General

§  Endocrine glands are ductless glands of internal secretion

§  Secretions being released into the surrounding insterstitium where there is copius vascularity

§  Endocrine secretions rapidly enter the bloodstream for delivery to distant organs

§  Action requires the presence of receptors at the target sites

§  Parenchyma of endocrine organs may be composed of individual cells or groups of cells arranged in clumps, cords, arrays, or lobues

§  Secretory products elaborated by endocrine glands include steroid hormones, peptide hormones, and amines

Discrete Endocrine Glands

§  Term indicates that these glands comprise tissue with the sole function of endocrine secretion.

Adrenal glands

Parathyroids

Thyroid

Pineal

Pituitary

§  These organs possess an abundance of parenchyma, with sparce CT or stroma

§  Highly vascularized, containing numerous fenestrated capillaries

§  Often, inclusion granules can be seen in the cytoplasm of the cells, and these are made of either lipid droplets as precursors to steroid hormone synthesis, or secretory granules for protein elaboration

§  These cells are found in close proximity to the vasculature for rapid distribution of the secretory product

Mixed Exocrine and Endocrine Glands

§  Some endocrine glands are components of other tissues that are both endocrine and exocrine in function

Organ	Exocrine function	Endocrine function	Endocrine component
Pancreas	Digestive enzymes	Glucagons (A) Insulin (B) Somatostatin (d)	Islets of langerhans
Testis	Sperm production	Testosterone	Leydig cell
Liver	Bile production	Albumin Clotting factors	Liver parenchyma
Kidney	Urine production	Rennin	Juxtaglomerular cells

APUD Cells

§  Amine Precursor Uptake and Decarboxylation

§  Unicellular glands that secrete low molecular weight peptides and protein with hormone-like activity called candidate or putative hormones.

§  Can store and concentrate both biogenic amines and their precursors in the cytoplasm

§  DO NOT stain with conventional H&E

§  DO stain with silver stains, thus referred to as Argentaffin ceels

§  Often found wedged or interspersed among other cells comprising the epithelial lining of a number of diverse organs and systems

§  Have a vast array of physiological functions

Distribution and secretory products of APUD cells
Cell name	Source	Polypeptide production
A	Pancreas	Glucagon
B	Pancreas	Insulin
C	Thyroid	Calcitonin
D	Stomach, small intestine, pancreas	Somatostatin
D1	Stomach, small/large intestine, pancreas	Vasoactive Intestinal polypeptide*
EC	Stomach, small/large intestine, pancreas	Motilin*, Substance P
G	Stomach, small intestine, pancreas	Gastrine
I	Small intestine	Cholecystokinin
K	Small intestine	Gastsric inhibitory peptide
N	Small intestine	Neurostensin
S	Small intestine	Secretin
* denote a candidate  or putative hormone

THYROID

Embryology

• Arises as a midline diverticulm of the floor of the pharynx
• Develops into bi-lobed organ
• Site of origin marked by permanent pit in the tongue (foramen caecum)
• During development, the thyroid receives a small, significant contribution from the ultimo-brachial pharyngeal pouches (give rise to the parafollicular cells)

Anatomy

• Thyroid is bilobed, bilaterally symmetrical
• Firm, smooth and red-tan in color
• Located in anterior neck
• An isthmus connects two lobes
• Surface may be faintly lobulated
• Follicles may be visible in cut sections

Histology and function

• Made up of follicles, sacs filled with colloid
• Follicles are lined with epithelium, which secrete colloid
• Surrounded by a rich capillary network
• Iodide in blood is captured by the epithelium, bound to protein, and stored in follicles as thyroid hormone
• Parafollicular cells (light cells or C cells)

Situated singly and in clusters between the follicles, and also intercalated between follicular cells

Visible as clear cells in some slides

Are the source of calcitonin

Difficult to distinguish in H&E stains, but argyrophilic

Total thyroiddectomy will not result in complete calcitonin deficiency  as the parathyroid and thymus contribut to calcitonin     production

§  Functional state of the thyroid can be determined by

Size and shape of the epithelium

Size of the follicles

Amount of colloid present

§  Height of the cells is the most important criteria

Columnar in appearance- organ is hyperactive

Flat in appearance- indicate inactivity

Height of cells is an index of TSH (thyroid stimulating or thyrotrophic hormone) activity

§  Follicular size also indicates thyroid activity

Large follicles mean inactivity and colloid/hormone storage

Small follicles and scanty colloid content mean increased activity

Regulation, Synthesis, Storage, and Release of Thyroid Hormones

§  Follicular cells synthesize and secrete thyroglobulin into the follicular lumen

§  Thyroglobulin is then taken back up and modified for synthesis and production of active forms of thyroid hormone

