ADRENAL GLANDS AND DIFFUSE ENDOCRINE SYSTEM. SKIN AND ITS APPENDAGES.
Using lectures (on the web-page of the department posted the presentation text and lectures), books, additional literature and other sources, students must to prepare the following theoretical questions:
1. Describe the cortex and medulla of the adrenals in terms of their histological structure, function, location, and embryonic origin.
2. Layers of the adrenal cortex in terms of each layer’s histological structure, the hormones secreted, and the layer’s location.
3. Roles of the pituitary, hypothalamus, and kidney in regulation of adrenocortical hormone secretion.
4. Functional relationship between the adrenal medulla and the nervous system.
5. Adrenocortical hormones role in adrenomedullary function regulation.
6. Alone endocrine cells origin and location.
7. APUD system. Paracrine (local) and distant regulation of human organs and systems.
8. Important skin’s functions and relation of them to its structure.
9. Major layers of skin and the basic tissue type that predominates in each.
10. Cell types commonly found in the epidermis and description of their structure, function, and location.
11. Layers of the epidermis of thick skin and description of the distinguishing structural features of each.
12. Steps in the processes of epidermal cell renewal and keratinization in relation to the epidermal layers.
13. Comparison of the 2 layers of the dermis.
14. Description of the important components of the skin derivatives.
15. Comparison of the 3 types of glands associated with the skin.
Glandula suprarenalis is a palsed yellowish organ formed by the union of two independent hormon producing glands, comprising of cortex and medulla of different origin, regulatory and phisiological significance, situated on the superior renal pole. The adrenal glands are paired organs, which 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-
Examination of a fresh section of adrenal gland shows it to be covered by a capsule of dense connective tissue. The gland consists of two concentric layers: a yellow peripheral layer, the adrenal cortex;-and a reddish-brown central layer, the adrenal medulla. Outside the glands are covered by connective tissue capsule,which Is divided into two layers-outer (dense) and inner (loose). Cortex-shows three cellular zones. Under the capsule lies a thin striated layer of small epithelial cells, whose division participates in regeneration of cortex. The endocrinocytes corticalls forms an epithelial layer which is oriented perpendicularly to the surface of the gland. The three principal cellular zones of the glands are:
1) zona glomerulosa
2) zona fasclculata
3) zona reticularis
Adrenocortical tissue is shown stippled; adrenal medullary tissue is shown black. Note the location of the adrenal glands at the superior pole of each kidney. Also there are shown extra-adrenal sites where cortical and medullary tissues are sometimes found.
The adrenal cortex and the adrenal medulla can be considered two organs with distinct origins, functions, and morphologic characteristics that unite during embryonic development. They arise from different germ layers. The cortex arises from coelomic intermediate mesoderm; the medulla consists of cells derived from the neural crest, from which sympathetic ganglion cells also originate. The general histologic 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.
Feedback mechanism of ACTH and glucocorticoid secretion. Solid arrows indicate stimulation; dashed arrows, inhibition. CRH, corticotropin-releasing hormone, ACTH, corticotropin.
The 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 support the secretory cells.
Blood Supply
Several arteries that enter at various points around their periphery supply the adrenal glands. The three main groups are the superior suprarenal artery, arising from the inferior phrenic artery; the middle suprarenal artery, arising from the aorta; and the inferior suprarenal artery, arising from the renal artery. The arterial branches form a subcapsular plexus from which arise three groups of vessels: arteries of the capsule; arteries of the cortex, which branch repeatedly to form the capillary bed between the parenchymal cells (these capillaries drain into medullary capillaries); and arteries of the medulla, which pass through the cortex before breaking up to form part of the extensive capillary network of the medulla.
A dual blood supply provides the medulla with both arterial (via medullary arteries) and venous (via cortical arteries) blood. The capillary endothelium is extremely attenuated and interrupted by small fenestrae that are closed by thin diaphragms. 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.
Adrenal Cortex
Because of the differences in disposition and appearance of its cells, the adrenal cortex can be subdivided into three concentric layers that are usually not sharply defined in humans: the zona glomerulosa, the zona fasciculate, and the zona reticularis. These zones occupy 15%, 65%, and 7%, respectively, of the total volume of the adrenal glands.
I). Zona glomerulosa is found in outer region (subcapsular zone) of the gland. It is
formed of small, polyhedral cells (endocrinocytes) arranded in rounded groups or convoluted columns, with duply staining nuclei, scanty basophllic cytoplasm with lipid droplets (very few). The cytoplasm displays many microtubules, large mitochondria and agranular endoplasmic reticulum. The mitohondria is characterized by lamellated cristae. The agranular endoplasmic reticulum is represented by small vesicles, between which are located ribosomes: characteristics of steroid producing cells. The Golgi apparatus is developed very well. The cells secrete hormone – aldosterone – mineral – corticold hormone, which affects electrolyte and water balance. Between the zona glomerulosa and fasciculata a narrow layer of nonspecialized cells is found. This layer is called intermediate or sudanphobic zone. The division of cells in this layer participates in the regeneration of reticular and fascicular zones. The zona glomerulosa is poorly developed in human beings.
2). Zona fascilulata – consist of large polyhedral cells with basophillc cytoplasm arranged in straight columns, two cells wide, with parallel fenestrated venous capillaries between them. The cytoplasm contains vany lipid droplets, phospholipids, fats, fatty acid, cholesterol embedded in complex agranular endoplasmic reticulum.
The mitochondria are typically spherical with tubular cristae, the Colgl complex is extensive. The side of the cells feeing the blood capillaries contains a layer of microvillis. The granular endoplasmic reticulum is well developed. Ribosomes lie freely in the cytoplasm. Along with light coloured cells are found dark colored cells which contain small atount of lipids, but high amount of ribonucleoprotein. In the dark cells are found well developed agranular endoplasmic reticulum and granular endoplasmic reticulum. The light and dark cells represent different functional entities of the endocrinocytes. The dark cells are concerned with the formation of enzymes which participate in formation of corticosteroid. Affer secretion of steroid the cell becomes light in color and prepares for the release of secretion into the blood. Cells of this zone produce glucocorticoid hormone – corticosterone, cortizon and cortisol (hydrocortizon). These hormones maintain the carbohydrate balance in the body.
Apart from it, it controls the guantity of protein and lipids, increases the process of phosphorylation in the body, leading to the formation of matter, rich in energy which is released for maintaing the basic processes of life support glucocorticoid helps in the process of gluconeogenes i.e. formation of glucose from protein and the deposition of glycogen in liver and myocardium and mobilization of tissue protein.
High concentratioh of glucocorticoid causes destriction of lymphocytes and eosinophils in the blood, causing lymphocytopenia and erytrocytopenia which causes changes in inflammatory responses of body.
3). Zona retlcuaris contains branching, interconnected columns of round cells whose cytoplasm consist of large deposits of agranular endoplasmic reticulum, lysosomes and pigment bodies which may indicate degenerative processes. The cristae of mitochondria are tubular in shape. The endoplasmic reticulum is primarily made up of vesicules with large amount of ribosomes. The cells secrete sex hormones – progesterone, oestrogen and androgen. However the formation of testosterone and other androgenic hormones dominate over the development of female hormones.
