1
Skin Structure and Biology

Wei-Meng Woo

Nanyang Technological University, Lee Kong Chian School of Medicine, Clinical Sciences Building, 11 Mandalay Road, Singapore, 308232, Singapore

1.1 Introduction

The integument system of an animal serves as a boundary to protect the interior organs from external assaults, prevents the loss of heat and water, and maintains osmotic pressure. The simplest form of integument is exemplified by the diploblastic (two germ layers: ectoderm and endoderm) body plan of cnidarians, such as hydra, whose single-cell layered ectoderm (integument) supports and protects its endoderm (guts: internal organ). In vertebrates, the integument include skin and specialized structures derived from the skin. These skin-derived specialized structures range from scales in reptiles, feathers in birds, to furs/hairs in mammals. Hairs, nails, claws, sweat glands, and teeth are skin derivatives and are also part of the integument of vertebrates [1,2]. Analogous to the diploblastic animals, in these triploblastic (three germ layers) animals, their ectoderm (epidermis) and mesoderm (dermis) protect their endoderms (internal organs).

In human, skin constitutes 15-20% of the body mass, as such, it is the largest organ of the human body. As the outermost layer, the human skin acts as an interface between our body and the environment; it protects the underlying tissues and internal organs and also responds to external stimuli, avoiding dangers and injuries.

As a physical barrier, skin provides the first line of defense against environmental hazards. Skin protects our body from UV damage, chemical and mechanical assaults, injuries, and invasion of microorganisms. From the interior, skin protects our body from water loss, preventing dehydration, which could be life-threatening. Furthermore, skin contributes to body temperature regulation, which is achieved by sweating and insulation. Through sweating and a water barrier function, the skin helps maintain the balance of water and electrolytes. The skin is also a sensory organ; with its touch, thermal, and pain sensors, it informs the brain of changes in the immediate environment. In addition to a physical barrier, the skin's protection against microbes also come from the its immune response and production of pathogen fighting peptides [3]. On a different note, perhaps part of a protection function (for the bone), vitamin D is synthesized in the skin.

In this chapter, the structure and organization of the human skin and its cellular composition and functions, with additional focus on the formation of the stratified epidermis and of a water barrier, will be introduced.

1.2 Skin Structure

1.2.1 Overview of Skin Tissue Organization

The skin organ consists of three tissue layers: from the surface to the interior are the epidermis, dermis, and hypodermis. The organization of these three tissue layers is also reflected in their names: the "epi-"dermis sits on top of the dermis, and the "hypo-"dermis sits below the dermis. Historically, and still a well-recognized definition, the epidermis and dermis form the cutaneous tissue (Latin - cutis: the skin). Under this definition, the skin is composed of only epidermis and dermis, whereas the hypodermis is the subcutaneous tissue, which is not part of the skin. The cutaneous tissue rests on the hypodermis, which connects and anchors the cutaneous tissue to the underlying fascia [4,5].

In mammals, the epidermis is a form of stratified squamous epithelium, which means it is layered (stratified) and scale-like (squamous). This is in contrast to the simple epithelium that is single layer, which can be found as lining of internal organs such as lungs and livers. The epidermis consists mostly of epithelial cells that are commonly known as keratinocytes, which are protein-rich epithelial cells with abundant keratins and keratohyalin. Keratinocytes in the outermost epidermal layer are flatten and enucleated, forming a scale-like or cornified pattern that is water impermeable, thereby contributing the most prominent function for the skin: water barrier. The dermis is a connective tissue with fibroblast cells interspersed in a collagen - elastin-based extracellular matrix. Blood vessels, lymphatic vessels [6], nerve endings [7], and appendages including hair follicles, sebaceous glands, and sweat glands reside in the dermis. The hypodermis is composed of adipose tissue, which serves as energy storage and insulation for the body and serves as a cushion for the skin. It is also the origin of some blood vessels that extend to the dermis.

