A number of different cells are found within the skin, with functions ranging from provision of structure through sensation, protection, and immunity. Langerhans cells are part of the macrophage/monocyte cell lineage and are antigen-presenting cells involved in immunity. Mast cells are found in the dermis and function as part of an allergic response. They are derived from bone marrow precursor cells. Activation of mast cells leads to histamine release and activation of various cytokines including interleukins, leukotrienes, and prostaglandins. These serve to increase vascular permeability, smooth muscle contraction and tissue inflammation. Merkel cells are found in the epidermis, and provide constant touch and pressure sensation. They are thought to be of neuroendocrine origin and are clinically relevant in that they can undergo malignant change resulting in an aggressive form of skin cancer. The keratinocyte is the predominant cell of the epidermis and provides a protective physical barrier and UV protection by the uptake of melanin produced by melanocytes. Schwann cells are found covering myelinated nerves and these tend to run within the subcutis, but may be found in the dermis. They serve to increase nerve conduction velocity.1
2. Which one of the following represents an epidermal cell that provides UV protection and pigmentation to the skin? Melanocytes are derived from the neural crest and have a key role in UV protection and skin pigmentation. They are responsible for the production of melanin which is a pigment produced in melanosomes. A common misunderstanding is that melanocytes retain the melanin pigment and are solely responsible for the increased skin pigmentation with tanning. However, it is the increased uptake by keratinocytes, following increased production by the melanocytes, that provides the increased skin pigmentation. The keratinocyte is the predominant cell of the epidermis and provides a protective physical barrier and UV protection by the uptake of melanin produced by melanocytes. Fibroblasts are the building blocks of the dermis and are responsible for collagen production. Macrophages are specialized cell types derived from blood monocytes that leave the circulation to differentiate in different tissues. They are involved in the detection, phagocytosis, and destruction of bacteria and other harmful organisms. In addition, they can also present antigens to T cells and initiate inflammation by releasing cytokines that activate other cells. Adipocytes are fat cells found within the subcutis. Their main role is lipid storage but also have roles within endocrine, nervous, and immune system function.1
All of the options are involved in skin sensation. The Meissner’s corpuscle is involved in light touch and dynamic two-point discrimination. It represents a type of unmyelinated nerve ending most commonly found in the fingertips and lips. A reduction in the number of Meissner’s corpuscles is observed with increasing age and may be partly responsible for age-related changes in manual dexterity.1 Naked nerve fibers or free nerve endings are the simplest of sensory receptors and are located along the dermoepidermal junction. They consist of multiple small terminal branches of afferent nerves and provide a primitive function for temperature, touch, and pain sensation. Merkel cells are associated with free nerve endings, particularly in thicker skin. They are also involved with constant touch and pressure sensation, providing a static two-point discrimination. Pacinian corpuscles are large sensory receptors involved in pressure, coarse touch, vibration, and tension. They are located in the deeper layers of the skin as well as in ligaments and joint capsules and have the appearance of an onion on microscopy. Pacinian corpuscles can be recognized when operating around nerve fibers and can be useful to guide dissection when trying to identify damaged or divided nerves, particularly in the palm and digits. Ruffini corpuscles are spindle shaped structures on microscopy found most often in the foot soles. They are associated with pressure and touch sensation.2