§  This is a bi-directional process

Thyroglobulin synthesis

§  Synthesized in the RER and modified in the golgi

§  Secreted into follicular lumen as a non-iodinated glycoprotein (colloid)

§  The tyrosine residues on the thyroglobulin will ultimately become the iodinated tyrosines of the active thyroid hormone

Uptake and oxidation of Iodide

§  Iodide is taken up into follicular epithelium by active transport

§  Is oxidized by the enzyme thyroperoxidase to iodine

§  This process occurs at the apex of the cell

§  Iodine is then released into the follicular lumen, and thyroglobulin iodination occurs at the tyrosines

§  This process occurs rapidly at the interface b/t the follicle and the microvillus border of the follicular cells

§  The iodinated form of thyroglobulin remains in the lumen, until stimulated by TSH

§  Thyroid hormone, both T₃ (triodothyronine) and T₄ (thyroxine) are synthesized and released

Liberation of T₃ and T₄

§  Luminal colloid is taken up by pinocytosis

§  Result vesicles fuse with lysosomes

§  Proteolytic cleavage of the iodinate thyroglubulin yields triiodothyronine and thyroxine

§  Ratio of T₃ and T₄ influence basal metabolic rates in the adult and influence growth and neurological development in the fetus

Thyroid hormone regulation

§  Thyroid stimulating hormone (TSH) from the anterior pituitary increases thyroid hormone (TH) production

§  By stimulation of all phases of TH synthesis

§  Control is via a simple negative feed back loop, in the that high levels of TH suppress TSH release and low levels of TH increase TSH release

Histology of the Thyroid

§  Stroma (CT)

Thyroid covered by loose CT which invaginates into the substance of the gland via finger-like protrusions called septa

Gland is divided into ill-defined lobes and smaller lobules

Septa become more delicate, eventually consisting of only reticular fibers

Within the stroma are found numerous nerves, lymphatics and blood vessels

§  Parenchyma (functional)

Most of the gland is comprosed of several million follicles

A single follicle is a ball of cells

The lumen being filled with the amorphous, eosinophilic colloid thyroglobulin that is tored, non-active form of thyroid hormone

N.B. they thyroid is the only endocrine organ that stores its secretory product in an extracellular environment

Epithelial cells lining the follicle are a single layer, resting on a basement membrane

Two cell types with dissimilar function and ultra structure comprise the epithelial layer

Folliculuar cells

Present in an overwhelming majority of the follicle lining cells

Are responsible for the synthesis of thyroid hormone

Active follicular cells contain all the expected organelles and markers for cells involved in protein synthesis

Marker:  euchromatic nuclei with nucleolus or nucleoli

Marker: beaucoup RER in the basal aspect of the cell

Marker:  well developed golgi for protein trafficing in the supra-aspect of the cell

Marker:  many secretory vesicles in the apical cytoplasm

Marker: abundance of lysosomes

Apex of cells is covered with short microvilli facing the lumen of the follicle

Shape and size of cells and follicles varies depending upon “active” state.

Parafollicular cells

Calcitonin secreting

Found individually or clustered within the follicular epithelium or scattered  in the stroma

Not possible to distinguish these cells with H&E

Cell types can be distinguished with TEM

Characteristic feature of these cells is presence of numerous membrane-bound secretory granules, containing calcitonin.

Calcitonin- reduces blood calcium levels (as name implies, to tone down)

Brief pathology

§  Hyporthyoridism

Dietary iodine deficiency

Lack of thyroid hormones and TSH levels become elevated

Chronic hypothyroidism in the adult reveals itself through fatigue, memory impairment, low body temperature

Results in Myxedema

§  Hyperthyroidism

May types and causes

Common is Graves Disease:  where a TSH-like antibody stimulaes the thyroid

A hypermetabolic state is reached:   nervousness, hypermetabolism, raised body temp. and degenerative weight loss)

Ocular protrusion is due to upper eyelid retracton and edema in the periorbital tissues (imp. Diagnostic feature)

Hyperplastic Goiter often associated

§  Athyreosis

Thyroid fails to develop

Common cause of cretinism

§  Thyroiditis

Most common form is Hashimoto’s disease

Usually occurs in middle-aged women

Enlargement occurs due to lymphoid infiltration and fibrosis

Parenchyma is small, with little colloid

Occasionally carcinoma is associated

Autoimmune reaction to thyroglubulin suspected

PARATHYROID

Embryology

• Arise from brachial pouches III and IV
• Parathyroids III migrate with thymus and come to rest at the inferior poles of the thyroid gland
• Parathyroids IV do not migrate as far, become superior pair of the parathyroids, near the superior poles of the thyroid.

