Histology of Skin
The epidermis consists mainly of a stratified squamous keratinized epithelium composed of cells called keratinocytes. There are also other three much less abundant epidermal cell types: pigment-producing melanocytes, antigen-presenting Langerhans cells, and epithelial cells called Merkel cells.
From the dermis, the epidermis consists of four layers of keratinocytes (or five layers in thick skin). The basal layer (stratum basale) is a single layer of basophilic cuboidal or columnar cells on the basement membrane at the dermal-epidermal junction. The stratum basale is characterized by intense mitotic activity and contains, along with the deepest part of the next layer, progenitor cells for all the epidermal layers. In addition to the basal stem cells for keratinocytes found here, a niche for such cells also occurs in the hair follicle sheaths that are continuous with the epidermis. The human epidermis is renewed about every 15 to 30 days, depending on age, the region of the body, and other factors. An important feature of all keratinocytes in the stratum basale is the cytoskeletal keratins, intermediate filaments about 10 nm in diameter. During differentiation, the cells move upward and the amount and types of keratin filaments increase until they represent half the total protein in the superficial keratinocytes.
The spinous layer (stratum spinosum) is normally the thickest layer, especially in the epidermal ridges, and consists of generally polyhedral cells having central nucleoli and cytoplasm actively synthesizing keratins. Just above the basal layer, some cells may still divide and this combined zone is sometimes called the stratum germinativum. The epidermis of thick skin subject to continuous friction and pressure has a thicker stratum spinosum with more abundant tonofibrils (keratin filaments at stratum germinativum assemble into microsocopically visible bundles called tonofibrils) and desmosomes.
The granular layer (stratum granulosum) consists of three to five layers of flattened cells, now undergoing the terminal differentiation process of keratinization. Their cytoplasm is filled with intensely basophilic masses called keratohyaline granules. Among the last activities of the keratinocytes, the lamellar granules (available in these keratinocytes) undergo exocytosis, producing a lipid-rich, impermeable layer around the cells. This material forms a major part of the skin's barrier against water loss. Together, keratinization and production of the lipid-rich layer also have a crucial sealing effect in skin, forming the barrier to penetration by most foreign materials.
The stratum lucidum, found only in thick sin, consists of a thin, translucent layer of flattened eosinophilic keratinocytes held together by desmosomes. Nuclei and organelles have been lost, and the cytoplasm consists almost exclusively of packed keratin filaments embedded in an electron-dense matrix.
The stratum corneum consists of 15 to 20 layers of squamous, keratinized cells filled with birefringent filamentous keratins. These fully keratinized or cornified cells (squames) are continuously shed at the epidermal surface as the desmosomes and lipid-rich cell envelopes breakdwon.
Thick skin is found on the palms of the hands, the soles of the feet, and corresponding surfaces of the fingers and toes. All five epidermal strata occur in thick skin. The epidermis of thick skin ranges between 0.4 mm and 0.6 mm thick. Thick skin contains sweat glands, but no hair follicles or sebaceous glands. Thin skin covers most of the body. The epidermis lacks the stratum lucidum, so it has only four layers. Thin skin contains the following accessories: hair follicles, sebaceous glands, and sweat glands. The epidermis of thin skin ranges from 0.075 mm to 0.150 mm thick.
Other Cells in Epidermis
The color of the skin is the result of several factors, the most important of which are the keratinocytes' content of melanin and carotene and the number of blood vessels (hemoglobin) in the dermis. Melanocyte is a specialized cell of the epidermis found among the cells of the basal layer and in hair follicles. Melanocytes synthesize melanin and transfer them into nearby keratinocytes.
The first step in melanin synthesis is catalyzed by tyrosinase (the source of melanin is tyrosine), a transmembrane enzyme in Golgi-derived vesicles. Tyrosinase activity converts tyrosine into 3,4 – dihydroxyphenylalanine (DOPA), which is then further transformed and polymerized into the different forms of melanin. Melanin pigment is linked to a matrix of structural proteins and accumulates in the vesicles until they form mature elliptical granules abuot 1 um long called melanosomes. Melanosomes are then transported via kinesin to the tips of the cytoplasmic extensions (Figure 18-7, one melanocyte plus the keratinocytes into which it transfers melanosomes make up an epidermal-melanin unit and the density of such units in skin is similar in all individuals). The neighboring keratinocytes phagocytose the tips of these dendrites, take in the melanosomes, and transport them by dynein toward their nuclei. The melanosomes accumulate within keratinocytes as a supranuclear cap that prior to keratinization absorbs and scatters sunlight, protecting DNA of the living cells from the ionizing, mutagenic effects of UV radiation.