Between the reticular zone and the medulla is found a zone of highly acidophilic cells called X-zone. Adrenal medulla is composed of groups and columns of phacochromocytes seperated by wide fenestrated capillaries. The chromaffin cells (chromaffinocytes) synthesis and expel adrenalin and noradrenalln into the sinusoids.
There are two types of chromaffinocytes depending upon their secreations. Light coloured ones called epinephrocytes, dark coloured ones norepinephrocytes. The cytoplasm of the cell is filled with secretory granules of 100-500 nm in diameter. The granules are filled with protein-kateholamine. Ioradrenalin containing cells, the vesicles are round or elipsold while in adrenalin containing cells, the vesicles are paler.
Specimen of adrenal gland. Stained with haematoxylin and eosin.
References. The layer immediately beneath the connective tissue capsule is the zona glomerulosa, in which the columnar or pyramidal cells are arranged in closely packed, rounded, or arched clusters surrounded by capillaries. The nuclei stain deeply, and the rather scanty cytoplasm contains basophilic material, which may be diffuse or, as in man, disposed in clumps. Lipid droplets, when present, are scarce and small in most animals, and may be numerous in others.
Mitochondria may be filamentous (in man), rodlike (in the guinea pig and cat), or spherical in the rat. The compact Golgi apparatus is juxtanuclear and may be polarized toward the capillary surface in some animals.
The next layer of cells is known as the zona fasciculata because of the arrangement of the cells in straight cords, one or two cells thick, 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. As a result of the dissolution of the lipids during tissue preparation, the fasciculata cells appear vacuolated in common histologic preparations.
This is the region, which may contain mitotic figures. The mitochondria appear generally to be less numerous than in the outer cortical zone. The Golgi apparatus is juxtanuclear, and in some animals appear to be somewhat less compact than in the zona glomerulosa.
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. The cytoplasm contains fewer lipid droplets. Toward the medulla there is variable number of “light” cells and “dark” cells which differ in their staining affinities. The nuclei of the light cells are pale-staining, while those of the dark cells are shrunken and hyperchromatic. Mitochondria are few in the former and numerous in the latter. The Golgi apparatus is compact or fragmented. The dark cells contain clumps of yellow or brownish pigment. Some as degenerating cells regards both the light and dark cells. Irregularly shaped cells with picnotic nuclei—suggesting cellular degradation—are often found in this layer. Cells of the adrenal cortex have the typical ultrastructure of steroid-secreting cells.
Fine structure of 2 steroid-secreting cells from the zona fasciculata of the human adrenal cortex. The lipid droplets (L) contain cholesterol esters. M, mitochondria with characteristic tubular and vesicular cristae; SER, smooth endoplasmic reticulum; N, nucleus; G, Golgi complex; Ly, lysosome; P, lipofuscin pigment granule. x25,700.
Histophysiology
Cells of the adrenal cortex do not store their secretory products in granules; rather, they synthesize and secrete steroid hormones only upon demand. Steroids, being low-molecular-weight lipid-soluble molecules, can freely diffuse through the plasma membrane and do not require the specialized process of exocytosis for their release.
The steroids secreted by the cortex can be divided into three groups, according to their main physiologic actions: glucocorticoids, mineralocorticoids, and androgens. The zona glomerulosa secretes mineraloeorticoids, primarily aldosterone, that maintain electrolyte (eg, sodium and potassium) and water balance. The zona fasciculata secrete the glucocorticoids cortisone and cortisol or, in some animals, corticosterone; these glucocorticoids regulate carbohydrate, protein, and fat metabofisrn. The zona reticularis produce androgens and perhaps estrogens in small amounts.
The location of the enzymes participating in aldosterone synthesis has been determined through differential centrifugation. The synthesis of cholesterol from acetate takes place in smooth endoplasmic reticulum, and the conversion of cholesterol to pregnenolone takes place in the mitochondria. The enzymes associated with the synthesis of progesterone and deoxycorticosterone from pregnenolone are found in smooth endoplasmic reticulum; those enzymes that convert deoxycorticosterone → corticosterone → 18-hydroxycorticosterone → aldosterone are located in mitochondria – a clear example of colaboration between two cell organelles.
The glucocorticoids, mainly cortisol and corticosterone, exert a profound effect on the metabolism of carbohydrates, as well as on that of proteins and lipids. In the liver, glucocorticoids promote the uptake and use of fatty acids (energy source), amino acids (enzyme synthesis), and carbohydrates (glucose synthesis) that are used in gluconeogenesis and glycogenesis (glycogen assembly). These hormones can stimulate the synthesis of so much glucose that the resulting high levels in the blood produce a condition similar to diabetes mellitus. Outside the liver, however, glucocorticoids induce an opposite, or catabolic, effect on peripheral organs (eg, skin, muscle, adipose tissue). In these structures, glucocorticoids not only decrease synthetic activity but also promote protein and lipid degradation. The by-products of degradation, amino and fatty acids, are removed from the blood and used by the synthetically active hepatocytes.
Glucocorticoids also suppress the immune response by destroying circulating lymphocytes and inhibiting mitotic activity in lymphocyte-forming organs.
The mineralocorticoids act mainly on the distal renal tubules as well as on the gastric mucosa and the salivary and sweat glands, stimulating the absorption of sodium. They may increase the concentration of potassium and decrease the concentration of sodium in muscle and brain cells.
Dehydroepiandrosterone is the only sex hormone that is secreted in significant physiologic quantities by the adrenal cortex. It has virilizing and anabolic effects, but it is less than one-fifth as potent as testicular androgens. For this reason, and because it is secreted in small quantities, it produces a negligible physiologic effect under normal conditions.
As in other endocrine glands, the adrenal cortex is controlled initially through the release of its corresponding releasing hormone stored in the median eminence. This is followed by secretion of adreno-corticotropic hormone, or corticotropin (ACTH), which stimulates the synthesis and secretion of cortical hormones (eg, glucocorticoids). 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.
Adrenal Medulla
The adrenal medulla is composed of polyhedral parenchymal 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. Medullary parenchymal cells arise from neural crest cells, as do the postganglionic neurons of sympathetic and parasympathetic ganglia. Parenchymal cells of the adrenal medulla can be regarded as modified sympathetic postganglionic neurons that have lost their axons and dendrites during embryonic development and have become secretory cells.
Medullary parenchymal cells have abundant membrane-limited electron-dense secretory granules. These granules contain one or the other of the catecholamines, epinephrine or nor-epinephrine. The secretory granules also contain ATP, proteins called chromogranins (which may serve as binding proteins for catecholamines), dopamine β-hydroxylase (which converts dopamine to norepinephrine), and opiate-like peptides (enkephalins).
A large body of evidence shows that two different types of cells in the medulla secrete epinephrine and norepinephrine. Epinephrine-secreting cells have smaller granules that are less electron-dense, and their contents fill the granule. Norepinephrine-secreting cells have larger granules that are more electron-dense; their contents are 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.