Anatomy

• Consists of two pairs of glands
• Each gland weighing 30-50 mg
• Gland are smooth, yellow-brown, flattened ovoid bodies

Histology and Function

• Parathyroids secrete parathormone
• Glands are essential for physiologic maintenance of circulating calcium concentrations
• Decrease circulating calcium stimulates increase PTH secretion
• This process increases the number of osteoclasts, resulting in greater calcium absorbtion from the bone matrix
• Renal excretion of calcium is also prevented, together with enhanced absorption of calcium from the GI tract
• Resulting in an overall increase in serum calcium levels

Histology of Parathyroids

• Stroma

A CT capsule envelopes these glands and sends delicate septa into the anterior portion, diving glands into course clumps of cells

Stroma contains abundant vasculature, nerves, lymphatics and unilocular fat

Fat content increase with age and remains a diagnostic tool for accurate identification

• Parenchyma

Two cell types

Chief (principal cells)

Make up the bulk of the parathyroid.

Cells are small and polygonal with clear or lightly basophilic staining cytoplasm

Cells are responsible for synthesis and release of parathormone (PTH)

PTH increase the concentration of ionized calcium in blood

Cells contain abundant RER, glycogen, secretory granules and prominent golgi apparatus.

Oxyphil cells

Located in parenchyma of parathyroids

Tend to be round and larger than chief cells

Stain intensely eosinophilic due to large numbers of mitochondria

Function uncertain, may be variant form of chief cells

Other cells

May be present, though difficult to locate

Are water-clear cells (wasserhelle)- extremely clear and apparent at times of high secretion

Transitional cells that are intermediate b/t water clear and chief cells

Possible evidence  of one cell type derived from another

• Parathyroid cells are arranged in cords and nests, separated by scanty fibrous stroma with abundant capillaries
• Occasional follicles containing protein and lined with columnar/cuboidal epithelia are present

Pathology

• Hyperparathyroidism

Excessive PTH release

Often due to tumors (adenomas)

Results in high serum calcium levels and subsequent formation of kidney stones

Ultimate renal failure

Bones become weak and porous due to increase osteoclast activity

• Hypoparathyroidism

Loss of parathyroid activity may occur following thyroidectomy

Results in serious decrease in ionzed serum calcium

Can lead to seizure, spastic muscle contraction, occasionally death

PTH administration together with calcium supplements treats problem adequately

• Hyperplasia

Gland enlarge up to 40 g., filled with water cear cells, have a pseudo-pod like protusions

Chief cell hyperplasia, symmetrical, occurs in patients with Zollinger-Ellison syndrome, a beta cell adenoma associated disease

ADRENALS

Embryology

• Arise from two separate primoridal: one ectodermal (medulla) and one mesodermal (cortex)
• Cortex develops from mesnchymal cells on the posterior body wall between the gonad and mesentery (urogenital ridge)
• Medulla is formed by ectodermal cell that migrate from the neural crest of the cortical region, passing via the celiac ganglion

Anatomy

• Adrenal are located in the retroperiotoneim, just above kidneys (suprarenal glands)
• Embedded in unilocular fat
• Weight- 4-6 g/adrenal
• Triangular in cross-section
• Outer cortex is yellow
• Inner cortex brown
• Medulla is gray
• Each gland has multiple arterial branches (superior, middle, inferior suprarenal aa)
• The arteries branch to form a subcapular plexus from which

a.     casular arteries

b.     arteries for the cortex- arborize extensively to form a fenestrated capillary bed between parenchymal cells and drain into medullary arteries

c.      branches that pass directly through the cortex to form capillary plexus of the medulla

• Only one major vein (adrenal or suprarenal vein)- the right entering the vena cava directly, the left draining into the left renal vein.

Histology and Function

Cortex

• Three zones: zona glomerulosa, zona fasciculate, zona reticularis
• When these layers are sharply defied, the ratio is approx 1:3:2
• This is a good guideline for determining where you are in the adrenal cortex
• The zona glomerulosa and zona fasciulata ofen have abundant lipid.

