Human_Histology

Fig. 19.16:. <

(a)+

(b)Maternal blood

with fetal capillaries lined with simple squamous epithelium and containing nucleated fetal RBC. In addition macrophages and fibroblasts are present in the mesodermal core. It is covered with thin layer of intensely stained syncytiotrophoblast and discontinuously arranged cytotrophoblast (Fig. 19.17). Because of the disappearance of cytotrophoblast and thinning of syncytiotrophoblast

Fig. 19.17:. <

(a)Villous showing central core of mesoderm with fetal capillaries

(b)Fetal capillaries lined with simple squamous epithelium and D9:

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the fetal capillaries move towards the periphery there by reducing the thickness of placental barrier.

Endocrine tissue is made up essentially of cells that produce secretions which are poured directly into blood. The secretions of endocrine cells are called hormones. Along with the autonomic nervous system, the endocrine organs co-ordinate and control the metabolic activities and the internal environment of the body.

Endocrine tissues are highly vascular. The secretory pole of an endocrine cell is toward the wall of a capillary (or sinusoid). (In exocrine glands, the secretory pole is toward the surface over which secretions are discharged).

HORMONES

Hormones travel through blood to target cells whose functioning they may influence profoundly. A hormone acts on cells that bear specific receptors for it. Some hormones act only on one organ or on one type of cell, while other hormones may have widespread effects.

On the basis of their chemical structure, hormones belong to four main types:

1.Amino acid derivatives, for example, adrenalin, noradrenalin, and thyroxine.

2.Small peptides, for example, encephalin, vasopressin, and thyroid releasing hormone.

3.Proteins, for example, insulin, parathormone, and thyroid stimulating hormone.

4.Steroids, for examples, progesterone, estrogens, testosterone, and cortisol.

DISTRIBUTION OF ENDOCRINE CELLS

Endocrine cells are distributed in three different ways:

Some organs are entirely endocrine in function. They are referred to as endocrineglands(or ductlessglands). Those traditionally included under this heading are the hypophysis cerebri (or pituitary), the pineal gland, the thyroid gland, the parathyroid glands, and the suprarenal (or adrenal) glands.

Groups of endocrine cells may be present in organs that have other functions. Several examples of such

tissue have been described in previous chapters. They include the islets of the pancreas, the interstitial cells of the testes, and the follicles and corpora lutea of the ovaries. Hormones are also produced by some cells in the kidneys, the thymus, and the placenta. Some authors describe the liver as being partly an endocrine gland.

Isolated endocrine cells may be distributed in the epithelial lining of an organ. Such cells are seen most typically in the gut (endocrine cells of the gut). Similar cells are also present in the epithelium of the respiratory passages. Recent studies have shown that cells in many other locations in the body produce amines that have endocrine functions. Many of these amines also act as neurotransmitters or as neuromodulators. These widely distributed cells are grouped together as the neuroendocrine system or the amine precursor uptake and decarboxylation (APUD) cell system.

HYPOPHYSIS CEREBRI

The hypophysis cerebri is also called the pituitary gland and is approximately the size of a pea. It is suspended from the floor of the third ventricle (of the brain) by a narrow funnel shaped stalk called the infundibulum, and lies in a depression on the upper surface of the sphenoid bone, called sella turcica.

The hypophysis cerebri is one of the most important endocrine glands. It produces several hormones some of which profoundly influence the activities of other endocrine tissues and is sometimes referred as “master endocrine gland”. Its own activity is influenced by the hypothalamus, and by the pineal body.

SUBDIVISIONS OF THE HYPOPHYSIS CEREBRI

The hypophysis cerebri has, in the past, been divided into an anterior part, the pars anterior; an intermediate part, the pars intermedia; and a posterior part the pars posterior (or pars nervosa) (Fig. 20.1 and Plate 20.1).

The pars anterior (which is also called the pars distalis), and the pars intermedia, are both made up of cells having a direct secretory function. They are collectively referred to as the adenohypophysis. An extension of the pars anterior surrounds the central nervous core of the infundibulum. Because of its tubular shape this extension is called the pars tuberalis. The pars tuberalis is part of the adenohypophysis.

The pars posterior contains numerous nerve fibers. It is directly continuous with the central core of the infundibular stalk which is made up of nervous tissue. These two parts (pars posterior and infundibular stalk) are together referred to as the neurohypophysis. The area in the floor of the third ventricle (tuber cinereum) immediately adjoining the attachment to it of the infundibulum is

Chapter 20 Endocrine System 251

called the median eminence. Some authorities include the median eminence in the neurohypophysis.

