THE SKIN (INTEGUMENTARY SYSTEM)
Rhonda Ghorbani, MD
Reading: Gartner and Hiatt, pp 229-244; Gartner, Hiatt, Strum, pp 215-227
Learning Objectives:
 List the basic functions of the skin and describe its overall structure
 Describe basic skin embryology
 State the names of the layers of the epidermis and how to distinguish them histologically
 Explain ultrastructural (electron microscopic) features of the epidermis and the epidermal/dermal
junction
 Describe the process of keratinization in the epidermis, hair, and nail
 Describe the formation of the water barrier in the epidermis
 Name the non-keratinocytic cells in the epidermis and state their functions
 Explain the structure and components of the dermis, including types of nerves and vascular
system
 State the segments and layers of the hair follicle
 Describe the relationship between hair size and phase of hair growth
 Describe the structure, location, and function of different types of cutaneous glands
 Describe the structure and growth of the nail
Key Words: arrector pili muscle, dermal papillae (dermal ridges), dermal sheath, dermis, duct of
sweat gland, epidermis, external root sheath, glassy membrane, hair bulb, hair follicle, hair
matrix, hair papilla, hair root, hair shaft, hypodermis, internal root sheath, interpapillary pegs (rete
pegs), Meissner's corpuscle, melanocytes of epidermis, melanosomes (melanin granules),
myoepithelial cell, Pacinian corpuscle, papillary layer of dermis, reticular layer of dermis, sebaceous
gland, stratum basale, stratum corneum, stratum granulosum, stratum lucidum, stratum spinosum,
sweat gland
INTRODUCTION
 Skin is one of the largest organs in the human body, representing 15-20% of total body weight. It
serves many functions, including:
S – SENSATION (it is a receptor for pain, pressure, touch, temperature)
C – CONVERSION (of precursor molecules into vitamin D)
R – REGULATION (of heat)
A – ABSORPTION (of certain lipid-soluble therapeutic substances)
P – PROTECTION (against injury of many kinds) & PREVENTION (of water loss)
E – EXCRETION (of waste products via sweat glands)
The skin can be divided into compartments
EMBRYOLOGY
 Epidermis: single-layered ectoderm  multilayered periderm  stratified squamous epithelium
o Vernix caseosa: desquamated periderm/epidermis; slippery; protective and aids in birth
 Dermis: mesoderm  mesenchyme  dermis composed of multiple cell types
 Hair: epidermal invagination  lanugo hairs (fine, lightly pigmented)  mature hairs
 Melanocytes: neural crest  become melanoblasts in mesenchyme  mature in epidermis
EPIDERMIS
 Avascular layers of keratinocytic and non-keratinocytic cells
 Thickness ranges from 0.1 – 1.0 mm, depending on location
o The terms “thin” and “thick” skin refer to the thickness of the epidermis
o Thin skin = hairy skin (most of the body)
o Thick skin = hairless skin (glabrous skin on palmar/plantar surfaces, i.e. palms/soles)
epidermis
KERATINOCYTES
 Squamous cells (forming a stratified epithelium) are the major cellular components of the epidermis
 Migrate from the basal layer to the superficial surface over a period of about 3-4 weeks
(approximately 26 days)
Stratum corneum = cornified layer or horny layer
Stratum lucidum
Stratum granulosum = granular layer
Stratum spinosum = spinous layer or prickle cell layer
Stratum basale or stratum germinativum = basal layer or
germinative layer
UPPER LAYERS OF EPIDERMIS
Stratum corneum:
 Multiple layers of “flake-like” cells
(a.k.a. squames) filled with keratin,
without nuclei or organelles
 Very thick on palms/soles because
exposed to friction
 Eventually shed from skin surface
Stratum lucidum:
 Homogeneous zone (eosinophilic or
red) between strata corneum and
granulosum
 Only present in thick skin
 Cells contain eleidin (remains of
broken-down keratohyaline granules)
Stratum granulosum:
 1-3 layers of flattened cells
 Contains keratohyaline granules
(basophilic or dark purple)
LOWER LAYERS OF EPIDERMIS (stratum Malpighi or Malpighian layer)
Stratum spinosum:
 Often the thickest layer
 Suprabasal cells are rounder and
superficial cells are flatter
Stratum basale:
 Single row of mitotically-active
columnar to cuboidal cells which
