The Endocrine System

The Endocrine System

The Endocrine System
INTRODUCTION & GENERAL FEATURES OF THE ENDOCRINE SYSTEM The endocrine system consists of cells, tissues and organs that synthesize and secrete hormones directly into blood and lymph capillaries. By contrast to exocrine glands, such as the salivary, mammary, and sweat glands, which pour their secretions onto a surface of the body by means of ducts, the endocrine glands have no ducts and are therefore sometimes called the ductless glands. The autonomic nervous system and the endocrine system work closely together to regulate the metabolic activities of the different organs and tissues of the body so as to maintain homeostasis. The activities of the autonomic nervous system and the endocrine system are integrated and coordinated by the hypothalamus (the neuroendocrine system). The autonomic nervous impulses releases neurotransmitter substances at nerve endings in order to obtain a rapid and localized response, whereas the endocrine system exerts a slower and more diffuse response by synthesizing and releasing into the bloodstream organic chemical substances (messengers) called hormones .

Hormones are molecules with specific regulatory effects, which may be disseminated throughout the body by the bloodstream where they may act on specific target organs or affect a wide range of organs and tissues. Other hormones act locally, often arriving at their site of action by way of specialized microcirculation. Hormones elicit specific and dramatic effects at very low concentrations, and they directly or indirectly affect all tissues . They regulate carbohydrate, protein, and lipid metabolism; the mineral and water balance in body fluids, growth; sex-related differences in body shape and sexual function; behavior, and emotions.

On the bases of chemical nature of the hormonal secretions, endocrine glands can be grouped into three chemical types: 1. Small proteins, or Polypeptide hormones: Which bind to specific receptors on target cell surfaces. They often stimulate the production of intracellular second messengers in the target cells. For example, the hormones of the anterior lobe of the pituitary & of the islets of Langerhans. 2. Steroid hormones: These lipid-soluble hormones easily cross target cell plasma membranes to directly affect cell function. They bind to specific binding proteins in the cytoplasm and the nucleus. The nuclear receptors bind to DNA and directly affect gene transcription. For example, the adrenocortical hormones, testosterone & the estrogens and progesterone 3. Amine hormones: For example, the thyroid and suprarenal medullary hormones.

Note: Cells secreting steroid hormones contain abundant smooth endoplasmic reticulum (SER), whereas those secreting peptide hormones contain abundant rough endoplasmic reticulum (RER).

Components of the System: The endocrine system is made up of cells that are found in 3 distinct anatomic distributions:- 1- Gathered together in one specialized organ to form an endocrine gland e.g. pituitary, thyroid, parathyroid and adrenal glands; 2- Forming discrete clusters in another specialized organ e.g. pancreas, ovary, testis, placenta ( when present); 3- Dispersed singly among other epithelial tissues, particularly in the gastrointestianal and respiratory tract, in which case they form part of what is referred to as the diffuse neuroendocrine system .

Origin: Endocrine glands develop as invaginations of epithelial surfaces, such as oral ectoderm or gut endoderm, and then pinch off, losing contact with the parent epithelium. Microscopic Structure: Endocrine glands typically contain secretory cells arranged as cords, clumps, or follicles that are in direct contact with abundant capillaries or sinusoids. Reflecting their active synthetic function, endocrine cells are usually characterized by prominent nuclei, abundant cytoplasmic organelles, especially mitochondria, endoplasmic reticulum, Golgi bodies and secretory vesicles.

Pituitary Gland

Pituitary Gland
LOCATION & GENERAL ORGANIZATION The pituitary gland (hypophysis cerebri), is suspended by a stalk from the hypothalamus at the base of the brain. It rests in a depression in the sphenoid bone called the sella turcica, behind the optic chiasma. Its normal dimensions in humans are about10x13x6mm, and weighs about 0.5g. Its two major divisions, the anterior lobe (adenohypophysis) and the posterior lobe (neurohypophysis), differ in embryonic origin, structure, and function.

Embryonic Origins. The adenohypophysis arises as an upward evagination of the ectoderm lining the primitive oral cavity. It contacts and fuses with the neurohypophyseal down-growth. The neurohypophysis arises as a down growth of the neural ectoderm of the hypothalamus and is therefore actually a part of the brain.