Zona glomerulosa

• Cells in this region form small nest of glomerules (1-3 cells across)
• Foamy appearance due to lipid droplets
• This zone is responsible for the production of the mineral corticoid: Aldosterone
• Aldosterone:

a hormone that modulates electrolytes in the blood

acts on salivary and swat glands and the kidneys

to reabsorb sodium at the expense of potassium (Na retained, K excreted)

NB this zone is NOT dependent on the pituitary;

Fasciulata is reticularis ARE dependent of the pituitary

Control of aldostrone secretion is conditioned by the Renin-Angiotensin system: (Remember SALT)

Zona Fasiculata

• Cells are arranged in long, straight columns, separated by capillaries
• They have a finely vaculoated eosinophilic cytoplasm
• Contain abundant lipid droplets that bestow the oft-used term of spongiocytes on these cells
• Lipid extracted during tissue processing
• Dependent upon ACTH (adrenocorticotrophic hormone) for maintenance of structure and function
• This zone secretes Glucocorticoids, 95% is Cortisol, following ACTH stimulation

Enhance glucose synthesis by liver to elevate blood sugar levels

Suppress inflammatory and immune responses

Cause catabolism (break down) of proteins, which may lead to muscle wasting (Remember SUGAR)

Zona Reticularis

• Inner most layer of cortex
• Cells form short, intertwining cords that abut on the medulla
• These cells are “lipid poor” with a pink cytoplasm containing abundant mitochondria
• Cells are rich in RNA
• Dependent upon ACTH for maintenance of structure and function
• This zone secretes androgens, primarily dehydroepiandrosterone (less potent than testostrone)
• Also progesterone and estrogen, following ACTH stimulation (Remember SEX)

Medulla

• Composed of pleomorphic cells (ie different shapes and sizes) ranging from polyhedral to circular, grouped in clumps and cords around sinusoidal vessels
• Separate cells secrete and contain epinephrine (80% of cells) and norepinehrine (20% of cells)
• These are strong reducing agents that can be oxidized with quinines and dichromates (chromaffins) to yield brown pigment (useful histochemical test)
• Sometimes referred to as Chromaffin cells (stain more basophilic than cortical cells with HE)
• Circulating catecholamines have similar effects on different organs to catecholamine s released by direct neural stimulation.
• However, the response can last 10x as long because hormones are only slowly removed from the blood.
• Effects of these hormones include

Elevatin heart rate

Elevating blood glucose

Splanchnic vasoconstriction etc.

Ie flight/fight functions

Remember:  SYMPATHETIC

Regualtion of Adrenal gland secretions

Cortex

• Zona glomerulosa

Aldosterone is secreted in response to circulating angiotensin levels

Also high serum K levels  can stimulate aldosterone release

Biochemical pathway of aldosterone release

Low BPà

Low BPà

Renin secretion from Kidneyà

Angiotensinà

Angiotensin Ià

Angiotension II à

Aldosteroneà

Na and water aborptionà

Increased BP and volume

• Zona fasciculate

Secretion of glucocorticoids is entirley dependent on ACTH form anterior pituitary

A negative feedback loop exits in which low concentrations of Cortisol cause increase ACTH production and vice versa

• Zona reticularis

Small, basal secretion of sex hormones which is affected by ACTH levels

Secretion of male sex hormones, androgens, has little effect other than development of secondary sex characteristics and in the development of sex oranges in early life

Adrenal Pathology

• Conn’s Syndrome

Zona Granulosa

Due to an independently functioning adenoma (benign) composed of glomerulosa-like cells which secrete large quantities of Aldosterone

Results in increase Na and water absorption leading to increase blood pressure

Concomitant loss of K results in hypokalemia with muscle weakness, changes in cardiac rhythm and general malaise

• Cushing’s Syndrome

Zona Fasiculata

From generalized hyperplasia

Secondary to an ACTH secreting tumor or directly to to a cortisol secreting tumor

Results are

fat deposition in neck and thorax

facial edema

weakening and wasting of muscle

acne

excessive growth of facial hair

• Adrenogenital syndrome

Zona Reticularis

Androgen secreting tumors affect individual differently, depending upon age and sex

Adult females may exhibit beard growth, deep voice, clitoral enlargement, and sometimes baldness

Prepubertal males can undergo precocious sex organ development

Infant females show pseudohermaphrodotism, with the presence of a phalloid organ, ovaries, and uterus

• Pheochromocytoma

Adrenal medulla

Sporadic hypertension

Excessive perpiration

Headaches

Palpitations

Temors

Nervousness

Irritability

Overall physical weakness

Caused by neoplasms in medulla

Tags: Adrenal glands, APUD cells, carcinoma, Decarboxylation, Endocrine glands, Exocrine glands, Hyperparathyroidism, Hyperplastic Goiter, insterstitium, Oxyphil, pancreas, Parathyroids, Parenchyma, Pineal, Pituitary, Stroma, thyroglobulin, thyroid, Thyroid stimulating hormone, TSH, zona fasciculate, zona glomerulosa, zona reticularis

This entry was posted on Wednesday, February 11th, 2009 at 5:01 am and is filed under Histology. You can follow any responses to this entry through the RSS 2.0 feed. Responses are currently closed, but you can trackback from your own site.