Physical Address
304 North Cardinal St.
Dorchester Center, MA 02124
In this chapter, the types and functions of skin in different parts of the body are described first, followed by the microstructure of the epidermis and dermis, and the appendages of skin, including the pilosebaceous units, sweat glands and nails. The development of skin, natural skin lines and age-related changes, and clinical aspects of skin, e.g. grafts, surgical skin flaps and wound healing, are also described. The integumental system includes the skin and its derivatives, hairs, nails, sweat and sebaceous glands; subcutaneous fat and deep fascia; the mucocutaneous junctions around the openings of the body orifices; and the breasts. Mucocutaneous junctions and breast tissues are covered in the appropriate regional sections.
The skin is the largest organ of the human body and constitutes approximately 15% of the total body weight. In an average 70 kg person, the skin weighs approximately 13 kg and has a surface area of about 2 m 2 . It covers the entire external surface of the body, including the external acoustic meatus, the lateral aspect of the tympanic membrane and the vestibule of the nose. It is continuous with the mucosae of the alimentary, respiratory and urogenital tracts, and fuses with the conjunctiva at the margins of the eyelids, and with the lining of the lacrimal canaliculi at the lacrimal puncta. The thickness of the skin ranges from 1.5 to 5.0 mm and depends mainly on its location.
The skin forms a self-renewing interface between the body and its environment. It provides an effective barrier against microbial organisms, and protects against mechanical, chemical, osmotic, thermal and ultraviolet radiation damage. It is an important site of immune surveillance against the entry of pathogens and the initiation of primary immune responses. For instance, the skin produces various antimicrobial peptides such as human cathelicidin LL-37, a small cationic peptide that can prevent the immunostimulatory effects of bacterial wall molecules such as lipopolysaccharide and therefore protect against endotoxaemia. It can inhibit neutrophil apoptosis and stimulate angiogenesis, tissue regeneration and release of cytokines such as interleukin (IL)-8. Specific innate immune defenses in the skin are present throughout the epidermis, dermis, hair follicles and appendages, and in the absence of skin diseases or trauma, provide a resilient buffer against external microorganisms ( ).
Skin performs many biochemical synthetic processes, including the formation of vitamin D under the influence of ultraviolet B (UVB) radiation and synthesis of cytokines and growth factors. Skin is the target of a variety of hormones such as thyroxine, androgens and oestrogens. These activities can affect the appearance and function of individual skin components, such as the sebaceous glands, the hairs and the pigment-producing cells.
Control of body temperature is an important function of skin, and is effected mainly by regulation of heat loss from the cutaneous circulation through the rapid increase or reduction in the flow of blood to an extensive external surface area. This process is also assisted by sweating. In disorders such as erythroderma, in which more than 90% of the skin is inflamed and red, insensible fluid losses can exceed several litres per day and can result in shock if treatment is not initiated promptly. Skin is involved in socio-sexual communication and can signal emotional states by means of muscular and vascular responses. It is a major sensory organ, richly supplied by nerve terminals and specialized receptors for touch, temperature, pain and other stimuli.
Skin has good frictional properties, assisting locomotion and manipulation by its texture. It is elastic, and can be stretched and compressed within limits. The outer surface is covered by skin lines, some of which are large and conspicuous while others are microscopic, or are only revealed after manipulation or incision of the skin.
The colour of human skin is derived from, and varies with, the amount of blood (and its degree of oxygenation) in the cutaneous circulation, the thickness of the cornified layer and the ratio of eumelanin (brown/black) to pheomelanin (red/yellow). Melanin has a protective role against UV radiation and acts as a scavenger of harmful free radicals. Ethnic variations in colour are mainly due to differences in the amount, type and distribution of melanin and are genetically determined. These genetic variants may also determine the prevalence of benign skin lesions such as freckles, as well as susceptibility to common forms of non-melanoma skin cancers and skin ageing ( ).
The appearance of skin is affected by many other factors, e.g. size, shape and distribution of hairs and of skin glands (sweat, sebaceous and apocrine), and changes associated with maturation, ageing, metabolism and pregnancy. The general state of health is reflected in the appearance and condition of the skin, and the earliest signs of many systemic disorders may be apparent in the skin.
Each square centimetre of skin contains approximately one million bacteria (comprising hundreds of distinct species) forming a complex community that also contains viruses and fungi. The exact composition of the community of these organisms varies across different body sites and depends on several factors, including sebaceous gland concentration, moisture content and temperature, host genetics and exogenous environmental factors. The multiple organisms are not just commensals but play a much bigger role in immune modulation and epithelial health ( ). Dissecting the nature of microbe–host interactions and discovering the factors that drive microbial colonization are likely to provide greater insight into the pathogenesis of skin diseases such as atopic dermatitis, and inform the development of potential new therapies.
