1. HISTOLOGY OF THE ENDOCRINE SYSTEM

2. ENDOCRINE SYSTEM
The endocrine system is the system of glands, each of which secretes different types of hormones directly into the bloodstream (some of which are transported along nerve tracts) to maintain homeostasis. The endocrine system in contrast to the exocrine system, which secretes its chemicals using ducts. The word endocrine derives from the Greek words "endo" meaning inside, within, and "crinis" for secrete.

3. Endocrine system Pituitary gland (hypophysis) Anterior pituitary
Posterior pituitary
Adrenal gland (suprarenal)
Adrenal cortex
Adrenal medulla
Thyroid gland
Follicles
Parafollicular cells
Parathyroid gland

4. THE PITUITARY GLAND

5.  the pituitary gland, or hypophysis, is an endocrine gland about the size of a pea and weighing 5 grams (0.18 oz) in humans. It is a protrusion off the bottom of the hypothalamus at the base of the brain, and rests in a small, bony cavity (sella turcica) covered by a dural fold (diaphragma sellae). The pituitary is functionally connected to the hypothalamus by the median eminence via a small tube called the infundibular stem (Pituitary stalk). The pituitary fossa, in which the pituitary gland sits, is situated in the sphenoid bone in the middle cranial fossa at the base of the brain. The pituitary gland secretes nine hormones that regulate homeostasis.

6. EMBRYOLOGICAL DEVELOPMENT

7. Structurally & functionally divided into 2 lobes:
1) Anterior lobe/Adenohypophysis (2/3(
2) Posterior lobe/neurohypophysis )1/3(.

10. The anterior pituitary lobe (adenohypophysis)
Master gland (adenohypophysis).
Consists of 2 parts in adults:
1. Pars distalis … known as the anterior pituitary.
rounded portion & the major endocrine part of the gland.
2. Pars tuberalis …
thin extension in contact with the infundibulum.
Pars intermedia…
Avascular tissue b/w anterior & posterior lobes, exists in fetus
(no longer present in adults). Much more functional in some lower animals, such as fish, amphibians, & reptiles.

11. The bulk of the adenohypophysis is pars distalis
The bulk of the adenohypophysis is pars distalis. That tissue is composed of winding cords of epithelial cells flanked by vascular sinusoids. In sections stained with dyes such as hematoxylin and eosin, three distinct cell types are seen among epithelial cells:
Acidophils have cytoplasm that stains red or orange
Basophils have cytoplasm that stains a bluish color
Chromophobes have cytoplasm that stains very poorly

14. Cells that contain the polypeptide hormones:
Acidophils
Cells that contain the polypeptide hormones:
Somatotropes which produce growth hormone
Lactotropes which produce prolactin
Basophils
Cells that contain the glycoprotein hormones:
Thyrotropes which produce thyroid stimulating hormone
Gonadotropes which produce luteinizing hormone or follicle-stimulating hormone
Corticotropes which produce adrenocorticotrophic hormone
Due the high carbohydrate content of the hormones within acidophils, they also stain bright purple with PAS stains.
Chromophobes
These are cells that have minimal or no hormonal content. Many of the chromophobes may be acidophils or basophils that have degranulated and thereby are depleted of hormone. Some chromophobes may also represent stem cells that have not yet differentiated into hormone-producing cells.

15. The pars intermedia is closely associated with pars nervosa and separated from the pars distalis by the hypophyseal cleft. This lobe of the pituitary shows considerable variation in size among species. It is small in man, but much larger in species such as amphibians. The pars intermedia contains large pale cells that often surround follicles filled with ill-defined "colloid". Melanocyte-stimulating hormone is the predominant hormone secreted by the pars intermedia

16. The neurohypophysis is known also as the pars nervosa
The neurohypophysis is known also as the pars nervosa. Anatomists distinguish between three areas of this organ, starting closest to the hypothalamus:
the median eminence
infundibular stalk
infundibular process
The infundibular process froms the bulk of the neurohypophysis is what is usually referred to as the posterior pituitary.
The bulk of the neurohypophysis is composed on largely unmyelinated axons from hypothalamic neurosecretory neurons. These axons have their cell bodies in the paraventricular and supraoptic nuclei of the hypothalamus. These neurons secrete oxytocin or antidiuretic hormone. Roughly 100,000 axons participate in this process to form the posterior pituitary. In addition to axons, the neurohypophysis contains glial cells and other poorly-defined cells called called pituicytes.

