The levels of organization of the skin and its accessory structures are listed below. You will be exploring these further in the coming pages.
- Molecular level – keratin, melanin and vitamin D
- Microscopic level – stem cells and skin cells
- Tissue level – epithelial and connective tissue
- Organ level – skin, consisting of the epidermis, dermis, and hypodermis, as well as hair, nails and glands
Molecular Level – Keratin and Melanin
Keratin is a group of fibrous proteins that give hair, nails, and skin their tough, water-resistant properties. Keratins are filaments formed from the polymerization of intermediate filament proteins. In addition to intra- and intermolecular hydrogen bonds, keratins have large amounts of the sulfur-containing amino acid cysteine, which forms disulfide bridges that confer additional strength.
Keratins are an excellent example of protein assembly. Keratins have an alpha-helix secondary structure in the central rod domain. Two keratin proteins then come together and the helices wind around themselves to form a quaternary structure of a coiled-coil dimer. These dimers then assemble into protofilaments and then filaments. The twists of twists are similar to fibers inside of ropes. However, keratins aren’t twisted by machines; they self assemble based on their primary structure.
Melanin is a class of photopigment (“photo,” meaning “light,” and “pigment,” meaning “colored material”) with a molecular structure that allows it to absorb UV (ultraviolet) radiation from the sun. Melanin transforms the energy from the radiation into harmless heat, and melanin prevents the indirect DNA damage from the sun that is responsible for many skin cancers. Melanin also gives skin, hair and eyes their color. Melanin is produced by specialty cells called melanocytes, inside special vesicles called melanosomes. About 10 days after initial sun exposure, melanin synthesis peaks, which is why pale-skinned individuals tend to suffer sunburns of the epidermis initially.
Albinism is a genetic disorder that affects (completely or partially) the coloring of skin, hair, and eyes. The defect is primarily due to the inability of melanocytes to produce melanin. Individuals with albinism tend to appear white or very pale due to the lack of melanin in their skin and hair. Melanin protects the DNA of skin cells from the harmful effects of UV rays from the sun. Individuals with albinism need more protection from the sun and must limit their outdoor activities. Treatment of this disorder usually involves addressing the symptoms.
Molecular Level – Vitamin D
The epidermal layer of human skin synthesizes the precursor to vitamin D when exposed to UV radiation. In the presence of sunlight, an isomer of vitamin D3, cholecalciferol, is synthesized from a derivative of the steroid cholesterol in the skin. The liver converts cholecalciferol to calcidiol, which is then converted to calcitriol (the active chemical form of the vitamin) in the kidneys. Vitamin D, which is really a hormone, is essential for normal absorption of calcium and phosphorous, which are required for healthy bones. In the present day, this hormone is added as a supplement to many foods including milk and orange juice, compensating for the need for sun exposure.
In addition to affecting bone health, Vitamin D is essential for general immunity against bacterial, viral and fungal infections. Recent studies are also finding a link between insufficient vitamin D and cancer.
Rickets is a disease of bone deterioration often caused by insufficient vitamin D, leading to insufficient calcium absorption. Children are especially prone to effects from this vitamin deficiency due to their rapid bone turnover and formation. In adults, the deficiency of vitamin D is called osteomalacia. Typically rickets is found in developing countries where malnutrition would prevent proper supply of calcium and dietary vitamin D.
Microscopic Level – Cells of the Epidermis
The epidermis (or epithelial layer) is stratified squamous epithelia, composed of four to five layers (depending on body region) of epithelial cells. The top layers of the epidermis are made up of keratinocytes, which are cells containing the protein keratin. The keratinocytes on the most superficial layer of the epidermis are dead, and periodically slough away, being replaced by cells from the deeper layers. As keratinocytes move superficially from the deeper layers, they lose cytoplasm and become flattened, allowing for many layers in a relatively small space.
Basal cells are an example of tissue-specific stem cells, meaning they can turn into a variety of cell types found in that tissue. Under normal conditions, daughter basal cells most commonly replace lost keratinocytes.