Although skin in different parts of the body is fundamentally of similar structure, there are many local variations in parameters such as thickness, mechanical strength, softness, flexibility, degree of keratinization (cornification), size and number of hairs, frequency and types of glands, pigmentation, vascularity and innervation ( Figs 7.1 – 7.4 ). Human skin is divided into two main types: hairless (glabrous) skin and hair-bearing skin. Hairless skin is found on the palms and soles where it has a grooved surface, with alternating ridges and sulci giving rise to the dermatoglyphics (fingerprints). In palmar and plantar skin, there is a compact cornified layer which may be up to 10 times thicker than in other body sites: this skin is thus also termed thick skin. There are, however, sites such as the lips and nipples, where hairless skin has a relatively thin cornified layer.
Hairless skin has numerous encapsulated sensory endings within the dermis, but lacks hair follicles and associated sebaceous glands. Hair-bearing skin (most thin skin bears hairs) has both hair follicles and sebaceous glands associated with the follicles. Hair follicle size, structure and density can vary between different body sites. Notably, scalp has large hair follicles whereas the forehead has only small, vellus hair-producing follicles. Some hair-bearing sites, such as the axilla, contain apocrine glands as well as eccrine sweat glands. Sebaceous gland function varies with age, being active in neonates, and from puberty onwards: the relative activity influences the composition of the skin surface lipids and the skin microbiome. There are regional variations in the structure of the dermal–epidermal junction, with more hemidesmosomes and anchoring fibrils in the skin of the leg than in the skin of the arm. In the dermis, the arrangement and size of elastic fibres varies, e.g. they are very large in perianal skin, whereas there are almost none in the scrotum. Cutaneous blood supply varies markedly between areas such as the eyelid and more rigid areas such as the fingertips.
The epidermis (see Figs 7.2 – 7.3 ) is a self-renewing stratified epithelial tissue consisting mainly of keratinocytes. Other cells within the epidermis include melanocytes (pigment-forming cells from the embryonic neural crest), Langerhans cells (immature antigen-presenting dendritic cells derived from bone marrow), lymphocytes and Merkel cells. Merkel cells may function as sensory mechanoreceptors or possibly as part of the dispersed neuroendocrine system and many are associated with nerve endings. Free sensory nerve endings are sparsely present within the epidermis.
The population of keratinocytes undergoes continuous renewal throughout life ( ). Turnover is mediated by epidermal stem cells in the basal layer of the epidermis which generate daughter cells that undergo a series of biochemical and physical changes as they migrate towards the surface of the skin to form the various layers of the epidermis. They transform from polygonal living cells to non-viable flattened squames full of intermediate filament proteins (keratins) embedded in a dense matrix of cytoplasmic proteins to form mature keratin.
The epidermis consists of several layers. The innermost layer, the basal layer (stratum basale) is succeeded by the spinous or prickle cell layer (stratum spinosum), granular layer (stratum granulosum), clear layer (stratum lucidum) and cornified layer (stratum corneum), which is the most superficial (see Fig. 7.4 ). The first three of these layers are metabolically active compartments through which cells pass and change their morphology as they undergo cellular differentiation. The more superficial layers of cells undergo terminal keratinization (cornification), which involves not only structural changes in keratinocytes, but also molecular and biochemical changes within the cells and their surroundings.
The epidermal appendages (pilosebaceous units, sweat glands and nails) are formed developmentally by the ingrowth of the epidermis.
The basal layer is the innermost layer of the epidermis, next to the dermis and is the site of epidermal cellular proliferation. It is in contact with a basal lamina, which is a thin layer of specialized extracellular matrix not usually visible by light microscopy ( Fig. 7.5 ; see Fig. 2.8 ). By transmission electron microscopy, the basal lamina consists of a clear lamina lucida adjacent to the basal cell plasma membrane and a darker electron-dense lamina densa ( Fig. 7.6 ). The basal plasma membranes of the basal keratinocytes, the extracellular basal laminae and the anchoring fibrils of type VII collagen within the subjacent dermal matrix (lamina fibroreticularis) which insert into the lamina densa, collectively form the basement membrane zone (BMZ) at the dermal–epidermal junction. This is a highly convoluted interface, particularly in thick, hairless skin, where dermal papillae (rete ridges) project into the epidermis, interlocking with adjacent downward projections of the epidermis (rete pegs) (see Fig. 7.4 ).