Antigen-presenting cells (APCs) called Langerhans cells, which are usually most clearly seen in the spinous layer, represent 2% to 8% of the epidermal cells. Cytoplasmic processes extend from these dendritic cells between keratinocytes of all the layers, forming a fairly dense network in the epidermis. Like other APCs, they develop in the bone marrow, move into the blood circulation, and finally migrate into stratified squamous epithelia where they are difficult to identify in routinely stained sections.
Langerhans cells bind, process, and present antigens to T lymphocytes in the same manner as immune dendritic cells in other organs. Microorganisms cannot penetrate the epidermis without alterting these dendritic cells and triggering an immune response. Langerhans cells, along with more scattered epidermal lymphocytes and other APCs in the dermis, make up a major component of the skin's adaptive immunity.
Merkel cells, or epithelial tactile cells, are sensitive mechanoreceptors essential for light touch sensation. They are abundant in highly sensitive skin like that of fingertips and at the bases of some hair follicles.
The dermis is the layer of connective tissue that supports the epidermis and binds it to the subcutaneous tissue. The thickness of the dermis varies with the region of the body and reaches its maximum of 4 mm on the back. The surface of the dermis is very irregular and has many projections (dermal papillae) that interdigitate with projections (epidermal pegs or ridges) of the epidermis, especially in skin subject to frequent pressure, where they reinforce the dermal-epidermal junction.
A basement membrane always occurs between the stratum basale and the dermis, and follows the contour of the interdigitations between these layers. Nutrients for keratinocytes diffuse into the avascular epidermis from the dermal vasculature through this basement membrane.
The dermis contains two sublayers with indistinct boundaries. The thin papillary layer, which includes the dermal papillae, consists of loose connective tissue, with types I and III collagen fibers, fibroblasts and scattered mast cells, macrophages, and other leukocytes. From this layer, anchoring fibrils of type VII collagen insert into the basal lamina, helping to bind the dermis to the epidermis. The underlying reticular layer is much thicker, consists of dense irregular connective tissue (mainly bundles of type I collagen), with more fibers and fewer cells than the papillary layer. A network of elastic fibers is also present, providing elasticity to the skin. Between the collagen and elastic fibers are abundant proteoglycans rich in dermatan sulfate.
Blood and Lymphatic vessels
Both dermal regions contain a rich network of blood and lymphatic vessels. Nutritive vessels form two major plexuses. 1.Between the papillary and reticular dermal layers lies the microvascular subpapillary plexus, from which capillary branches extend into the dermal papillae and form a rich, nutritive capillary network just below the epidermis. 2.A deep plexus with larger blood and lymphatic vessels lies near the interface of the dermis and the subcutaneous layer.
Lymphatic vessels begin in the dermal papillae and converge to form two plexuses located with the blood vessels.
The subcutaneous layer consists of loose connective tissue that binds the skin loosely to the subjacent organs, making it possible for the skin to slide over them. This layer contains adipocytes that vary in number in different body regions and vary in size according to nutritional state. The extensive vascular supply at the subcutaneous layer promotes rapid uptake of insulin or drugs injected into this tissue.
The integument is more than just a wrapping around the body. It serves many varied functions, including protection, prevention of water loss, temperature regulation, metabolic regulation, immune defense, sensory reception, and excretion.
The skin acts as a physical barrier that protects the entire body from physical injury, trauma, bumps, and scrapes. It also offers protection against harmful chemicals, toxins, microbes, and excessive heat or cold. Paradoxically, it can absorb certain chemicals and drugs. Thus, the skin is said to be selectively permeable because some materials are able to pass through it, while others are effectively blocked. The epidermis is designed to withstand stresses and regenerate itself continuously throughout a person's lifetime. The skin also protects deeper tissues from solar radiation, especially ultraviolet rays. When exposed to the sun, the melanocytes become more active and produce more melanin, thus giving the skin a darker, tanned look. Even when you get a sunburn, the deeper tissues (muscles and internal organs) remain unaffected.