Diagram of an adrenal medullary cell showing the role of several organelles in synthesizing the constituents of secretory granules. Synthesis of norepinephrine and conversion to epinephrine take place in the cytosol.
All adrenal medullary cells are innervated by cholinergic endings of preganglionic sympathetic neurons. Unlike the cortex, which does not store steroids, cells of the medulla accumulate and store their hormones in granules.
Epinephrine and norepinephrine are secreted in large quantities in response to intense emotional reactions (e.g., fright). Secretion of these substances is mediated by the preganglionic fibers that innervate medullary cells. 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. These effects are part of the organism’s defense reaction to stress (the fight-or-flight response). During normal activity, the medulla continuously secretes small quantities of these hormones.
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 a diffuse source of catecholamines.
Fetal, or provisional, Cortex
In humans and some other animals, the adrenal gland of the newborn is proportionately larger than that of the adult. At this early age, a layer known as the fetal, or provisional, cortex is present between the medulla and the thin permanent cortex. This layer is fairly thick, and its cells are disposed in cords. After birth, the provisional cortex undergoes involution while the permanent cortex—the initially thin layer—develops, differentiating into the three layers (zones) described above. A major function of the fetal cortex is the secretion of sulfate conjugates of androgens, which are converted in the placenta to active androgens and estrogens that enter the maternal circulation. This layer in adult has no lipid inclusions and can’t be stained with sudan (so called sudanophobic zone).
Regeneration of the adrenal gland
Cortical cells are particularly susceptible to injury. They are replaced by mitosis probably throughout the cortex, with a greater tendency for this to take place in the transition zone between zona glomerulosa and zona fasciculata. Another layer of stem cells one can find between the capsule and zona glomerulosa. Between zona reticularis and adrenal medulla is situated X-zone, in which one can see cells with acidophilic cytoplasm. Successful transplantation seems to require the presence of a capsule. It is more successful also in totally adrenalectomized animals. The medulla does not survive transplantation readily.
Adrenal Dysfunction
A common disorder of the adrenal medulla is pheochromocytoma, a tumor of its cells that causes hyperglycemia and transient elevations of blood pressure. These tumors can also develop in extramedullary sites.
Disorders of the adrenal cortex can be classified as hyperfunctional or hypofunctional. Tumors of the adrenal cortex can result in excessive production of glucocorticoids (Gushing syndrome) or aldosterone (Conn syndrome). Gushing syndrome is most often (90%) due to a pituitary adenoma that results in excessive production of ACTH; it is rarely caused by adrenal hyperplasia or an adrenal tumor. Excessive production of adrenal androgens has little effect in men. 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.
Adrenocortical insufficiency (Addison disease) is mainly caused by autoimmune destruction of the adrenal cortex (80 %) or it can be a complication of tuberculosis (20 %). The signs and symptoms suggest failure of secretion of both glucocorticoids and mineralocorticoids by the-adrenal cortex.
Carcinomas of the adrenal cortex are rare, but most are highly malignant. About 90% of these tumors produce steroids associated with endocrine glands.
skin
The skin is far more than a simple hide, which covers the body. Instead, it is a vital, protective barrier that serves as the body’s first line of defense in a hostile world. The skin responds to internal as well as external challenges, and it is of fundamental importance in the maintenance of homeostasis. Destruction of large amounts of skin will results in death; thus this protective covering is truly one of the vital organs of the body.
The skin functions as a receptor organ in continuous communication with the environment and protects the organism from impact and friction injuries. Melanin, a pigment produced and stored in the cells of the epidermis, provides further protective action against the sun’s ultraviolet rays. Glands of the skin, blood vessels, and adipose tissue participate in thermoregulation, body metabolism, and the excretion of various substances. Under the action of soar radiation, vitamin l>, is formed from precursors synthesized by the epidermal layer. Because skin is elastic, it can expand to cover large areas in conditions associated with swelling, such as edema and pregnant.
The skin is the heaviest single organ of the body, accounting for about 16% of total body weight and, in adults, presenting 1.2-
Beneath the dermis lies the hypodermis or subcutaneous tissue, a loose connective tissue that may contain a pad of adipose cells, the panniculitis adiposus. The hypodermis, which is not considered part of the skin, binds skin loosely to the subjacent tissues and corresponds to the superficial fascia of gross anatomy.
Specimen of skin (fingertip).
Stained with Hematoxylin and Eosin.
Specimen of scalp skin.
Stained with Haematoxylin and Eosin.
EPIDERMIS
The epidermis is the thin surface layer of the skin. It consists mainly of a stratified squamous keratinized epithelium, which has 6 layers: stratum basale, stratum spinosum, stratum granulosum, stratum lucidum, and stratum corneum.
The epidermis varies from 0,07 to
Stratum Basale (Stratum Germinativum). The stratum basale consists of a single layer of basophilic columnar or cuboidal cells resting on the basal lamina at the dermal-epidermal junction. Desmosomes bind the cells of this layer together in their lateral and upper surfaces. Hemidesmosomes, found in the basal plasmolemma, help, bind these cells to the basal lamina. Main cells of this layer are: basal epidermal cells, melanocytes, Langerhans cells, and Merkel’s cells. The stratum basale is characterized by intense mitotic activity (basal epidermal cells) and is responsible, in conjunction with the initial portion of the next layer, for constant renewal of epidermal cells. The human epidermis is renewed about every 15-30 days, depending on age, the region of the body, and other factors. All cells in the stratum basale contain intermediate keratin filaments about 10 nm in diameter. As the cells progress upward, the number of filaments increases until they represent half the total protein in the stratum corneum.
Stratum Spinosum: The stratum spinosum consists of cuboidal, or slightly flattened, cells with a central nucleus and a cytoplasm whose processes are filled with bundles of keratin filaments. These bundles converge into many small cellular extensions, terminating with desmosomes located at the tips of these spiny projections. The cells of this layer are firmly bound together by the filament-filled cytoplasmic spines and desmosomes that punctuate the cell surface, giving a spine-studded appearance. These tonofilament bundles, visible under the light microscope, are called, tonoflbrils; they end at and insert into the cytoplasmic densities of the desmosomes. The filaments play an important role in maintaining cohesion among cells and resisting the effects of abrasion. The epidermis of areas subjected to continuous friction, and pressure (such as the soles of the feet) has a thicker stratum spinosum with more abundant tonoflbrils and desmosomes.
Stratum spinosum of the skin from the sole of the foot (thick skin) showing the spiny projections that strongly bind the cells of this layer together to resist abrasion. Pararosaniline–toluidine blue stain. Medium magnification.
High magnification of cells from the stratum spinosum. This section was processed to identify keratin by immunocytochemistry and shows the bundles of keratin filaments (tonofilaments) in the cells and their spines (intercellular bridges).
