Skin

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Description

Skin is part of the integumentary system and is the largest and primary protective organ of the human body. It covers the body's entire external surface and serves as a first-order physical barrier against the outer environment.

Structure

The skin is made up of three layers.

• The epidermis, the outermost layer of skin, provides a waterproof barrier and contributes to skin tone.
• The dermis, found beneath the epidermis, contains connective tissue, hair follicles, blood vessels, lymphatic vessels, and sweat glands.
• The deeper subcutaneous tissue (hypodermis) is made of fat and connective tissue.

Epidermis

The epidermis is further divided into:

• 5 layers on thick skin like the palms and soles (stratum basale, stratum spinosum, stratum granulosum, stratum lucidum, and stratum corneum)
• 4 layers in other places (lacking the stratum lucidum)

The epidermis is a stratified squamous epithelium that contains four to five layers depending on its location:

1. Stratum Basalis (Basal cell layer): It is deepest and closest to the dermis. The stratum basale contains basal keratinocytes, immune cells such as Langerhans cells and T cells, and melanocytes that provide the skin with pigmentation. Keratinocytes from this layer evolve and mature as they travel outward/upward to create the remaining layers.
2. Stratum Spinosum (Prickle cell layer): This layer compromises most of the epidermis and contains several layers of cells connected by desmosomes who keep cells tightly bound to one another and resemble "spines"
3. Stratum Granulosum (Granular cell layer): This layer contains several layers of cells that contain lipid-rich granules. In this layer, cells begin to immortalize and lose their nuclei, as they move away from the nutrients located in the deeper tissue. Keratinocytes in the stratum granulosum contain cysteine- and histidine-rich granules, which bind keratin filaments together.
4. Stratum Lucidum: This layer is only present in the thick skin of soles and palms and consists of mostly immortalized cells. It is a thin, clear layer of dead keratinocytes. Instead of keratin, keratinocytes in the stratum lucidum contain eleidin, a clear intracellular protein, which gives this layer its transparent appearance.
5. Stratum Corneum (Keratin layer):  It is the outermost layer of the epidermis. This keratinized layer serves as a protective overcoat and due to keratinization and lipid content, this layer allows for the regulation of water loss by preventing internal fluid evaporation.

Dermis

Dermis lies deep to the epidermis. It is a thick layer of connective tissue consisting of collagen and elastin which contributes to skin’s strength and flexibility, respectively. It also contains nerve endings, blood vessels, and adnexal structures such as hair shafts, sweat glands, and sebaceous glands.

The dermis is divided into two layers:

• Papillary dermis (the upper layer): The apical layer of dermis folds to form papillae that extend into the epidermis like tiny finger-like projections and is referred to as the papillary dermis. It contains capillaries that facilitate the transport of nutrients.
• Reticular dermis (the lower layer): The lower layer of the dermis is referred to as the reticular dermis. It contains skin appendages such as hair follicles, sebaceous glands, and sweat glands. The presence of a dense concentration of collagenous and reticular fibers interwoven within this layer makes the reticular dermis is significantly thicker than the papillary dermis.

Both dermal layers contain fibroblasts, myofibroblasts, and immune cells such as macrophages, lymphocytes, and mast cells. Fibroblasts synthesize an extracellular matrix comprising of collagen, proteoglycans, and elastic fibers that provide the structural integrity of the dermis. 

Hypodermis

• The hypodermis is the third and deepest layer, consisting mainly of adipose tissue.
• Skin adipose tissue stores energy in the form of fatty acids and functions as an endocrine organ important for glucose homeostasis and lipid metabolism.
• This layer consists of fibrocytes and adipocytes and is rich in proteoglycans and glycosaminoglycans, which confer mucus-like properties to the layer. This layer also produces a variety of mediators such as growth factors, adipokines, and cytokines, and contains multiple immune cells.
• Subcutaneous fat serves as an insulating layer for the body, as fat is a poor conductor of heat.