give rise to other keratinocytes
DESMOSOMES
 Cells of the stratum spinosum are joined together by desmosomes (a.k.a. macula adherens),
which are visible only by electron microscopy
 Desmosomes are composed of:
o Desmogleins and cadherins (transmembrane glycoproteins)
o Plaques (composed of desmoplakins): 2 per desmosome (one associated with each
cell)
 Tonofibrils within the cytoplasm of the cell attach to the plaque
desmogleins
& cadherins
plaque
intermediate
filaments
KERATINIZATION
 Keratohyaline granules are rich in histidine, cystine, and filaggrin
 Filaggrin combines with cytoplasmic filaments in the process of keratinization
 Cells undergo keratinization after leaving the stratum granulosum and entering the stratum
corneum
 Keratinization involves breakdown of nucleus and organelles and thickening of plasma
membrane
 Stratum corneum = dead cells with thick plasma membranes, cytoplasmic filaments, and
interfilamentous matrix
 Types of keratin:
o Soft keratin: produced via granules (e.g. in the epidermis)
o Hard keratin: produced without granules (e.g. in the hair and nails)
 It is hard because there are many disulfide bonds
WATER BARRIER
 Lipid-containing lamellar granules (a.k.a. Odland bodies) are produced by the Golgi of
keratinocytes and are discharged into the intercellular space by cells of the stratum
granulosum
 Released lipid localizes to the lower stratum corneum, forming a barrier to water loss
NON-KERATINOCYTIC CELLS OF EPIDERMIS
 There are three types of cells other than keratinocytes within the epidermis:
o Melanocytes
o Langerhans cells
o Merkel cells
 Of the three cell types, only melanocytes can be seen by routine H&E staining
melanocyte
MELANOCYTES
 Round cells with clear cytoplasm and basophilic nuclei by H&E stain
 Have long dendritic processes (not visible by H&E) which extend between keratinocytes
 Located within the basal layer of the epidermis and in hair follicles
 Do not establish desmosomal attachments with keratinocytes; instead, they bind to the basal
lamina via hemidesmosomes
 Contain premelanosomes (visible only by electron microscopy), which are membrane-bound
spherical and elliptical organelles produced by Golgi
 Premelanosomes have a finely ordered lamellar internal structure which becomes obscured as
melanin is produced and deposited
 Fully-formed melanosomes are transferred to keratinocytes via melanocytes’ dendritic processes
via cytocrine secretion
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The enzyme tyrosinase is responsible for the production of melanin within premelanosomes:
tyrosine  3,4-dihydroxyphenylalanine (DOPA)  dopaquinone  melanin
Skin color is influenced by:
o Melanin: pigment within melanosomes
 Types: eumelanin (usual type) and pheomelanin (blonde and red hair)
 Number of melanocytes in normal skin is constant among races – approximately 1
melanocyte per 4-10 basal keratinocytes – but may vary from region to region within
an individual
 Degree of skin pigmentation is dependent on melanosomes in keratinocytes – their
number, size, location within the cell (closer to the nucleus in fair-skinned), stability,
and degree of melanization
 Tanning is due to increased rates of melanin darkening, transfer of melanosomes to
keratinocytes, and melanin production
 Increased pigment shields nucleic acids and proteins from UV radiation
 Gray hairs are due to decreased number and activity of melanocytes in follicular bulbs
o Oxyhemoglobin: in dermal vascular bed
o Carotenes: food pigment in fat-containing tissues
o Exogenous minerals (e.g. tattoos)
o Hemoglobin breakdown products (e.g. hemosiderin, bilirubin)
MERKEL CELLS
 Located within stratum basale
 Highest concentration in digits, orogenital regions, and hair follicles
 Contain electron-dense granules by electron microscopy
 Establish desmosomal attachments with neighboring cells
 The base of each cell is in contact with an afferent nerve ending coming up from the dermis
 Have a receptor function
Langerhans cell
Merkel cell
keratinocyte
melanocyte
EPIDERMAL-DERMAL JUNCTION (EDJ)
 The EDJ forms an undulating interface visible by routine light microscopy as downward
