Pathology 104

Dental Histology M. Hall

2002

Skin

(G & H Chap.14)

The skin is the heaviest organ of the body--it comprises about 16% of the total body weight and it forms the external covering of the body. It consists of two distinct layers--the epidermis, which is composed of stratified squamous epithelium, and the dermis, which is composed of fibrous connective tissue. Beneath the dermis there is another layer of connective tissue, looser than that of the dermis, called the hypodermis, which binds the skin loosely to underlying tissues. The hypodermis is not considered as part of the skin. Associated with the skin are epidermal derivatives which include the hair, nails, sweat glands and sebaceous glands.

Functions of skin

1) Provides protection against physical injury.

2) It is waterproof and protects against water loss.

3) It serves as a large receptor for general sensation from the external environment (pain, pleasure, touch, temperature).

4) Protects against UV irradiation.

5) Converts precursor molecules into Vitamin D.

6) Functions in heat regulation through blood flow and sweating.

7) Excretes certain substances through the sweat glands.

There are two general types of skin, thick skin and thin skin. The difference between thick and thin skin is largely one of degree. Let’s look at thick skin since this has the best definition of the layers which comprise the epidermis. Thick skin occurs on the palms of the hands and the soles of the feet, where there are no hairs. These are areas of the body which are subject to tremendous abrasion, particularly if you run around barefoot chasing tonight's dinner, or do manual work—(research/medicine/dentistry are not considered manual work).

Epidermis

This is a layer of stratified squamous epithelium, and in thick skin consists of five distinct layers. The deepest layer, which sits on a basement membrane, is called the stratum basale or stratum germinativum, and it is here that cell division occurs. The newly produced cells move to the surface of the skin, and during their progression differentiate into all the other layers of the skin. Above the stratum basale is the stratum spinosum, consisting of cells which appear to have delicate spinous processes. These are sometimes called “prickle cells” because of the way they look. The prickles are actually desmosomes (maculae adherens), where adjacent cells make contact. This layer is several cells thick and merges into the stratum granulosum, whose flattened cells contain dark-staining granules. Above this granular layer is the stratum lucidum, in which the flattened cells are undergoing a process of keratinization. The nucleus and cytoplasmic organelles become disrupted, and the cell becomes filled with the protein, keratin. Outermost is the stratum corneum which is composed of clear, scale-like cells without nuclei--cells which are constantly being lost from the surface. Some 1.5 to 2 pounds of them are shed from your skin every year. These cells are filled with keratin, the most insoluble, indigestible protein in the body. The thickness of the stratum corneum increases in areas that are constantly exposed to friction.

Elsewhere in the body, the epidermis is considerably thinner, and all layers are reduced. Only the stratum spinosum and stratum corneum are constantly present.

Cells of the Epidermis

There are five cell types in the epidermis, the keratinocyte, the melanocyte, the Langerhans cell the Merkel cell and the dendritic cell.

Keratinocytes are the most numerous cells in the epidermis; they are the cells that become keratinized, and that synthesize and secrete a water barrier between the cells, consisting of a complex glycolipid.

The cells of the stratum basale contain the typical cellular organelles, and additionally contain 10 nm intermediate filaments called tonofilaments. As the cells move through the stratum spinosum, the synthesis of tonofilaments continues, and they become grouped into bundles. Towards the top of the stratum spinosum, the keratinocyte begins the synthesis of keratohyaline granules. The keratohyaline granules eventually fill much of the cell, and it is these granules which give the cells of the stratum granulosum its granular appearance. The keratohyaline granules contain a protein called filaggrin, the function of which appears to be to bind the tonofibrils together, converting them into keratin. Keratin owes its insolubility, its stability, and its toughness to numerous disulfide (S-S) crosslinks between its chains of amino acids. The transformation of the cell from the stratum granulosum into a keratinized cell of the stratum corneum involves the breakdown of the nucleus and other organelles and the thickening of the plasma membrane. Finally, now in the stratum corneum, there is a timed desquamation of the surface keratinized cells. This loss of dead keratinized cells from the free surface of the skin stimulates the division of cells within the basal layer of the epidermis. At the same time that the keratinocytes produce keratin, they also produce lamellar bodies which contain a glycolipid which they secrete. This glycolipid spreads to fill the intracellular spaces, forming a barrier to the absorption or loss of water from the underlying tissues.

