The integumentary system is an extraordinary body system, which includes the largest and most visible organ, the skin. The skin forms the integumentary system when combined with the accessory structures of hair, nails, and glands. As the only organ of the body, which is readily available to be inspected and judged by all, the skin’s very visible characteristics play a unique role in every individual’s well-being. A conceptual framework for recognizing and understanding diseases of the skin relies on principles of diagnosis common to medicine and nursing, namely, historical and social factors, physical examination, and laboratory techniques. To relate these principles of diagnosis and treatment to clinicopathologic events in dermatology, it is important to start with an overview of the skin. The skin is composed of three layers: epidermis, dermis, and subcutaneous fat accounting for 15% to 20% of the body’s weight (Figure 1-1). Disease may localize exclusively in one or all of these layers. There is considerable regional variation in the relative thickness of these layers. The more common skin conditions take into account a diverse spectrum of clinical pathology, which may be characterized by inflammation (noninfectious), pigmentary abnormalities, infection and infestation, benign and malignant cellular proliferations, and disease where the basic mechanisms are relatively obscure. To conceptualize skin disorders effectively, it is essential to consider the changes in the structure and function of the skin and to understand the specific clinical pathology related to the changes. The healthy integumentary system is a complex, dynamic system providing diverse functions (Table 1-1), including:

A. Protection

1. An intact stratum corneum provides a physical barrier against foreign substances and bacteria.

2. Mechanical strength is provided by intercellular bonding in the epidermis and collagen, elastin, and ground substance in the dermis.

3. Subcutaneous tissue acts as a shock absorber.

4. Melanin screens and absorbs ultraviolet radiation.

B. Homeostasis

1. The skin prevents dehydration through loss of internal fluids and electrolytes.

2. The skin limits absorption of external fluids and gases.

C. Excretion

1. The glands of the skin excrete waste products, in addition to sweat, which is mostly water and electrolytes.

2. The waste products excreted can include urea, lactic acid, bile, ammonia, and even alcohol.

D. Thermoregulation

1. Body temperature is controlled by:

a. Conduction of heat from the skin to the air or other objects

b. Radiation of heat from the body surface

c. Convection of heat by air currents

d. Evaporation of perspiration

2. The cutaneous vasculature plays an important role in body temperature regulation. Blood vessels:

a. Dilate when the external environment is warm to promote heat loss

b. Constrict in a cold environment to conserve heat

E. Vitamin D production

1. Ultraviolet light converts 7-dehydrocholesterol to vitamin D3 in the epidermis.

2. Vitamin D3 is converted in the kidneys into the active form of vitamin D.

F. Sensory perception

1. The system contains mechanoreceptors and unmyelinated nerve fibers.

2. Touch, pressure, temperature, pain, and itch are transmitted.

G. Psychosocial

1. The skin, nails, and hair influence sexual attraction, general well-being, and self-image. Outward expressions of anxiety, fear, and anger are visible through sweating, pallor, and flushing.

2. Different societies and culture greatly influence how one accepts or rejects outward appearance of this body system.

H. Wound healing

1. The skin can repair and regenerate itself.

2. These important wound healing abilities are influenced by multiple internal and external factors.

A. Epidermis (Figure 1-2)

1. The epidermis is the outermost structure of the skin. It:

a. Contains multiple layers of cells (stratified)

b. Has considerable regional variation, depending on the site:

(1) Thickest on palms and soles, approximately 1.5 mm

(2) Very thin on eyelid, less than 0.4 mm

c. Is without lymphatic and vascular channels, and connective tissue; therefore, it derives its nutritional support from the underlying dermis.

2. Keratinization:

a. The epidermis rejuvenates itself through the process of keratinization. Epidermal keratinization is the process of morphological and biochemical differentiation of the keratinocyte, beginning in the basal cell layer and ending in the stratum corneum as a horn or cornified cell.

3. Keratin:

a. Keratin, the major product of the cornified cell, is a highly resistant, insoluble, fibrous protein. It represents the end product of a differentiated epidermal keratinocyte.

b. Keratinization also involves synthesis of several other proteins and additional substances such as keratohyalin granules, which act as glue.

4. Layers of the epidermis:

a. There are five layers in the epidermis.

b. The layers are named to reflect the stage the keratinocytes are in during the process of keratinization.

c. These layers are not independent of each other but rather are interrelated and continuous phases of the life of a keratinocyte. Keratinocytes move up as they age (Figure 1-2).

