an outer keratinising stratified squamous epithelium which is self-regenerating - the epidermis

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1 Skin Structure. The skin has four major functions: protection, sensation perception, thermoregulation, and metabolism. The skin provides protection against ultraviolet light and mechanical, chemical and thermal insults; its relatively impermeable surface prevents dehydration and acts as a physical barrier to invasion by microorganisms. The skin is also the largest sensory organ in the body and contains a variety of receptors for touch, pressure, pain and temperature. In humans, skin is a major organ of thermoregulation. The body is insulated against heat loss by the presence of hairs and subcutaneous adipose tissue. Heat loss is facilitated by evaporation of sweat from the skin surface and increased blood flow through the rich vascular network of the dermis. Subcutaneous adipose tissue constitutes a major store of energy, mainly in the form of triglycerides. Vitamin D is synthesised in the epidermis and supplements that derived from dietary sources. Structurally, the skin has three main layers: an outer keratinising stratified squamous epithelium which is self-regenerating - the epidermis an underlying tough supporting and nourishing layer of fibroelastic tissue - the dermis a variable deep layer, mainly adipose and areolar tissue - the hypodermis or subcutis. In addition there are specialised epithelial appendages such as sweat glands, hair follicles and sebaceous glands, which arise as down-growths into the dermis from the epidermis during embryological development. Within this basic pattern there are 1

2 variations in structure at different sites on the body surface according to the major function of the skin at that site; for example, the soles of the feet have a very thick protective keratin layer and an epidermis with a complex inter-digitation with the underlying dermis to resist the strong shearing frictional forces in walking. This micrograph shows the general structure of thin human skin from the middle of the back. The top layer is thin epidermis with an overlying layer of keratin. The external surface of the epidermis is smooth and flat, but the junction between epidermis and thick dermis is marked by downward folds of epidermis (rete ridges) offering resistance to separation of the epidermal surface due to shearing. The dermis comprises two layers: the papillary dermis (PD) just beneath the epidermis (fine collagen, elastic fibres, small blood vessels arising from the vascular plexus (BV); and the thicker, stronger reticular dermis (RD) (large compact collagen fibres and thick elastin fibres). Within the dermis also reside the skin appendages and their ducts (an eccrine gland is seen at bottom right) and larger blood vessels, nerves and some nerve endings. This coloured scanning electron micrograph of the skin showing the superficial stratum corneum (pale brown), above the lower layers of the epidermis (pink) and the dermis (grey brown). 2

3 The Epidermis. The layers of the epidermis are best seen in thick skin, e.g. plantar and palmar areas. Cells produced by mitosis in the germinal basal layer adjacent to the dermis undergo maturational changes concerned with the production of keratin. The outer keratinised layer is shed continuously and is replaced by the progressive movement and maturation of cells from the germinal layer; thus all of the cells of this lineage are often described as keratinocytes. The rate of mitosis in the germinal layer generally equals the rate of desquamation of keratin from the outer surface; in humans, the process of maturation of a basal cell through to desquamation takes from 25 to 50 days, being more rapid in areas exposed to heavy frictional forces. The phases of this dynamic process are represented in four morphological layers: The stratum basale or basal layer (B) is the germinal layer of the epidermis. Mitotic activity in this layer provides a constant supply of new keratinocytes to replace those lost by normal wear and tear. The cells of this layer are cuboidal and form a single layer separated from the dermis by a basement membrane. The basal aspect of each germinal cell is highly irregular and bound to the basement membrane by numerous hemidesmosomes. Like the cells of the adjacent stratum spinosum, small cytoplasmic projections extend across the intercellular spaces to abut upon those of adjacent cells; desmosomes bind these contact points. Mitotic figures are most 3

4 frequently observed in this layer but cell division also occurs to a lesser extent in the stratum spinosum. The stratum spinosum or prickle cell layer (S), so named for the 'prickly' appearance of the cells at high magnification, contains cells which are in the process of growth and early keratin synthesis. The cells of this zone are relatively large and polyhedral in shape and have numerous cytoplasmic 'prickles' bound by desmosomes to adjacent cells. Prominent nucleoli and cytoplasmic basophilia indicate active protein synthesis. A fibrillar protein cytokeratin, the predominant synthetic product of these cells, aggregates to form intracellular fibrils known as tonofibrils which converge upon the desmosomes of the cytoplasmic 'prickles'; tonofibrils become more prominent towards the stratum granulosum. Tonofibrils are also found in small numbers in the cells of the stratum basale. The stratum granulosum or granular layer (G) is characterised by intracellular granules which contribute to the process of keratinisation. The cells of this layer are characterised by numerous, dense basophilic granules which crowd the cytoplasm and tend to obscure the tonofibrils. The chemical nature of these 4