Electron micrographs of the stratum spinosum. A: A cell of the stratum spinosum with melanin granules and the cytoplasm full of tonofilaments. The arrows show the spines with their desmosomes. x8400. B and C: The desmosomes from A, in greater detail. Note that a dense substance appears between the cell membranes and that bundles of cytoplasmic tonofilaments (F) insert themselves on the desmosomes. B, x36,000; C, x45,000.
Section of the stratum spinosum showing the localized deposits of melanin covering the cell nuclei. Melanin protects the DNA from the UV radiation of the sun. This explains why people with light skin have a higher incidence of skin cancer than do people with dark skin. The highest concentration of melanin occurs in the cells that are more deeply localized; these cells divide more actively. (The DNA of cell populations that multiply more actively is particularly sensitive to harmful agents.)
All mitoses are confined to what is termed the malpighian layer, which consists of both the stratum basale and the stratum spinosum.
Stratum Granulosum. The stratum granulosum consists of three to five layers of flattened polygonal cells whose cytoplasm is filled with coase basophilic granules called keratohyalin granules. Beginning with this layer, all cells aге named keratinoeytes (keratin-producing cells), because they take place in process, which is named keratinization. These granules contain a phosphorylated histidine-rich protein as well as proteins containing cystine. The numerous phosphate groups account for the intense basophilia of keratohyalin granules, which are not surrounded by a membrane.
Another characteristic structure in the cells of the granular layer of epidermis that can be seen with the electron microscope is the-membrane-coated lamellar granule, a small ovoid or rod-like structure containing lamellar disks that are formed by lipid bilayers. These granules fuse with cell membrane and discharge their contents into the intercellular spaces of the stratum granulosum, where they are deposited in the form of sheets containing lipid. The function of this extruded material is similar to that of intercellular cement in that it acts as a barrier to penetration by foreign materials and provides a very important sealing effect in the skin. Studies of keratinized and nonkeratinized human oral epithelium show no penetration by peroxidase and lanthanum tracers in the regions where this material fills the extracellular space. Formation of this barrier, which appeared first in reptiles, was one of the important evolutionary events that permitted development of terrestrial life.
Diagram of a melanocyte. Its processes extend into the interstices between keratinocytes. The melanin granules are synthesized in the melanocyte, migrate to its processes, and are transferred into the cytoplasm of keratinocytes.
Diagram of a melanocyte, illustrating the main features of melanogenesis. Tyrosinase is synthesized in the rough endoplasmic reticulum and accumulated in vesicles of the Golgi complex. The free vesicles are now called melanosomes. Melanin synthesis begins in the stage II melanosomes, where melanin is accumulated and forms stage III melanosomes. Later, this structure loses its tyrosinase activity and becomes a melanin granule. Melanin granules migrate to the tips of the melanocyte’s processes and are then transferred to the keratinocytes of the malpighian layer.
Electron micrograph of human skin containing melanocytes and keratinocytes. Note the greater abundance of melanin granules in the keratinocyte at right than in the adjacent melanocyte. The clear material at the bottom is dermal collagen. x1800.
Stratum Lucidum. The stratum lucidum is formed by several (3-4) layers of flattened, closely packed cells; in the section it appears as a pale, wavy stripe, with retractile droplets, called eleidin, instead of the keratohyalin granules. Usually little remains of the nucleus in such cells.
Stratum Corneum. The stratum corneum consists of 15-20 layers of flattened nonnucleated keratinized cells whose cytoplasm is filled with a birefiingent filamentous scleroprotein, keratin. Keratin contains at least six different polypeptides. Three polypeptide chains coil around one, another to form subunits of the tonofilament. At least one of the polypeptides is different from the others in the subunit, allowing great diversity in composition. Nine of the three-chain subunits coil around each other, forming a filament about 10 nm in diameter. End-to-end aggregation of three-chain subunits increases the length of the tonofilament. The composition of tonofilaments changes as epidermal cells differentiate. Basal cells contain polypeptides of lower molecular weight, whereas, more differentiated cells synthesize the higher-molecular-weight polypeptides. Tonofilaments are packed together in a matrix contributed by the keratohyalin granules.
After keratinization, the cells consist of only fibrilar and amorphous proteins and thickened plasma membranes; they are called horny cells. Lysosomal hydrolytic enzymes play a role in the disappearance of the cytoplasmic organelles. These cells are continuously shed at the surface of the stratum corneum.
This description of the epidermis corresponds to its most complex structure in areas where it is very thick, as on the soles of the feet. In thin skin, the stratum granulosum and the stratum lucidum are often less well developed, and the stratum corneum may be quite thin.
In psoriasis, a common skin disease, there is an increase in the number of proliferating cells in the stratum basale and the stratum spinosum as well as a decrease in the cycle time of these cells. This results in greater epidermal thickness and more rapid renewal of epidermis—7 days instead of 15-30 days. Melanocytes.
The color of the skin is the result of several factors, the most important of which are its content of melanin and carotene, the number of blood vessels in the dermis, and the color of the blood flowing in them.
Eumelanin is a dark brown pigment produced by the melanocyte, a specialized cell of the epidermis found beneath or between the cells of the stratum basale and in the hair follicles. The pigment found in red hair is called pheomelanin and contains cysteine as part of its structure. Melanocytes are derived from neural crest cells. They have rounded cell bodies from which long irregular extensions branch into the epidermis, running between the cells of the strata basale and spinosum. Tips of these extensions terminate in invaginations of the cells present in the two layers. The electron microscope reveals a pale-staining cell containing numerous, small mitochondria, a well-developed Golgi complex, and short cisternae of rough endoplasmic reticulum. Intermediate filaments, about 10 nm in diameter, are also present. Although melanocytes are not attached to the adjacent keratinocytes by desmosom.es, they, are, bound to the basal lamina by hemi-desmosomes.
Melanin is synthesized in the melanocyte, with tyrosinase playing an important role in the process. As a result of tyrosinase activity, tyrosine is transformed first into 3,4-dihydroxyphenylalanine (dopa) and then into dopaquinone, which is converted, after a series of transformations, into melanin. Tyrosinase is synthesized on ribosomes, transported in the lumen of the rough endoplasmic reticulum of melanocytes, and accumulated in vesicles formed in the Golgi complex.
Four stages can be distinguished in the development of the mature melanin granule:
Stage I: A vesicle is surrounded by a membrane and shows the beginning of tyrosinase activity and fonnation of fine granular material; at its periphery, electron-dense strands have an orderly arrangement of tyrosinase molecules on a protein matrix..
Stage II: The vesicle (melanosome) is ovoid and shows, in its interior, parallel filaments with a periodicity of about 10 nm or cross-striations of about the same periodicity. Melanin is deposited on the protein matrix.
Stage Ш: Increased melanin formation makes the periodic fine structure less visible.
Stage IY: The mature melanin granule is visible in the light microscope, and melanin completely fills the vesicle. No ultrastructure is visible. The mature granules are eilipsoid.
Once formed, melanin granules migrate within cytoplasmic extensions of the melanocyte and are transferred to cells of the strata germinativum and spinosum of the epidermic. This transfer has been directly observed in tissue cultures of skin.