FLOAT NOT FOUND
The majority of basal keratinocytes are columnar to cuboidal in shape, with large (relative to their cytoplasmic volume), mainly euchromatic nuclei and prominent nucleoli (see Fig. 7.3 ). The cytoplasm contains variable numbers of melanosomes and keratin filament bundles corresponding to the keratin tonofilaments of classical electron microscopy. In the basal keratinocytes, these keratins consist mostly of keratin 5 (K5) and keratin 14 (K14) proteins. The plasma membranes of interconnecting cells are coupled by desmosomes; those of the basal keratinocytes are linked to the basal lamina by hemidesmosomes (see Figs 7.5 – 7.6 , 1.27 ). Melanocytes (see Fig. 7.13 ), Langerhans cells (see Figs 7.16 – 7.17 ) and Merkel cells (see Fig. 3.29 ) are interspersed among the basal keratinocytes. Merkel cells are connected to keratinocytes by desmosomes, but melanocytes and Langerhans cells lack these specialized contacts. Intraepithelial lymphocytes are present in small numbers.
Keratinocyte stem cells are found within the basal layer of the epidermis ( ): they are thought to reside mainly in the interfollicular epidermis in the troughs of rete pegs, and in the outer root sheath bulge of the hair follicle and in sebaceous glands. Their progeny, called transit (or transient) amplifying cells, also reside within the basal layer and pass through a few rounds of proliferation before terminally differentiating. The activity of epidermal stem cells and transit amplifying cells in the basal layer provides a continuous supply of differentiating cells that move suprabasally, eventually forming the cornified (corneocyte) layer of the epidermis.
Epidermal stem cells and their differentiated progeny are organized into columns, the epidermal proliferation units. Several layers of prickle and granular cells overlie a cluster of 6–8 basal cells, forming a columnar proliferative unit. Each group of basal cells consists of a central stem cell with an encircling ring of transit amplifying proliferative cells and postmitotic maturing cells. From the periphery of this unit, postmitotic cells transfer into the prickle cell layer. The normal total epidermal turnover time is between 52 and 75 days. In some skin disorders, the turnover rates and transit times are significantly shortened, e.g. in psoriasis, the total epidermal turnover time may be as little as 8 days. In homeostatic conditions, the multiple stem cell populations in skin generally contribute only to the differentiation programme of restricted local cells. However, following injury that inflicts systemic and local environmental change, the various stem cell populations, e.g. those in hair follicles, may display remarkable plasticity, responding to wound-induced stimuli by exiting their niche and participating in re-epithelializing damaged tissue. This process may involve a transient or permanent switch of their tissue regeneration programme depending upon the particular type of wound. Understanding the molecular basis of the ‘switch’ is likely to have considerable relevance to improving wound healing and developing the field of regenerative medicine.
The prickle cell layer (stratum spinosum) (see Fig. 7.3 ; Fig. 7.7 ), consists of several layers of closely packed keratinocytes that are connected to each other by desmosomes, the specialized cell–cell junctions that provide tensile strength and cohesion to the layer. When a section of skin is stained by haematoxylin and eosin and viewed by routine light microscopy, intercellular bridges corresponding to the locations of the desmosomes are seen between the dehydrated keratinocytes, giving these suprabasal cells their characteristic spiny appearance. However, ultrastructurally, the desmosome junctions have a tight laminated appearance ( Fig. 7.8 ) . The cytoplasm of these keratinocytes contains prominent bundles of cytokeratin filaments, mostly cytokeratins 1 (K1) and 10 (K10), arranged concentrically around a euchromatic nucleus and attached to the dense plaques of the desmosomes and melanosomes, either singly or aggregated within membrane-bound organelles (compound melanosomes). Langerhans cells (see Fig. 7.16 ) and occasional lymphocytes are present in the prickle cell layer.
FLOAT NOT FOUND
Extensive changes in keratinocyte structure occur in the 3–4 layers of flattened cells in the granular layer, also known as the stratum granulosum ( ). The nuclei become pyknotic and begin to disintegrate. Organelles such as ribosomes and membrane-bound mitochondria and Golgi bodies degenerate. Cytokeratin filament bundles become more compact and associated with irregular, densely staining keratohyalin granules (see Fig. 7.7 ). Small round granules (100 × 300 nm) with a lamellar internal structure (lamellar granules, Odland bodies, keratinosomes) also appear in the cytoplasm. Keratohyalin granules contain a histidine-rich, sulphur-poor protein, profilaggrin, which becomes modified to filaggrin as the cell reaches the cornified layer. Defects in the filaggrin protein, as a result of loss-of-function mutations in the filaggrin ( FLG ) gene, have been shown to cause ichthyosis vulgaris, a common dry scaly skin condition, as well as being a major risk factor for atopic eczema ( ). In addition, copy number variation in the FLG gene may influence the amount of filaggrin in the skin and also contribute to the pathogenesis of both dry skin and eczema ( ). The degradation products of filaggrin, including urocanic acid, contribute to the formation of natural moisturizing factor, a key component of the epidermal barrier function.