ADENOHYPOPHYSIS

Pars Anterior

The pars anterior consists of cords of cells separated by fenestrated sinusoids. Several types of cells, responsible for the production of different hormones, are present (Plate 20.2).

Using routine staining procedures the cells of the pars anterior can be divided into:

Chromophil cells that have brightly staining granules in their cytoplasm

Chromophobe cells in which granules are not prominent.

252Textbook of Human Histology

Chromophil Cells

Chromophil cells are further classified as acidophil when their granules stain with acid dyes (like eosin or orange G); or basophil when the granules stain with basic dyes (like hematoxylin). Basophil granules are also periodic acid Schiff (PAS) stain positive. The acidophil cells are often called alpha cells, and the basophils are called beta cells (Plate 20.2).

Electron microscope (EM) examination shows that both acidophil and basophil cells contain abundant dense cored vesicles in the cytoplasm.

Both acidophils and basophils can be divided into subtypes on the basis of the size and shape of the granules in them. These findings have been correlated with those obtained by immunochemical methods—these methods allow cells responsible for production of individual hormones to be recognized. The following functional types of cells have been described.

Types of Acidophil Cells

Somatotrophs produce the somatropic hormone [also called somatotropin (STH), or growth hormone (GH)].

This hormone controls body growth, specially before puberty.

Mammotrophs (or lactotrophs) produce the mammotropic hormone [also called mammotropin, prolactin (PRL), lactogenic hormone, or LTH] which stimulates the growth and activity of the female mammary gland during pregnancy and lactation.

Types of Basophil Cells

The corticotrophs (or corticotropes) produce the corticotropic hormone (also called adreno-corticotropin or ACTH). This hormone stimulates the secretion of some hormones of the adrenal cortex. The staining characters of these cells are intermediate between those of acidophils and basophils. The cells are, therefore, frequently considered to be a variety of acidophils. In the human hypophysis their cytoplasm is weakly basophilic and PAS positive. The granules in the cells contain a complex molecule of pro-opio-melano-cor- ticotropin. This is broken down into ACTH and other substances.

Other corticotropic hormones that have been identified are -lipotropin ( -LPH), -melanocyte stimulating hormone ( -MSH)and -endorphin.

Thyrotrophs (or thyrotropes) produce the thyrotropic hormone (thyrotropin or TSH) which stimulates the activity of the thyroid gland.

Gonadotrophs (gonadotropes, or delta basophils) produce two types of hormones each type having a different action in the male and female.

In the female, the first of these hormones stimulates the growth of ovarian follicles. It is, therefore, called the follicle stimulating hormone (FSH). It also stimulates the secretion of estrogens by the ovaries. In the male the same hormone stimulates spermatogenesis.

In the female, the second hormone stimulates the maturation of the corpus luteum, and the secretion by it of progesterone. It is called the luteinizing hormone (LH). In the male the same hormone stimulates the production of androgens by the interstitial cells of the testes, and is called the interstitial cell stimulating hormone (ICSH).

Chromophobe Cells

These cells do not stain darkly as they contain very few granules in their cytoplasm. Immunocytochemistry shows that they represent cells similar to the various types of chromophils mentioned above (including mammotrophs, somatotrophs, thyrotrophs, gonadotrophs or corticotrophs).

Added Information

Somatotrophs constitute about 50%, mammotrophs about 25%, corticotrophs 15–20%, and gonadotrophs about 10% of the cell population of the pars anterior

Somatotrophs are located mainly in the lateral parts of the anterior lobe. Thyrotrophs are concentrated in the anterior, median part; and corticotrophs in the posterior, median part. Gonadotrophs and mammotrophs are scattered throughout the anterior lobe

The size of dense cored vesicles (seen by EM) is highly variable. It is about 400 nm in somatotrophs, about 300 nm in mammotrophs, 250–700 nm in corticotrophs and 150–400 nm in gonadotrophs.

Pars Tuberalis

The pars tuberalis consists mainly of undifferentiated cells. Some acidophil and basophil cells are also present.