18. An interesting histologic feature of the neurohypophysis is the presence of Herring bodies. When viewed with an electron microscope, these are dilated areas or bulges in the terminal portion of axons that contain clusters of neurosecretory granules. The granules contain oxytocin or antidiuretic hormone, along with their associated neurophysins. Herring bodies often are seen in association with capillaries. They are somewhat difficult to identify unambiguously by light microscopy; in the image to the right, the label might better say "probable Herring bodies".

19. THYROID AND PARATHYROID GLAND

20. System
Endocrine
Artery
superior thyroid artery, inferior thyroid artery,
Vein
superior thyroid vein, middle thyroid vein, inferior thyroid vein,
Nerve
middle cervical ganglion, inferior cervical ganglion
Lymph
pretracheal, prelaryngeal, jugulo-diagastric,and lympahtics of thymus
Precursor
neural crest mesenchyme and third and fourth pharyngeal pouchendoderm

21. THYROID GLAND
located anteriorly in cervical region, just inferior to thyroid cartilage; two lobes connected by thin isthmus
largest purely endocrine gland in body

23. The thyroid gland is composed of many spherical hollow sacs called thyroid follicles. In this tissue section, each follicle (A) appears as an irregular circle of cells. The principal cells, which surround the follicle are simple cuboidal epithelium. These follicles are filled with a colloid (B), which usually stains pink. The principal cells use the thyroglobulin and iodide stored in the colloid to produce the primary thyroid hormones - including thyroxine.
Between these follicles are the parafollicular cells (C) which produce calcitonin.

26. Disorders of the thyroid gland: Hyperthyroidism
Increased metabolic rate (thyrotoxicosis)
Causes
overmedication in thyroid gland failure
increased hormone due to thyroid gland diseases – primary
increased hormone due to TSH - secondary

27. Graves Disease 80-90% of all hyperthyroidism
One of most common autoimmune diseases in US
Mostly women
Antibody that acts like TSH
Gland is diffusely enlarged & smooth

29. Thyroiditis Inflammation of thyroid Mostly chronic Presents as goiter
autoimmune
Presents as goiter

30. Hasimoto Thyroiditis Most common type in US
One of most common causes of goiter & hypothyroidism
Antibodies that block TSH

31. Neoplasms of Thyroid Gland
Not common
Neoplastic masses are more likely to
be solitary masses
“cold”
in younger patients
in males
Most are from nodular goiter

32. Adenomas Carcinomas Bbnign epithelial cells of follicles
from follicular epithelium
uncommon
papillary
most common
> 90% survive 5 yrs
follicular
more aggressive
medullary
from specialized nonepithelial cells that secrete calcitonin
aggressive
anaplastic
most aggressive
most fatal within a year

33. PARATHYROID GLAND
 4 glands in 2 pairs usually close to upper and lower poles of thyroid lobe ● May be found anywhere along pathway of descent of branchial pouches ● 10% have 2-3 glands; 5% have 5 glands, 0.2% have 6 glands ● Upper pair arises from fourth branchial cleft and descends with thyroid gland; usually at cricothyroid junction ● Lower pair arises from third branchial cleft and descends with thymus; usually near inferior thyroid ● Other locations: carotid sheath, anterior mediastinum, intrathyroidal; glands tend to be bilaterally symmetrical ● Stromal fat increases to 30% at age 25; percent fat is related to constitutional percent fat, but reduced in dying individuals; mean is 17% with wide variation