Eccrine sweat glands are found within the skin throughout the body and are involved in thermoregulation by the production of watery hypotonic fluid, whereas apocrine glands produce thickened secretions in the axilla and groin. These are involved in conditions such as hidradenitis suppurativa where patients have recurrent infective episodes affecting the axilla or groin. Ruffini endings are slow adapting mechanoreceptors found in the skin and are high in density in the nail bed region and foot sole. The bulb of Krause are bulbous capsules in the skin containing sensory nerve endings, which may be mechanoreceptors, but which are also thought to be thermoreceptors specifically sensitive to cold. They become activated by temperatures less than 20° C. They occur more superficially in the skin than heat receptors. Sebaceous glands are usually found in association with hair follicles, the so-called “pilosebaceous unit” and are responsible for the secretion of sebum. Ectopic sebaceous glands without attached follicles may be found as tiny yellow papules near mucocutaneous junctions, particularly the upper lip, and in the buccal mucosa (Fordyce’s spots). They may also be found in the areolae of the breasts, where they are known as Montgomery’s tubercles. Like Fordyce’s spots, the sebaceous gland in a Montgomery’s tubercle opens directly onto the surface.1
The epidermis consists of four or five layers, depending on the anatomic location. The layers from superficial to deep may be remembered using the mnemonic “come let’s get some beer.” The layers are as follows: stratum corneum, stratum lucidum, stratum granulosum, stratum spinosum, and stratum basale. The upper two layers contain nonviable keratinocytes, while the deepest two layers consist only of viable keratinocytes. The stratum granulosum is the transition zone and is three to four layers thick. It contains both viable and nonviable cells. It has clinical relevance in melanomas as the Breslow thickness is measured from this layer to the deepest part of the tumor. The stratum corneum and stratum lucidum do not contain viable cells. The stratum basale is a single layer and contains melanocytes, tactile cells, granular dendrocytes, and mitotically active keratinocytes. The stratum spinosum contains only viable keratinocytes. The stratum lucidum is translucent but is not present in the axilla or face (Fig. 16.1).1
The stratum corneum or cornified layer of the skin is only found in glabrous areas which are the sole of the foot and palm. These areas represent the thickest areas of skin and provide excellent protective function. Sometimes these areas are used as skin graft donor sites when palm or foot sole defects are being reconstructed. Two passes are required with the dermatome. The first pass removes the superficial layer of keratinocytes and the second removes a deeper layer used as a graft. The original layer is then replaced on the donor site.
Ground substance is an amorphous transparent material with a semifluid gel consistency. It allows metabolite diffusion and comprises glycosaminoglycans in the form of hyaluronic acid and proteoglycans. Hyaluronic acid is an important component of ground substance and is used as an injectable filler to plump out the dermis for management of rhytids, for filling contour deformities or replacing volume loss with age. The dermis comprises two layers: the more superficial papillary dermis and the deeper reticular dermis. The ratio of collagen types I to III differs according to dermal layer, with the papillary dermis having a higher concentration of type III collagen. Dermal thickness has significant variability according to the anatomic location. The scalp, back, palms, and foot soles are generally thickest and the eyelids are thinnest. The papillary dermis is much thinner than the reticular dermis (approximately 1/20th) and has a thickness more similar to the epidermis. Mature elastic fibers are only present in the reticular dermis. Understanding of the different skin layers and being able to recognize them clinically is useful when managing trauma injuries such as burns. Burns are classified according to depth and can be first degree, second degree, or third degree. First degree burns do not involve the dermis and heal quickly. Third degree burns involve the entire dermis and adnexal structures and have a prolonged healing time that means they are usually excised and skin grafted. Second degree burns can be either superficial or deep and will involve different levels of the dermis. In general, the more superficial dermal burns can heal within a few weeks because the dermal appendages are present and facilitate re-epithelialization. In deeper dermal burns this will not be possible and they are generally treated the same as full-thickness burns. Fig. 16.1 Layers of the skin with adnexal structures. Stratum corneum Stratum lucidum Stratum granulosum Stratum spinosum Stratum basale Papillary dermis Reticular dermis Dermis Epidermis Hypodermis
