Skin Main Functional Areas The skin can be divided into three main functional areas. These are the: epidermis – the major protective layer derived from the fetal ectoderm; dermis – the major support layer – of mesodermal original; skin appendages composed of cells derived from both ectoderm and mesoderm (hair follicle, sebaceous gland, apocrine sweat gland, eccrine sweat gland, and nails). in addition a fourth area, the subcutaneous fat, may be involved in deeply situated skin lesions such as erythema nodosum.
The Epidermis Four main layers and sometimes another one additional : cornified or horny layer - outer non-nucleated barrier layer; granular layer – the zone where epidermal nuclei disintegrate; spinosus or prickle cell layer – the bulk of the living epidermal keratinocytes; bazal layer – the only keratinocytes in normal epidermis which undergo cell division. These layers are best seen if a piece of thick, weight-bearing skin, such as that from the sole of the foot, is examined under the microscope. In this skin, a fifth layer can sometimes be seen just above the granular layer – the stratum lucidum.
Cell Types Seen in the Epidermis keratinocyte – the main cell type; melanocyte – found in the basal layer, the pigment-producing cell; Langerhans cell – found in the mid- dermis – an important immunologically competent cell; Merkel cell – found in the around the basal layer. A member of the amine precursor uptake and decarboxylation (APUD).
The keratinocyte The keratinocyte forms the great bulk of the cells in the epidermis. In normal skin, keratinocyte division takes place only in the basal layer, so mitotic figures should not normally be seen above this level. After cell division, one daughter keratinocyte remains in the basal layer and the other moves upwards through the epidermis. The keratinocyte is committed to terminal differentiation and death. Within the prickle cell layer, highly specialized cellular bridges, called desmosomes connect the keratinocytes to each other, and these can frequently be seen under the light microscope at high power. There are no desmosomes between keratinocytes and melanocytes, or Langerhans cells, or Merkel cells. There are hemidesmosomes between the basal layer keratinocytes and the underlying basement membrane. In the granular layer, the living keratinocytes are involved in a complex series of biochemical changes during which the cell nuclei disintegrate, forming the granules seen in the cytoplasm. Above this level there is the non-nucleated stratum corneum, or cornified layer.
Epidermis Development and Maturation Development and maturation of normal healthy epidermis in this pattern is called ortokeratosis, and produced an outer layer of non-nucleated, dead, flat keratinocytes. In some diseases the maturation pattern is different, and there is no granular layer, but an outer layer of nucleated squamous cells - that pattern is parakeratosis (psoriasis). It is calculated that the transit time for a daughter keratinocyte in the basal layer of normal skin to reach the outer surface is around days. In psoriasis this is reduced to 8-10 days.
The Epidermis Strength The strength of the epidermis depends on the cohesion of the keratinocytes. They produce a structural protein, alpha-keratin, which aggregates to form tonofilaments. These tonofilaments are continuous with the desmosomes and are easily seen in the electron microscope as large cytoplasmic bundles. Another communication channel between keratinocytes is a gap junction, tiny channels, which connect the cytoplasm of neighboring cells to each other.
Keratin synthesis abnormalities Normally, the basal layer of the epidermis synthesizes keratin 5 and 14 Genetic disturbances in the genes coding for these keratin causes the disease epidermolysis bullosa simplex While the suprabasal keratinocytes synthesize keratin 1 and 10, and abnormalities give rise to bullous ichthyosiform erythroderma or epidermolytic hyperkeratosis.
ICAM; HLA-antigens Cell adhesion molecules – ICAM – is expressed on the surface of keratinocytes and forms one half of a lock and key arrangement between these keratinocytes and lymphocytes. In the normal epidermis, the only cells that normally express the MHC class 2 antigens HLA-DR, -DP, and – DQ are the Langergans cells.
The melanocyte The melanocyte has multiple dendrites and these dentritic processes stretch between adjacent keratinocytes. On facial skin there may be as many as one melanocyte for every five basal layer keratinocytes, but in the lower back skin this ratio is usually closer to one in 20. Numbers of melanocytes are the same in equivalent body sites in white and black skin, but the rate of production of pigment and its distribution is different.
Melanin synthesis Melanocytes synthesize the pigment melanin. Melanin granules are seen on ultrastructural examination as small, black, electron-dense, intracytoplasmic structures – the melanosomes. The pigment is formed from DOPA on premelanosomes and this biochemical reaction is catalyzed by the presence in the melanocyte of the enzyme dopa-oxidase and tyrosinase, which are not present in surrounding keratinocytes or other non-melanocytic cells.
Other epidermal cells The Langerhans cells are immunologically competent and may act as antigen present cells. L.C. in normal skin is the only cell to express MNS class 2 antigens and carry receptors for complement. The Merkel cells– their exact normal function is not known but is thought to be related to cutaneous sensation.