(1) Germinating or basal cell layer (stratum basale, also called stratum germinativum): the basal cell layer is the innermost layer of the epidermis. It consists of a single layer of elongated cells. Each cell divides (mitosis) into two daughter cells. One remains as “basal cell,” the other migrates upward through the remainder of the epidermis.

(2) Prickle cell or spiny layer (stratum spinosum): the prickle cell layer consists of many rows of flattened polygonal cells that are held together by “prickles” or “spines.” These prickles are desmosomes, which are small thickenings in an intracellular bridge.

(3) Granular cell layer (stratum granulosum): the granular cell layer is most prominent on the palms and soles. It consists of one to three layers of flattened, irregularly shaped cells that have large numbers of keratohyalin granules. Keratohyalin granules comprise particulate materials that have a high sulfur-protein content. Keratinocytes lose their nucleus in this layer, thereby becoming nonviable.

(4) Glassy layer (stratum lucidum): the stratum lucidum is made up of one or more rows of distended irregular cells. It is an even, colorless, translucent, or shiny band. The stratum lucidum is almost nonexistent except on thicker skin areas such as palms and soles.

(5) Horny cell layer (stratum corneum): the horny cell layer consists of anucleated, cornified cells. They are also known as horn cells. The nucleus and other cytoplasmic organelles have been totally degraded. The remaining material is predominantly keratin. Other substances include water, water-insoluble proteins, amino acids, sugars, urea, minerals, and lipids. These act as buffers and lubricants.

(a) Cells of the epidermis are continuously being shed or desquamated from the stratum corneum.

(b) It takes approximately 14 days for the keratinocyte to travel from the basal cell layer to the stratum corneum. Once in the stratum corneum, it takes another 14 days before it is shed.

(c) New cells are formed in the basal cell layer at the same rate cells are shed in the stratum corneum.

5. Functions of the horny cell layer:

a. The stratum corneum serves many functions for the epidermis and the skin in general:

(1) It functions as the body’s major physical barrier by being relatively impermeable to water and electrolytes.

(2) It resists damaging chemicals, provides physical toughness, impedes passage of electrical
currents, and retards the proliferation of microorganisms through its relatively dry surface.

(3) The stratum corneum also functions as a reservoir for topical medications.

b. Although the stratum corneum is an effective barrier to most substances, some are able to pass through. Substances can be transported through the skin by three pathways:

(1) Through adnexal orifices (pilosebaceous unit) and sweat glands

(2) Through the intercellular spaces between the cornified cells

(3) Directly through the cornified cells

B. Cells in the epidermis

1. Keratinocytes account for at least 80% of the cellular components of the epidermis. They have the specialized function of producing keratin. During keratinization, the keratinocytes change shape (flatten), lose organelles, form fibrous protein (keratin), become dehydrated, and thicken their cell membrane (see discussion above).

2. Melanocyte cells:

a. Embryonic development: melanocytes are the pigment-producing cells of the epidermis. Embryonically, they are derived from the neural crest, and by the 8th week of development, melanocytes enter the epidermis. In the fetal epidermis, melanocytes are found at suprabasal levels. When the fetus is fully developed, they are located in the basal cell layer. Failure of the melanocyte to migrate to the basal cell layer results in entities such as blue nevus and mongolian spots.

b. Regional variation: melanocytes are present on all parts of the body with regional variation. There are more melanocytes on the face than on the abdomen. Ratios of melanocytes to keratinocytes vary from 1:4 to 1:10. Advancing age leads to a greater shift favoring keratinocytes.

c. Melanosome/melanin: within the cytoplasm of melanocytes are special organelles called melanosomes. Melanin is stored in the melanosome and is synthesized through the conversion of the colorless amino acid, tyrosine. There are two types of melanin. Eumelanins account for brown and black colors. Pheomelanins account for yellow to reddish brown colors.

d. Epidermal melanin unit: melanocytes are dendritic cells. Their dendrites extend for long distances in the epidermis. This allows one melanocyte to be in contact with many keratinocytes. The interaction of the melanocyte and keratinocyte forms a biologic unit called the epidermal melanin unit. Melanosomes are transferred from the dendrite of the melanocyte to keratinocytes by a process called apocopation. The keratinocyte phagocytizes the melanin-filled tips of the melanocytes. Once transferred to the keratinocyte, the fully melanized melanosomes are partially degraded by lysosomal enzymes or desquamated with cornified cells.

e. Melanin production: melanin production is controlled by genetics, hormones, and the environment. The number of melanocytes in the epidermis is the same regardless of race or sex:

(1) It is the amount of melanin in the keratinocyte that determines skin color. The difference in the skin color among individuals is the result of the differences in level of synthetic activity including degree of melanization and rate of degradation of the melanosome within the keratinocyte.