A. Adenohypophysis: General structure: The adenohypophysis consists of glandular epithelial cell arranged in cords separated by the many sinusoidal capillaries of the secondary capillary plexus. It is not directly innervated by hypothalamic nerves; only by autonomic fibers from carotid plexus. Subdivisions. 1- The pars distalis (pars anterior) is the largest pituitary subdivision. 2- The pars tuberalis, its superior extension, forms a partial sleeve around the infundibulum of the neurohypophysis. 3- The pars intermedia is a narrow band of adenohypophyseal tissue bordering the neurohypophysis.

Each secretory cell in the adenohypophysis synthesizes and stores one of the following hormones: follicle-stimulating hormone (FSH),luteinizing hormone (LH), thyrotropin (thyroid–stimulating hormone (TSH), adrenocorticotropic hormone (ACTH), growth hormone (GH), prolactin.These hormones control the secretory activities of many other glands. Their release is regulated by specific releasing or inhibiting hormones produced by the hypothalamus and delivered to the adenohypophysis by the blood in the hypophyseal portal system.

Pars Distalis (pars anterior): Is formed of cords of aggregated cells interspersed with capillaries of the primary capillary plexus. There are 3 main cell types, which may be distinguished by the affinity of their cytoplasmic granules for different stains: chromophobes and chromophils (acidophils,basophils). The few fibroblasts present produce reticular fibers that support the cords of hormone-secreting cells. Chromophobes. These cells stain poorly and appear clear or white in tissue sections. They make up about 50% of the epithelial cells in the pars anterior. They include (1) undifferentiated non-secretory cells, which may be stem cells; (2) partly degranulated chromophils, containing sparse granules ; and (3) follicular cells, the predominent chromophobe type, which form a stromal network that supports the chromophils.

Chromophils (Acidophils & Basophils) These hormone-secreting cells of the adenohypophysis stain intensely owing to the abundant cytoplasmic secretory granules in which hormones are stored. There is a specific cell type for each hormone. Usually larger than chromophobes, chromophils are subdivided into two classes :

a. Acidophils Secrete proteins and stain intensely with eosin and orange G, but not with Periodic Acid Schiff (PAS). Make up about 35-40% of the epithelial in the pars distalis (pars anterior). More abundant in the gland periphery, they are usually smaller than basophils with larger and more numerous granules. The acidophils include two major hormone-secreting cell types; somatotropes produce growth hormone (GH, somatotropin) ,and mammotropes produce prolactin.


b. Basophils Secrete glycoproteins and stain with hematoxylin and other basic dyes, and are PAS- positive. Make up about 10-15% of the epithelial cells in the pars distalis (pars anterior). More abundant in the core of the gland, they are usually larger than acidophils, with fewer and smaller granules. The three major hormone-producing basophils produce four major hormones: Gonadotropes (FSH&LH), .Corticotropes produce adrenocorticotropin (ACTH). Thyrotropes produce thyrotropin (TSH).

Cell types in the Hypophysis. Stain: modified azan. Oil immersion.

Pars Tuberalis : This funnel-shaped superior extension of the pars distalis surrounds the infundibular stem (like an incomplete collar along the anterior and lateral surfaces of the infundibulum). Its histology is similar to the pars distalis, but it contains mostly gonadotropes.


Pars Intermedia :This is a band or wedge of adenohypophysis between the pars distalis and pars nervosa; it is rudimentary in humans.It contains Rathke’s cysts, small, irregular, colloid- containing cavities lined with cuboidal epithelium that are remnants of Rathke’s pouch.It also contains scattered clumps and cords of basophilic cells, or melanotropes, which secrete melanocyte-stimulating hormone (Я-MSH, which regulates the formation of melanin- the pigment found in the skin, and in portions of the eyes and brain)