34. ● Composed primarily of chief cells and fat with thin fibrous capsule dividing gland into lobules ● May have a pseudofollicle pattern resembling thyroid follicles (pink material is PAS positive) Chief cells: ● 6-8 microns, polygonal, central round nuclei, contain granules of parathyroid hormone (PTH) ● Basic cell type, other cell types are due to differences in physiologic activity ● 80% of chief cells have intracellular fat ● Chief cell is most sensitive to changes in ionized calcium Oxyphil cells: ● Slightly larger than chief cell (12 microns), acidophilic cytoplasm due to mitochondria ● No secretory granules ● First appear at puberty as single cells, then pairs, then nodules at age 40 Water clear cell: ● Abundant optically clear cytoplasm and sharply defined cell membranes ● Chief cells with excessive cytoplasmic glycogen

35. Because the parathyroids (A) are embedded in the thyroid tissue, their tissues are often found with the thyroid tissue. The chief cells that make up this gland are smaller and darker staining than those of the thyroid. At higher magnifications, we could see that the chief cells appeared in "ribbons" or "cords." These cells secrete parathyroid hormone (PTH) Recall that you are only responsible for recognizing this tissue when it appears with the thyroid gland.

37. Chief cells
Oxyphilic nodule
Clear cells

38. THE ADRENAL GLANDS

39. Outline Introduction Adrenal cortex Cortical hormones Adrenal Medulla
Medical application.

40. Introduction
The adrenal glands are paired organs that lie near the superior poles of the kidneys, embedded in adipose tissue .
They are flattened structures with a half-moon shape; in the human, they are about 4–6 cm long, 1–2 cm wide, and 4–6 mm thick.

41. …………….
Together they weigh about 8 g, but their weight and size vary with the age and physiological condition of the individual.
Examination of a fresh section of adrenal gland shows that it is formed by two concentric layers: a yellow peripheral layer, the adrenal cortex; and a reddish-brown central layer, the adrenal medulla

42. ……
The adrenal cortex and the adrenal medulla can be considered two organs with distinct origins, functions, and morphological characteristics that became united during embryonic development.
They arise from different germ layers. The cortex arises from the coelomic epithelium, whereas the cells of the medulla derive from the neural crest, from which sympathetic ganglion cells also originate.

43. ……
The general histological appearance of the adrenal gland is typical of an endocrine gland in which cells of both cortex and medulla are grouped in cords along capillaries.
The dense connective tissue capsule that covers the adrenal gland sends thin septa to the interior of the gland as trabeculae.
The stroma consists mainly of a rich network of reticular fibers that supports the secretory cells.

44. ……

45. Blood Supply
The adrenal glands are supplied by several arteries that enter at various points around their periphery.
The branches of these arteries can be divided into three groups: arteries that irrigate the capsule; cortical arteries, branching into capillaries that irrigate the gland cells of the cortex and that eventually reach the medullary capillaries;
and medullary arteries, which pass through the cortex and form an extensive capillary network in the medulla.

46. ………..
The cells of the medulla are, thus, bathed with both arterial blood from the medullary arteries and venous blood originating from the capillaries of the cortex.
The capillary endothelium is extremely attenuated and interrupted by small fenestrae that are closed by thin diaphragms.

47. ...... A continuous basal lamina is present beneath the endothelium.
Capillaries of the medulla, together with capillaries that supply the cortex, form the medullary veins, which join to constitute the adrenal or suprarenal vein

49. Adrenal Cortex
The cells of the adrenal cortex , which have the typical ultrastructure of steroid-secreting cells, do not store their secretory products in granules;
rather, they synthesize and secrete steroid hormones upon demand.

50. ……
Steroids, being low-molecular-weight lipid-soluble molecules, diffuse through the plasma membrane and do not require the specialized process of exocytosis for their release.

51. ……
Because of the differences in disposition and appearance of its cells, the adrenal cortex can be subdivided into three concentric layers whose limits are usually not sharply defined in humans :
the zona glomerulosa, the zona fasciculata, and the zona reticularis.
These layers occupy 15%, 65%, and 7%, respectively, of the total volume of the adrenal glands.

53. ……
The layer immediately beneath the connective tissue capsule is the zona glomerulosa, in which columnar or pyramidal cells are arranged in closely packed, rounded, or arched cords surrounded by capillaries

55. ……
The next layer of cells is known as the zona fasciculata because of the arrangement of the cells in one- or two-cell thick straight cords that run at right angles to the surface of the organ and have capillaries between them .
The cells of the zona fasciculata are polyhedral, with a great number of lipid droplets in their cytoplasm.