(2) There is also evidence that tyrosinase activity also plays a role in melanization. Dark-skinned people produce melanosomes that are larger than light-skinned people, resulting in more melanin synthesis. Tyrosinase activity is also increased in blacks.

(3) The size of melanosomes is the principal factor in determining how they will be distributed in the keratinocyte. The larger melanosomes of dark-skinned people are packaged individually in a membrane within the cytoplasm of the keratinocyte. In light-skinned people, smaller melanosomes are package in membrane-bound complexes in the keratinocyte.

f. Hormonal influence: hormones profoundly influence melanin pigmentation, but their precise action at the cellular level is unknown. It is presently believed that the melanocyte-stimulating hormone (MSH) causes a dispersion of melanosomes within melanocytes. Regional variations exist in the sensitivity of the epidermal melanin units to specific hormones:

(1) In pregnancy, there is increased pigmentation of the nipples and areolae, and to a lesser extent, an increased pigmentation of facial skin, midline of the abdomen, and genitalia. This is due to an increase in the number of active melanocytes. The hormones primarily responsible for the color changes are estrogen, progesterone, and possibly MSH.

(2) The same phenomenon occurs in women taking birth control pills.

g. Pigment variation: areas of leukoderma or “whitening” of the skin can be caused by different phenomena:

(1) In vitiligo, the affected skin becomes white because melanocytes are destroyed, leading to a decrease in their number.

(2) There are different types of albinism in which there is partial or complete absence of pigment in the skin, hair, and eyes. Albinism results from defects in the production and distribution of melanin. These defects can be found in the enzyme tyrosinase, melanosome development, or in the type of melanin produced.

(3) Local areas of increased pigmentation are due to a variety of causes:

(a) The typical freckle is caused by localized increased production of pigment by a normal number of melanocytes.

(b) Nevi are benign proliferations of melanocytes.

(c) Melanomas are the malignant counterparts of nevi.

h. Ultraviolet light: the most important function of melanin is to shield the skin from the sun’s ultraviolet rays by absorbing its radiant energy. The absorption spectrum of melanin encompasses the entire range of ultraviolet and visible light.

(1) Melanosomes function to scatter and absorb ultraviolet light:

(a) Exposure to ultraviolet light expedites the transfer of melanosomes to keratinocytes.

(b) When the skin is tanned by ultraviolet light, an increased number of melanosomes are manufactured and available for transfer to the keratinocyte.

(c) In light-skinned people, chronic sun exposure also “tricks” the melanocyte into producing larger melanosomes.

(d) The pattern of distribution of the melanosome in the keratinocyte then resembles that of dark-skinned people.

3. Langerhans cells:

a. Langerhans cell is another dendritic cell found in the epidermis. They are found in the granular, spinous, and basal cell layers of the epidermis. Occasionally, they are seen in the normal dermis. Langerhans cells are derived from bone marrow precursor cells.

b. The Langerhans cell population is self-maintaining. There is a relatively constant number of these cells being maintained by intraepidermal mitosis and migration from the connective tissue. Langerhans cells account for approximately 4% of the epidermal cell population.

(1) Function of Langerhans cells:

(a) They are immunocompetent cells involved in the uptake, processing, and presentation of antigen to lymphocytes.

(b) It is thought that Langerhans cells are the first line of immunologic defense in the skin acting as initial receptors for the cutaneous response to external antigens.

(c) Experimental evidence shows that Langerhans cells are directly involved in allergic contact hypersensitivity.

(d) There is a decreased number of Langerhans cells in patients with skin diseases such as psoriasis and sarcoidosis.

(e) Langerhans cells are also functionally impaired by ultraviolet radiation. UVB and PUVA treatments lead to morphologic, antigenic, and enzymatic changes within the Langerhans cell. Research is under way to learn the implications of this information.

4. Merkel cells:

a. Merkel cells are also found in the basal cell layer. They are collected in specialized structures called tactile discs or touch domes. The most distal part of the Merkel cell is embedded in the dermis. Merkel cells are present in the nonhairy or smooth skin of the digits, lips, regions of the oral cavity, and outer root sheath of hair follicles.

5. Embryonic development:

a. Merkel cells originate from either the neural crest or ectoderm. They are joined to keratinocytes by “spines” or desmosomes, which project from their cytoplasm.

b. Merkel cells have characteristic organelles. They are membrane-bound granules that contain neurotransmitter substances. Distal to the granules is an unmyelinated neurite or terminal neuraxon.