Collagen is a protein that forms the key building blocks for skin, bone, cartilage, and tendon. The basic structure consists of three left-handed polypeptide helices wound together to form a right-handed helix. Collagen comprises of two alpha-1 and one alpha-2 chains; each of these are formed by amino acid sequences, glycine-prolene-X and glycine-X-hydroxyprolene. There are more than 20 types of collagen and of these, type I represents 90% of the body total. Type II is found in the cornea and hyaline cartilage. Other important types are III and IV. Type III predominates in immature wounds, vessel, and bowel walls. Type IV is found in the basement membrane (Table 16.1). Table 16.1 Five Types of Collagen Type Structure Distribution Type I Hybrid of two chains Bone Low in hydroxyzine and glycosylated hydroxyzine Tendon Skin Dentin Ligament Fascia Arteries Uterus Type II Relatively high in hydroxyzine and glycosylated hydroxyzine Hyaline cartilage Eye tissues Type III High in hydroxyzine Skin Contains interchain disulfide bonds Arteries Uterus Bowel wall Type IV High in hydroxyzine and glycosylated hydroxyzine Basement membrane May contain large globular regions Type V Similar to type IV Basement membrane
Cutis laxa is a very rare condition associated with degeneration of elastic fibers in the dermis. The name is derived from Latin meaning “loose skin” as it results in hyperextensible skin with the appearance of premature aging. It can be autosomal dominant, recessive, or crosslinked and in general recessive inheritance results in the most severe form. It is often most noticeable on the face, neck, axilla, and groin. It can also affect connective tissues of the lungs, heart, vessels, and joints. In spite of this, wound healing is normal and it is considered safe to proceed with surgery. In contrast, the other options are all associated with abnormal wound healing. Deficiencies in iron, copper, and vitamin C all interfere with collagen production. Cutis hyperelastica is also known as Ehlers-Danlos syndrome and is a connective tissue disorder with abnormal collagen cross-linking resulting in poor wound healing and thin friable skin. Hutchinson-Gilford and Werner’s syndromes are both types of progeria (premature aging conditions) and wound healing is impaired.
Ehlers-Danlos syndrome is also known as Cutis hyperelastica. It has an incidence of 1:400,000, with variable inheritance patterns. It is a connective tissue disorder with an abnormality of collagen cross-linking. This results in hypermobile joints and thin, friable, and hyperextensive skin. Patients have poor wound healing and a tendency for hypertrophic scarring. Surgery should be avoided when possible. Cutis laxa is a rare connective tissue disorder in which the skin becomes inelastic and hangs loosely due to degeneration of elastic fibers, but healing is normal. Parkes-Weber syndrome is characterized by an extremity port-wine stain with a deeper venous and lymphatic malformation and an arteriovenous fistula. Pseudoxanthoma elasticum is a condition with a combination of cutaneous, ocular, and cardiac manifestations. Skin manifestations include yellow plaques that typically involve the neck, first appearing in adolescence. Progeria is a rare autosomal recessive condition with features of premature aging in children. Patients first present with signs such as failure to thrive and retarded growth. They display abnormal skin laxity and loss of subcutaneous fat associated with poor wound healing.
Pseudoxanthoma elasticum is a progressive disorder characterized by the accumulation of deposits of calcium and other minerals (mineralization) within elastin fibers. A common finding is the presence of yellow colored plaques to the neck, axillae, and flexor surfaces of joints, which first appear in adolescence. Because the mineralization can affect elastin fibers throughout the body, the manifestations of pseudoxanthoma elasticum include ocular, cardiovascular, and gastrointestinal problems. Hutchinson-Gilford syndrome is also known as progeria, an autosomal recessive condition associated with premature aging in children. It is very rare with an incidence of 1:1,000,000 and patients first present with signs such as failure to thrive, retarded growth, craniosynostoses, micrognathia, baldness, and prominent ears. They display abnormal skin laxity and loss of subcutaneous fat associated with poor wound healing. Cutis laxa is also known as elastolysis and is extremely rare with only a few hundred cases reported worldwide. It is a hypoelastic condition with degeneration of elastin fibers so the skin loses its elastic recoil and becomes hyperextensible. This gives an appearance of premature aging and is associated with an increased risk of ventral hernia and cardiopulmonary problems. However, hound healing remains normal. Werner’s syndrome (also known as adult progeria) is also a rare autosomal recessive condition with features of premature aging. Other associated features include altered skin pigmentation, microangiopathy, diabetes, scleroderma-like skin, and a high-pitched voice. Wound healing is affected by this condition and elective surgery should be preferentially avoided.