The lamellar granules release their hydrophobic glycophospholipid contents into the intercellular space both within the granular layer and between the granular and the cornified layers. These glycophospholipids form an important component of the permeability barrier of the epidermis: permeability is also regulated by tight junctions within the middle and upper parts of the granular layer ( Fig. 7.9 ).
The clear layer is only found in thick palmar or plantar skin. It stains more strongly than the cornified layer with acidic dyes (see Fig. 7.6 ), is more optically refractile and often contains nuclear debris. Ultrastructurally, the cells contain compacted keratin filaments and resemble the incompletely keratinized cells that are occasionally seen in the innermost part of the cornified layer of thin skin.
The cornified layer (see Figs 7.3 , 7.7 ) is the final product of epidermal differentiation ( ). It consists of closely packed layers of flattened polyhedral squames or corneocytes ( Fig. 7.10 ), ranging in surface area from 800 to 1100 μm 2 . These cells overlap at their lateral margins and interlock with cells of apposed layers by ridges, grooves and microvilli. In thin skin, this layer may be a few cells deep, but in thick skin it may be more than 50 cells deep. The plasma membrane of the corneocytes appears thicker than that of other keratinocytes, partly due to the cross-linking of a soluble precursor, involucrin, at the cytoplasmic face of the plasma membrane, in the complex insoluble cornified envelope. The outer surface is also covered by a monolayer of bound lipid. The intercellular region contains extensive lamellar sheets of glycolipid derived from the lamellar granules of the granular layer. The cells lack a nucleus and membranous organelles, and consist entirely of a dense array of keratin filaments embedded in a cytoplasmic matrix composed partly of filaggrin derived from keratohyalin granules. The cornified layer has physical and chemical properties that vary across the layer, providing different amounts of absorption, hydration and mechanical defence ( Fig. 7.11 ) . FLOAT NOT FOUND FLOAT NOT FOUND
Under normal conditions, the production of epidermal keratinocytes in the basal layer is matched by the loss of corneocytes from the cornified layer. Desquamation of these cells is normally imperceptible. When excessive, it may appear as dandruff on the scalp or the flaking or peeling skin that follows sunburn. The thickness of the cornified layer can be influenced by local environmental factors including chronic scratching, which can lead to a considerable thickening of the whole epidermis including the cornified layer.
Keratins are the intermediate filament proteins found in all epithelial cells. There are two types: type I (acidic) and type II (neutral/basic). They form heteropolymers, are co-expressed in specific pairs and are assembled into 10 nm intermediate filaments. Fifty-four different functional keratin genes are recognized in humans ( ). They are expressed in highly specific patterns according to the stage of cellular differentiation. Antibodies to individual keratins are useful analytical tools ( Fig. 7.12 ). Keratins K5 and K14 are expressed by basal keratinocytes. Keratins K1 and K10 are synthesized suprabasally. In the granular layer the filaments become associated with keratohyalin granules containing profilaggrin, a histidine-rich phosphorylated protein. As the cells pass into the cornified layer, profilaggrin is cleaved by phosphatases into filaggrin, which causes aggregation of the filaments and forms the matrix in which they are embedded. Other types of keratin expression occur elsewhere, particularly in hair and nails, where highly specialized hard keratin is expressed. This becomes chemically modified and is much tougher than in the general epidermis.
The epidermis serves as an important barrier to trans-epidermal loss of water and other substances through the body surface (apart from in sweating and sebaceous secretion). This is possible in part because of the presence of an epidermal lipid layer that consists of a variety of lipids that are synthesized in the epidermis. These include triglycerides, fatty acids, phospholipids, cholesterol, cholesterol esters, glycosphingolipids and ceramides. Furthermore, 7-dehydrocholesterol, an intermediate molecule in the cholesterol biosynthesis pathway and a precursor of vitamin D, is synthesized in the skin. The content and composition of epidermal lipids change with differentiation ( ). Phospholipids and glycolipids first accumulate within keratinocytes above the basal layer, but higher up they are broken down and are practically absent from the cornified layer. Cholesterol and its esters, fatty acids and ceramides accumulate towards the surface and are abundant in the cornified layer. The lamellar arrangement of the extracellular lipids is a major factor in their barrier function.