5 keratohyalin granules is distinct from that of the fibrous protein of the tonofibrils. The process of keratinisation is thought to involve the combination of tonofibril and keratohyalin elements to form the mature keratin complex. This increases the thickness of the cell membrane in the cells higher up in the layer (indicated by yellow arrows). In the outermost aspect of the stratum granulosum, cell death occurs due to rupture of lysosomal membranes; released lysosomal enzymes may play an important role in the final process of keratinisation. The stratum corneum or cornified layer (C) consists of flattened, fused cell remnants composed mainly of the fibrous protein, keratin. The dead and dying cells of this surface layer are flattened, devoid of nuclei and other organelles and filled with mature keratin. In the deeper aspect of this layer, the cornified cells retain their desmosomal junctions and the intracellular keratin has an ordered pattern. Towards the surface, the desmosomes and internal structure of the cells become completely disrupted, a process which precedes desquamation. 5

6 An additional layer found only in the skin of the palms and soles is the stratum lucidum. It is very narrow, and lying between the st. granulosum and the st. corneum it is considered to be transitional zone, made up of flattened, dead cells, with abundant keratin proteins. Its role is to reduce friction and shear stress in the upper layers of the skin. Other cells in the epidermis. Melanocytes are responsible for the synthesis and release of the brown pigment, melanin, which is largely responsible for skin coloration. They are located in the basal layer of the epidermis and appear as round cells with pale-staining cytoplasm scattered infrequently between the low columnar basal cells. From this cell body there are numerous long cytoplasmic processes which run in the spaces between the keratinocytes of the stratum spinosum. Melanocyte cytoplasm contains specialised membrane-bound oval granules called premelanosomes and melanosomes which synthesise the pigment melanin. Tyrosine is converted into dihydroxyphenylalanine (DOPA) which is then polymerised into melanin; the melanin pigment binds to protein, and the melanoprotein is transferred along cytoplasmic processes to be transferred into the cytoplasm of basal and stratum spinosum keratinocytes, the highest concentration being in basal cells. The amount of melanin deposited varies from race to race, but racially white-skinned individuals can increase the amount of melanin synthesised and deposited by increasing skin exposure to UV light. 6

7 Langerhans cells are present in all layers of the epidermis, but are most easily seen in the stratum spinosum; they also occur around blood vessels in the papillary dermis. Their cytoplasm contains characteristic Birbeck granules, which are rod-like structures with regular cross-striations, one end of which frequently distends in a vesicle so that they resemble a tennis racket. These are antigen-presenting cells and are an important component of the immune defence mechanism. The Dermis. The dermis lies beneath the epidermis and contains abundant collagen, and lesser amounts of elastic and reticular fibres, together with extra cellular matrix (ECM). IN areas of continual mechanical stress the dermis inter-digitates with the epidermis to form an uneven border of dermal papillae, which correspond to Rete ridges on the underside of the epidermis. Together with the hemidesmosomes between the keratinocytes of the st. basale and the basal lamina facing the dermis, the interface between the dermis and epidermis forms a site of strong, resistant attachment. The dermis provides a flexible but robust base for the epidermis and contains a generous vascular supply for the metabolic support of the avascular epidermis and for thermoregulation. The dermis is divided into two zones, a superficial thin papillary dermis and the more extensive deeper reticular dermis. 7

8 The papillary dermis is loose and contains very fine interlacing collagen fibres. It contains venules, arterioles and capillary loops, as well as lymphatics and fine nerve twigs from the sensory nerve endings, known as Meissner's corpuscles. The reticular dermis consists of coarse irregularly situated bundles of collagen within which are the blood vessels that join the plexus of vessels in the papillary dermis with the larger deeper vessels at the junction between dermis and subcutis. Elastin is an important constituent of both layers of the dermis. In the reticular layer the elastic fibres are long and thick and follow the course of the collagen bundles. In the papillary dermis the elastic fibres are very fine and scanty. The cellular component of the dermis is mainly the fibroblasts which are responsible for the production of collagen and elastin, but lymphocytes, mast cells and tissue macrophages involved in non-specific defence and immune surveillance are also present. 8

9 Several important skin functions are attributable to the structural components of the dermis. The arrangement of blood vessels in the dermis into vascular plexuses provides capillary networks directed towards, but not penetrating, the epidermis, and other vessels occur around various glands and hair follicles in the deep dermis. Blood within the dermis can bypass many of the capillaries by entering numerous arteriovenous anastomoses (shunts), so when blood flows in the upper most capillary plexuses, it may be cooled by the evaporation of sweat from the surface of the skin. Conversely, when the temperature is lower, blood can bypass the superficial capillaries so it is not cooled, and body heat is retained. Skin appendages. Skin has a variety of appendages, principally hairs, sebaceous glands and sweat glands, which are derived embryonically from the surface epithelium (epidermis). The distribution, arrangement and detailed structure of the appendages vary from one part of the skin to another but nevertheless the general structure conforms to a basic pattern. The diagram stands as a generalised example only, as individual sections of skin rarely demonstrate all these features. 9