Blood Supply and Hypophyseal Portal System: 1. Primary capillary plexus. This profusion of capillaries lies in the upper infundibular stalk and lower median eminence; it extends into the pars tuberalis. The plexus receives blood from the anterior and posterior superior hypophyseal arteries (from the circle of Willis) and drains into the hypophyseal portal veins. 2. Hypophyseal portal veins. These small veins and venules lie mainly in the middle and lower infundibular stalk and in portions of the pars tuberalis. They receive blood from the primary capillary plexus and carry it directly to the secondary capillary plexus in the pars distalis. (Vessels carrying blood directly from one capillary plexus to another without returning to the general circulation are defined as “Portal vessels”). 3. Secondary capillary plexus. This rich fenestrated capillary plexus located throughout the pars distalis also penetrates the pars tuberalis and pars intermedia.There are also some connections between this capillary bed and that in the pars nervosa. The capillaries between the clumps and cords in the pars distalis belong to this plexus, which receives venous blood directly from the hypophyseal portal veins and arterial blood from the anterior inferior hypophyseal arteries. It is drained by the inferior hypophyseal veins into the internal jugulars.


Hypothalamic Releasing and Inhibiting Hormones:These small peptides are synthesized in the neuron (neurosecretory) cell bodies in the hypothalamic nuclei and are released by their axon terminals into the primary capillary plexus. They pass through the hypophyseal portal venules and into the secondary capillary plexus, from which they diffuse into the adenohypophysis to stimulate or inhibit the hormone release by acidophils and basophils. 1. Releasing hormones.Corticotropin-releasing hormone (CRH) synthesized in the paraventicular nucleus; stimulates corticotropes to release ACTH.Gonadotropin-releasing hormone (GnRH), synthsized in the supraoptic an arcuate nuclei; stimulates gonadotropes to release FSH and LH.Thyrotropin –releasing hormone (TRH) stimulates thyrotropes to release TSH (thyrotropin). 2. Inhibiting hormones.Somatostatin (GHIH [growth hormone-inhibiting hormone]) synthesized in the suprachiasmatic nuclei that inhibits somatotropes from releasing growth hormone (GH,somatotropin). It also inhibits the secretion of glucagon, insulin,and other hormones associated with the gastrointestinal tract.Dopamine (a prolactin-inhibiting hormone (PIH), is a neurotransmitter synthesized in the arcuate nuclei that inhibits prolactin release from mammotropes.


B. Neurohypophysis: Origin: The neurohypophysis arises as a downgrowth of the neural ectoderm of the hypothalamus and is therefore actually a part of the brain. General structure: The neurohypophysis contains abundant axons whose cell bodies are located mainly in the supraoptic and paraventricular nuclei of the hypothalamus. Subdivisions: 1-The infundibulum consists of the a) infundibular stem (neural stalk) and the b) median eminence. The infundibular stem carries axons from the hypothalamus to the pars nervosa and contains the capillary loops of the primary capillary plexus. The median eminence of the tuber cinereum, a funnel-shaped extension of the hypothalamus. 2-The pars nervosa (infundibular process) is the expanded lobe of the neurohypophysis; it contains axon terminals and numerous capillaries. The subdivisions of the neurohypophysis all exhibit similar microscopic structure. The neurohypophysis has three major structural components; A) axons, B) capillaries, and C) pituicytes .

A. Axons of Neurosecretory Cells: The neurohypophysis stains poorly if at all. It contains many unmyelinated axons whose cell bodies are located mainly in the supraoptic and paraventricular nuclei of the hypothalamus. Axons passing from these nuclei to the pars nervosa are together termed the hypothalamohypophyseal tract. The axons contain neurosecretory granules and exhibit large granule-filled dilations called Herring bodies. The neurosecretory materials in these granules, synthesized and packaged in the above-mentioned cell bodies, include the following products: 1. Neurohypophyseal hormones. 2. Neurophysins. 3. Adenosine triphosphate (ATP).

Hypophysis: pars distaiis, pars intermedia, and pars nervosa. Stain: mallory-azan & orange G.


1. Neurohypophyseal hormones. The hypothalamic neurons terminating in the neurohypophysis release oxytocin and antidiuretic hormone around the capillaries in this part of the pituitary. Oxytocin (amino-acid peptide) synthesized mainly by cells of the paraventricular nucleus. It stimulates milk ejection by the mammary glands and stimulates uterine smooth muscle contraction during copulation and childbirth. Antidiuretic hormone (ADH, arginine vasopressin) is amino-acid peptide synthsized mainly by cells in the supraoptic nucleus. It stimulates water resorption by the renal medullary collecting ducts and contraction of vascular smooth muscle. 2. Neurphysins Are binding proteins that complex with neurohypophyseal hormones. 3. Adenosine triphosphate (ATP) Acts as a chemical energy source for neurosecretion.