Melanocytes Skin color is determined largely by the presence of blood vessels in the dermis and the brownish pigment, melanin, which occurs as granules in the basal layers of the stratum spinosum. The cells which make this pigment are melanocytes. These are rounded cells with long dendritic processes, which live at the base of the epidermis. These cells produce melanin by a process which involves the transformation of tyrosine into dihydroxyphenylalanine (DOPA) by the enzyme, tyrosinase, and the subsequent transformation of DOPA into melanin.

Tyrosine--------------------DOPA-------------------------Melanin

tyrosinase

This process occurs in membrane-bound bodies called melanosomes. The mature melanosomes are then transferred into keratinocytes, where they accumulate above the nucleus, thus protecting the nuclei of dividing cells from the harmful effects of solar radiation. Thus, the keratinocytes act as a depot for melanin, and actually contain more of this pigment than do melanocytes. The numbers of melanocytes per unit area varies from one region of the body to the other, but it is not influenced by sex or race. As the pigment-containing epidermal cells move towards the surface, the pigment (along with other cell components) is gradually destroyed by lysosomal activity of the keratinocytes.

For psychosocial reasons (but certainly not medical ones), a good tan has come to be associated in the public mind with good health. Countless hours of roasting in the sun are spent in an effort to increase the melanin content of the epidermis. We not only want our skin to be tanned by the sun, we want it to be youthful-looking too. We don’t want our birthday suits to grow old. We don’t want flabby flesh, pouches, and wrinkles.

Dermatologists are now agreed that the major environmental cause of aging of the skin has been identified. And it turns out to be tissue damage caused by the ultraviolet wavelengths of the sun. If you compare the skin on the back of a farmer’s neck with that on his buttocks, the truth of this conclusion will be obvious to you. Skin protected from ultraviolet radiation hardly ages at all, and the continual replacement of the epidermal cells prevents the accumulation of injuries in the cells most likely to encounter them. However, when the skin is exposed to bright sunlight, the rate of cell damage rises sharply. The radiation is absorbed primarily by proteins, denaturing them, and by the nucleic acids, provoking lesions that destroy the genetic apparatus in epidermal and dermal cells alike. Special DNA repair enzymes act to counteract the damage. In the hereditary disease, Xeroderma pigmentosum, these repair enzymes are deficient. Affected individuals suffer premature aging of the skin and multiple skin cancers at an early age. Extended exposure to bright sunlight is not good for the skin. Instead, it is exceedingly harmful to the skin. It increases the rate of the normal aging of skin, which is accompanied by extensive cross-linking of collagen fibers and the loss of elastic fibers, both of which contribute to the development of wrinkles. It is also the leading cause of skin cancer.

Langerhans cells are located primarily in the stratum spinosum, and display properties of phagocytic cells. They function in the immune system as antigen presenting cells.

Merkel cells are located in the stratum basale. They contain granules which contain catecholamines. The base of a Merkel cell makes contact with the expanded terminal disk of a nerve fiber, forming a special receptor which functions as a mechanoreceptor (detection of touch).

Dendritic cells are found throughout the epidermis. They are antigen presenting cells

Dermis

The dermis is composed of dense, irregularly arranged connective tissue. Fibroblasts, macrophages and mast cells are the most common cell types. The connective tissue of the dermis binds it to the subjacent layer, the hypodermis. The junction between the dermis and the epidermis is uneven, consisting of branching ridges, mounds, valleys and craters. Ridges of epidermis project down into the dermis; these are called epidermal ridges. Between these ridges, pegs or papillae of dermis project upward; these are called dermal papillae. The pattern of the dermal papillae is paralleled by grooves and ridges on the outer surface of the epidermis, and these surface epidermal skin patterns are the familiar “fingerprints” which are characteristic of each individual. The dermal papillae contain blood vessels, as well as nerve endings.

