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Introduction to Skin Histology

The skin is the largest organ of the body.  As the primary interface between ourselves and our environment, the skin serves several distinct functions.

The microscopic anatomy of skin reflects this functional complexity, with each functional specialization implemented by particular features of cell and tissue structure.


The skin has two principal layers.

Epidermis, the epithelial layer of skin, is primarily protective.  This layer, consisting of keratinized stratified squamous epithelium, is tough, relatively impermeable, and self-replacing.  These functional qualities are conferred by the epidermis' principal cell type, the keratinocyte.

The quality of the epidermis differs from place to place in the body (see regional differences).  The quality of the epidermis can also be altered by various disease states which influence the rate of cell division and the quality of cell differentiation.

The epidermis displays several layers.  These layers are not distinctly different tissues (unlike epidermis and dermis, for example) but rather reflect visible changes or stages along the continuous process of keratinocyte maturation, or keratinization.

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Stratum corneum.  Cells of the cornified layer are dead, protective keratinized "squames", eventually sloughed off.
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Stratum granulosum.  Cells in the granule-cell layer accumulate keratohyalin, visible as darkly stained granules.  The presence of this layer is diagnostic for keratinized stratified squamous epithelium.
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Stratum spinosum.  Cells of the "prickle-cell" layer are attached to one another by desmosomes ("spines") and reinforced by tonofilaments.  These cells gradually move outward as new cells are formed from the basal layer (below).
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Stratum basale / stratum germinativum. Cells of the basal layer are attached to the basement membrane (dashed line) by hemidesmosomes.  When a basal cell divides, one of the daughters migrates upward to replenish outer layers of cells.
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The dermis lies beneath the epidermis, separated from the epithelium by the basement membrane (white dashed line).

Keratinocytes

The epidermis consists primarily of keratinocytes.  Scattered among the keratinocytes are a few other cell types -- melanocytes, Langerhans cells, and Merkel cells

Keratinocytes, which comprise most of the epidermis, are characterized by numerous intercellular junctions (desmosomes), reinforced by intracytoplasmic tonofilaments.  

 Each desmosome is one spot of attachment.  At high magnification, the desmosomes are visible as fine "prickles" extending across the gap (intercellular space) between adjacent keratinocytes.  In between these junctions lie intercellular channels which permit nutrients to diffuse from dermis into epidermis.   (More.)

Keratinocytes in the stratum basale of the epidermis can undergo mitosis.  The formation of new cells in this basal layer gradually pushes previously formed cells upward through the stratum spinosum.  As keratinocytes approach the surface of the epidermis, they accumulate intracellular keratin and secrete a waxy material into the intercellular space; these changes are visible in the stratum granulosum, a distinctive layer which is diagnostic for a keratinized epithelium.  As maturing keratinocytes seal off the intercellular spaces through which they receive nutrients, they eventually die and form the stratum corneum, a tough and relatively inpermeable layer of hardened, dead cells.  Eventually, as cells reach the surface, they are sloughed off.  The entire epidermis above the basal layer is replenished (replaced by new cells) within about two weeks.  Replacement is accelerated by injury.

The stages in keratinocyte maturation appear as layers in the epidermis, so that a section across the epidermis illustrates the entire process.  

See the Elektronenmikroskopischer Atlas im Internet for (mostly unlabelled) EM images of epidermis.

 


Other epidermal cell types

Scattered among the much more numerous keratinocytes are several other epidermal cell types -- melanocytes, Langerhans cells, and Merkel cells.  Because these cells lack the tough reinforcement and desmosomal attachments that characterize keratinocytes, they commonly shrink during preparation and appear surrounded by a clear "halo".   (Together these cell types are all quite distinct from keratincytes.  But they are difficult to distinguish from one another without special techniques.)

Melanocytes manufacture the pigment melanin.  Melanocytes appear as small cells, usually in or near the stratum basale.  They have thin cytoplasmic processes (not evident in ordinary histological preparations) which extend between nearby keratinocytes and serve to transfer melanosomes (melanin-containing granules) into adjacent keratinocytes.  Because of this transfer, most pigment-containing cells in the epidermis are normally keratinocytes rather than melanocytes.  Melanocytes are derived from neural crest and migrate to their final position in the epidermis.  This developmental propensity for travel may contribute to the dangerously metastatic potential of melanomas.

Langerhans cells are antigen-presenting cells which participate in the surveillance function of the immune system.  (Antigen-presenting cells acquire foreign materials [antigens] and pass them along to lymphocytes.)  Langerhans cells are smaller than keratinocytes, with relatively clear cytoplasm, usually located within the stratum spinosum or stratum basale.  Langerhans cells are dendritic cells, with extensive cytoplasmic processes extending between keratinocytes to sample intruding antigens throughout the epidermis.  (more)

Merkel cells are small cells associated with nerve endings in epidermis.  Their function has long been uncertain, but they seem to be involved in neural development and tactile sensation.  Recent evidence supports a role for Merkel cells in light touch, "suggesting that these cells form an indispensible part of the somatosensory apparatus" (Science 324:1580, 2009; also see The Journal of Neuroscience 32(10): 3296-3300, doi: 10.1523/JNEUROSCI.5307-11.2012 ).   Some uncommon skin cancers derive from Merkel cells.