B. Fenestrated capillary plexus: Surrounds the axon terminal in the pars nervosa, these capillaries pick up the neurosecretory products and convey them to the general circulation. C. Pituicytes : These are highly branched glial cells whose processes surround and support the unmyelinated axons. Pituicytes form about 25% of the neurohypophysis.

Diseases of the anterior lobe of the pituitary : Pituitary tumors, e.g. Chromophobe adenoma, Excessive production of the growth hormone GH by the somatotrope cells of the pars anterior or by tumors of these cells can produce abnormal growth of the skeleton, such as: Gigantism (in the young before the epiphysis in long bones fuse with diaphysis). Acromegaly (a form of abnormal skeletal and soft tissue growth that occurs after adolescence, following the fusion of the epiphysis in long bones with the diaphysis. A deficiency in the GH secreted by the somatotrope cells of the pars anterior during childhood leads to pituitary dwarfism). Growth does not stop entirely, and different parts of the body are in relatively normal proportion. Disease of the posterior lobe of the pituitary : Diabetes Insipidus, (a syndrome results from a lesion of the supraoptic nuclei of the hypothalamus and a failure of these cells to synthesize the ADH, or from the destruction of hypothalamohypophyseal tract, and other causes. Characteristically, the patient suffers from polydepsia & polyuria.


THYROID GLAND


THYROID GLAND In healthy adults the thyroid lies anterior to the larynx and has two lobes connected by an isthmus. Each lateral lobe is about 5cm. long, 3-4cm. wide, 2-3cm. deep. In the healthy adult, the thyroid weighs 15-20g. Embryologically the thyroid develops from a down growth of endoderm arising near the root of the tongue and called the thyroglossal duct, which atrophies and leaves a nodule of thyroid tissue at its correct anatomic site. It is a labile gland and varies in size and structure in response to a large number of factors, among which are sex, age, nutrition ,temperature, season & iodine content. The thyroid is enclosed by a thin collagenous capsule from which internal septa penetrate the parenchyma, dividing it into irregular lobules. The glandular component of the thyroid is composed of epithelium arranged as tightly-packed spherical structural units of varying size called thyroid follicles.

Thyroid follicles: Each lobule consists of numerous (about 30 million follicles in human) spherical follicles . Each follicle is lined by a single layer of specialized thyroid epithelium which rests on a basement membrane & encloses a lumen filled with thyroid colloid , a pink-staining (eosinophilic) homogenous proteinaceous material rich in thyroglobulin. The follicles are surrounded by a basal lamina and reticular fibers. A network of blood vessels, including fenestrated capillaries, course through the sparse connective tissue between follicles. Small unmyelinated nerve fibers are present in the walls of the thyroid arteries, most of these terminate in plexuses around the blood vessel. The follicles, vary in size and appearance according to the region of the gland and its functional activity.

Thyroid gland (general view) . Stain H&E. Low magnification .

Thyroid gland follicles. Stain: H&E. High magnification.

Thyroid Follicular Cells: Structure: Using light microscopy shows that cell height ranges from squamous in inactive gland to columnar during stimulation. Intercellular boundaries are distinct, nuclei are generally rounded in shape, cytoplasm basophilic and contains lipid droplets. When examined with the electron microscope, the apices of the cells display microvilli that lengthen with increased activity of the cells. There are well developed RER and Golgi, which are necessary for the production and secretion of protein material. During an active secretory phase the thyroid follicular cells show more prominent endoplasmic reticulum & free ribosomes, the Golgi enlarges, the surface microvilli increase in number and length, and intracytoplasmic droplets appear. Stimulation by pituitary TSH, signaling an increase energy demand, increases synthesis and secretion.

Thyroid gland follicles. Stain: H&E. High magnification.

Normal function: Thyroid follicular cells differ from other endocrine cells in that they store an intermediate form of their secretory products extracellularly in colloid rather than internally in cytoplasmic granules. The follicular cells secrete into the cavity of the follicle: 1) thyroglobulin: a glycoprotein molecules that contain the amino acid (tyrosine) 2) iodine molecules, 3) enzymes.