projections of the epidermis (epidermal ridges or rete ridges or epidermal pegs or interpapillary
pegs) and corresponding upward projections of the papillary dermis (dermal ridges or dermal
papillae)
o These projections interdigitate to increase surface area and to reinforce the connection
(i.e. promote adhesion) between epidermis and dermis
o Fingerprints (only present in thick skin) are caused by prominent dermal ridges but are
not recognizable as distinct entities by light microscopy
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The basal laminae separate the epidermis from the dermis and form a network of components
keeping the epidermis connected to the dermis
Most EDJ components are only visible by electron microscopy
Regions of the EDJ:
o Basal keratinocyte
o Lamina lucida: electron-lucent zone
o Lamina densa: electron-dense zone
o Sublamina densa: uppermost papillary dermis
Individual structures of the EDJ:
o Hemidesmosome: attaches basal keratinocyte to basal lamina
 Structurally identical to the desmosome except there is no adjacent cell with a
complimentary device
 Has an intracellular component along the basal plasma membrane to which
tonofilaments attach
 Has an extracellular component within the lamina lucida
o
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Anchoring filament: attaches hemidesmosome to basal lamina
 Extends from inner plasma membrane to lamina densa
Anchoring fibril: tethers epidermis to dermis
 Extends from lamina densa into papillary dermis, terminating on an anchoring
plaque
 Traps collagen within a fibrillar network which enhances attachment
DERMIS
 Composed of collagen, elastic fibers, ground substance (amorphous extracellular material) and
fibroblasts
o Collagen accounts for > 70% of skin’s dry weight
o Type I collagen is the most abundant, followed by type III (in adults)
o Provides support and strength to the skin
 Contains blood and lymphatic vessels, nerve endings, and cutaneous adnexal structures
 Contains striated muscle fibers in the face and neck
 Contains smooth muscle fibers in the external genitalia and areola
 Divided into two regions:
o Papillary dermis: superficial loose connective tissue
o Reticular dermis: deeper dense connective tissue
 Thicker than papillary dermis, although thickness varies among different parts of
the body
 May contain adipocytes (fat cells)
BLOOD VESSELS
 Horizontal plexuses of superficial (in upper reticular dermis) and deep (in lower reticular dermis)
arterioles and venules joined by vertical communicating vessels
 Superficial vescular plexus sends capillaries into dermal papillae which nourish the epidermis
 Blushing results from capillary dilatation
NERVES
 Efferent nerve fibers: innervate blood vessels, adnexal structures, smooth muscle
 Free afferent nerve endings: nociceptors (pain receptors) in epidermis and dermis
 Encapsulated nerve endings: nerve end organs
o Meissner corpuscle: mechanoreceptor (tactile)
 Located high in dermal papillae of palms, soles, digits, nipples, lips
 Cylindrical or pear-shaped
 Zigzag arrangement of unmyelinated terminal afferent nerve fibers with
supporting (laminar) cells thought to be Schwann cells
 Can be seen by routine light microscopy but difficult to locate
o Pacinian corpuscle: mechanoreceptor (pressure)
 Located in deep dermis or subcutis of weight-bearing and sensitive areas
 Ovoid; resembles a cut onion
 Contains a terminal afferent nerve fiber which loses its myelin after entering
the corpuscle, and has supporting (laminar) cells thought to be Schwann
cells
Meissner corpuscle
Pacinian corpuscle
Plate 11-4, Figure 3, pg 233
Plate 11-4, Figure 4, pg 233
CUTANEOUS ADNEXAL STRUCTURES (SKIN ADNEXAE)
 There are different types of adnexal structures within the skin, mainly within the dermis:
o Pilosebaceous unit = hair follicle + sebaceous gland
 Sebaceous glands may exist independently in limited locations
o Eccrine gland
o Apocrine gland
HAIR FOLLICLE
 Present over entire body except: sides and volar surfaces of hands/feet, lips, around urogenital
orifices
 Rate of hair growth: few tenths of 1 mm/day
 Hair functions: protection (of nasal passage from particulate matter, of scalp from sun, of eyes