Innervation

• The skin is innervated by sensory nerves expressing receptors that can sense pain (nociceptors), itch (pruriceptors), temperature (thermoreceptors), and touch (low-threshold mechanoreceptors). These receptors are present as nerve free endings.
  1. Nociceptive nerves are in close contact with hair follicles and epithelial cells with their free nerve endings terminating at various levels of the epidermis
  2. Merkel cells are involved in mechanosensation (light touch) theses are oval-shaped cells interspersed in the basal layer of the epidermis and innervated with sensory fibers. 
  3. Meissner’s corpuscles are localized in the papillary dermis and are sensitive to touch
  4. Pacinian corpuscles are located in the reticular dermis and are responsive to pressure and vibration. Both types of corpuscles are supplied by Aα and Aβ sensory nerve fibers that are situated in the sensory ganglia.
  5. Thermoreceptors, critical for sensing thermal differences between the skin and the external environment, are expressed on both heat- and cold-sensitive nerves, with the skin being more densely populated by cold-sensitive nerves. Activation of thermally sensitive nerves to either heat or cold results in vasodilation, vasoconstriction, sweating, or shivering.
• Other mechanoreceptors are present in the skin as corpuscles.
• Cell bodies of nerves innervating the skin are present in the trigeminal and dorsal root ganglia.

Function

• It also regulates temperature and
• protects against ultraviolet (UV) light, trauma, pathogens, microorganisms and toxins.
• plays an important role in immunologic surveillance,

• sensory perception,
• control of insensible fluid loss, and
• homeostasis in general.

The skin is also highly adaptive with different thicknesses and specialized functions in different body sites.

Clinical Relevance

Skin as an Immune Organ

Skin protects the host from invasion by employing physical barriers, biomolecules, immune and non-immune cell intricate network and skin structures

Physical Barrier

Corneocytes in the Stratum Corneum contribute to the barrier function of the epidermis. These cells are arranged in “bricks and mortar” fashion interspersed by lipids such as ceramides, cholesterol, and free fatty acids. Each corneocyte contains a lipid envelope linked to keratin filament bundles that fill the intracellular compartments of the corneocyte, thus increasing its rigidity. The stratum corneum is made of three layers and it is both an outside‒in barrier to prevent the entry of foreign substances and microorganisms, and an inside‒out barrier to prevent water loss. Junction adhesion molecules and tight junction proteins (Claudin-1/zonula occludins-1) found in epidermal layers also add to the formation of the physical barrier. Disruptions in the expression or function of these components may cause improper barrier formation or skin disorders or inflammatory conditions in the skin. Studies have shown that the skin of patients with atopic dermatitis has reduced expression levels of ZO-1 and claudin-1.

Skin pH

Skin pH is acidic and ranges between 4 to 6 The body’s internal environment maintains a near-neutral pH (7–9). There is a gradient of 2–3 units between the SC and underlying epidermis and dermis. Recent research suggests skin pH depends on several key enzymes involved in the synthesis and maintenance of a competent skin barrier. Age, anatomic site, sebum, sweat, genetic predisposition affect the pH along with the use of creams, soaps, and cosmetics.Various mechanisms maintain a low pH of the skin.

• Enzymatic processes and fatty acids, sweat glands in the SC lower the pH of the skin.
• Sweat glands secrete a vast collection of antimicrobial peptides, which restrain various microbes' growth on the skin. During rigorous physical exercise, dermcidin, an antimicrobial peptide, is secreted by the sweat glands onto the skin's epidermal surface. Research suggests that dermcidin gets activated in salty and slightly acidic sweat, which can perforate microbe membranes, allow water, and charged Zinc in sweat to gush across the cell membrane, kill the microbe.
• Besides, the physiological pH of the skin is for commensal bacteria such as Staphylococcus epidermidis, which helps in preventing pathogenic strains such as Staphylococcus aureus from establishing infections in the host.