Lecture outline:

Skin
  Epidermis
    The 5 layers of epidermis, and how skin grows
    The 4 cell types of epidermis (keratinocytes, melanocytes, Merkel cells, Langerhans cells)
  Dermis
    The 2 layers of dermis: papillary and reticular

Skin appendages
    Hair and its associated structures:
    Hair follicles
    Sebaceous glands
    Arrector pili muscles
    Apocrine sweat glands
    Eccrine sweat glands
    Nails

Two examples of sensory innervation of the skin
    Pacinian corpuscles
    Meissner's corpuscles

Skin consists of Epidermis and Dermis.

Hypodermis is not part of the skin. It consists of subcutaneous connective tissue and fat, representing the superficial fascia that covers the entire body.

Skin is divided into two types, thick and thin. This distinction refers to the epidermal layer only. The dermis can be much thicker in thin skin (eg, upper back) than in thick skin.

Key features of each are:

Thick skin

• Occurs on palms and soles
• 5 distinct layers of keratinocytes, with an especially thick stratum corneum
• Has eccrine sweat glands
• Lacks hair follicles, sebaceous glands, arrector pili muscles

Thin skin

• Occurs everywhere on body except palms and soles
• 4 layers of keratinocytes (no stratum lucidum, thin stratum corneum)
• Has eccrine sweat glands
• Has hair follicles, sebaceous glands, arrector pili muscles

Epidermis has 5 layers: Stratum basale, stratum spinosum, stratum granulosum, stratum lucidum and stratum corneum

How skin grows: Keratinocytes are born in stratum basale, a single layer of mitotically active cells that sits on the dermis. As new keratinocytes are formed, the previous layer is pushed toward the surface, moving into the next layer, the stratum spinosum. This is the thickest layer of the epidermis. The cells have cytoplasmic spines, and are attached to one another via desmosomes, giving them a "prickly" appearance in the histological preparation. From there, the cells move into the stratum granulosum, the last layer where cells possess nuclei. S. Granulosum cells contain visible keratohyalin granules, giving this layer its name. In stratum basale and spinosum, keratinocytes make tonofilaments, which become grouped into tonofibrils. As the keratinocytes progress into stratum granulosum, a substance in that layer's keratohyalin granules combines with the tonofibrils, converting them to keratin. As the keratin accumulates, the cells become denucleated and dessicated and they move through stratum lucidum to the outermost layer, stratum corneum. Stratum lucidum is present only in thick skin, and is considered to be a subdivision of stratum corneum by some histologists. Stratum corneum consists of flattened, dessicated cells filled with keratin filaments and coated with a glycolipid that serves a water barrier function.

From Embryology course

In this layer, keratinocytes have visible cytoplasmic spinous extensions, giving rise to the name "prickle cells". This feature can be seen in the light microscope. Neighboring keratinocytes are connected to one another by desmosomes.

Left: the spinous processes connecting two stratum spinosum cells are clearly evident, as are the darkly stained tonofilaments (T) (keratin filaments) located within them.

Right: higher magnification reveals that the spinous processes of adjacent keratinocytes (K) are attached to one another by desmosomes (D).

Melanocytes are responsible for the synthesis of the brown pigment melanin, which underlies skin coloration. These cells are interspersed among the keratinocytes of the stratum basale, with each extending processes to contact a number of keratinocytes. Melanin is transported to the contact points in melanosomes, where it is transferred to the keratinocytes by phagocytosis.

Increased exposure to UV light, such as occurs in sunlight, leads to an increase in melanin production, and thus protection from the harmful effects of the radiation.

The critical enzyme involved in converting tyrosine into melanin is tyrosinase. Freckles are produced by spots of increased melanin production, and darken with increased exposure to the sun.

The number of melanocytes is nearly the same for all races, with differences in skin color arising from the amount and location of melanin in the keratinocytes.

In albinism (lack of skin pigmentation), individuals lack tyrosinase, and thus cannot form melanin.

In adults, one third of all tumors are of the skin. Most of these tumors derive from the basal cells, the squamous cells of the stratum spinosum, and melanocytes. They produce, respectively, basal cell carcinomas, squamous cell carcinomas, and melanomas. The first two types of tumors can be diagnosed and excised early and consequently are rarely lethal. Skin tumors show an increased incidence in fair-skinned individuals residing in regions with high amounts of solar radiation. Malignant melanoma is an invasive tumor of melanocytes. Dividing rapidly, malignantly transformed melanocytes penetrate the basal lamina, enter the dermis, and invade the blood and lymphatic vessels to gain wide distribution throughout the body.