10 Hairs. Hairs are highly modified keratinised structures produced by hair follicles which are essentially cylindrical down-growths of the surface epithelium ensheathed by collagenous tissue. 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 vascular tissue, the dermal papilla. A bundle of smooth muscle cells, the arrector pili muscle, is attached to the follicular sheath and is inserted into the dermal papillary zone. Contraction of the arrector pili causes the hair to become erect and pulls down its point of insertion, producing the effect known as 'goose-bumps'. The arrector pili muscles are innervated by the sympathetic nervous system and pilo-erection is activated by cold or fear. In furry animals, hair erection traps a 10

11 thicker layer of air over the skin surface thus increasing insulation against heat loss; hair erection also makes the animal appear larger and is thus a protective mechanism in dangerous circumstances. These functions are probably of little physiological significance in humans. However, contraction of the arrector pili may play some part in expulsion of sebum from sebaceous glands. Sebaceous glands. One or more sebaceous glands are associated with each hair follicle; these glands secrete an oily substance called sebum onto the hair surface in the upper part of the follicle. Sebum acts as a waterproofing and moisturising agent for the hair and skin surface. Sweat glands. In most areas of the skin, sweat glands are simple, coiled tubular glands which secrete a watery fluid onto the skin surface by the process of merocrine secretion. The coiled, secretory portions of these glands are an important component of the thermoregulatory mechanism in humans. When the body requires heat loss, skin blood flow and sweat production are increased; evaporation of sweat causes cooling of the skin surface and loss of beat from the underlying vascular bed. Merocrine (eccrine) sweat glands are innervated by cholinergic fibres of the sympathetic nervous system; sweating is stimulated not only by excessive body heat but also by fear-provoking stimuli. A different type of sweat gland is found in the skin of the axilla and genital regions of humans. In contrast to the merocrine sweat glands, these glands are believed to secrete by the apocrine process and are thus called apocrine sweat glands. They also differ in that they produce a viscid secretion which is discharged into hair follicles rather than directly onto the surface. Apocrine sweat glands are innervated by adrenergic fibres of the sympathetic nervous system. Fingernails The dorsal skin surface of the tip of each finger and toe forms a highly specialised appendage, the nail (N), consisting of a dense keratinised plate, the nail plate, which rests on a stratified squamous epithelium called the nail bed. The proximal 11

12 end of the nail, the nail root (R), and the underlying nail bed extend deeply into the dermis to lie in close apposition to the distal interphalangeal joint, and the dermis beneath the nail plate is firmly attached to the periosteum of the distal phalanx (DP). Nail growth occurs by proliferation and differentiation of the epithelium underlying the nail root (known as the nail matrix), and the nail plate slides distally over the rest of the nail bed which does not actively contribute to nail growth. Reflecting its proliferative activity, the nail matrix is thicker than that of the rest of the nail bed and exhibits pronounced epidermal ridges; on the surface, the distal part of the nail matrix is marked by the white crescent-shaped lunular at the base of the nail. The skin overlying the root of the nail is known as the nailfold (F) and its highly keratinised free edge is known as the eponychium (E). The skin beneath the free end of the nail is known as the hyponychium (H). 12

13 The skin circulation. The circulation of the skin has an unusual arrangement which accommodates several different requirements: nutrition of the skin and appendages, increased blood flow to facilitate heat loss, and decreased blood flow to minimise heat loss in cold conditions whilst maintaining adequate nutritional flow. A The arteries supplying the skin are located deep in the hypodermis from which they give rise to branches passing upwards to form two plexuses of anastomosing vessels. The deeper plexus lies at the junction of the hypodermis and dermis and is known as the cutaneous plexus; the more superficial plexus lies just beneath the dermal papillae and is known as the subpapillary plexus. Branches of the cutaneous plexus supply the fatty tissue of the hypodermis, the deeper aspect of the dermis and capillary networks which envelop the hair follicles and deep sebaceous glands and sweat glands. The subpapillary plexus supplies the upper aspect of the dermis and the capillary networks around the superficial appendages. The subpapillary plexus also gives rise to a capillary loop in each dermal papilla. The venous drainage of the skin is arranged into plexuses broadly corresponding to the arterial supply. Numerous shunts provide direct arteriovenous communications which play an important role in thermoregulation by controlling blood flow to the appropriate part of the dermis. The skin also has a rich lymphatic drainage which forms plexuses corresponding to those of the blood vascular system. 13