The basement membrane The basement membrane divides the epidermis from the dermis, and is a complex multi-layered structure. Hemidesmosomes attach the basal layer keratinocytes to the lamina lucida (laminin here) area. Below this level is the sub-basal dense plate through which anchoring filaments (type 7 collagen here) connect the lamina lucida to the lamina densa (type 4 collagen here).
The dermis The dermis is organized into two distinct areas: the papillary dermis – superficial zone beneath the epidermis with thin, delicate colagen fibers and is highly vascularized; the reticular dermis: composes the bulk of the dermis, is less vascular and demonstrates thick, well-organized collagen bundles
Dermis Cells There are tree main cell types in the dermis: the fibroblast – responsible for making collagen, elastin and proteoglycans; the macrophage – acts as a general scavenger; The mast cell – an important cell in type 1 immunological reactions and interactions with the eosinophil.
Components of the dermis Collagen fibers (70-80%) for resiliency Elastic fibers (1-3%) for elasticity Proteoglycans (primarily hyaluronic acid) to maintain water within the dermis and compose amorphous ground substance around collagen and elastic fibers.
Other dermal components Vasculature - the blood supply to both epidermis and dermis is through a very rich anastomosing superficial and deep plexus of small blood vessels. Lymphatics - in normal skin the lymphatic drainage system is not visible, but this is also a profuse network, running from the reticular dermis to the local lymph nodes. Nerves – both free nerve endings and specialized receptors will be seen in the dermis. These nerve endings are important for the sense of touch, heat, cold, pain, itch mecanical stimuli. Striking specialized corpuscular receptors, the Pacinians and Meissners, serve as mechanoreceptors for pressure and vibration. Smooth and striated muscle in small quantities
The skin appendages The pilosebaceous unit The eccrine sweat glands The nails. The pilosebaceous unit includes the: hair follicle sebaceous gland erector pili muscle apocrine gland in some sites, for example axilla.
The hair follicle Is the result of interaction between downgrowth of fetal ectoderm, which will form the hair shaft, and the vascular hair bulb papilla, which is derived from fetal mesoderm. The hair shaft itself is a complex multilayered structures with an outer cortex and an inner medulla. There are three recognizable types of hair: the coarse terminal hairs of the scalp the coarse terminal hairs of the scalp the androgen-dependent terminal hair on the male chin, in the axilla, and the pubic region the androgen-dependent terminal hair on the male chin, in the axilla, and the pubic region and a fine growth vellous hair on all body sites. and a fine growth vellous hair on all body sites. Three hair phases: anagen, catagen and telogen. At any time 80 per cent of scalp hair is growing in anagen, and the remaining 20 per cent either resting – in catagen – or being shed – in telogen.
The sebaceous glands Are clusters of cells with a small dark nucleus and a foamy cytoplasm. They cluster around the hair shafts and their secretion is formed by total destruction of the cells, a mechanism called holocrine secretion. This secretion drains into the hair follicle and is discharged on the surface through the hair follicle opening. Sebaceous glands are seen in large numbers on the face, chest, and upper back.
The apocrine sweat glands Are found predominantly in the axilla, with a few seen also in the skin of the groin. They have a secretory component seen in the deeper dermis. The secretory section has a very wide lumen, and the cells lining this lumen will be seen to be composed of columnar epithelium which appears to form glandular secretion by a nipping off of the tops of the cells, a process known as decapitation (holo-merocrine) secretion. The excretory channels of the apocrine glands most commonly drain into the canal of the hair shaft and sebum passes from here out on to the surface of the epidermis.
The eccrine sweat glands Are seen at all body sites (excepting lips, nailbeds and glans penis) and are anatomically independent from the other appendages. Their secretory components are much smaller than those of the apocrine gland, with a smaller lumen. The excretory duct of these gland winds upward in a spiral pattern through the dermis and epidermis to the surface; type of secretion – merocrine without cell destruction.
The nails Are very highly modified skin appendages. The nail itself, or nail plate, grows out from the nail matrix and rests on the underlying nail bed. The pale halo at the proximal end of the nail is called the lunula, and around the edge of this there is a protective rim of cuticle. Nails may become involved in a number of skin diseases, such as psoriasis and fungal infection. The average time for a fingernail to grow out completely from base to outer edge is approximately 6 months, and for toenails the time is 6-18 months or even longer.
The subcutaneous fat The subcutis, or subcutaneous fat, is arranged into distinct fat lobules which are divided by fibrous septae composed primarily of collagen. Blood vessels, nerves and lymphatics are also found in the fibrous septae.
The skin functions Two main functions of epidermis: keratin-genesismelanin-genesis Other three important functions of epidermis: barrier function (toxins, UV, etc.) prevention of desiccation immune surveillance (Langerhans cells)
The skin functions Two main functions of epidermis: Temperature regulation through control of cutaneous blood flow and sweating, achieved by dermal vessels and eccrine sweat glands Mechanical protection of underlying structures, achieved primarily by the collagen and hyaluronic acid. Three main functions of subcutis: Caloric reserve Heat insulator Shock absorber