The dermis is divided into two merging layers--the papillary layer and the reticular layer. The papillary layer consists of loose connective tissue and lies immediately beneath the epidermis. The reticular layer consists of dense irregular connective tissue and is found beneath the papillary layer.

The dermis has a rich network of blood vessels, which is important in nourishment of the skin and in temperature regulation. Arteries form a plexus on the under surface of the dermis. Branches are given off to supply the sweat glands and hair follicles. Other branches continue upward to form a rich plexus between the reticular and papillary layers.

Glands of the skin

Three types of glands are commonly found in skin: eccrine sweat glands, apocrine sweat glands, and sebaceous glands.

Eccrine sweat glands are distributed over the entire surface of the body with only the lips, glans penis and nail bed being free of them. They are most numerous on the palms and soles, but here they respond not to temperature but to emotional stimuli. The electrical resistance of the skin of the palms is decreased by such sweat gland activity. This phenomenon is used in “lie-detectors.” The greatest concentration of eccrine sweat glands which respond to thermal stimulation occurs on the head and on the back of the hands. The secretory portion of eccrine sweat glands, located in the dermis, is a simple tube coiled into a ball. The tube is lined by a single layer of cells with a prominent basement membrane and is enclosed by myoepithelial cells, which can contract to aid the excretion of sweat. The excretory duct is a continuation of this tube. In this duct, there is a double layer of cuboidal lining cells (stratified cuboidal epithelium). The duct enters the epidermis at the apex of an epidermal ridge, then spirals until it opens on the surface of the epidermis.

The eccrine sweat glands produce a watery solution which contains NaCl, urea, uric acid, and ammonia. The glands are activated by sympathetic nerve impulses arising in the brain stem, when nerve centers are stimulated by rising blood temperature. Evaporation of the sweat from the skin causes cooling in the extensive capillary loops surrounding the dermal papillae.

Apocrine sweat glands produce a thicker, more complex secretion. They have a localized and rather sexy distribution: you will find them in the axilla and circumanal region, areola of the breast, mons pubis, labia minora and scrotum. Modified apocrine sweat glands are also found in the ear canal, where they are called ceruminous glands. The apocrine glands contain only a single secretory cell type. The are much larger (3-5 mm diameter) than eccrine sweat glands, and lie deep in the dermis or in the upper region of the hypodermis, while the duct usually opens into a hair follicle. Apocrine sweating occurs largely in response to strong emotions such as fear, pain, and sex. Thus, in a fearful, painful or sexy situation, be on the lookout for blanched skin (due to the secretion of epinephrine), eccrine sweat on the palms, and apocrine sweat in the armpit and groin. Apocrine sweat is initially odorless but acquires its distinctive odor due to bacterial decomposition. Nowadays we frantically roll on or spray in an effort to eradicate the characteristic odor of the unclean axilla. Thus, most deodorants contain antibacterial ingredients.

Sebaceous glands are found associated with hair follicles, but also occur on the lips, glans penis, labia minora, and nipples where, as you may know, there are no hairs. They are not found in the skin of the palms and soles. They are acinar glands that usually have several acini opening into a short duct which is lined with stratified squamous epithelium, which is continuous with the stratum Malpighii (stratum basale plus the stratum spinosum) of the epidermis. The secretory portions of the gland, the acini, are completely filled with a stratified epithelium. Basally, the cells are flattened and basophilic. These are the young cells. As they mature, lipid droplets begin to accumulate in a spongy, bulging cytoplasm. The nuclei shrink, and the gorged cells burst and are shoved into the lumen by the younger cells, yielding a secretion known as sebum, which helps to keep the skin from drying out. Thus, sebaceous glands are holocrine--the whole darn cell is secreted.

Maturation of sebaceous and apocrine sweat glands is regulated by hormones, attaining full growth at puberty. This is the result of increased circulating sex hormones (androgens). During the period of rapid maturation, the sebaceous glands tend to get plugged up, forming “blackheads” and infected, yielding the common ailment known as acne. Today this is very successfully treated with antibiotics or derivatives of vitamin A. Castration is also an effective treatment for acne (why?).