Steps involved in the formation of T3 and T4: a ) Synthesis and storage of thyroglobulin. 1.The amino acids are absorbed from the blood stream & formed into poly-peptides in the RER, 2 The carbohydrate mannose is added to the molecule within the RER, 3 When the molecule arrives at Golgi apparatus galactose is added and the thyroglobulin molecule is formed. 4 The thyroglobulin molecules are now packaged into vesicles that are discharged from the luminal surface of the cell by exocytosis.

b) Uptake and oxidation of iodide. 1. Iodide is absorbed from the blood and is oxidized to iodine by the enzyme peroxidase within the follicular cells. 2.The iodine molecules are then concentrated within the cells and finally passed out into the cavity of the follicle.



c) Iodination of thyroglobulin and formation of thyroid hormone Once the thyroglobulin and iodine reach the follicular cavity, formation of the two hormones tetraiodothyronine (thyroxine T4) and triiodothyronine(T3) starts and stored in the thyroglobulin colloid in the cavity of the follicle and may remain there for as long as 3 months . (T3 &T4 are iodinated derivatives of Tyrosine). Although T4 makes up 90% of the thyroid hormone produced, it is less potent than T3. d) Thyroid hormone secretion. Stimulation by TSH causes the follicular cells to pinocytose portions of the colloid, forming vesicles containing iodinated thyroglobulin. These vesicles fuse with lysosomes carrying enzymes that cleave the thyroglobulin. The T4 and T3 released in this way diffuse out of the secondary lysosomes, pass through the cytoplasm and cross the basolateral plasma membrane to reach the bloodstream (a process called endocytosis).

e) Targets and effects of thyroid hormones. T3 and T4 act throughout the body to increase basal metabolic rate (i.e, the rate at which cells use glucose), promote cell growth, increase heart rate, raise body temperature, and generally enhance all energy- requiring cell functions. They also act on the TRH-secreting cells of the hypothalamus and the thyrotropes in the adenohypophysis to reduce TSH secretion .

Parafollicular Cells ( C Cells): These cells have the following characteristics, they are: 1.Interspersed among the follicular cells or in clusters between the follicles. 2.Are larger than the follicular cells. 3.Lie within the follicular basement membrane. 4.Are oval in shape. 5.The cytoplasm stains poorly with standard stains and typically appears clear or white. 6.Electron micrographs reveal numerous small secretory granules. 7.Secrete the peptide hormone calcitonin in response to high blood calcium.

Calcitonin causes calcium uptake by cells and increased calcium deposition in bone, lowering blood calcium (an effect on blood calcium levels opposite that of the parathyroid hormone). Parafollicular cells are not under the control of pituitary gland but are stimulated by hypercalcemia and suppressed by hypocalcemia.

Abnormal Function : a. Hyperthyroidism. Overproduction of thyroid hormone (thyrotoxicosis, Graves disease) which is most common in middle-aged women, the thyroid gland is diffusely enlarged. Hyperthyroidism may also occur in the multinodular goiter of the elderly, where the thyroid gland exhibits multiple areas of enlargement. b. Hypothyroidism. Occurs in two forms, cretinism in infants & children and myxedema in adults. Enlargement of thyroid gland not associated with hyper or hypothyroidism or tumor, e.g. Simple goiter: This is an enlargement of the thyroid gland not associated with hyperthyroidism, hypothyroidism, thyroiditis, or tumor. Iodine deficiency is the most common cause, and the condition occurs more frequently in women. Thyroiditis: Inflammatory disease of the thyroid gland is not common, and in many cases the cause is unknown. Tumors : Benign thyroid tumors occur in the form of adenomas. Carcinoma of the thyroid gland is relatively rare.

PARATHYROID GLANDS

PARATHYROID GLANDS Parathyroid glands are usually four small glands (3x6mm with a total weight of about 0.4g.), yellowish brown, ovoid structures that are related to the posterior border of the thyroid gland, one at each of the upper and lower poles usually in the capsule that covers the lobes of the thyroid. Sometimes, they are found embedded in the thyroid gland and may be found in the mediastinum lying beside the thymus (because parathyroid and thymus originate from 3ed and 4th pharyngeal pouches.