Pars Intermedia

This is poorly developed in the human hypophysis. In ordinary preparations the most conspicuous feature is the presence of colloid filled vesicles (Fig. 20.2). These vesicles are remnants of the pouch of Rathke. Beta cells, other secretory cells, and chromophobe cells are present. Some cells of the pars intermedia produce the melanocyte stimulating hormone (MSH) which causes increased pigmentation of the skin. Other cells produce ACTH. Endorphins are present in the cytoplasm of secretory cells.

Note: The secretion of hormones from the adenohypophysis is under control of the hypothalamus as described later.

Fig. 20.2: Hypophysis cerebri. Pars posterior (left) and pars intermedia (right). 1–colloid; 2–capillary; 3–clumps of cells (including some acidophils and basophils)

(Schematic representation)

NEUROHYPOPHYSIS

Pars Posterior (Pars Nervosa)

The pars posterior consists of numerous unmyelinated nerve fibers which are the axons of neurons located in the hypothalamus (Fig. 20.2). Most of the nerve fibers arise in the supraoptic and paraventricular nuclei. Situated between these axons there are supporting cells of a special type called pituicytes. These cells have long dendritic processes many of which lie parallel to the nerve fibers. The axons descending into the pars posterior from the hypothalamus end in terminals closely related to capillaries.

The pars posterior of the hypophysis is associated with the release into the blood of two hormones.

Vasopressin: (Also called the antidiuretic hormone or ADH): This hormone controls reabsorption of water by kidney tubules.

Oxytocin:Itcontrolsthecontractionofsmoothmuscleofthe uterus and also of the mammary gland.

These two hormones are not produced in the hy-

pophysis cerebri at all. They are synthesized in neurons located mainly in the supraoptic and paraventricular nuclei of the hypothalamus. Vasopressin is produced mainly in the supraoptic nucleus, and oxytocin in the paraventricular nucleus. These secretions (which are bound with a glycoprotein called neurophysin) pass down the axons of the neurons concerned. In axoplasm hormone is in the form of secretory vesicles (granules) and reaches the axon terminals in the pars posterior. The collection of these secretory granules at the terminal portion of axonal processing is called as Herring bodies (Fig. 20.3). Here they are released into the capillaries of the region and enter the general circulation.

BLOOD SUPPLY OF THE HYPOPHYSIS CEREBRI

The hypophysis cerebri is supplied by superior and inferior branches arising from the internal carotid arteries.

Chapter 20 Endocrine System 253

Fig. 20.3: The relationship between hypothalamus and the pars posterior of the hypophysis cerebri (Schematic representation)

Some branches also arise from the anterior and posterior cerebral arteries. The inferior hypophyseal arteries are distributed mainly to the pars posterior. Branches from the superior set of arteries supply the median eminence and infundibulum. Here they end in capillary plexuses from which portal vessels arise. These portal vessels descend through the infundibular stalk and end in the sinusoids of the pars anterior. The sinusoids are drained by veins that end in neighboring venous sinuses.

The above arrangement is unusual in that two sets of capillaries intervene between the arteries and veins. One of these is in the median eminence and the upper part of the infundibulum. The second set of capillaries is represented by the sinusoids of the pars anterior. This arrangement is referred to as the hypothalamo-hypophyseal portal system (Fig. 20.4).

Clinical Correlation

The vessels descending through the infundibular stalk are easily damaged in severe head injuries. This leads to loss of function in the anterior lobe of the hypophysis cerebri.

CONTROL OF SECRETION OF HORMONES

OF THE ADENOHYPOPHYSIS

The secretion of hormones by the adenohypophysis takes placeunderhighercontrolofneuronsinthehypothalamus, notably those in the median eminence and in the infundibular nucleus. The axons of these neurons end in relation to capillaries in the median eminence and in the upper part of the infundibulum.

Different neurons produce specific releasing factors (or releasing hormones) for each hormone of the adenohypophysis. (For details of hypothalamic nuclei and the releasing

factors produced by them see the author’s TEXTBOOK OF HUMAN NEUROANATOMY). These factors are released into the capillaries. Portal vessels arising from the capillaries carry these factors to the pars anterior of the hypophysis. Here they stimulate the release of appropriate hormones. Some factors inhibit the release of hormones. The synthesis and discharge of releasing factors by the neurons concerned is under nervous control. As these neurons serve as intermediaries between nervous impulses and hormone secretion they have been referred to as neuroendocrine transducers. Some cells called tanycytes, present in ependyma, may transport releasing factors from neurons into the cerebrospinal fluid (CSF), or from CSF to blood capillaries. They may thus play a role in control of the adenohypophysis.