56. ……
As a result of the dissolution of the lipids during tissue preparation, the fasciculata cells appear vacuolated in common histological preparations.
Because of their vacuolization, the cells of the fasciculata are also called spongyocytes

59. ……
The zona reticularis , the innermost layer of the cortex, lies between the zona fasciculata and the medulla; it contains cells disposed in irregular cords that form an anastomosing network.
These cells are smaller than those of the other two layers.
Lipofuscin pigment granules in the cells are large and quite numerous. Irregularly shaped cells with pyknotic nuclei—suggesting cell death—are often found in this layer.

60. Cortical hormones
The steroids secreted by the cortex can be divided into three groups, according to their main physiological action: mineralocorticoids, glucocorticoids, and androgens .
The main product of the zona glomerulosa is a mineralocorticoid called aldosterone;
the zona fasciculata and possibly the zona reticularis secrete glucocorticoids, especially cortisol; the zona reticularis produces dehydroepiandrosterone, a weak androgen

62. Control of the Adrenal Cortex
The secretion of glucocorticoids is controlled initially through the release of corticotropin-releasing hormone in the median eminence, followed by secretion of adrenocorticotropic hormone (ACTH, corticotropin) by the pars distalis of the hypophysis

63. ……
Free glucocorticoids may then inhibit ACTH secretion. The degree of pituitary inhibition is proportionate to the concentration of circulating glucocorticoids; inhibition is exerted at both the pituitary and hypothalamic levels .
Aldosterone secretion is controlled primarily by renin-angiotensin and secondarily by ACTH.

64. MEDICAL APPLICATION
Because of the feedback mechanism of adrenal cortex control, patients who are treated with corticoids for long periods should never stop taking these hormones suddenly:
secretion of ACTH in these patients is inhibited, and thus the cortex will not be induced to produce corticoids, causing a severe misbalance in the levels of sodium and potassium.

65. Adrenal Medulla
The adrenal medulla is composed of polyhedral cells arranged in cords or clumps and supported by a reticular fiber network.
A profuse capillary supply intervenes between adjacent cords, and there are a few parasympathetic ganglion cells.

66. ……
The medullary cells arise from neural crest cells, as do the postganglionic neurons of sympathetic and parasympathetic ganglia.
Thus, the cells of the adrenal medulla can be considered modified sympathetic postganglionic neurons that have lost their axons and dendrites during embryonic development and have become secretory cells.

68. ……
Medullary cells have abundant membrane-limited electron-dense secretory granules, 150–350 nm in diameter.
These granules contain one or the other of the catecholamines, epinephrine or norepinephrine.
The secretory granules also contain adenosine triphosphate (ATP), proteins called chromogranins (which may serve as binding proteins for catecholamines),

69. ……
dopamine  -hydroxylase (which converts dopamine to norepinephrine), and opiatelike peptides (enkephalins)

70. …….
A large body of evidence shows that epinephrine and norepinephrine are secreted by two different types of cells in the medulla.
When observed with the transmission electron microscope epinephrine-secreting cells show smaller and less electron-dense granules, whose contents fill the granule.

71. Norepinephrine-secreting cells have larger, more electron-dense granules. Their content is irregular in shape, and there is an electron-lucent layer beneath the surrounding membrane. About 80% of the catecholamine output of the adrenal vein is epinephrine.

72. ……
Unlike the cortex, which does not store steroids, cells of the medulla accumulate and store their hormones in granules.
The adrenal medullary cells are innervated by cholinergic endings of preganglionic sympathetic neurons.
Glucocorticoids produced in the cortex, which reach the medulla through capillaries that bathe cells of the cortex, constitute another mechanism of control.

73. MEDICAL APPLICATION
Epinephrine and norepinephrine are secreted in large quantities in response to intense emotional reactions, such as fright, that are part of an alarm reaction (the fight-or-flight response).
Secretion of these substances is mediated by the preganglionic fibers that innervate medullary cells.