The normal adult human parathyriod is surrounded by a thin fibrous capsule from which a delicate septa pass into the gland carrying the blood vessels and merge with the reticular fibers supporting elongated cord-like clusters of secreting cells between which lie sinusoidal capillaries.

The parenchyma of the parathyroid glands in adults contains 3 types of cells: 1. Adipocytes, 2 .Chief cells, 3. Oxyphil cells. 1. Adipocytes : Appear in the parenchyma at puberty and gradually increase in number until about the age of 40, from then on remaining a fairly constant proportion of entire gland, though their number may decrease in old age. They form a background stroma in which the chief and oxyphil cells are arranged in cords and nests close to a fine network of capillary vessels.



Normal function. Chief cells secrete parathyroid hormone (PTH) in response to low blood calcium. PTH, a peptide hormone, increases blood calcium by acting at three target sites : In bone, PTH increases bone resorption . In the kidneys, it increases phosphate excretion and calcium reabsorption and causes activation of a vitamin D precursor. In the intestines, PTH ( perhaps by activating vitamin D ) causes increased absorption of calcium by the intestinal mucosa. Increased blood calcium levels decrease PTH secretion.

Abnormal function: a. Hyperparathyroidism. Excessive PTH secretion (caused by adenoma or hyperplasia of the parathyroid) elevates serum calcium and decreases serum phosphate . The raised levels of blood calcium in this disease may cause abnormal calcium deposits in the arteries and kidneys (repeated occurrence of renal stones); excessive calcium loss from bones and also affects central and peripheral nervous systems. b. Hypoparathyroidism. Insufficient PTH secretion disrupts the neuromuscular function. The resulting low blood calcium leads to spontaneous and uncontrolled firing of action potentials. In peripheral nerves this may cause spastic muscle contraction or tetany. The spontaneous firing of neurons in the brain may cause behavioral effects as well.

ADRENAL (SUPRARENAL) GLANDS

ADRENAL (SUPRARENAL) GLANDS
The body has two adrenal glands, one of which is located superior to each kidney. In the human, they are about 4-6cm long, 1-2cm wide & 0.5cm thick, and both may weigh about 15gm. Each gland is surrounded by a thick connective tissue capsule that sends septa into the interior of the gland. They are divisible by embryonic origin, structure, and function into cortex and medulla.

Adrenal Cortex Embryonic origin. The adrenal cortex derives from coelomic intermediate mesoderm. Structure in adults. Cells of the adrenal cortex have the characteristic steroid-synthesizing cell structure (polygonal or rounded, with a central nucleus and pale- staining, acidophilic cytoplasm that often contains many lipid droplets, abundant SER , mitochondria containing enzymes), The supracortex has three layers or zones: a) zona glomerulosa, b) zona fasciculata, c) zona reticularis.

Adrenal (suprarenal) gland: cotrex and medulla. Stain H&E .

a. Zona glomerulosa. This outermost cortical layer lies directly under the capsule. Constitutes about 15% of adrenal volume. Composed of small compact cells arranged in form of arched clusters (glomeruli), separated by stroma composed largely of thin-walled capillaries. The cells contain scanty lipid droplets. Ultrastructurally : The cells contain well developed SER and comparatively little RER. The cells of this layer secrete mineralocorticoids

b. Zona fasciculata. This middle layer of the cortex, constitutes 65% of adrenal volume. Its cells form straight cords or columns (usually 2-3 cells wide) perpendicular to the organ surface. The columns are separated by capillaries. Ultrastructurally, the cells have prominent RER. Characteristic small round or ovoid mitochondria . Extensive lipid vacuoles. The surfaces of cells adjacent to capillaries may show small microvilli extending to the capillary wall. Its cells produce glucocorticoids and some adrenal androgens.

c. Zona reticularis. This innermost layer of the adrenal cortex. Constitutes 7% of adrenal volume. Its cells are arranged in a anastomosing network of irregular cords with capillary network closely apposed to the cell membranes. Its cells are smaller and more acidophilic than those in the fasciculata and contain fewer lipid droplets, more mitochondria, and many lipofuscin granules. Ultrastructurally : The cells posses prominent SER, prominent electron-dense irregular aggregations of lipofuscin, as well as lysosomes and oval or long mitochondria. The reticularis and fasciculata seem to constitute a single functional zone, with the reticularis producing most of the glucocorticoids and adrenal androgens.