from sun and sweat), reduction of heat loss, decoration
SEGMENTS OF THE HAIR FOLLICLE
Infundibulum: from skin surface to
opening of sebaceous duct
Isthmus: from opening of sebaceous duct
to arrector pili muscle insertion
Inferior segment: from arrector pili
muscle insertion to base of follicle
Plate 11-2, Figure 1, pg 229
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The infundibulum is a continuation of the epidermis
o It contains the pilosebaceous canal, through which the hair shaft and sebum pass
o The intraepidermal segment is called the acrotrichium
The arrector pili muscle is a bundle of smooth muscle which attaches to the connective sheath
surrounding the hair follicle
o Arrector pili muscle contraction results in “goose pimples” (erect hair follicles)
o The hair bulb is the bulbous base of the follicle which contains the dermal hair papilla (a
connective tissue invagination) and the pluripotential hair matrix (which gives rise to the
six cell layers of the hair and inner root sheath)
Bulb
Dermal hair papilla
Plate 11-3, Figure 1, pg 231
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Phases of hair growth
o Anagen (growing)
o Catagen (involuting)
o Telogen (resting)
ANAGEN
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CATAGEN
TELOGEN
Hair length is related to the amount of hair in the anagen phase; therefore, the anagen phase lasts
for years on the scalp but is shorter for other regions of the body
Hair size:
o Terminal: long, coarse, heavily pigmented; produced by long follicles; spend a long time
in anagen; e.g. scalp, axilla, pubis
o Vellus: short, thin, lightly pigmented; produced by small follicles; spend a long time in
telogen
 Conversion of terminal to vellus hairs is one of the causes of baldness
Hair follicle layers from outermost to innermost:
o Connective tissue (fibrous) sheath
o Glassy (basement) membrane
o External (outer) root sheath: layer of clear
(due to abundant glycogen) cells continuous
with the basal layer of the epidermis; does
not arise from the hair matrix
o Internal (inner) root sheath: dissolves at the
level of the sebaceous duct opening
 Henle’s layer: first layer to cornify
 Huxley’s layer
 Cuticle
o Hair (a.k.a. hair shaft): keratinized
 Cuticle
 Cortex
 Medulla: last layer to cornify
Graphic 11-2, pg 225
HAIR FOLLICLE IN CROSS-SECTION
Plate 11-3, Figure 2, pg 231
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Melanin production by melanocytes in the hair follicle contributes to hair shaft pigmentation
Hair follicle keratinization:
o Hair shaft layers (medulla, cortex, and cuticle) keratinize without granules; thus, hair
keratin is hard keratin
o Inner root sheath layers keratinize via trichohyaline granules, which stain eosinophilic (in
contrast to basophilic keratohyaline granules in the epidermis); thus, inner root sheath
keratin is soft keratin
 When fully keratinized cells of the inner root sheath reach the isthmus, they
disintegrate; therefore, they do not contribute to the exiting hair
o Outer root sheath keratinization is called tricholemmal keratinization (tricho- meaning
hair), and it also occurs without granules, producing hard keratin
 This occurs at the isthmus, after the inner root sheath has disintegrated
SEBACEOUS GLAND
 Present in all skin except palms and soles
 Most numerous and most productive on scalp and face
 Largest on nose, forehead, and upper back
 Hormonally responsive (therefore, well-formed in neonates and during the reproductive years, but
small and inactive during other periods of life)
 Formed by cells of the outer root sheath, usually several lobulated glands (saccules) to one hair
follicle
 Periphery of gland: germinative (basal) cells
 Center of gland: larger cells filled with lipid vacuoles
 Central cells disintegrate to form an oily product called sebum (holocrine secretion)
 Sebum is discharged into the sebaceous duct, which opens into the sebaceous canal in the lower
infundibulum of the hair follicle
Graphic 11-2, pg 225
ECCRINE GLAND (SWEAT GLAND)
 Located over the entire body except: lips, some external genital structures, external auditory canal
 Embryology: downgrowths from periderm into mesenchyme