Merkel cells are sensitive mechanoreceptors located in the epidermis, especially in sensitive areas such as the fingertips. They differ from other skin mechanoreceptors in that they appear to contain neurosecretory vessicles and form a synaptic junction with the sensory nerve ending contacting the cell.

Langerhans cells (L) lie among the keratinocytes of the stratum spinosum. These cells play a role in cell-mediated immune responses in the skin, with one role being to phagocytose foreign antigens. They originate from precursor cells that travel from the bone marrow to the epidermis, where they differentiate into Langerhans cells. They extend long processes (CP) that radiate out from the cell body to interdigitate between the keratinocytes. Langerhans cells are continually replaced by precursor cells arriving from the bone marrow. They can be identified with special stains in the light microscope (right figure) and by the presence of distinctive Birbeck granules in EM.

The papillary layer lies immediately beneath the epidermis, and is composed of loose (areolar) collagenous connective tissue, mixed with networks of thick elastic fibers. It contains the capillary loops that support, but do not penetrate the epidermis. It also contains Meissner's corpuscles, which are very sensitive mechanoreceptors. The intimate interdigitation of the dermal papillae with epidermal ridges strengthens the attachment of epidermis to dermis.

The reticular layer lies below the papillary layer and is composed of dense, irregular collagenous connective tissue, with the collagen fibers lying mostly parallel to the surface. This layer contains sweat glands, sebaceous glands, hair follicles and arrector pili muscles. This layer also contains two types of deep encapsulated mechanoreceptors: Pacinian corpuscles and Ruffini corpuscles.

Structure of the hair follicle:

M: medulla, moderately keratinized core of hair shaft

Cx: cortex, highly keratinized layer, forming the bulk of the hair

Cu: cuticle, highly keratinized, hard, thin covering on surface of hair

IRS: internal root sheath, lightly keratinized cells that disintegrate, leaving space into which sebum is secreted by sebaceous glands

ERS: external root sheath, invagination of epidermis, not involved in hair formation

GM: glassy membrane, thickened basal lamina, separating dermis from follicle epithelium

CT: connective tissue sheath, lies between glassy membrane and dermis

DP: dermal papilla, vascularized loose connective tissue that inserts into bulb

Hairs are composed of keratinized cells that develop from hair follicles, tubular invaginations of the epidermis. Hair formation occurs in the bulb, the expanded base of the hair follicle. The bottom of the bulb, where a vascularized loose connective tissue invaginates into the bulb, is called the dermal papilla (DP). The cells that create the hair are the germinal matrix cells, which are immediately adjacent to the dermal papilla.

The dividing cells of the germinal matrix form undergo keratinization, and form the hair shaft. These cells are homologous to the stratum basale of the epidermis. The hair shaft has three layers, the medulla in the center, the cortex and the cuticle. These layers are formed according to the closeness of the matrix cells to the center of the dermal papilla. The most central matrix cells undergo moderate keratinization to form the medulla, or core of the hair shaft. The cells outside these become the the highly keratinized cortex, which forms the bulk of the hair. The outermost cells also undergo keratinization to become the hard thin cuticle on the surface of the hair. The cuticle consists of overlapping, keratin plates clearly visible in the scanning electron microscope (right photo). Continued mitosis of new cells in the germinal matrix pushes the hair upwards at a rate of 1 cm per month.

Hair pigmentation comes from melanocytes at the base of the follicle that transfer melanosomes to the cells of the cortex.

Left: Longitudinal section along hair follicle, showing a sebaceous gland located along the shaft of the follicle.

Right: cross-section through hair follicle, showing sebaceous glands adjacent to the follicle.

Sebaceous glands secrete sebum, an waxy oily substance that coats the hair follicle and skin surface. Sebaceous glands, most common on the face, scalp and forehead, develop as an outgrowth of the external root sheath of the hair follicle. During maturation, the entire sebaceous gland cell becomes filled with sebum, which consists of a mixture of cholesterol and triglycerides. In an example of holocrine secretion, eventually the cell breaks open and both the sebum and the cell contents are discharged into the pilosebaceous canal. These destroyed cells are replaced by mitosis of the basal cells at the periphery of the gland.