Added Information

Recent studies indicate that circulation in relation to the hypophysis cerebri may be more complex than presumed earlier. Some points of interest are as follows:

The entire neurohypophysis (from the median eminence to the pars posterior) is permeated by a continuousin either direction. The capillaries provide a route through which hormones released in the pars posterior can travel back to the hypothalamus, and into CSF.

Some veins draining the pars posterior pass into the adenohypophysis. Secretions by the adenohypophysis may thus be controlled not only from the median eminence, but by the entire neurohypophysis.

parsposterior may be reversible providing a feedback from adenohypophysis to the neurohypophysis.

Clinical Correlation

Gigantism: When growth hormone (GH) excess occurs prior to epiphyseal closure, gigantism is produced. Gigantism, therefore, occurs in prepubertal boys and girls and is much less frequent than acromegaly. The main clinical feature in gigantism is the excessive and proportionate growth of the child. There is enlargement as well as thickening of the bones resulting in considerable increase in height and enlarged thoracic cage.

Acromegaly: Acromegaly results when there is overproduction of GH in adults following cessation of bone growth and is more common than gigantism. The term “acromegaly” means increased growth of extremities (acro=extremity). There is enlargement of hands and feet, coarseness of facial features with increase in soft tissues, prominent supraorbital ridges and a more prominent lower jaw which when clenched results in protrusion of the lower teeth in front of upper teeth

(prognathism).

Diabetes Insipidus: and neoplastic lesions of the hypothalamo-hypophyseal axis, destruction of neurohypophysis due to surgery, radiation, head known and are labeled as idiopathic. The main features of diabetes insipidus are excretion of a very large volume of dilute! " # $ %$%& polydipsia.

THYROID GLAND

Thyroid is a bi-lobed gland. Each lobe is situated on either side of trachea, below larynx, in lower neck. The two lobes are connected to each other by isthmus in front of trachea. Among endocrine glands, thyroid is unique as it stores

large quantity of its hormonal secretion extracellularly as colloid in contrast to other endocrine glands which store very small quantities intracellularly as secretory granules only.

STRUCTURE OF THYROID GLAND

The thyroid gland is covered by a fibrous capsule. Septa extending into the gland from the capsule divide it into lobules. On microscopic examination each lobule is seen to be made up of an aggregation of follicles. Each follicle is lined by follicular cells, that rest on a basement membrane. The follicle has a cavity which is filled by a homogeneous material called colloid (which appears pink in hematoxylin and eosin stained sections) (Plate 20.3). The spaces between the follicles are filled by a stroma made up

Chapter 20 Endocrine System 255

of delicate connective tissue in which there are numerous capillaries and lymphatics. The capillaries lie in close contact with the walls of follicles.

Apart from follicular cells the thyroid gland contains C-cells (or parafollicular cells) which intervene (here and there) between the follicular cells and the basement membrane (Plate 20.3). They may also lie in the intervals between the follicles. Connective tissue stroma surrounding the follicles contain a dense capillary plexus, lymphatic capillaries and sympathetic nerves.

Follicular Cells

The follicular cells vary in shape depending on the level of their activity (Fig. 20.5). Normally (at an average level of activity) the cells are cuboidal, and the colloid in

Fig. 20.5: Variations in appearance of thyroid follicles at different levels of activity (Schematic representation)

the follicles is moderate in amount. When inactive (or resting) the cells are flat (squamous) and the follicles are distended with abundant colloid. Lastly, when the cells are highly active they become columnar and colloid is scanty. Different follicles may show different levels of activity (Fig. 20.5).

With the EM a follicular cell shows the presence of apical microvilli, abundant granular endoplasmic reticulum, and a prominent supranuclear Golgi complex. Lysosomes, microtubules and microfilaments are also present. The apical part of the cell contains many secretory vacuoles (Fig. 20.6).

The activity of follicular cells is influenced by the thyroid stimulating hormone (TSH or thyrotropin) produced by the hypophysis cerebri. There is some evidence to indicate that their activity may also be increased by sympathetic stimulation.

The follicular cells secrete two hormones that influence the rate of metabolism. Iodine is an essential constituent of these hormones. One hormone containing three atoms of iodine in each molecule is called triodothyronine or T3. The second hormone containing four atoms of iodine in each molecule is called tetraiodothyronine, T4, or thyroxine. T3 is much more active than T4.

