Anatomy, Physiology, and Embryology

Embryology of the Skin

The human skin develops from two special embryonic tissues, the ectoderm and the mesoderm. Epidermal tissue is derived from the embryonic ectoderm. The dermis and subcutaneous tissue are derived from the embryonic mesoderm. The developmental interactions between mesoderm and ectoderm ultimately determine the nature of human skin. Interestingly, neural tissue and epidermal tissue are both derived from the ectoderm. It is believed that calcium signaling is critical in determining the fate of the ectoderm and its differentiation into either epidermis or neural tissue.

At approximately 4 weeks after conception, a single layer of ectoderm is present, surrounding a thicker layer of mesoderm. Two weeks later, this ectodermal layer has separated into two different components: an outer periderm and an inner basal layer, which is connected to the underlying mesoderm. At 8 weeks after conception, the epidermis has developed into three separate layers: the periderm, an intermediate layer, and the basal cell layer. The dermal subcutaneous tissue is now beginning to develop, and a distinct dermal subcutaneous boundary can be seen by the end of the eighth week. Between weeks 10 and 15 after conception, the beginning of the skin appendages can be seen.

The formation of hair follicles is initiated by a complex genetic mechanism that causes the dermis to direct certain basal epidermal cells to congregate and form the rudimentary hair follicle. This process occurs in a highly organized fashion beginning from the scalp and working caudally to the lower extremity. At the same time, the hair follicles are developing and the dermal papillae are beginning to form. The hair follicles continue to differentiate throughout the second trimester, and the hair of the fetus can be seen at approximately 20 weeks after conception. This first hair is known as lanugo hair and is almost always shed before delivery.

The fingernails and toenails develop from ectoderm that invaginates into the underlying mesoderm by the fourteenth week after conception. By the fifth month, the fetus has fully developed fingernails and toenails. The fingernails fully develop slightly before the toenails.

Melanocytes are specialized cells derived from neural crest tissue. These cells form along the neural tube. Melanocytes migrate in a specific pattern laterally and then outward along the trunk. Melanocytes can be seen in the epidermis by the middle of the first trimester, but they are not functional until the end of the second trimester. The density of melanocytes is highest during the fetal period and decreases thereafter until young adulthood. Melanocytes are beginning to make their first melanosomes and are capable of transferring melanin pigment to adjacent keratinocytes by approximately 5 months after conception. Melanocytes are not fully functional until birth. Langerhans cells are specialized immune surveillance cells that appear within the epidermis at approximately 40 days after conception. In contrast to melanocytes, the density of Langerhans cells increases with time.

By late in the second trimester, the periderm begins to shed. This shedding results in the vernix caseosa, a whitish, cheese-like material that covers the fetus. It is believed to have a protective function. At the beginning of the third trimester, the individual epidermal layers can be seen, including the stratum basale, stratum granulosum, stratum spinosum, and stratum corneum. Keratinization begins to occur during the second trimester, first in the appendageal structures and then in the epidermis. The thickness of the epidermis in a newborn closely approaches that in an adult. The significant difference is that the skin barrier function in a newborn is not as fully developed as in an adult and therefore is more vulnerable to infection and external insults.

By studying the embryology of the skin, one can gain insight into the mechanisms of certain genetic disorders. For example, one of the more studied groups of genetic diseases are the congenital blistering diseases. The various types of epidermolysis bullosa are all caused by genetic defects in proteins responsible for adhesion of keratinocytes. A firm understanding of the embryology of skin development is essential for understanding the pathogenesis of these diseases and ultimately for developing a mechanism to detect and therapeutically treat them.

Normal Skin Anatomy

The human skin, taken collectively, is the largest organ in the human body. On average, it weighs between 4 and 5 kg. It is vitally important to life. The skin is made up of three distinct layers: the epidermis, the dermis, and the subcutaneous tissue; some anatomists do not include the subcutaneous tissue as part of the skin and classify it separately as the hypodermis. Each of these layers plays a pivotal role in the execution of day-to-day functions of the skin. The skin's main function is to protect the interior of the body from the exterior environment. It performs this role in many fashions: It acts as a semipermeable barrier to both hydrophilic and hydrophobic substances; it is the first line of immunological defense against invading microbes; it contains many components of the adaptive and innate immune system; and it has many physiological roles, including metabolism of vitamin D.

The majority of the epidermis is made up of keratinocytes. It also contains melanocytes, Langerhans cells, and Merkel cells. The epidermis is avascular and receives its nutrition from the superficial vascular plexus of the papillary dermis.

Melanocytes are derived from neural crest and are responsible for producing the melanin family of pigments, which are packaged in melanosomes. Melanocytes are found in equal density in all humans, but darker-skinned individuals have a higher density of melanosomes than those with lighter skin. This is the reason for color variation among humans. Eumelanin, the predominant type of melanin protein, is responsible for brown and black pigmentation. Pheomelanin is a unique variant of melanin that is found in humans with red hair.

The skin is found in continuity with the epithelial lining of the digestive tract, including the oral mucosa and the anal mucosa. Distinct transition zones are seen at these interfaces. The skin also abuts the conjunctival mucosa of the globe and the mucosa of the nasal passages. The skin and its neighboring epithelial components supply the human body with a continuous barrier to protect it from the external world.

Many appendageal structures are present throughout the skin. The major ones are the hair follicles, their associated sebaceous glands, and the eccrine glands. Most of the skin is hair bearing. Fine vellus hairs make up the preponderance of the skin's hair production. Terminal hairs are much thicker and are found on the scalp, eyebrows, and eyelashes; in the axilla and groin areas; and in the beard region in men. Glabrous skin, which is devoid of hair follicles, includes the vermilion border of the lips, the palms, the soles, the glans penis, and the labia minora.

Human skin varies in thickness. It is thickest on the back, and the thinnest areas are found on the eyelids and the scrotum. Regardless of thickness, all skin possesses the same immunological function and barrier activity.

Various appendageal structures are found in higher densities in certain regions of the skin. Sebaceous glands are located predominantly on the face, upper chest, and back. These glands play an instrumental role in the pathomechanism of acne vulgaris. Because sebaceous glands are attached to hair follicles, they are found only on hair-bearing skin. Eccrine sweat glands, on the other hand, are found ubiquitously. The highest densities of eccrine glands are on the palms and soles. The other main sweat glands of the skin, the apocrine glands, are found almost exclusively in the axillae and the groin. The apocrine glands, like sebaceous glands, are found only in conjunction with hair follicles.

Nails are composed of specialized keratin proteins. These keratins make a hard nail plate that is believed to be important for protection, grasp, and defense. Fingernails and toenails are made of the same keratin structure and in the same manner. The only difference is that the fingernails grow slightly faster than the toenails. The average thumbnail takes 6 months to replace itself, whereas the average great toenail takes 8 to 12 months.

Skin is also an important means of communication with other humans. The sense of touch is mediated through specialized receptors within the skin. One cannot underestimate the importance of this function in the formation of human relationships.