 Highest concentration in the palms, soles, forehead, axilla [note: in these regions, the eccrine
glands respond primarily to emotional stimuli, whereas those in other regions respond to thermal
stimuli]
 Functions: thermoregulation (cooling results from sweat evaporation) and excretion
 Secretory portion:
o Located in deep dermis or upper subcutis
o 2 different types of secretory cells: staining differences may not be prominent by H&E
 Clear cells: contain glycogen; located between dark cells and myoepithelial cells
 Dark cells: contain mucopolysaccharide; located luminally
o Merocrine secretion
o Surrounded by a row of myoepithelial cells, which contract to move secretions out of
gland
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Duct portion:
o Stratified cuboidal epithelium without myoepithelial cells
o Leaves the secretory portion as a coiled duct, then becomes straight
o Spirals through the epidermis to the skin surface as the acrosyringium
Sweat is a watery solution low in protein; it contains NaCl, urea, uric acid, and ammonia
Innervated by the sympathetic nervous system and stimulated by cholinergic transmitters in
response to heat and acute stress
APOCRINE GLAND
 Located in axilla, areola, perineum, circumanal region, external genitalia, external ear canal
(ceruminous glands), and eyelid (Moll’s glands)
 Small and nonfunctional until puberty
 Secretory portion:
o Located in deep dermis or upper subcutis
o Up to 10x greater diameter than eccrine gland
o Single row of cuboidal cells with abundant eosinophilic cytoplasm
o Called “apocrine” because it looks like the cell apex is being pinched off (a.k.a.
decapitation secretion), but it is actually merocrine (exocytotic) secretion
o Surrounded by a row of myoepithelial cells, which contract to move secretions out of
gland
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Duct portion:
o Two layers of cuboidal cells and an inner cuticle but no myoepithelial cells
o Travels from the secretory portion and empties into the infundibulum of the hair
follicle, above the entrance of the sebaceous duct
Considered a type of sweat gland but are not “the sweat glands”
Secreted product becomes odiferous as the result of bacterial decomposition
Innervated by sympathetic nervous system and stimulated by adrenergic transmitters in
response to emotional and sensory stimuli
SUBCUTIS (HYPODERMIS; PANNICULUS ADIPOSUS; SUBCUTANEOUS FAT)
 Deep to dermis and superficial to skeletal muscle
 Lobules of adipose tissue surrounded by fibrous tissue septae
NAIL
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Nail plate: keratinized plate on the dorsal surface of the terminal digits
o Complete regeneration after removal: 5-6 months on finger & 1-1.5 years on toe
o Inserts into lateral and proximal grooves in skin
o Overhung by lateral nail fold and proximal nail fold, which are skin folds
Nail bed: layers of epithelial cells upon which the nail plate rests
o Continuous with strata basale and spinosum of epidermis
o Does not have a stratum granulosum
o Has long, narrow, sometimes pointed rete ridges and dermal papillae
o Overlies a richly vascular dermis that is contiguous with distal phalangeal periosteum
Nail root: proximal part of nail buried under proximal nail fold
Nail matrix: germinative epithelium of basaloid cells under the root that differentiates into the nail
plate (keratinizes without granules  hard keratin) and into some of the cells of the nail bed
Lunula: crescent-shaped pale area near the root, just distal to the proximal nail fold
o Especially prominent on the thumb
o Thought to be due to thick layer of matrix (obscuring pink color imparted by blood
vessels) and incomplete cornification of nail
Eponychium (cuticle): cornified edge of proximal nail fold
o Seals off potential space between fold and nail
Hyponychium: epidermal thickening distal to nail bed that joins to undersurface of free edge of
nail plate
o Separated from volar (palm/sole) skin by the distal groove (not really a groove, but a
slightly elevated margin)
o Cornifies like volar skin
INTEGUMENT (SKIN) LABORATORY
SLIDES 10 and 39 – Thick Skin (HEEL or BIG TOE)