74. ……
Vasoconstriction, hypertension, changes in heart rate, and metabolic effects such as elevated blood glucose result from the secretion and release of catecholamines into the bloodstream.
During normal activity, the medulla continuously secretes small quantities of these hormones.

75. ……
Medullary cells are also found in the paraganglia (collections of catecholamine-secreting cells adjacent to the autonomic ganglia) as well as in various viscera.
Paraganglia are, thus, a diffuse source of catecholamines.

76. Adrenal Dysfunction MEDICAL APPLICATION
One disorder of the adrenal medulla is pheochromocytoma, a tumor of its cells that causes transient elevations of blood pressure. These tumors can also develop in extramedullary sites.

77. continues Rare catecholamines producing tumors
Prevalence is 1- 2% in hypertensives
It can be fatal
No sex predilection
Maximum incidence between the ages of 20 and 50 years, though they can occur at any age.
In general, it is said that 10% are bilateral, 10% are extra-adrenal, 10% occur in childhood and that 10% are malignant.

78. The clinical features
An important clinical feature is hypertension
Sustained in about 50% of cases
50% have paroxysmal HT lasting for minutes to 1 hour (usualy 15 minutes)
HT due to Pheo. has a triad of characteristics (sweating attacks, tachycardia and headache)
Orthostatic HT (60%)
Crises may be precipitated (infections, stress, anxiety etc)

79. Diagnosis (basal levels)
Demonstration of increased levels of
Plasma catecholamines (95% sensitivity)
Urinary vanilyl mandelic acid (VMA- 90% sensitivity
Urinary matanephrines (95% sensitivity)

80. ……
Disorders of the adrenal cortex can be classified as hyperfunctional or hypofunctional. Tumors of the adrenal cortex can result in excessive production of glucocorticoids (Cushing syndrome) or aldosterone (Conn syndrome).
Cushing syndrome is most often (90%) due to a pituitary adenoma that produces excessive ACTH; it is rarely caused by adrenal hyperplasia or an adrenal tumor.

81. ……
Excessive production of adrenal androgens has little effect in men. However, hirsutism (abnormal hair growth) is seen in women, and precocious puberty (in boys) and virilization (in girls) are encountered in prepubertal children.
These adrenogenital syndromes are the result of several enzymatic defects in steroid metabolism that cause increased biosynthesis of androgens by the adrenal cortex.

82. ……
Adrenocortical insufficiency (Addison disease) is caused by destruction of the adrenal cortex in some diseases.
The signs and symptoms result from failure of secretion of both glucocorticoids and mineralocorticoids by the adrenal cortex.

83. The endocrine pancreas
The islets of langerhans appears as circular or oval areas containing pale staining cells with H ‘n’ E stain.
The endocrine portion is associated with numerous small blood vessels and capillaries.
The cells are polyhedral, the use of special stains identifies three major types of cells; these are alpha, beta, delta and PP cells.

84. Alpha cells (A-cells)
The alpha cells occupy the central part of the islets and they form 20% of the islet cells.
These cells secrets glucagon, a hormone which increases the blood levels of glucose.

85. Beta cells (B cells)
The beta cells occupy a peripheral position in the islets. These cells constitute 75%-80% of the islets cells and they are important in the body because they secret insulin.
Insulin when secreted it enters the blood stream and become available to cells of the body. It allows glucose to be utilized by the cells, without insulin glucose will not be utilized.

86. slide

88. Delta cells (D- cells)
The delta cells occupy a central position in the islets and form only about 5% of the islets cell population.
It is thought that the delta cells secret either serotonin or pancreatic gastrin.

89. PP cells
These are very rare cells in man but well demonstrated in guinea pigs, rats and rabbits. The PP cells secret the pancreatic polypeptide, a hormone which stimulates the chief cells of the stomach to produce more pepsinogen. Pepsinogen is the precursor of the enzyme pepsin.
Islets of langerhans are most numerous in the tail of the pancreas and they become less in number at the head.

90. The end.

91. References Human Anatomy and Physiology (3rd ed.). Benjamin/Cummings.
Janqueira, Carneiro-Basic Histology-Text and Atlas 11 edition
Platzer, Werner (2008). Color atlas of human anatomy:
Ganyaka,Sebastian,2012