Groups of secretory cells with numerous
fenestrated capillaries
o Secretes insulin and glucagon

HISTOLOGY 18