Melanocytes are melanin pigment-producing cells derived from the neural crest ( Figs 7.13 – 7.14 ). They are present in the epidermis and its appendages, oral epithelium, some mucous membranes, uveal tract (choroid coat) of the eyeball, parts of the middle and internal ear, and in the pial and arachnoid meninges, principally over the ventrolateral surfaces of the medulla oblongata. The cells of the retinal pigment epithelium, developed from the outer wall of the optic cup, also produce melanin, and neurones in different locations within the brainstem (e.g. the locus coeruleus and substantia nigra) synthesize a variety of melanin called neuromelanin. In humans there are two classes, the brown–black eumelanin and the red–yellow pheomelanin, both derived from the substrate tyrosine. Most natural melanins are mixtures of eumelanin and pheomelanin; pheomelanic pigments, trichochromes, occur in red hair.
Melanocytes are dendritic cells and lack desmosomal contacts with apposed keratinocytes, although hemidesmosomal contacts with the basal lamina are present. In routine tissue preparations, melanocytes appear as clear cells in the basal layer of the epidermis. The numbers per unit area of epidermis range from 2300 per mm 2 in cheek skin to 800 per mm 2 in abdominal skin. It is estimated that a single melanocyte may be in functional contact via its dendritic processes with up to 30 keratinocytes. The nucleus is large, round and euchromatic, and the cytoplasm contains intermediate filaments, a prominent Golgi complex and vesicles and associated rough endoplasmic reticulum, mitochondria and coated vesicles, together with a characteristic organelle, the melanosome.
The melanosome is a membrane-bound structure that undergoes a sequence of developmental stages during which melanin is synthesized and deposited within it by a tyrosine–tyrosinase reaction. Mature melanosomes move into the dendritic processes along the surfaces of microtubules and are transferred to keratinocytes through their phagocytic activity ( ). Keratinocytes engulf and internalize the tip of the dendrite, so that the contained melanosomes are pinched off into the keratinocyte cytoplasm. Here, they may exist as individual granules in heavily pigmented skin, or be packaged within secondary lysosomes as melanosome complexes in lightly pigmented skin. In basal keratinocytes they can be seen to accumulate in a crescent-shaped cap over the distal part of the nucleus. As the keratinocytes progress towards the surface of the epidermis, melanosomes undergo degradation, and melanin remnants in the cornified layer form dust-like particles. Melanosomes are degraded more rapidly in light-skinned than in dark-skinned individuals, in whom melanosomes persist in cells of the more superficial layers. Melanosomes are acidic, which explains why the larger melanosomes present in dark skin types are associated with a more acidic skin surface (pH 4.3), compared to lighter skin types (pH 5.3). Melanosomes (and their melanin content) are mainly found in basal keratinocytes ( Fig. 7.15 ).
Melanin protects the skin against the harmful effects of UV radiation on DNA and is also an efficient scavenger of damaging free radicals. However, a high concentration of melanin may adversely affect synthesis of vitamin D in darker-skinned individuals living in northern latitudes. Melanin pigmentation is both constitutive and facultative. Constitutive pigmentation is the intrinsic level of pigmentation and is genetically determined, whereas facultative pigmentation represents reversible changes induced by environmental agents, e.g. UV and X-radiation, chemicals and hormones. Racial variations in pigmentation are due to differences in melanocyte morphology and activity rather than to differences in number or distribution. In skin with naturally heavy pigmentation, the cells tend to be larger and more dendritic and to contain more large, late-stage melanosomes than the melanocytes of paler skins. The keratinocytes in turn contain more melanosomes, individually dispersed, whereas in light skins the majority are contained within secondary lysosomes to form melanosome complexes ( ).
The response to UV light includes immediate tanning with pigment darkening and can occur within minutes as a result of photo-oxidation of pre-existing melanin. Delayed tanning occurs after about 48 hours, and involves stimulation of melanogenesis within the melanocytes, and transfer of additional melanosomes to keratinocytes. There may also be some increase in size of active melanocytes, and in their apparent numbers, mainly through activation of dormant cells.
Langerhans cells are dendritic antigen-presenting cells that are distributed throughout the basal and prickle cell layers of the epidermis and its appendages, although their dendritic processes extend between tight junctions in the granular layer ( , ) ( Figs 7.16 – 7.17 ). They are also present in other stratified squamous epithelia, including the buccal, tonsillar and oesophageal epithelia, as well as the cervical and vaginal mucosae, and the transitional epithelium of the bladder. In the eye, they are found in the conjunctiva but not in the cornea. In routine haematoxylin and eosin histological preparations, they appear as clear cells. They enter the epidermis from the bone marrow during development to establish the postnatal population (460–1000/mm 2 , 2–3% of all epidermal cells, with regional variations), which is maintained by continual replacement from the marrow.