Melanin granules are essentially injected into keratinocytes. Once inside the keratinoc;/te, melanin granules accumulate in the supranuclear region of the cytoplasm, thus protecting the nuclei from the deleterious effects of solar radiation.
Although melanocytes synthesize melanin, epithelial cells act as a depot and contain more of this pigment than do melanocytes. Within the keratinocytes, melanin granules ijse with lysosomes—the reason that melanin disappears in upper epithelial cells. In this interaction between keratinocytes and melanocytes, which creates the pigmentation of the skin, the important factors are the rate of formation of melanin granules within the melanocyte, the transfer of the granules into the keratinocytes, and their ultimate disposition by the keratinocytes. A feedback mechanism may exist between melanocytes and keratinocytes.
Incubating fragments of epidermis in dopa can easily see melanocytes. This compound is converted to dark brown deposits of melanin in melanocytes, a reaction catalyzed by the enzyme tyrosinase. This method makes it possible to count the number of melanocytes per unit area of the epidermis. Such studies show that these cells are not distributed at random among keratinocytes; rather, there is a pattern in their distribution, called the epidermal-melanin unit (epidermal proliferative unit). In humans, the ratio of dopa-positive melanocytes to keratinocytes in the stratum basale is constant within each area of the body but varies from one region to another. For example, there are about 1000 melanocytes/mm2 in the skin of the thigh and 2000/mm2 in the skin of the scrotum. The number of melanocytes per unit area is not influenced by sex or race; differences in skin color are due mainly to differences in the number of melanin granules in the keratinocytes.
The color of the skin depends on three factors: its inherent color is predominantly yellow; the vascular bed gives a reddish hue; melanin is responsible for varying shades of brown. This pigment, formed in melanocytes accumulates in varying amounts as fine granules within the cells of the stratum germintativum, particularly in its basal layer. As these cells move toward the surface, the granular pigment becomes a finely distributed dust, sometimes seen in the stratum corneum. The pigmentation of the skin of the Negro is due to the greater amount of pigment in all the layers of the epidermis.
Darkening of the skin (tanning) after exposure to solar radiation (wavelength of 290-320 ran) is the result of a two-step process. First, a physicochemical reaction darkens the preexisting melanin and releases it rapidly info the keratinocytes. Next, the rate of melanin synthesis in the melanocytes accelerates, increasing the amount of this pigment.
In humans, lack of Cortisol from the adrenal cortex causes overproduction of adrenocorticotropic hormone, which increases the pigmentation of the skin. An example of this is Addison disease, which is caused by dysfunction of the adrenal giands.
Albinism, a hereditary inability of the melanocytes to synthesize melanin, is caused by the absence of tyrosinase activity or the inability of cells to take up tyrosine. As a result, the skin is not protected from solar radiation by melanin, and there is a greater incidence of basal and squamous cell carcinomas.
The degeneration and disappearance of entire melanocytes results in a depigmentation disease called vitiligo.
Langerhans cells, star-shaped cells found mainly in the, stratum spinosum of the epidermis, represent 2-8% of the epidermal cells. They are provided with Jong, irregular processes, which penetrate the intercellular spaces and follow the intercellular outlines. They are jone marrow-derived macrophages that are capable of binding, processing, and presenting antigens to T lymphocytes, thus participating in the stimu lation of these cells. Consequently, they have a significant role in immunologic skin react ions.
Merkel’s Cells generally present in the thick skin of palms and soles, somewhat resemble the epidermal epithelial cells but have small dense granules in their cytoplasm. The composition of these granules is not known. Free nerve endings that form an expanded terminal disk are present at the base of Merkel’s cells. These cells may serve as sensory mechanoreceptors, although other evidence suggests that they have functions related to the diffuse neuroendocrine system.
DERMIS
The dermis is the connective tissue that supports the epidermis and binds it to the subcutaneous tissue (hypodermis). The thickness of the dermis varies according to the region of the body and reaches its maximum of
The thickness of the derma cannot be measured exactly, because it passes over without sharp borders into the subcutaneous layer. The average thickness is approximately 1 to
A basal lamina is always found between the stratum germinativum and the papillary layer of the dermis and follows the contour of the interdigitations between these layers. Underlying the basal lamina is a delicate net of reticular fibers, the lamina reticularis. This composite structure is called the basement membrane and cain be seen with the light microscope.
The dermis contains two layers with rather indistinct boundaries—-the outermost papillary layer and the deeper reticular layer. The thin papillary’ layer is composed of loose connective tissue; fibroblasts and other connective tissue ceils, such as mast cells and macrophages, are present. Extravasated leukocytes are also seen. The papillary layer is so called because it constitutes the major part of the dermal papillae. From this layer, special collagen fibrils insert into the basal lamina and extend into the dermis. They bind the dermis to the epidermis and are called anchoring fibrils.
The reticular layer is thicker, composed of irregular dense connective tissue (mainly type I collagen), and therefore has more fibers and fewer cells than does the papillaiy layer. The principal glycosaminoglycan is dermatan sulfate. The dermis contains a network of fibers of the elastic system, with the thicker fibers characteristically found in the reticular layer. From this region emerge fibers that become gradually thinner and end by inserting into the basal lamina. As these libers progress toward the basal lamina, they gradually lose their amorphous elastin component, and only the microfibrillar component inserts into the basal lamina. This elastic network is responsible for the elasticity of the skin.
Photomicrograph of thin skin stained for fibers of the elastic system. Note the gradual decrease in the diameter of fibers as they approach the epidermis. The thick fibers are elastic fibers. Those with an intermediate diameter are elaunin fibers. The very thin superficial fibers are oxytalan fibers formed by microfibrils that insert into the basement membrane. Weigert’s stain. Medium magnification.
With age collagen fibers thicken and collagen synthesis decreases. Elastic fibers steadily increase iumber and thickness, so the elastin content of human skin increases approximately fivefold from fetal to adult life. In old age, extensive cross-linking of collagen fibers, the loss of elastic fibers, and degeneration of these fibers caused by excessive exposure to the sun (solar elastosis) cause the skin to become more fragile, lose its suppleness, and develop wrinkles. In several disorders, such as: cutis laxa arid Ehlers-Danlos syndrome, there is a considerable increase in skin and ligament extensibility caused by defective collagen-fibril processing.
The dermis has a rich network of blood and lymph vessels. In certain areas of the skin, blood can pass directly from arteries to veins through arteriovenous anastomoses, or shunts. These shunts play a very important role in temperature regulation. In addition to these components, the dermis contains such epidermal derivatives as the hair follicles and sweat and sebaceous glands.
There is a rich supply of nerves in the dermis, and the effector nerves to the skin are postganglionic fibers of sympathetic ganglia of the paravertebral chain. No parasympathetic innervation is present, The afferent nerve endings form a superficial dermal network with free nerve endings, a hair follicle network, and the innervation of encapsulated sensory organs.
