Introduction to Skin Histology

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.  Recent research:   "Shedding light on skin color," Science 346: 934-936 

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 especially with repeated exposure to sunlight) 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.  

• sweat glands
• hair follicles, sebaceous glands
• nails
• innervation
• vasculature

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.

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Sweat glands

Sweat glands are simple tubular glands lined by cuboidal epithelium.  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.

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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.  

• A network of nerve endings detects deflection of the hair shaft and also controls piloerection (hair "standing on end", or "goose bumps").
• Piloerection is effected by smooth muscle, with a small bundle of smooth muscle cells called the arrector pili attached to the connective tissue sheath around each hair follicle.
• Sebaceous glands secrete oil into the hair follicle.

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.

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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.

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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.

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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.

• Recent research:   "The gentle touch receptors of mammalian skin," Science 346: 950-54.

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

• Free nerve endings (no conspicuous, specialized structures) terminate within the epidermis, penetrating almost to the stratum corneum.
• Merkel's touch corpuscles are nerve endings associated with Merkel cells at the base of the epidermis in thick (glabrous) skin of palms and soles.
• Meissner's corpuscles (images at right) are encapsulated endings in dermal papillae, most common in palmar and plantar skin, especially in fingertips.
• Pacinian corpuscles, located deeper in dermis (image at right), are simple nerve endings but are each encapsulated by multilamellar, ovoid structures resembling small onions.  Pacinian corpuscles respond to deep pressure.
• Ruffini endings have numerous fine branches from a single axon within the fluid-filled space of a single thin capsule.
• Hair follicle receptors are unencapsulated nerve endings wrapped around hair follicles.

The distribution of sensory nerve endings varies from place to place in the body (see regional differences).  

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.

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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).

• Thickness of epidermis.
  • Skin on palms of hands and soles of feet has much thicker epidermis than other regions of skin (up to a millimeter or more, with many cell layers).  
    This so-called thick skin also lacks hair follicles and sebaceous glands.  Thick skin has an especially well-developed, abrasion-resistant stratum corneum.
  • Elsewhere epidermis is substantially thinner than palms and soles, typically with only a few cell layers.  Nonetheless, its thickness varies from region to region -- e.g., commonly about a half-millimeter over most of the body, but as thin as a tenth of a millimeter over eyelids.
• Thickness of dermis.
  • Dermis is commonly one to two millimeters in thickness.
  • Dermis is quite thin in the eyelid (about half a millimeter) and quite thick (several millimeters) over the back.
  • Dermal papillae are most pronounced beneath the epidermis of thick skin.
• Size and concentration of hair follicles / hair shafts.
  • Rather obviously, hairs are thicker and longer on the scalp, axilla, and pubis than on most other regions.
  • Less obviously, tiny hair (vellus hair) occurs even on seemingly hairless regions like eyelids.
  • Hair is absent from "thick skin" of palmar and plantar skin.
• Size and concentration of sebaceous glands.
  • Certain regions of the body (e.g., nose, forehead) are notorious for large and active sebaceous glands.
  • Sebaceous glands are absent from "thick skin" of palmar and plantar skin.
• Size and concentration of sweat glands.
  • The distribution of sweat glands varies over the body, with high concentrations in palmar and plantar skin.  (Incidently, sweat glands of palms and soles respond more to mental and emotional stress than to heat stress.)
  • Large apocrine sweat glands are concentrated in axillary, pubic and perianal areas.  These sweat glands are responsible for "body odor", by including organic substances (and, consequently, bacteria) in their secretions.
• Type and concentration of sensory nerve endings.
  • Different sensory modalities are concentrated in different regions.  
  • Skin of fingertips has the highest concentrations of Meissner's and Pacinian corpuscles.
  • Tactile resolution varies tremendously from region to region, as can be readily demonstrated by a two-point discrimination test.  (Unbend a paperclip so that the two ends can pressed simultaneously against the skin.  Then, with randomly varying touches from one or both ends, see how far apart the ends need to be before the two-end touch is felt as two distinct touches.  The greatest difference is likely to be found between fingertip and the back of the trunk.)
• Presence of muscle.
  • Bundles of smooth muscle may be found in the dermis of nipple, areola, scrotum, penis, and perianal region.
  • In non-human mammals, skeletal-type muscle may be found in dermis (allowing, for example, horses to "twitch" a patch of skin to discourage biting flies).