The epidermis and dermis are physically separated by a basement membrane. By contrast, dermis and hypodermis are not physically separated. The basement membrane consists of extracellular matrix components that the epidermis attaches to; this kind of attachment mechanically supports the epidermis. The epidermal-dermal junction undulates with finger-like projections of the dermis into the epidermis, forming a dermal pattern termed the dermal papilla. Fingerprints are the results of the ridges that formed by dermal papillae under our fingertips. In addition to providing mechanical support for the epidermis, dermis also supports the epidermis with nutrients via its blood vessels in the dermal papillae.

1.2.1.1 Thick Skin and Thin Skin

The human skin can be categorized as thick skin and thin skin, based on skin compositions, epidermal thickness, and epithelial layers, although the most earliest notable difference is the epidermal thickness. Thick skin is found in areas where abrasion occurs frequently, including the palms, soles, fingers, and toes. Thin skin covers a large proportion of the body, most of the thin skin have hairs, so thin skin is also known as hairy skin. By contrast, thick skin is hairless - they do not have hair follicles nor do they have sebaceous glands. However, thick skin has more sweat glands and sensory receptors than thin skin.

Figure 1.1 (a) Thick skin and (b) thin skin (hairy skin). Thick skins are found in the palms, soles, and at the surface of fingertips and toes. Thin skins cover most part of the body, and they contain hair follicles thus also known as hairy skins. While thick skin has thicker epidermis, their dermis is thinner, and they lack hair follicles, sebaceous glands and arrector pili muscle. In thick skin, there are more sensory receptors such as Meissner's and Pacinian corpuscles. APM: arrector pili muscle, SG: sebaceous gland. Red: arteriole, blue: venules, green: nerve fibers, Meissner's corpuscle (near epidermis).

As their names imply, thick skin is thicker than thin skin (Figure 1.1). The thickness of thin skin is around 1-2?mm, whereas thick skin can reach a thickness of 6?mm. This is prominent at the epidermis level where the thick skin epidermis is considerably thicker than thin skin epidermis. The individual epithelial layers of the thick skin are thicker than those layers in the thin skin, especially the outermost layer, the stratum corneum, which can become remarkably thick. Another distinct feature of thick skin is that they have five epithelial layers with a distinct stratum lucidum below the stratum corneum, while in thin skin there are four epithelial layers (Figure 1.1 and Section 1.2.2 ). Underneath the epidermis, dermal papillae in thick skin are more regular and deeper than those in thin skin, although dermis of thick skin is relatively thinner.

The thickness of human skin varies at different body locations [8-12]. The thickness of human epidermis ranges from 0.05 to 1?mm, whereas the dermis is about 1-2?mm thick. The thinnest skin is found on the eyelids: the epidermis of eyelids is 0.04?mm, the dermis of eyelids is 0.3?mm. In contrast, the epidermis of the palms and soles is 1.6?mm, whereas the dermis on the back reaches 3?mm.

1.2.2 Epidermis

As mentioned in the overview (Section 1.2.1 and subsection 1.2.1.1), the human epidermis is a stratified squamous epithelium and is categorized as thin and thick skins. The epidermis in thin skins consists of four layers of epithelial cells, while in thick skins there are five layers of epithelial cells (Figure 1.2). In thin skin, from the bottom to the top, or from deep to superficial, the epidermal layers are the stratum basale (basal cell layer), stratum spinosum (spinous layer or suprabasal layer), stratum granulosum (granular cell layer), and stratum corneum (cornified layer). In thick skin, an additional layer, the stratum lucidum, is present between strata granulosum and corneum. These five layers are further introduced in Subsections 1.2.2.1-1.2.2.5.

Figure 1.2 Schematic diagram of five epithelial layers in the epidermis of thick skin. The stratum lucidum is absent in thin skin. The epidermis is connected to the dermis via the basement membrane.

The stratified epidermis consists predominantly of epithelial cells known as keratinocytes, which express a substantial amount of keratin proteins that form keratin filaments and keratohyalin. At the epidermal layer level, keratinocytes of each epidermal layer are characterized by the expression of a specific pair of keratin proteins, usually a basic and an...