Fig. 20.6: Ultrastructure of a follicular cell of the thyroid gland (Schematic representation)

Synthesis of Thyroid Hormone

The synthesis and release of thyroid hormone takes place in two phases (Flowchart 20.1). In the first phase, thyroglobulin (a glycoprotein) is synthesized by granular endoplasmic reticulum and is packed into secretory vacuoles in the Golgi complex. The vacuoles travel to the luminal surface where they release thyroglobulin into the follicular cavity by exocytosis. Here the thyroglobulin combines with iodine to form colloid. Colloid is iodinated thyroglobulin.

In the second phase particles of colloid are taken back into the cell by endocytosis. Within the cell the iodinated thyroglobulin is acted upon by enzymes (present in lysosomes) releasing hormones T3 and T4 which pass basally through the cell and are released into blood.

Hormone produced in the thyroid gland is mainly T4 (output of T3 being less than 10%). In the liver, the kidneys (and some other tissues) T4 is converted to T3 by removal of one iodine molecule. T3 and T4 circulating in blood are bound to a protein [thyroxine binding globulin, TBG]. The bound form of hormone is not active.

C-cells (Parafollicular Cells)

They are also called clear cells, or light cells. The cells are polyhedral, with oval eccentric nuclei. Typically, they lie between the follicular cells and their basement membrane. They may, however, lie between adjoining follicular cells; but they do not reach the lumen. In some species many parafollicular cells may lie in the connective tissue between the follicles and may be arranged in groups. With the EM

Flowchart. 20.1: Some steps in the formation of hormones by the thyroid gland

the cells show well developed granular endoplasmic reticulum, Golgi complexes, numerous mitochondria, and membrane bound secretory granules.

Note: C-cells share features of the APUD cell system and are included in this system.

C-cells secrete the hormone thyrocalcitonin. This hormone has an action opposite to that of the parathyroid hormone on calcium metabolism. This hormone comes into play when serum calcium level is high. It tends to lower the calcium level by suppressing release of calcium ions from bone. This is achieved by suppressing bone resorption by osteoclasts.

Clinical Correlation

Hyperthyroidism: Hyperthyroidism, also called thyrotoxicosis, is a hypermetabolic clinical and biochemical state caused by excess production of thyroid hormones. The condition is more frequent in females and is associated with rise in both T3 and T4 levels in blood, though the increase in T3 is generally greater than that of T4.

Hypothyroidism: Hypothyroidism is a hypometabolic clinical state resulting from inadequate production of thyroid hormones for prolonged periods, or rarely, from resistance of the peripheral tissues to the effects of thyroid hormones. The clinical manifestations of hypothyroidism, depending upon the age at onset of disorder, are divided into two forms:

Contd…

Chapter 20 Endocrine System 257

contd…

Cretinism or congenital hypothyroidism is the development of severe hypothyroidism during infancy and childhood.

Myxedema is the adulthood hypothyroidism.

Graves’ disease: Graves’ disease, also known as Basedow’s disease, primary hyperplasia, exophthalmic goiter, and diffuse toxic goiter, is characterized by a triad of features:

Hyperthyroidism (thyrotoxicosis)

Diffuse thyroid enlargement

Ophthalmopathy.

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PARATHYROID GLANDS

The parathyroid glands are so called because they lie in close relationship to the thyroid gland. Normally, there are two parathyroid glands, one superior and one inferior, on either side; there being four glands in all. Sometimes there may be as many as eight parathyroids.

STRUCTURE OF PARATHYROID GLANDS

Each gland has a connective tissue capsule from which some septa extend into the gland substance. Within the gland a network of reticular fibers supports the cells. Many fat cells (adipocytes) are present in the stroma (Plate 20.4).

The parenchyma of the gland is made up of cells that are arranged in cords. Numerous sinusoids lie in close relationship to the cells.

CELLS OF PARATHYROID GLANDS

The cells of the parathyroid glands are of two main types:

Chief cells (or principal cells)

Oxyphil cells (or eosinophil cells).

Chief Cells

The chief cells are much more numerous than the oxyphil cells.

With the light microscope the chief cells are seen to be small round cells with vesicular nuclei. Their cytoplasm is clear and either mildly eosinophil or basophil. Sometimes the cell accumulates glycogen and lipids and looks ‘clear’. Three types of chief cells (light, dark, and clear) have been described.

With the EM active chief cells are seen to have abundant granular endoplasmic reticulum and well developed Golgi complexes. Small secretory granules are seen, specially