The deepest layer of the epidermis and the most superficial layer of the dermis give out projections that interlock with each other (like Velcro) and strengthen the bond between the epidermis and the dermis. The projections originating in epithelial cells of the bottom layer of the epidermis are called desmosomes, and the ones originating in the dermis are called dermal papillae. Think of the projections as a formation of folds of cellular matter. The greater the fold, the stronger the connections made.
Merkel cells are sensory receptors that detect light touch. They form synaptic connections with sensory nerves that carry touch information to the brain. These cells are abundant on the surface of the hands and feet.
Melanocytes are cells in the bottom layer of epidermis that produce the pigment melanin, which gives hair and skin its color. Individuals whose melanocytes produce more melanin have darker skin color. Cellular extensions of the melanocytes reach up in between the keratinocytes.
Dendritic or Langerhans cells are tissue macrophages that contribute to the immune function of the skin. They engulf foreign organisms and signal to the immune system. Since the skin is in constant contact with the environment, it is important to have immune cells to help destroy any pathogens that might get past the cell barrier of the epidermis.
Eczema is an allergic reaction that manifests as dry, itchy patches of skin that resemble rashes. Normally it is useful to have immune cells in the skin, but they can also lead to dysfunction if they become overactive. In eczema, this excess activity may be accompanied by swelling of the skin, flaking, and in severe cases, bleeding. Other allergic (immune-mediated) reactions include hives. Symptoms of these conditions are usually managed with moisturizers and topically with corticosteroid or antihistamine creams that reduce the inflammatory immune response.
Cancer in general is initiated because of DNA damage that accumulates in a particular cell over time. Exposure to UV rays from the sun can ultimately lead to mutations in the genomes of various skin cells. Accumulation of genetic mutations over a period of time, in addition to other possible causes, can trigger cells to grow out of control. The normal signals that control cell divisions (even stem cells have these controls) are lost, and cells grow to form a tumor, or mass of cells. While some tumors are benign (stay in one place), some produce cells that dislodge from the tumor and establish tumors in other areas of the body. In other words, they metastasize and form secondary tumors.
Basal Cell Carcinoma
Basal cell carcinoma is caused by mutations that lead to lack of control over the growth of stem cells located in the stratum basale. It is the most common form of all cancers that occur in the United States. The head, neck, arms, and back are most susceptible, due to long-term sun exposure. Although UV radiation is the main culprit, exposure to other agents, such as electromagnetic radiation or carcinogenic chemicals, can also lead to this type of cancer. Injury to the skin due to open sores, tattoos, burns, etc. may be predisposing factors as well. Basal cell carcinoma usually starts as an uneven patch, bump, growth, or scar on the skin surface and responds best to treatment when caught early. Complete surgical excision of the lesion usually cures this form of cancer.
Squamous Cell Carcinoma
Squamous cell carcinoma is the second most common skin cancer, and affects the keratinocytes. Lesions are usually scaly and red and are most common on the scalp, ears, and hands. If not removed, they can metastasize. Surgery and radiation are used to cure squamous cell carcinoma.
Melanoma affects melanocytes, the pigment-producing cells in the epidermis. It is the most fatal of all skin cancers, as it is highly metastatic and can be difficult to detect before it has spread. Melanomas usually appear as asymmetrical brown and black patches with uneven borders and a raised surface. Treatment typically involves surgical excision and immunotherapy.
The skin contains many tissue types. The epidermis is classified as epithelial tissue composed of stratified squamous epithelia. The dermis is made of different types of connective tissues including areolar and dense irregular connective tissue, and histiocytes (tissue macrophages). The hypodermis contains areolar connective tissue, adipose tissue, and glands.
The epidermis is mainly made up of stratified (layered) squamous (flat) epithelial cells. Epithelial cells found in the different layers of the epidermis have different shapes. Stratification (layering) is important in the epithelial tissue of the integumentary system, which forms a barrier. Epithelial cells found in other systems have other surface cell shapes, including cube-like (cuboid) and column-like (columnar) in a single layer (simple) or multiple cell layers (stratified).