Fetal, or provisional,cortex. The thickest adrenal layer before birth, it is located between the medulla and the immature thin permanent cortex. After birth, the fetal cortex regresses and the permanent cortex develops the three layers described above.

Normal function. The adrenal cortex produces three types of steroid hormones: a. Mineralocorticoids. Consisting mainly of aldosterone, these are produced by the zona glomerulosa in response to angiotensin II and to lesser extent by ACTH. Aldosterone controls water and electrolyte balance mainly by stimulating sodium absorption by the distal renal tubules but also by affecting the gasric mucosa and salivary glands. b. Glucocorticoids. Mainly cortisol and corticosterone, these are produced by the zona reticularis in response to ACTH and by the fasciculata after prolong stimulation. Glucocorticoids control carbohydrate metabolism, especially by stimulating carbohydrate synthesis in the liver. Glucocorticoids also suppress the immune response by decreasing circulating lymphocytes and eosinophils. c. Adrenal androgens. These androgens, are secreted in response to ACTH by the zona reticularis and, and after prolonged stimulation, by the fasciculata. The musculinizing and anabolic effects of adrenal androgens resemble those of testosterone but are less potent.

Abnormal function: a. Hypersecretion .Cushing”s syndrome is caused by hypersecretion of cortisol and often of androgens. Its symptoms include truncal obesity, a moon face, high blood sugar, hirsutism, amenorrhea, acne, and emotional lability.Conn”s syndrome caused by hypersecretion of aldosterone causes sodium and water retention, increasing blood pressure (hypertension). b. Hyposecretion. Chronic hypofunction of adrenal cortex (eg, Addison”s disease) causes low serum glucose, sodium, chloride, and bicarbonate and high serum potassium ( It can be induced by giving large doses of glucocorticoids therapeutically, this suppresses ACTH by the pituitary so that adrenal cortex produce No native steroid hormone ). Decreased adrenal androgen synthesis in women may cause the loss of pubic and axillary hair.

Adrenal Medulla

Embryonic origin. The adrenal medulla derives from the neural crest. Structure. The adrenal medulla is composed of groups of epithelial cells supported by a delicate connective tissue that is richly supplied by blood sinusoids. It contains two major cell types: a) chromaffin cells b) ganglion cells.

a. Chromaffin cells. Also known as pheochromocytes, These are the predominant medullary cell type. They contain large nuclei and cytoplasmic granules that become brown when exposed to chromium salts; for this reason, they are sometimes referred to as chromaffin cells. The chromaffin cells synthesize and secrete catecholamines (norepinephrine and epinephrine). The hormones are released into the venous sinusoids in response to stimulation by the preganglionic sympathetic nerve fibers. Ultrastructurally, chromaffin cells shows well developed Golgi complex a few profiles of RER, many oval mitochondria, and membrane bound cytoplasmic granules. There are two types of chromaffin cells: 1.Cells that produce norepinephrine have granules that possess a very dense core. 2. Cells that secrete epinephrine have homogenous granules and not so dense. Some cells of the medulla are thought to produce serotonin in addition to epinephrine.

b. Ganglion cells. Are few parasympathetic ganglion cells which exhibit typical morphologic characteristics of autonomic ganglion cells (large, multipolar cells, randomly distributed throughout ganglion, have large and ovoid nuclei, mostly eccentric.

Normal function. These include the production of two types of catecholamines (epinephrine and norepinephrine) n response to preganglionic sympathetic stimulation (e g. stress). Epinephrine increases heart rate and dilates blood vessels to the organs needed to combat or escape stress, such as cardiac and skeletal muscle. It dilates bronchioles and constricts vessels in organs (e.g, skin, digestive tract, kidneys) that are not essential in reacting to stress. Norepinephrine constricts blood vessels in nonessential organs. By increasing peripheral resistance, it increases blood pressure and blood flow to the heart, brain, and skeletal muscle. Abnormal function. Hypersecreting chromaffin cell tumors (pheochromocytoma) cause a sustained stress response (especially hypertension) even in the absence of stress. Ganglion cell tumors (neuroblastomas and ganglioneuromas) are more common, especially in children.

