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Structure and function of the skin, hair and nails

Skin, skin is a wonderful thing,

Keeps the outside out and the inside in.

Anon.

It is essential to have some background knowledge of the normal structure and function of any organ before you can hope to understand the abnormal. Skin is the icing on the anatomical cake, it is the decorative wrapping paper, and without it not only would we all look rather unappealing, but also a variety of unpleasant physiological phenomena would bring about our demise. You have probably never contemplated your skin a great deal, except in the throes of narcissistic admiration, or when it has been blemished by some disorder, but hopefully by the end of this first chapter you will have been persuaded that it is quite a remarkable organ, and that you are lucky to be on such intimate terms with it.

Skin structure

The skin is composed of two layers: the epidermis and the dermis (Figure 1.1). The epidermis, which is the outer layer, and its appendages (hair, nails, sebaceous glands and sweat glands), are derived from the embryonic ectoderm. The dermis is of mesodermal origin.

Figure 1.1 The structure of the skin. The relative thickness of epidermis and dermis varies considerably with body site.

The epidermis

The epidermis is a stratified squamous epithelium, with several well-defined layers.

Keratinocytes

The principal cell type is known as a keratinocyte. Keratinocytes, produced by cell division in the deepest layer of the epidermis (basal layer), are carried towards the skin surface, undergoing in transit a complex series of morphological and biochemical changes known as terminal differentiation (keratinization) to produce the surface layer of tightly packed dead cells (stratum corneum or horny layer), which are eventually shed. In health, the rate of production of cells matches the rate of loss so that epidermal thickness is constant. Epidermal kinetics are still not fully understood, particularly the balance between stem cells and those cells which differentiate into fully functional keratinocytes. This differentiation process is under genetic control and mutations in the genes controlling epidermal function are responsible for a variety of diseases, such as atopic eczema and the ichthyoses.

So-called intermediate filaments, present in the cytoplasm of epithelial cells, are a major component of the architectural construction of the epidermis (the cytoskeleton). The intermediate filaments are composed of proteins known as keratins, each of which is the product of a different gene. Pairs of keratins are characteristic of certain cell types and tissues. The mitotically active keratinocytes in the basal layer express the keratin pair K5/K14, but differentiation progresses as the cells migrate towards the epidermal surface and the expression of K5/K14 is down-regulated and that of K1/K10 is induced.

As cells reach the higher layers of the epidermis, the filaments aggregate into keratin fibrils under the influence of a protein known as filaggrin (filament-aggregating protein) - filaggrin is derived from its precursor profilaggrin, present in keratohyalin granules, which constitute the granules in the granular layer. Derivatives of the proteolysis of filaggrin are major components of natural moisturizing factor (NMF), which is important in the maintenance of epidermal hydration. Loss-of-function mutations in FLG, the gene encoding filaggrin, have profound effects on epidermal barrier function, underlying ichthyosis vulgaris and strongly predisposing to atopic eczema; carriers of these mutations have reduced levels of NMF in the stratum corneum.

In the final stages of terminal differentiation, the plasma membrane is replaced by the cornified cell envelope, composed of several proteins the production of which is also under genetic control. Cells that have developed this envelope and have lost their nucleus and organelles constitute the corneocytes of the stratum corneum.

Basal layer

Now let us look at the layers more closely (Figure 1.2). The basal layer, which is one to three cells thick, is anchored to a basement membrane that lies between the epidermis and dermis.

Figure 1.2 The epidermis. Contrary to expectation, keratinocytes are highly active cells. Note how their appearance changes (along with their function) as they transit the epidermal layer.

Melanocytes

Interspersed among the basal cells are melanocytes - large dendritic cells derived from the neural crest - which are responsible for melanin pigment production. Melanocytes contain cytoplasmic organelles called melanosomes, in which melanin is synthesized from tyrosine. The melanosomes migrate along the dendrites of the melanocytes and are transferred to the keratinocytes in the prickle cell layer. In white people, the melanosomes are grouped together in membrane-bound melanosome complexes, and they gradually degenerate as the keratinocytes move towards the surface of the skin. The skin of black people contains the same number of melanocytes as that of white people, but the melanosomes are larger, remain separate and persist through the full thickness of the epidermis.

The main stimulus to melanin production is ultraviolet (UV) radiation. Melanin protects the cell nuclei in the epidermis from the harmful effects of UV radiation. A suntan is a natural protective mechanism, not some God-given cosmetic boon created so that you can impress the neighbours on your return from an exotic foreign trip! Unfortunately, this does not appear to be appreciated by the pale, pimply, lager-swilling advert for British manhood who dashes on to the beach in Ibiza and flash fries himself to lobster thermidor on day one of his annual holiday.

Skin cancers are extremely uncommon in people of dark-skinned races because their skin is protected from UV damage by the large amounts of melanin that it contains. However, albinism in people of colour greatly predisposes them to skin cancer because their production of melanin is impaired and they are therefore without its protective influence.

Prickle cell layer

Above the basal layer is the prickle cell/spinous layer. This acquires its name from the spiky appearance produced by the intercellular bridges (desmosomes) that connect adjacent cells. Important in cell-cell adhesion are several protein components of desmosomes (including cadherins (desmogleins and desmocollins) and plakins). Production of these is genetically controlled, and abnormalities have been detected in some human diseases.

Scattered throughout the prickle cell layer are Langerhans' cells. These dendritic cells contain characteristic racquet-shaped 'Birbeck' granules. Langerhans' cells are probably modified macrophages that originate in the bone marrow and migrate to the epidermis. They are the first line of immunological defence against environmental antigens (see the section on 'Functions of the Skin').

Granular cell layer

Above the prickle cell layer is the granular layer, which is composed of flattened cells containing the darkly staining keratohyalin granules (which contain filaggrin). Also present in the cytoplasm of cells in the granular layer are organelles known as lamellar granules (Odland bodies). These contain lipids and enzymes, and they discharge their contents into the intercellular spaces between the cells of the granular layer and stratum corneum - providing the equivalent of 'mortar' between the cellular 'bricks', and contributing to NMF and the barrier function of the epidermis.

Stratum corneum

The cells of the stratum corneum are flattened, keratinized cells that are devoid of nuclei and cytoplasmic organelles. Adjacent cells overlap at their margins, and this locking together, in combination with intercellular lipid, forms a very effective barrier. The stratum corneum varies in thickness according to the region of the body. It is thickest on the palms of the hands and soles of the feet. The stratum corneum cells are gradually abraded by daily wear and tear. If you bathe after a period of several days' avoidance of water (a house without central heating, in mid-winter, somewhere in the Northern Hemisphere, is ideal for this experiment), you will note that as you towel yourself you are rubbing off small balls of keratin - which has built up because of your unsanitary habits. When a plaster cast is removed from a fractured limb after several weeks in situ, there is usually a thick layer of surface keratin, the removal of which provides hours of absorbing occupational therapy.

Figure 1.3 shows the histological appearance of normal epidermis.

Figure 1.3 Section of skin stained with haematoxylin and eosin, showing the appearance of a normal epidermis. 'Rete ridges' (downward projections of the pinker epidermis) interdigitate with 'dermal papillae' (upward projections of the dermis). Note the dark pink flattened cells of the stratum corneum at the...