HYPODERMIS (SUBCUTANEOUS TISSUE)
The subcutaneous tissue layer consists of loose connective tissue that binds the skin loosely to the subjacent organs, making it possible for the skin to slide over them. It has collagenous and a few elastic fibers pass directly into those of the derma and run in all directions, mainly parallel to the surface of the skin. Where the skin is flexible, the fibers are few; where it is closely attached to the underlying parts, as on the soles and palms, they are thick and numerous. The hypodermis often contains fat cells that vary in number according to the area of the body and vary in size according to nutritional state. The fatty tissue of the subcutaneous layer on the abdomen may reach a thickness of
Thе subcutaneous layer is penetrated everywhere by large blood vessels and nerve trunks and contains many nerve endings.
EPIDERMAL DERIVATIVES
Epidermal derivatives include: hairs, nails, sebaceous glands, sweat glands.
HAIRS
Hairs are elongated keratinized structures derived from invaginations of epiderma epithelium. Their color, size, and disposition vaiy according to race, age, sex, and region of the body. Hairs are found everywhere on the body except on the palms, soles, lips, glans penis, clitoris, and labia minora. The face has about 600 hairs/cm2, and the remainder of the body has about 60/cm2. Hairs grow discontinuously and have periods of growth followed by periods of rest. This growth does not occur synchronously in all regions of the body or even in the same area; rather, it tends to occur in patches. The duration of the growth and rest periods also varies according to the region of the body. Thus, in the scalp, the growth periods (anagen) may last tor several years, whereas the rest periods (catagen and telogen) average 3 months. Hair Agrowth in such regions of the body as the scalp, face, and pubis is strongly influenced not only by sex hormones—especially androgens—but also by adrenal and thyroid hormones.1
Each hair arises from an epidermal invagination, the hair follicle, that during its growth period has a terminal dilatation called a hair bulb. At the base of the hair bulb, a dermal papilla can be observed. The dermal papilla contains a capillary network that is vital in sustaining the hair follicle. The loss of blood flow or the vitality of the dermal papilla will result in death of the follicle. The epidermal cells covering this dermal papil la form the hair root that produces and is continuous with the hair shaft, which protrudes beyond the skin.
During periods of growth, the epithelial cells that make up the hair bulb are equivalent to those in the stratum germinativum of the skin. They divide constantly and differentiate into specific cell types. In certain types of thick hairs, the cells of the central region of the root at the apex of the dermal papilla produce large, vacuolated, and moderately keratinized cells that form the medulla of the hair. Root cells multiply and differentiate into heavily keratinized, compactly grouped fusiform cells that form the hair cortex.
Farther toward the periphery are the cells that produce the hair cuticle, a layer of cells that are cuboidal midway up the bulb, and then become tall and columnar. Higher up, they change from horizontal to vertical, at which point they fonn a layer of flattened, heavily keratinized, shingle-like cells covering the cortex. These cuticle cells are the last cell type in the hair follicle to differentiate.
The outermost cells give rise to the internal root sheath, which completely cowers the initial part of the hair shaft. The internal sheath is a transient structure whose cells degenerate and disappear above the level of the sebaceous glands. Hie external root sheath is continuous with epidermal cells and, near the surface, shows all the layers of epidermis. Near the dermal papilla, the external root sheath is thinner and is composed of cells corresponding to the stratum germinativum of the epidermis.
Separating the hair follicle from the dermis is a noncellular hyaline layer, the glassy membrane, which results from a thickening of the basal lamina. The dermis that surrounds the follicle is denser, forming a sheath of connective tissue. Bound to this sheath and connecting it to the papillary layer of the dermis are bundles of smooth muscle cells, the arreetor pili muscles. They are disposed in an oblique direction, and their contraction results in the erection of the hair shaft to a more upright position. Contraction of arreetor pili muscles also causes a depression in the skin where the muscles attach to the dermis. This contraction produces the “gooseflesh” of common parlance.
Hair follicle. The follicle has a bulbous terminal expansion with a dermal papilla. The papilla contains capillaries and is covered by cells that form the hair root and develop into the hair shaft. The central cells (A) produce large, vacuolated, moderately keratinized cells that form the medulla of the hair. The cells that produce the cortex of the hair are located laterally (B). Cells forming the hair cuticle originate in the next layer (C). The peripheral epithelial cells develop into the internal and external root sheaths. The external root sheath is continuous with the epidermis, whereas the cells of the internal root sheath disappear at the level of the openings of the sebaceous gland ducts (not shown).
Relationships between the skin, hair follicle, arrector pili muscle, and sebaceous and sweat glands. The arrector pili muscle originates in the connective tissue sheath of the hair follicle and inserts into the papillary layer of the dermis, where it ends.
Hair color is created by the activity of melanocytes located between the papilla and the epithelial cells of the hair root. The epithelial cells produce the pigment found in the medullar}’ and cortical cells of the hair shaft. The melanocytes produce and transfer melanin to the epithelial cells by a mechanism similar to that described for the epidermis.
Although the keratinization processes in the epidermis and hair appear to be similar, they differ in several ways:
The epidermis produces relatively soft keratinized outer layers of dead ceils that adhere slightly to the skin and desquamate continuously. The opposite occurs in the hair, which has a hard and compact keratinized structure.
Keratinization in the epidermis occurs continuously and over the entire surface, it is intermittent in the hair and occurs only in the hair root. The hair papilla has an inductive action on the covering epithelial cells, promoting their proliferation and differentiation. Injuries to the dermal papillae thus result in the loss of hair.
Contrary to what happens in the epidermis, where the differentiation of all cells in the same direction gives rise to the final keratinized layer, cells in the hair root differentiate into various cell types that differ in ultrastructure, histochemical character sties, and function. Mitotic activity in hair follicles is influenced by androgens.
NAILS
Nails are plates of keratinized epithelial cells on the dorsal surface of each distal phalanx. The proximal part of the nail, hidden in the nail groove, is the nail root. The epithelium of the fold of skin covering the nail root consists of the usual layers of cells. The stratum corneum of this epithelium forms the eponychium, or cuticle. The nail plate, which corresponds to the stratum corneum of the skin, rests on a bed of epidermis called the nail bed. Only the stratum basale and the stratum spinosum are present in the nail bed. Nail plate epithelium arises from the nail matrix. The proximal end of the matrix extends deep to the nail root. Cells of the matrix divide, move distally, and eventually cornify, forming the proximal par: of the nail plate. The nail plate then slides forward over the nail bed (which makes no contribution to the formation of the plate). The distal end of the plate becomes free of the nail bed and is worn away or cut off. The nearly transparent nail plate and the thin epithelium of the nail bed provide a useful window on the amount of oxygen in the blood by showing the color of blood in the dermal vessels.
GLANDS OF THE SKIN
Sebaceous Glands. Sebaceous glands are embedded in the dermis over most of the body surface. There are about 100 of these glands per square centimeter over most of the body, but the frequency increases to 400-900/cm2 in the face, forehead, and scalp. The sebaceous glands are scattered over the surface of the skin (except in the palms, soles and the sides of the feet where there are no hairs). They vary from 0.2 to
Sebaceous gland. This is a holocrine gland, because its product is secreted with the remnants of a dead cell. Stem cells (arrows) in the base of the gland proliferate to replace the lost cells. Collagen fibers are stained in red. PSP stain. Medium magnification.