Sebum is thought to contribute to the maintenance of skin texture and hair flexibility. It also appears to have a critical role in the development of acne. Sebum production greatly increases at puberty. The breakdown of triglycerides in sebum to fatty acids by skin bacteria may contribute to skin lesions of acne.

Arrector pili muscles are smooth muscles connected at one end to the papillary layer of the dermis and at the other to the hair follicle sheath. Contraction of these muscles (upon sympathetic stimulation) produces the erection of the hairs and puckering of skin called "goosebumps".

Apocrine sweat glands are mainly located in the armpit, breasts, and anal region. They produce a milky, slightly viscous secretion. The secretory portion of the gland is deep in the dermis or superficial hypodermis, and has a much wider lumen than the eccrine secretory glands. The secretory cells are usually low cuboidal, as can be seen in the figure (right). The ducts of the apocrine glands appear similar to those of the eccrine glands. A key difference is that apocrine ducts always empty into the canals of hair follicles. Apocrine sweat glands actually secrete via a merocrine process (exocytosis), thus their name is a misnomer.

These glands become functional only at puberty. They are innervated by the sympathetic nervous system. Apocrine secretion occurs in response to emotional stimuli but not to heat. This type of sweat is odorless upon secretion, but develops a distinctive odor when metabolized by skin bacteria.

The eccrine sweat glands are the main sweat gland of the body. They have an important role in thermoregulation, cooling the body via evaporation of sweat from the skin. They can generate up to 10 liters of sweat per day. These are simple coiled tubular glands located in the deep dermis or superficial hypodermis. Eccrine sweat glands are innervated by the sympathetic component of the autonomic nervous system. They utilize a merocrine method of secretion.

Secretory portion: Single layer of cuboidal to low columnar epithelial cells. Includes clear cells, dark cells and myoepithelial cells. Contractions of the myoepithelial cells expel sweat from the gland.

Duct portion: Double layer of cuboidal cells. Delivers sweat to a pore at the epidermal surface.

Three components of eccrine sweat glands: secretory acini, secretory ducts, myoepithelial cells.

Upper left: Secretory portion, including secretory acini and ducts.
Lower left: Secretory acini and myoepitelial cells.
Upper right: Cross-sections of secretory ducts, showing the characteristic bilayer of cuboidal cells.
Lower right: Secretory duct rising to the epidermal surface.

Nails are slightly curved plates of hard keratin that cover the dorsal surface of the ends of the fingers and toes. The nail plate (N) is equivalent to the stratum corneum of skin. It consists of closely compacted scales of hard keratin and rests on the nail bed. The proximal part of the nail, the root, is buried in a fold of skin. The epithelial cells of the nail bed are continuous with the stratum basale and stratum spinosum of the epidermis. The cells of the nail bed, under the root of the nail, comprise the matrix and serve as a source for new cells. Cells of the matrix divide, migrate toward the root of the nail, and at the root differentiate and produce the keratin of the nail. As the nail grows it slides over the nail bed. Other specializations of the nail include the eponychium, or cuticle (E), which is the edge of the skin fold covering the root of the nail, the distal phalanx (DP) and the skin beneath the free end of the nail, the hyponychium (H).

Skin has a number of sensory receptors, including free nerve endings, hair receptors, Meissner's corpuscles, Pacinian corpuscles, Ruffini corpuscles and Merkel receptors. These subserve the modalties of mechanoreception, including light discriminative touch, crude touch and vibration, as well as thermoreception and pain. Here we will cover the two mentioned in the laboratory guide, the Pacinian corpuscle and the Meissner's corpuscle.

Skin has a number of sensory receptors, including free nerve endings, hair receptors, Meissner's corpuscles, Pacinian corpuscles, Ruffini corpuscles and Merkel receptors. These subserve the modalties of mechanoreception, including light discriminative touch, crude touch and vibration, as well as thermoreception and pain. Here is a photograph of free nerve endings wrapping around a hair follicle bulb.

Pacinian corpuscles are encapsulated mechanoreceptors especially adapted to detect pressure and vibration. They are located in deep dermis and hypodermis. They have a distinctive onion-like appearance due to a tight Schwann cell wrapping around the bare sensory nerve ending.

Meissner's corpuscles are encapsulated mechanoreceptors especially sensitive to light touch. They are located near the surface, in the dermal papillae just beneath the epidermis.

Although difficult to see in H&E stained preparations, Meissner's corpuscles (M) are readily visible with a silver stain.