Hair

Hairs are keratinized filaments which develop from an invagination of the epidermis called the hair follicle. They are found everywhere on the body except on the palms, soles, lips, glans penis, clitoris, and labia minora. Hair growth of certain regions of the body, such as the scalp, face, pubis, and axilla, is strongly influenced by sex hormones, especially androgens, as well as by adrenal and thyroid hormones. Color of the hair is due to melanin pigments.

The outermost part of the hair follicle is a downgrowth of the epidermis called the external root sheath. Hair follicles extend down through the dermis into the underlying subcutaneous connective tissue. Down deep is where the action is. What sticks out is dead. The business end is 4 to 5 millimeters beneath the surface. At its deepest point, the hair follicle forms a bulb-like expansion, the hair bulb, which is invaginated by connective tissue to form a dermal papilla. The dermal papilla contains a capillary network which is vital in sustaining the hair follicle. During periods of hair growth, the epithelial cells that make up the bulb are equivalent to those of the stratum germinativum of the skin. (The basal cells of the hair bulb are equivalent to the basal cells of the epidermis). They divide constantly and differentiate into all of the cell types that constitute the mature hair. After division, the cells are pushed upward where they increase in volume, become elongated vertically, and specialize to form the hair. As in the epidermis, the cells are gradually keratinized on the way to the surface. A rather hard keratin is produced. About two-thirds of the way up the follicle, the sebaceous glands are formed by an outgrowth from the root sheath. Every hair follicle is joined to a sebaceous gland, and the gland secretes its product into the space around the hair, from where it reaches the skin surface.

Melanocytes are present in the upper part of the bulb of the hair follicle. These melanocytes produce and transfer melanin to the epithelial cells by a mechanism which is similar to that described for the epidermis. With age, pigment production drops off, leading to the appearance of gray or white hairs.

There is a constant loss and replacement of hair. An individual scalp hair lasts from 2 to 5 years; eyebrow and eyelash hairs last for 4 to 5 months.

Smooth muscle fibers, the arrector pili muscles, extend from the upper surface of the dermis to attach to the hair follicle just below the level of the sebaceous glands. These muscles, which are innervated by the sympathetic division of the autonomic nervous system, contract under stresses of emotion or cold. Upon contraction, the hairs are drawn into vertical position and the skin around them forms slight elevation, producing “gooseflesh”. This makes cats look scary to other cats but it not of much use to people.

Because of our cultural hang-up with a full head of hair, the transplantation of plugs of hair from the rear of the scalp to a bald area has been successfully used to re-establish hair on a bald pate. The castrated male does not go bald. If balding has begun at the time of castration it will cease. The same is true for acne. Men castrated before puberty do not develop acne (why?). So you men can choose between a full head of hair or a full sex life.

Nails

Nails are also a derivative of skin. In fact, nails are a sort of regionally hardened stratum corneum. The epithelium which underlies the posterior nail is called the nail matrix (consisting of the s. germativum and s. spinosum), and this is the region from which the nail grows. As growth continues, the nail simply glides forward over the nail bed. If the nail is removed, a new one will soon glide out to replace it (as long as the nail matrix is not destroyed).

Nerve supply to the skin

You all know how painful a minor "papercut" of the skin is. This is because the skin contains numerous sensory receptors which are the peripheral terminals of sensory neurons. There are both free and encapsulated nerve endings in the epidermis and the dermis. In addition, the skin contains efferent nerve fibers which innervate the blood vessels, sweat glands, and smooth muscles (myoepithelial cells) associated with the sweat glands. Two types of encapsulated nerve endings are readily apparent in your slides:

Pacinian corpuscles are located in the hypodermis and bear a strong resemblance to the cut face of an onion; they may measure 1 mm or more in their long axis. A myelinated nerve fiber penetrates the corpuscle, after which it loses its myelin sheath. Pacinian corpuscles are pressure receptors and are especially numerous in skin which has great sensitivity, such as the fingertips.

Meissner’s corpuscles are touch receptors which are located in the dermal papillae immediately under the epidermis. They are cylindrical in shape and resemble a turban. They too contain the unmyelinated terminal of afferent nerve fibers.