The nucleus is euchromatic and markedly indented, and the cytoplasm contains a well-developed Golgi complex, lysosomes (which often contain ingested melanosomes) and a characteristic organelle, the Birbeck granule, which is the ultrastructural hallmark of the Langerhans cell. The latter are discoid or cup-shaped, or have a distended vesicle resembling the head of a tennis racket; in section they often appear as a cross-striated rod 0.5 μm long and 30 nm wide. When stimulated by antigen, Langerhans cells migrate out of the epidermis to lymphoid tissues (see Fig. 4.14 ). Their numbers are increased in chronic skin inflammatory disorders, particularly of an immune aetiology, such as some forms of dermatitis.
Merkel cells (see Commentary 1.4 ) are present as clear oval cells, singly or in groups, in the basal layer of the epidermis and in the outer root sheath of some large hair follicles. They are thought to be derived embryologically from the epidermis, although a neural crest origin has been considered. They can only be distinguished histologically from other clear cells (melanocytes and Langerhans cells) by immunohistochemical and ultrastructural criteria.
The plasma membrane of a Merkel cell has short, stiff processes that interdigitate with the adjacent basal keratinocytes to which it is attached by small desmosomes. The cytoplasm contains numerous closely packed intermediate filaments (mostly K8 and K18, but also K19 and K20) and characteristic 80–110 μm dense-core granules. The basal plasma membranes of many Merkel cells are closely opposed to the membrane of an axonal terminal that conveys the sensation of touch. They are slowly adapting mechanoreceptors that respond to directional deformations of the epidermis and the direction of hair movement by releasing a transmitter from their dense-core cytoplasmic granules. There is evidence that a subpopulation of Merkel cells lacks axonal contact and may serve a neuroendocrine function locally.
Merkel cells can undergo malignant transformation and give rise to a rare and aggressive tumour called a Merkel cell carcinoma (see Commentary 1.4 ) that typically presents with a painless, rapidly growing nodule on sun-exposed sites. The Merkel cell polyomavirus is clonally integrated in about 80% of Merkel cell carcinomas; the remaining 20% have a large number of ultraviolet-associated mutations.
The dermis lies beneath the epidermis and is 15–40 times thicker than the epidermis, depending on the anatomical site (see Figs 7.1 , 7.4 ). It is vital for the survival of the epidermis: important morphogenetic signals are exchanged at the interface between the two both during development and postnatally.
The dermis is an irregular, moderately dense connective tissue composed of an interwoven collagenous and elastic network in an amorphous ground substance of glycosaminoglycans, glycoproteins and bound water. It also contains nerves, blood vessels, lymphatics and epidermal appendages. Mechanically, the dermis provides considerable strength to the skin by virtue of the number and arrangement of its collagen fibres (which give it tensile strength) and its elastic fibres (which allow it to stretch and recoil). The density of its fibre meshwork, and therefore its physical properties, varies with different parts of the body, and with age and gender.
The dermis can be divided into two zones: a narrow, superficial papillary layer and a deeper reticular layer. The boundary between these two zones is indistinct. Fibroblasts, the main cell type of human dermis, are heterogeneous and at least four distinct sub-populations have been defined ( ). At a cellular level, different types of fibroblasts may have different properties with regard to Wnt (wingless gene family) signalling and responsiveness to interferon-γ. Their roles in the organisation of the extracellular matrix and tissue morphogenesis are only partially characterized: from a clinical perspective, future strategies involving ex vivo expansion or in vivo ablation of specific types of fibroblasts may have therapeutic applications in improving wound healing and reducing tissue fibrosis ( ).
Adult dermal collagen is mainly of types I and III, in proportions of 80–85% and 15–20% respectively. Type I collagen fibres are coarse and found predominantly in the deeper reticular dermis, and the finer type III collagen is found in the papillary dermis and around blood vessels. Type IV collagen is found in the basal lamina between epidermis and dermis, and around Schwann cells of peripheral nerves and endothelial cells of vessels. Types V, VI and VII are minor collagenous components of the dermis. Elastic fibres form a fibrous network interwoven between the collagen bundles throughout the dermis and are more prominent in some regions, e.g. the axilla.