See the Elektronenmikroskopischer Atlas im Internet for (mostly unlabelled) EM images of Merkel cells.


Dermis

The dermis consists of dense, fibrous connective tissue whose predominant connective tissue component is collagen.  

Like ordinary connective tissue throughout the body, connective tissue of the dermis serves several distinct functions.  

Within the dermis are embedded several other structures, including epidermal appendages (sweat glands and hair follicles) as well as blood vessels and nerve endings.  

The connective tissue of the dermis grades into hypodermis, without a sharp transition or distinct boundary.  

Over most of the body, hypodermis is characterized by adipocytes and may comprise a thick layer of adipose tissue.  In some sites (e.g., "dimples"), hypodermis is fibrous and binds the dermis to underlying structures.

Blood vessels are generally larger in the deeper layers of skin, with only capillaries in the papillary layer of the dermis.


The appearance of the skin can have considerable clinical significance.  The skin is readily accessible for examination (no invasive procedures needed), and its color and texture can reveal much about underlying physiology.

Color:  Skin is moderately transparent.  Light which penetrates the skin is reflected back from varying depths by epidermal cells, by collagen, and by blood.  

Melanin produced by melanocytes and stored in basal keratinocytes contributes a yellow/brown color to the epidermis.  If the epidermis is not heavily pigmented, light readily penetrates into the dermis.

Collagen scatters light from the dermis without altering its color.  Hence, the whiteness of "white" skin is primarily a reflection of collagen.

Hemoglobin in red blood cells scatters red light and is responsible for the pinkness of unpigmented skin.  The relative amount of pink in any given patch of skin reflects how closely blood approaches the base of the epidermis (i.e., how much collagen intervenes to scatter white light before red blood cells can absorb the non-red colors).

Each of these elements contributes to the apparent color of skin.  Variations in skin color in different parts of the body (see regional differences) are based on variations in these elements, most especially the amount of pigment, the thickness of dermis, and the degree of perfusion in dermal capillaries.

Perhaps most significantly, blood flow through the dermis is highly variable and is regulated in response to many conditions (heat, pain, fluid balance, inflammation, emotional reaction).  Resulting variations in pinkness can provide indicators of underlying physiology, both locally and systemically.  Obvious examples include inflammation, overheating, dehydration, shock, and even embarrassment (i.e., blushing) .

Texture:  Skin texture is affected the thickness and smoothness of the epidermis, by the quality of fibers in the dermis, and by the amount of fluid in dermal connective tissue.

Because the epidermis is continually being replenished by cell divisions among basal keratinocytes and because this tissue is exposed to a variety of insults, the epidermis is especially prone to disturbances of growth.  See any pathology book for examples.

The connective tissue fibers of the skin are permanent, enduring without replacement (except by repair after injury) throughout life.  Although collagen is quite durable, elastin commonly deteriorates with age and loses its elasticity.  This is easily demonstrated by a "pinch test".  In youthful skin, loose skin that has been pinched into a ridge quickly returns to its normal position when released.  Elderly skin commonly remains in its deformed position, returning more slowly if at all.  

Both edema (accumulation of excess fluid in connective tissue) and dehydration can dramatically alter the appearance of skin.


Skin includes several specialized structures, including epidermal appendages (sweat glands, hair follicles, nails) as well as blood vessels and nerve endings which travel through the dermis.  

Epidermal appendages play an especially important role in recovery from superficial scrapes and burns.  Even when the epidermis has been removed over a fairly large area, it can grow back quickly from the epithelial cells which remain in deeper hair follicles and/or sweat glands.  Third-degree burns are so serious precisely because tissue damage extends deep enough into the dermis to destroy these sources of replacement cells.


Sweat glands

Sweat glands are simple tubular glands.  The secretory portion of the gland lies deep in the dermis, where the tubule is twisted into a fairly compact tangle.  A duct communicates outward through the overlying dermis and the epidermis.

The secretory portion is comprised of larger cells than the duct.  These cells form a simple cuboidal epithelium, along with interspersed myoepithelial cells (which can expel sweat by contraction).

Cells comprising the duct, or conducting portion of the tubule, usually form a two-layered stratified cuboidal epithelium.  These cells are usually stained more intensely than those comprising the secretory portion of the tubule.  As fluid flows through the duct, its composition is modified by reabsorption of certain elements from the fluid.  (This is primarily a means of conserving salt.)