When several glands are connected with one hair, they lie at the same level. On the lips, about the corners of the mouth, on the glans penis and the interna} fold of the prepuce, on the labia minora, and on the mammary papilla the sebaceous glands are independent of hairs and open directly on the surface of the skin; to this category also belong the meibomian glands of the eyelids. The sebaceous glands in mucocutaneous junctions are more superficial than those associated with hairs.
The secretory portions of the sebaceous glands are rounded sacs (alveoli). As a rule, several adjacent alveoli form a mass like a bunch of grapes, and all of them open into a short duct; in this way a simple branched gland results. Much Jess frequently, only one alveolus is present. In the meibomian glands of the eyelids there is one long, straight duct, from which a row of alveoli projects.
A basement membrane supported by a thin layer of fibrillar connective tissue forms the wall of the alveoli. Along the internal surface is a single layer of thin cells with round nuclei. Toward the center of the alveoli a few cells comity, but most of them become larger, polyhedral, and gradually filled with fat droplets. The central portion of the alveoli is filled with large cells distended with fat droplets. The nuclei gradually shrink and then disappear, and the cells break down into fart) detritus, which mixes with horny scales. This is the oily secretion of the gland, and it is excreted onto the hair and upon the surface of the epidermis.
The ducts of sebaceous glands are lined by stratified squamous epithelium continuous with the external root sheath of the hair and with the malpighian layer of the epidermis.
In sebaceous glands, the secretion results from the destruction of the epithelial cells and is, therefore, of the holocrine type; it is followed by a regenerative multiplication of epithelial elements. This product comprises, a complex mixture of lipids that includes triglycerides, waxes, squalene, and cholesterol and its esters. In the body of the gland, mitoses are rare in the cells lying on the basement membrane; they are numerous, however, in the cells close to the walls of the excretory ducts, whence the new cells move into the secretory regions.
Sebaceous glands begin to function at puberty. The primary controlling factor of sebaceous gland secretion in men is testosterone; in women it is a combination of ovarian and adrenal androgens.
Flow of sebum is continuous, and a disturbance in the normal secretion and flow of sebum is one of the reasons for the development of acne, a chronic inflammation of obstructed sebaceous glands. It occurs mainly during puberty.
The functions of sebum in humans are largely unknown. It may have weak antibacterial and antifungal properties. Sebum does not have any importance in preventing water loss.
Sweat Glands
Sweat glands are widely distributed in the skin except for certain regions, such as the glans penis.
The eccrine (merocrine) sweat glands are simple, coiled tubular glands whose ducts open at the skin surface. Their ducts do not divide, and their diameter is thinner than that of the secretory portion. The secretory part of the gland is embedded in the dermis; it measures approximately
Two types of cells have been described in the secretory portion of eccrine sweat glands. Dark cells (mucoid cells) are pyramidal cells that line most of the luminal surface of this portion of the gland. Their basal surface does not touch the basal lamina. Secretory granules containing glycoproteins are abundant in their apical cytoplasm. Clear cells are devoid of secretory granules. Their basal plasmalemma has the numerous invaginations characteristic of cells involved in transepithelial salt and fluid transport. The ducts of these glands are lined by stratified cuboidal epithelium.
Low-magnification photomicrograph of a section of sweat gland. This is a simple coiled tubular gland. H&E stain.
Section of sweat gland. Note the duct lined by stratified cuboidal epithelium. The myoepithelial cells, whose contraction helps to discharge the glandular secretion, surround the secretory portion. H&E stain. Medium magnification.
Fluid secreted by eccrine sweat glands is not viscous and contains little protein. Its main components are water, sodium chloride, urea, ammonia, and uric acid, its sodium content of 85 mEq/L is distinctly below that of blood (144 mEq/L), and the cells present in the sweat ducts are responsible for sodium absorption. The fluid in the lumen of the secretory portion of the gland is an ultrafiltrate of the blood plasma. This ultrafiltrate is derived from a network of capillaries that intimately envelop the secretory region of each gland. After its release on the surface of the skin, sweat evaporates, cooling the surface,
In addition to eccrine sweat glands, another type of sweat gland—the apocrine gland-—is present in .the axillary, areolar, and anal regions. Apocrine glands are much larger (3-
VESSELS and NERVES OF THE SKIN
The arterial vessels that nourish the skin form two plexuses. One is located between the papiliarv and reticular layers, the other between the dermis and the subcutaneous tissue. Thin branches leave these plexuses and vascularize the dermal papillae. Each papilla has only one arterial ascending branch and one venous descending branch. Veins are disposed in three plexuses, two in the position described for arterial vessels and the third in the middle of the dermis. Arteriovenous anastomoses with glomera are frequent in the skin. Lymphatic vessels begin as closed sacs in the papillae of the dermis and converge to form two plexuses, as described for the arterial vessels.
One of the most important functions of the skin, with its abundant sensory innervation, is to receive stimuli from the environment. In addition to Bret: nerve endings in the epidermis and cutaneous glands, receptors are present: in the dermis and subcutaneous tissue; they are more frequently found in the dermal papillae The hair follicles possess a rich network of nerve endings that are essential; in the processing of tactile impressions from the environment
TUMORS OF THE SKIN
One third of al humors are of the skin. Most of these tumors derive from the basal cells, the squamous cells of the stratum spinosum. and melanocytes. They produce, respectively, basal cell carcinomas, squamous cell carcinomas, and melanomas. The first two types of tumors can be diagnosed and excised early and consequently are rarely lethal. Skin tumors show an increased incidence in fair-skinned individuals residing in regions with high amounts of solar radiation. Malignant melanoma is an invasive tumor of melanoses. Dividing rapidly, malignantly transformed melanocytes penetrate the basal lamina, enter the dermis, and invade the blood and lymphatic vessels to gain wide distribution throughout the body. Malignant melanoma represents approximately 1-3% of all tumors.
IMMUNOLOGIC ACTIVITY IN THE SKIN
Because of its large size, the skin has an impressive number of lymphocytes and antigen-presenting cells (Langerhans cells), and because of its location it is in close contact with many antigenic molecules. For these reasons, the epidermis has an important role in some types of immune responses. Most lymphocytes found in the skin are “homed” in the epidermis. It has been shown that keratinocytes of the stratum basale produce a local messenger (thymopoietin) that promotes T cells terminal maturation in the skin. These basal keratinocytes have three cell proteins (markers) also found in thymus epithelial reticular cells. Like thymus epithelial cells, they can produce interleukin-1 when stimulated.
Students’ Practical Activities:
Students must know and illustrate such histological specimens:
Specimen 1. Adrenal gland.
Haematoxylin and Eosin.
The adrenal gland is seen to be divided into an outer cortex and a pale-stained inner medulla. Capsule, invests the gland and provides external support for a delicate collagenous framework supporting the secretory cells.