Adrenal Blood Supply : 1. Arteries. Three main arteries supply each adrenal gland : a. The superior suprarenal from the inferior phrenic, b. the middle suprarenal from the aorta, and c. the inferior suprarenal from the renal. These arteries penetrate the capsule separately, and their branches anastomose to form a subcapsular arterial plexus. This plexus gives rise to three groups of arteries: a. The arteries of the capsule b. The arteries of the cortex, which branch to form the cortical capillaries that pass between the secretory cells and drain into the medullary capillaries, and c. The arteries of the medulla, which traverse the cortex without branching until they reach the medulla, where they form the medullary capillaries. 2. Medullary capillaries receive a double blood supply from arteries of both the cortex and medulla and converge to form several medullary veins. 3. Medullary veins converge to form a single large suprarenal vein. 4. The suprarenal vein arises at the core of the medulla and drains into the renal vein or directly into the inferior vena cava.

PINEAL GLAND

PINEAL GLAND

Is also known as the epiphysis cerebri, or pineal body. In the adult, this small flattened conical structure measuring approximately 6-10mm long and 5-6mm wide, and weighing about 120mg is located just below the posterior end of the corpus callosum of the brain.

It is covered on its outer surface by pia mater which forms the capsule. Extending into the interior of the gland from the capsule are a number of fibrous trabeculae that incompletely divide the parenchyma into poorly defined lobules of various size. The trabeculae carry the blood vessels and unmyelinated nerves into the substance of the gland. The pineal gland is composed of groups of cells called pinealocytes supported by astroglial cells.

A. Pinealocytes : Structure. The pinealocytes are large neuron-like cells possessing extensive processes that are intertwined with the processes of the astroglial cells. Pinealocytes are often arranged in rosettes, where several cells surround a central fibrillary area composed of cell processes directed towards a small capillary vessel. With H&E stain, they have pink-staining cytoplasm and dark-staining irregular or lobate nuclei. Pinealocytes are often arranged in rosettes, where several cells surround a central fibrillary area composed of cell processes directed towards a small capillary vessel. With silver stain, they exhibit long cytoplasmic processes that terminate as swellings close to blood capillaries. Stored in the terminal swellings are vesicles containing monoamines and polypeptide hormones. The cells produce melatonin, which induces rhythmic changes in the secretions of the hypothalamus, pituitary and gonads, and is said to act as an endocrine transducer.

Normal function. Although the function of the pineal gland is not fully understood, the gland has been shown to contain melatonin, serotonin, and norepinephrine. The release of norepinephrine from the postganglionic sympathetic fibers stimulates the pinealocytes to increase their output of melatonin. The concentration of melatonin in the blood conform to a circadian rhythm, being higher during darkness and lowest during the day. Cyclic changes in plasma melatonin levels follow changes in environmental lighting, but the precise relationship is still unknown. Melatonin may both help establish circadian rhythms and have antigonadotropic effects that delay onset of sexual maturity. Abnormal function. Pinealomas are tumors of the pineal cells. As they increase in size, they may obstruct the cerebral aqueduct of Sylvius of the midbrain, producing hydrocephalus. Occasionally, the tumor destroys the pineal gland and causes precocious puberty.

B. Astroglial Cells: Also known as interstitial cells, these glialike cells have elongated heterochromatic nuclei that stain more heavily than those of the parechyma. These cells have long cytoplasmic processes that contain a large number of intermediate filaments. They are found around blood vessels and between clusters of pinealocytes. They are indistinct unless specially stained. The pineal gland has a rich blood supply and is innervated by sympathetic and parasympathetic nervous systems. In addition signals from retina arrive indirectly. Concretions of calcified material called brain sand (corpora arenacia) accumulate within the astroglial cells and connective tissue of the pineal gland, progressively with age. These deposits, are useful to radiologists, because they serve as a landmark and assists in determining whether the pineal gland has been displaced laterally by a space-occupying lesion within the skull.