Prevention of Water Loss
The epidermis is water resistant and helps prevent unnecessary water loss. Water cannot easily enter or exit the skin, unless it is specifically secreted by the sweat glands. The skin also prevents the water within the body cells and in the extracellular fluid from leaking out. When the skin is severely burned, a primary danger is dehydration, because the individual has lost the protective skin barrier, and water can escape from body tissues.
Although the integument is water resistant, it is not entirely waterproof. Some interstitial fluids slowly escape through the epidermis to the surface, where they evaporate into the surrounding air, a process called transepidermal water loss (TEWL). About 500 mL of water is lost daily by evaporation of moisture from the skin or from respiratory passageways during breathing. Insensible perspiration is the release of water vapor from sweat glands under "normal" circumstances when we are not sweating. In contrast, sensible perspiration is visible sweating. On most parts of the skin, water vapor released from sweat glands during insensible perspriation mixes with sebaceous secretions (sebum) to produce a thin, slightly acidic film (pH 4-6) over the surface of the epidermis. This film helps slow down TEWL by forming an oily barrier over the surface of the skin. The acidic nature of the barrier also prevents the invasion of certain bacteria.
Body temperature is influenced by vast capillary networks and sweat glands in the dermis. When the body is too warm and needs to dissipate heat, the diameter of the blood vessels in the dermis enlarges to permit more blood flow through the dermis, and sweat glands release fluid onto the skin surface (evaporation). As relatively more blood flows through these dermals vessels, the warmth from the blood dissipates through the skin, and the body cools off by evaporation of the sweat. Conversely, when the body is cold and needs to conserve heat, the blood vessels in the dermis constrict to reduce blood flow. In an effort to conserve heat, more blood is shunted to deeper body tissues, and relatively less blood flows in the dermal blood vessels.
The arrector pili muscle, a small bundle of smooth muscle cells, extends from the midpoint of the fibrous sheath to the dermal papillary layer. Contraction of these muscles pulls the hair shafts to a more erect position, usually when it is cold in an effort to trap a layer of warm air near the skin. In regions where hair is fine, contraction of arrector pili muscles is seen to produce tiny bumps on the skin surface "goose bumps" where each contracting muscle distorts the attached dermis.
PS: The termoregulatory function of skin involves numerous arteriovenous anastomoses or shunts located between the two major plexuses. The shunts decrease blood flow in the papillary layer (see Figure ) to minimize heat loss in cold conditions and increase this flow to facilitate heat loss when it is hot, thus helping maintain a constant body temperature.
Vitamin D3 is a cholesterol derivative synthesized from cholecalciferol, which is produced by some epidermal cells when they are exposed to ultraviolet radiation. Calcitriol is synthesized from the cholecalciferol by some endocrine cells in the kidney. Calcitriol, the active form of vitamin D3, is a hormone that promotes calcium and phosphorus absorption from ingested materials across the wall of the small intestine. Thus, the synthesis of vitamin D3 is important in regulating the levels of calcium and phosphate in the blood. As little as 15 minutes of direct sunlight a day may provide your body with its daily vitamin D requirement.
The epidermis contains a small population of immune cells. These immune cells (derived from a type of white blood cell), called epidermal dendritic cells, or langerhans cells, play an important role in initiating an immune response by phagocytizing pathogens that have penetrated the epidermis and also against epidermal cancer cells.
The skin contains numerous sensory receptors. These receptors are associated with nerve endings that detect heat, cold, touch, pressure, texture, and vibration. Because your skin is responsible for perceiving many stimuli, it needs different sensory receptor types to detect, distinguish, and interpret these stimuli.
With its large surface and external location, the skin functions as an extensive receiver for various stimuli from the environment. Diverse sensory receptors are present in skin, including both simple nerve endings with no Schwann cell or collagenous coverings and more complex structures with sensory fibers enclosed by glia and delicate connective tissue capsules.
- Merkel cells
- Free nerve endings
- Root hair plexuses
- Meissner corpuscles
- Lamellated (pacinian) corpuscles
- Krause end bulbs
- Ruffini corpuscles
Excretion by Means of Secretion
Skin exhibits an excretory function when it secretes substances from the body during sweating. Sweating, or sensible perspiration, occurs when the body needs to cool itself off. Notice that sweat sometimes feels "gritty" because of the waste products being secreted onto the skin surface. These substances include water, salts, and urea, a nitrogen-containing waste product of body cells. In addition, the skin contains sebaceous glands that secrete an oily material called sebum, which lubricates the skin and hair.