The adrenal cortex can be seen to consist of three histological zones which are named according to the arrangement of the secretory cells: zona glomerulosa, zona fasciculata, zona reticularis. The zona glomerulosa lying beneath the capsule consists of short columnar cells closely packed in ovoid groups or in columns which may form arcs. The zona fasciculata consists of polyhedral cells considerably larger than those of the zona glomerulosa. They are arranged as anastomosing “cords” of cells with a marked radial orientation, extending between the zona glomerulosa and the reticularis. The zona reticularis consists of an irregular network of branching cords and clumps of glandular cells separated by numerous wide capillary sinusoids. The glandular cells are much smaller than those of the adjacent zona fasciculata.
The adrenal medulla is composed of closely packed clumps of secretory cells supported by a fine reticular network containing numerous wide capillaries. The secretory cells of the adrenal medulla have large, granular nuclei and extensive strongly basophilic cytoplasm.
Illustrate and indicate:1. Capsule; 2. Adrenal cortex: a) zona glomerulosa; b) zona fasciculata; c) zona reticularis; 3. Adrenal medulla: a) chromaffin cells; b) sinusoidal capillaries.
Specimen 2. Adrenal cortex.
Sudan black.
Note that the cytoplasm of cells zona fasciculata is even richer in smooth endoplasmic reticulum and lipid droplets that the zona glomerulosa and this may confer a foamy appearance of the cells. In this specimen you see lipid droplets in cells of zone fasciculata look like black drops of different sizes. Lipid droplets of secretory cells of zona glomerulosa, when present, are scarce and small. Cells of zona reticularis contain few lipid droplets, so cytoplasm stains more strongly.
Illustrate and indicate: 1. Lipid droplets in the cytoplasm of secretory cells of zona fasciculate.
Specimen 3 Skin (fingertip).
Haematoxylin and Eosin.
The general structure of skin is illustrated in this preparation of thick skin from the fingertip. The epidermis consists of a stratified squamous keratinising epithelium which, in this site, has an extremely thick keratinised surface layer. A prominent feature of the skin of the fingertips, palms and soles of the feet is a pattern of surface ridges formed by the epidermis; this pattern is unique to each individual. Epidermis is represented of five morphological layers:
1. Stratum basale: the cells of this layer are cuboidal and form a single layer separated from the dermis by a basement membrane too thin to be resolved by light microscopy.
2. Stratum spinosum: the so-called ‘prickle cells’ of this zone are relatively large and polyhedral in shape and have extremely numerous cytoplasmic ‘prickles’ bound by desmosomes to adjacent cells.
3. Stratum granulosum: the cells of this layer have numerous, dense basophilic granules which crowd the cytoplasm and tend to obscure the tonofibrils.
4. Stratum lucidum: is only present in extremely thick skin, and appears as a homogeneous layer between the stratum granulosum and the keratinised layer.
5. Stratum corneum: the morphology and staining characteristics of this layer are strikingly different from that of the underlying layers. The stratum corneum consists of layers of fused, flattened cells devoid of organelles and filled with mature keratin.
The epidermis is supported by the dermis, a layer of dense fibro-elastic tissue. The dermis merges with the loose connective tissue of the hypodermis which consists largely of adipose tissue; in this site, adipose tissue acts as a soft, shock-absorbing layer. Numerous sweat glands arc located in the dermis and hypoderms and discharge their secretions on to the skin surface via long excretory ducts.
Illustrate and indicate: 1. Epidermis: a) stratum basale; b) gstratum spinosum; c) stratum granulosum; d) stratum lucidum; e) stratum corneum; 2. Dermis: a) papillary layer; b) reticular layer; 3. Sweat glands: a) secretory portion; b) duct.
Specimen 4. Scalp skin.
Haematoxylin and Eosin.
The structure of the skin differs considerably from one part of the body to another, the principal differences being in epidermal thickness, the size, density and state of activity of the hair follicles, and the nature and density of sweat glands and sensory receptors.
The skin of the sclap is robust due to a thick, densely collagenous dermis, and the hair follicles which are essentially cylindrical downgrowths of the surface epithelium ensheated by connective tissue, they are numerous and closely parked. Hair growth takes place within a terminal expansion of the follicle, the hair bulb, which consists of actively dividing epithelial cells surrounding a papilla of connective tissue, the dermal papilla. The follicles of the scalp are particularly long and have more numerous sebaceous glands than those of other areas. Note the arrector pili muscles extending from the base of the follicles towards the upper dermis. Merocrine sweat glands are numerous though less prominent than in the skin of the trunk and limbs due to the profusion of other appendages.
Illustrate and indicate: 1. Epidermis; 2. Papillary layer; 3. Reticular layer; 4. Hair root: a) hair bulb; b) dermal papillae; c) external epithelial radicular vagina; d) hair bursa; 5. Sebaceous gland; 6. Arrector pili muscle; 7. Hypodermis: a) adipocytes.
REFERENCES:
A-Basic:
1. Practical classes materials
http://intranet.tdmu.edu.ua/data/kafedra/internal/histolog/classes_stud/English/medical/III%20term/17%20Adrenal%20glands%20and%20diffuse%20endocrine%20system.%20Skin%20and%20its%20appendages.htm
http://intranet.tdmu.edu.ua/ukr/kafedra/index.php?kafid=hist&lengid=eng&fakultid=m&kurs=2&discid=Histology, cytology and embryology
3. Stevens A. Human Histology / A. Stevens, J. Lowe. – [second edition]. –Mosby, 2000. – P. 264-274
4. Wheter’s Functional Histology : A Text and Colour Atlas / [Young B., Lowe J., Stevens A., Heath J.]. – Elsevier Limited, 2006. – P. 338-341
5. Inderbir Singh Textbook of Human Histology with colour atlas / Inderbir Singh. – [fourth edition]. – Jaypee Brothers Medical Publishers (P) LTD, 2002. – P. 193-206, 309-314,
6. Ross M. Histology : A Text and Atlas / M. Ross W.Pawlina. – [sixth edition]. – Lippincott Williams and Wilkins, 2011. – P. 780-784
B – Additional:
1. Eroschenko V.P. Atlas of Histology with functional correlations / Eroschenko V.P. [tenth edition]. – Lippincott Williams and Wilkins, 2008. – P. 402-407
2. Junqueira L. Basic Histology / L. Junqueira, J. Carneiro, R. Kelley. – [seventh edition]. –
3. Charts:
http://intranet.tdmu.edu.ua/index.php?dir_name=kafedra&file_name=tl_34.php#inf3
4. Disk:
http://intranet.tdmu.edu.ua/data/teacher/video/hist/
5. Volkov K. S. Ultrastructure of the main components of body / K. S. Volkov. – Ternopil : Ukrmedknyha, 1999. – P. 36-40, 84-88
http://intranet.tdmu.edu.ua/data/books/Volkov(atlas).pdf
http://en.wikipedia.org/wiki/Circulatory
http://www.meddean.luc.edu/LUMEN/MedEd/Histo/frames/histo_frames.html
http://www.udel.edu/biology/Wags/histopage/histopage.htm