Sweat glands are vital for thermoregulation.  They also influence water and ion balance.

The primary function for sweating is evaporative cooling of the body.  Thus, the amount of sweat is regulated as a function of body temperature.  

However, sweat also contains salt.  Normally, sweat which comes out on the surface of the skin has a lower salt concentration than the precursor fluid produced by the secretory cells of the sweat gland.  Salt is reabsorbed by the duct of the sweat gland.  The effectiveness of this salt reabsorption is regulated by aldosterone (the hormone responsible for maintaining electrolyte homeostasis) in response to bodily salt balance.

There are two types of sweat glands, ordinary eccrine sweat glands found over most of the body, and large apocrine sweat glands of axillary, pubic, and perianal regions.

Both types of sweat glands have the same basic shape, but apocrine glands have taller cells and much larger diameter.


Hair follicles

Hair follicles are tubular invaginations lined by stratified squamous epithelium similar to epidermis.

Toward the bottom of each follicle, processes of cell division, growth, and maturation similar to those in the epidermis yield a cylindrical column of dead, keratinized cells (the hair shaft) which gradually extrudes from the follicle.  (For details, consult your histology textbook.)

Hair follicles are associated with sebaceous glands as well as nerve endings and smooth muscle to form the pilosebaceous apparatus.  

Hair growth is moderately complex, resulting in considerable variation in appearance of hair follicles related to growth phase (i.e., anagen, catagen, and telogen, or growing, regressing, and resting) and to body region, age, and gender.


Sebaceous glands

Sebaceous glands are associated with hair follicles.  The complex of hair follicle, hair shaft, and sebaceous gland is sometimes called the pilosebaceous apparatus.  

Histologically, sebaceous glands quite different from all other glands.  They are holocrine glands, which means that the whole cell is secreted.  The process of holocrine secretion is more similar to maturation of keratinocytes than to ordinary glandular function.  Cells formed by mitosis at the base of the gland are pushed toward the surface as new cells form below.  Along the way, the cells become packed with lipid and then die.  The secretion consists of breakdown-products of the cells themselves, which extrude into the lumen of the associated hair follicle.  So, basically, sebaceous glands are small masses of epidermal cells in which sebum (a mixture of lipids) accumulates rather than keratin.  

The dying cells in sebaceous glands provide a good opportunity to learn the appearance of pyknotic nuclei, one of the more conspicuous signs of cell death.


Nails

Please consult an in-depth text (e.g., Chapter 3, Histology for Pathologists, Sternberg, 1998; newer edition: Mills, Histology for Pathologists, 3rd ed., 2007) if you desire histological details on fingernails and toenails.


Meissner's corpuscles
Pacinian corpuscle

Innervation

The skin is richly innervated, served by a variety of sensory nerve endings which respond to a variety of modalities (e.g., pressure, vibration, heat, cold, itch, pain) and by motor nerve endings which control blood flow, sweat secretion, and piloerection.

For richer information on the following, see Neuroscience Online, Somatosensory systems.

Except for the characteristic capsules of Meissner's and Pacinian corpuscles, nerve endings are inconspicuous in ordinary histology preparations of skin.  

Special stains are generally used to observe nerve endings.  And except for these same, fairly conspicuous encapsulated endings, the functional details of most sensory endings remain obscure.  For more information on tactile sensation, see Principles of Neural Science by Kandel, Schwartz and Jessel.

Peripheral nerves (i.e., bundles of axons, within a connective tissue sheath or epineurium) can often be found in dermis, with smaller branches toward the surface (i.e., often near sweat glands or hair follicles) and larger branches in deeper layers (often running parallel to blood vessels).  The following examples show nerves in dermis.


The papillary layer of the dermis is richly supplied with capillaries, while larger blood vessels may be found in deeper levels of the dermis.

Since the skin does not have a very high metabolic demand for nutrients and oxygen, this rich vascular network serves mainly for regulation of body temperature.  Essentially, regulation of the amount of blood flowing through superficial capillaries allows for either conservation or dissipation of body heat.

Arteriovenous shunts, controlled by associated sphincters, allow blood to bypass capillaries and flow directly from arteries into veins.  These shunts occur in both deep and superficial dermis.


Regional Differentiation

Skin varies markedly over different parts of the body.  All of the components of skin contribute to this variation.  Consult a textbook for illustrations (e.g., pp. 42-43 in Histology for Pathologists, Sternberg, 1998; newer edition: Mills, Histology for Pathologists, 3rd ed., 2007).


Functions of Skin

This skin serves several functions simultaneously.  


Comments and questions: dgking@siu.edu

SIUC / School of Medicine / Anatomy / David King

http://www.siumed.edu/~dking2/intro/skin.htm
Last updated:  7 March 2012 / dgk