The epidermis contains several cell types of different origins, including keratinocytes (95 percent of the cells are keratinocytes), melanocytes, Langerhans cells and Merkel cells. The epidermis does not contain blood vessels or nerves, but Merkel cells provide signals to the sensory neurons below this layer in the dermis. Since there are no blood vessels, living cells of the epidermis are nourished by diffusion from the capillaries of the dermal papillae below.
While the epidermis is composed of epithelial cells, the dermis is composed of connective tissue. The dermis connects the epidermis to the hypodermis and provides structure and elasticity from collagen and elastin fibers. These proteins are made by fibroblasts found in the dermis. Collagen and elastin work together: collagens provide strength; elastins, as the name implies, are elastic and allow for distension. The skin must remain strong to protect you from abrasions and other cuts. However, the skin also needs to be able to deform and, hopefully, return to its original shape.
The permanent folds in the skin caused by a lack of “retraction” are called wrinkles. Wrinkling in the skin is caused by habitual facial expressions, aging, sun damage, smoking, poor hydration, and various other factors. Wrinkling is a surprisingly complex phenomenon. Primarily, sun or other damage to the skin causes a breakdown in collagen and elastin as well as a breakdown in the replacement of these extracellular matrix proteins in the dermis.
Stretch marks usually accompany rapid weight gain during puberty and pregnancy as well as during the rapid gain of muscle associated with weight lifting. When the dermis (and possibly the hypodermis) is stretched beyond its limits of elasticity, the skin stretches to accommodate the excess pressure. In some cases, the dermis can’t adequately fill in over the stretched areas and may actually tear, causing the epidermis to become thin and making the underlying blood vessels more visible. They initially have a reddish hue, but lighten over time as the tissue repairs itself and heals. Other than for cosmetic reasons, treatment of stretch marks is not required. They occur most commonly over the hips and abdomen.
Pigmentation of the Skin
Skin contains different types of melanin, including pheomelanin, which is reddish, and eumelanin, which is dark brown. The amount and types of melanin produced is under genetic control. The combinations of the different types of melanin result in the wide range of skin colors and tones seen in humans. While the number of melanocytes do not vary too much between individuals, the skin tone depends on the amount and type of melanin produced by these cells. If a person has more eumelanin producing melanocytes, that person would have darker skin color. The predominance of pheomelanin is responsible for the reddish coloration of hair in some individuals.
Exposure to the sun causes melanin to build up, because sun exposure stimulates keratinocytes to secrete a peptide hormone that in turn stimulates melanocytes into producing melanin. The melanocytes produce and then transfer the melanin to keratinocytes. This buildup of melanin results in the darkening of the skin, or a tan. Increased melanin also protects the skin’s DNA from UV ray damage to some extent, although even very dark-skinned individuals can get skin cancer. Melanin synthesis does not peak until about 10 days after initial sun exposure, which is why pale-skinned individuals tend to suffer sunburns of the epidermis initially. Individuals with darker skin can also get sunburns, but are more protected than light-pigmented individuals.
Melanosomes, the cellular organelles that contain melanin, are temporary structures and are eventually destroyed by fusion with lysosomes, which makes tanning impermanent. Too much sun exposure can eventually lead to wrinkling of the skin due to destruction of the cellular structure of the skin, and in severe cases it can cause sufficient DNA damage to result in skin cancer. An uneven distribution of melanocytes in the skin results in the appearance of freckles.
Sunscreen and UVA and UVB Radiation
“UV” is an abbreviation for “ultraviolet.” Ultraviolet radiation is a portion of the electromagnetic spectrum between visible light and x-rays. The sun emits two ranges of ultraviolet light that penetrate earth’s atmosphere: UVA and UVB. UVB radiation is partially absorbed by the ozone layer, but some still reaches the surface of the Earth. UVA radiation is not filtered, and all of it reaches the surface of the Earth. One of the functions of our integumentary system is to protect us from this UV radiation. Exposure to this radiation can cause skin damage and cancer. Sunscreens are designed to protect our skin from UV radiation. Sunscreens with a sun protection factor (SPF) of 15 or more provide good protection from UVB radiation. To be protected from UVA radiation, you must have a “broad-spectrum” product.