Two major categories of cell are present in postnatal dermis, permanent and migrant, as is typical of all general connective tissues ( Ch. 2 ). The permanent resident cells include cells of organized structures such as nerves, vessels, cells of the arrector pili muscles, and fibroblasts, which synthesize all components of the dermal extracellular matrix. The migrant cells originate in the bone marrow (see Fig. 4.12 ) and include macrophages, mast cells, eosinophils, neutrophils, T and B cells (including antibody-secreting plasma cells), and dermal interstitial dendritic cells, which are capable of immune surveillance and antigen presentation.
The papillary layer is a relatively thin zone immediately subjacent to the dermal–epidermal junction. It provides mechanical anchorage, metabolic support and trophic maintenance to the overlying epidermis, as well as supplying sensory nerve endings and blood vessels. The cytoskeleton of the basal epidermal keratinocytes is linked to the fibrous matrix of the papillary dermis through the attachment of keratin filament bundles to hemidesmosomes, then via anchoring filaments of the basal lamina, to the anchoring fibrils of type VII collagen, which extend into the papillary dermis. This arrangement provides a mechanically stable substratum for the epidermis.
The superficial surface of the dermis is shaped into numerous papillae or rete ridges, which interdigitate with rete pegs in the base of the epidermis and form the dermal–epidermal junction at their interface. The papillae have round or blunt apices, which may be divided into several cusps. In thin skin, especially in regions with little mechanical stress and minimal sensitivity, papillae are few and very small, while in the thick skin of the palm and sole of the foot they are much larger, closely aggregated, and arranged in curved parallel lines following the pattern of ridges and grooves on these surfaces (see Fig. 7.1 ). Lying under each epidermal surface ridge are two longitudinal rows of papillae, one on either side of the epidermal rete pegs, through which the sweat ducts pass on the way to the surface. Each papilla contains densely interwoven and fine bundles of types I and III collagen fibres. Elastic fibres are not fully formed in the papillary dermis. Also present is a capillary loop (see Fig. 7.4 ), and in some sites, especially in thick hairless skin, Meissner's corpuscle nerve endings. (see Figs 3.29 , 3.30 )
The reticular layer is much thicker than the papillary dermis. Its bundles of collagen fibres are coarser and more compacted and form a strong but deformable three-dimensional lattice that contains a variable number of elastic fibres. The mostly parallel orientation of the collagen fibres may be related to local mechanical forces on the dermis and may be involved in the development of skin lines. In the reticular dermis, the elastic fibres are composed of amorphous elastin surrounding microfibrils within the centre of the elastic fibres. The elastic fibres lose their elastin component at the intersection of the reticular and papillary dermis, whereas the microfibrils continue into the papillary dermis as naked microfibrils that organize horizontally as elaunin fibres and vertically as oxytalan fibres.
The hypodermis (subcutaneous tissue) is a layer of loose connective tissue of variable thickness that merges with the deep aspect of the dermis. It is often adipose, particularly between the dermis and musculature of the body wall ( Fig. 7.18 ). It mediates the increased mobility of the skin, and its adipose component contributes to thermal insulation, acts as a shock absorber and constitutes a store of metabolic energy. Subcutaneous nerves, vessels and lymphatics travel in the hypodermis, their main trunks lying in its deepest layer, where adipose tissue is sparse. In the head and neck the hypodermis also contains striated muscles, e.g. platysma, which are remnants of more extensive sheets of skin-associated musculature found in other mammals (panniculus adiposus). FLOAT NOT FOUND
The amount and distribution of subcutaneous fat varies according to gender: it is generally more abundant and more widely distributed in females, whereas it diminishes from the trunk to the extremities in males. The total amount of subcutaneous fat tends to increase in both males and females in middle age. (At any age, the amount of adipose tissue reflects the quantity of lipid stored in adipocytes rather than a change in the number of cells.) There is an association with climate (rather than ancestry): superficial fat is more abundant in colder geographical regions. The hypodermis is most distinct on the lower anterior abdominal wall, where it is rich in elastic tissue and appears many-layered as it passes through the inguinal regions into the thighs. It is well differentiated in the limbs and the perineum, but is thin where it passes over the dorsal aspects of the hands and feet, the sides of the neck and face, around the anus, and over the penis and scrotum. It is almost absent from the external ears and atypical in the scalp and in the palms and soles.
The layers of the skin, including the subcutaneous tissues are tethered tightly together by connective tissue bands, the retinacula cutis ( Fig. 7.19 ), forming densely packed ligament-like structures in some parts (Herlin et al 2014).
The pilosebaceous unit consists of the hair and its follicle with an associated arrector pili muscle, sebaceous gland and sometimes an apocrine gland (see Fig. 7.1 ; Fig. 7.20 ). Not all elements of the unit occur together in all body regions.