Functions of Skin

This skin serves several functions simultaneously.  

• Containment -- Skin prevents loss of body fluid.
  • Although the stratum spinosum is permeable to water, the epidermis becomes relatively impermeable in the stratum granulosum and stratum corneum.
  • Damage to extensive areas of epidermis, e.g. by burns, renders the skin highly permeable and constitutes a medical emergency.
     
• Protection -- Skin resists abrasion and penetration, and blocks the entry of foreign material.

  • Epidermis serves as a simple mechanical barrier.  This is probably the most obvious function for skin.
  • Keratinocytes are crucial for the barrier function, both in their tonofilaments and desmosomes which establish the mechanical integrity of the epidermis and in their formation of hardened squames in the stratum corneum.
  • Melanocytes produce melanin pigment, which shields underlying cells from ultraviolet light.
    Recent research:   "The melanoma revolution: From UV carcinogenesis to a new era in therapeutics," Science 346: 945-949; "Shedding light on skin color," Science 346: 934-936
    
  • Collagen of the dermis provides main strength to resist tearing.  The thickness of the dermis is correlated with vulnerability to injury.
     
• Immunological surveillance and defense -- Immune cells of skin stand ready to defend against invasion by microorganisms.
  • Langerhans cells detect foreign antigens in the epidermis.
  • Mast cells stand ready to trigger an inflammatory response if the skin is injured or the epidermal barrier is breached.
  • Recent research:   "Dialogue between skin microbiota and immunity," Science 346: 954-959.
     
• Wound healing -- Skin is extremely effective at regenerating after damage.
  • Cells in the basal layer of the epidermis respond quickly to damage, proliferating and migrating to cover the site of injury (moving in under the scab).
  • Epithelial replacement can spread from deep hair follicles and sweat glands if the surface epidermis has been damaged over an extensive area.
  • Fibroblasts also become activated by injury, to proliferate and to manufacture new collagen.  The resulting scar may be eventually remodelled into a nearly-normal configuration of fibers. 
  • 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.
  • Recent research:   "Advances in skin grafting and treatment of cutaneous wounds," Science 346: 941-945.
     
• Sensation -- Skin receives several modalities of tactile information over the entire body, from a variety of receptors.

  • Recent research:   "The gentle touch receptors of mammalian skin," Science 346: 950-54.

  
  
• Thermoregulation -- Skin controls the transfer of heat across the body's surface, facilitating as needed both heat retention and heat dissipation.
  • Sweat glands are vital for thermoregulation.  Even when the external temperature is higher than body temperature, evaporation of sweat can cool skin below the core temperature.  Normal thermoregulatory sweating is often insensible, with sweat evaporating as quickly as it forms.  Sweat which drips from the body (e.g., during heavy exercise in humid weather) is much less inefficient, as the body tries to compensate more-or-less ineffectively for rising internal temperature.
  • Under normal circumstances, skin is cooler than the body core.  Thus increasing or decreasing blood flow through capillaries in the papillary layer of dermis can dissipate or conserve body heat.
  • Fat of the hypodermis can serve as effective insulation.  Regulation of blood flow into the dermis determines the extent which this insulation is used (to conserve heat) or bypassed (to dissipate heat).
     
• Communication -- Skin releases visual and pheromonal signals (blushing, body odor, nervous sweating).  

Comments and questions: dgking@siu.edu

SIUC / School of Medicine / Anatomy / David King

https://histology.siu.edu/intro/skin.htm
Last updated:  25 September 2021 / dgk