Hairs are filamentous cornified structures present over almost the entire body surface. They grow out of the skin at an angle (see Fig. 46.1 ), as is evident in the sloping of the hairs on the dorsum of forearm, hand and fingers towards the ulnar side. Hairs are absent from several areas of the body, including the thick skin of the palms, soles, the flexor surfaces of the digits, the thin skin of the lip, umbilicus, nipples, glans penis and clitoris, the labia minora and the inner aspects of the labia majora and prepuce. The presence, distribution and relative abundance of hair in certain regions such as the face (in males), pubis and axillae, are secondary sexual characteristics that play a role in socio-sexual communication. There are individual variations in density, form, distribution and pigmentation. Hairs assist in thermoregulation, e.g. on the scalp they provide some protection against injury and the harmful effects of solar radiation. They also have a sensory function.
Hair density varies from approximately 600 per cm 2 on the face to 60 per cm 2 on the rest of the body. In length, hairs range from less than a millimetre to more than a metre, and in width from 0.005 to 0.6 mm. They can be straight, coiled, helical or wavy, and differ in colour depending on the type and degree of pigmentation. Curly hairs tend to have a flattened cross-section, and are weaker than straight hairs. Over most of the body surface, hairs are short and narrow (vellus hairs) and in some areas these hairs do not project beyond their follicles, e.g. in eyelid skin. In other regions they are longer, thicker and often heavily pigmented (terminal hairs); these include the hairs of the scalp, the eyelashes and eyebrows, and the postpubertal skin of the axillae and pubis, and the moustache, beard and chest hairs of males. The presence in females of coarse terminal hairs in a male-like pattern is termed hirsutism and can be familial or a sign of an endocrine disorder involving excess androgen production.
The hair follicle (see Figs 7.1 , 7.20 ; Fig. 7.21A ) is a downgrowth of the epidermis containing a hair. It may extend deep (3 mm) into the hypodermis, or may be superficial (1 mm) within the dermis. Typically, the long axis of the follicle is oblique to the skin surface; with curly hairs it is also curved. There are cycles of hair growth and loss, during which the follicle presents with different appearances. In the anagen phase, the hair is actively growing and the follicle is at its maximal extent of development. In the involuting or catagen phase, hair growth ceases and the follicle shrinks. During the resting or telogen phase, the inferior segment of the follicle is absent. This is succeeded by the next anagen phase. Further details of the hair growth cycle are given below.
The anagen follicle has several regions. The innermost part is the inferior segment, which includes the hair bulb region extending up to the level of attachment of the arrector pili muscle at the follicular bulge. Between this point and the site of entry of the sebaceous duct is the isthmus, above which is the infundibulum, or dermal pilary canal, which is continuous with the intraepidermal pilary canal. Below the sebaceous duct, the hair shaft and follicular wall are closely connected, and towards the upper end of the isthmus the hair becomes free in the pilary canal. Below the infundibulum, the follicle is surrounded by a thick perifollicular dermal coat containing type III collagen, elastin, sensory nerve fibres and blood vessels, and into which the arrector pili muscle fibres blend. A thick, specialized basal lamina, the glassy membrane, marks the interface between dermis and the epithelium of large hair follicles.
The hair bulb forms the lowermost portion of the follicular epithelium and encloses the dermal hair papilla of connective tissue cells ( Fig. 7.21B ). The dermal hair papilla is an important cluster of inductive mesenchymal cells, which is required for hair follicle growth in each cycle throughout adult life; it is a continuation of the layer of adventitious mesenchyme that follows the contours of the hair follicle. The hair bulb generates the hair and its inner root sheath. A hypothetical line drawn across the widest part of the hair bulb divides it into a lower germinal matrix and an upper bulb. The germinal matrix is formed of closely packed, mitotically active pluripotential keratinocytes, among which are interspersed melanocytes and some Langerhans cells. The upper bulb consists of cells arising from the matrix. These migrate apically and differentiate along several lines. Those arising centrally form the hair medulla. Radially, successive concentric rings of cells give rise to the cortex and cuticle of the hair and, outside this, to the three layers of the inner root sheath. The latter are, from innermost to outer, the cuticle of the inner root sheath, Huxley's layer and Henle's layer. Henle's layer is surrounded by the outer root sheath, which forms the cellular wall of the follicle (see Fig. 7.21 ). Differentiation of cells in the various layers of the hair and its inner root sheath begins at the level of the upper bulb and is asynchronous, beginning earliest in Henle's layer and Huxley's layer.
Become a Clinical Tree membership for Full access and enjoy Unlimited articles
If you are a member. Log in here