Begin by holding the slide up to the light…
1. The basophilic rim around the outer portion of the tissue on one side is the epidermis.
Note that the epidermis is no more than a couple of millimeters thick, even in this
example of thick skin.
2. The pink layer underlying the epidermis is the dermis.
3. The subcutaneous tissue (the hypodermis or subcutis) contains adipose tissue, which
produces a pale, lacy or lobulated appearance. The dermis itself may contain a small
amount of fat, particularly in association with adnexal structures.
Now, place your slide under the microscope…
Questions: What makes thick skin “thick”
What is the commonest cell type in the epidermis?
What are the ‘clear cells’ – rounded cells with dense nuclei and pale staining cytoplasm in basal
layer)?
Name two other cells types in the epidermis PLUS their function(s)
Are there blood vessels in the epidermis?
1. Identify the layers of the epidermis (stratum corneum, stratum lucidum, stratum
granulosum, stratum spinosum, stratum germinativum) and the epidermal-dermal
junction.
Next, move on to examination of the dermis.
 Low power: identify papillary and reticular dermis, rete ridges, dermal papillae,
superficial and deep blood vessels, eccrine (sweat) glands, and eccrine ducts
 High power: identify nerve endings; examine the cellular composition of the
dermis
 Meissner’s corpuscles in dermal papillae may be difficult to see in
your slides. These are cylindrical or pear-shaped. View them on
the demonstration slide.
Questions:
 What are some functions of the rete ridges and dermal papillae?
 What is the major component of the dermis and how does it differ between the
papillary and reticular dermis?
 How can you differentiate between eccrine glands and eccrine ducts based on their
location and their cell layers?
 What skin appendages are not present on this (or any) slide of thick skin?
2. The hypodermis is predominantly composed of adipose tissue. Look for Pacinian
corpuscles (although they may not be present on every slide).
SLIDE 9 – SCALP (thin skin)
1. Identify once more the epidermal and dermal layers. Note the differences between thin
skin (H-7) and thick skin (H-135 and H-111): the thinner overall epidermis, reduced
thickness of the stratum corneum, absence of an identifiable stratum lucidum, reduced
prominence of rete ridges, and presence of pilosebaceous units.
2. Low power: identify the following:
 Three segments of the hair follicle: infundibulum, isthmus, inferior segment;
note how deeply the hair follicles extend in the scalp.
 Sebaceous gland
3. High power: identify the following:
 Layers of the hair follicle: inner and outer root sheath
 Look for red-staining trichohyaline granules in the middle layer
of the inner root sheath
 Other features of the hair follicle
 Connective tissue sheath: surrounds the follicle
 Hair bulb: note the keratinocytes and melanocytes
 Dermal hair papilla: identify the dermal connective tissue
extending into the bulb; some slides may show nerve endings
and blood vessels in the hair papilla
 Hair: looks gold-brown and grainy on H&E-stained slides
 Arrector pili muscle
Questions:
3. Why do the cells of the outer root sheath appear “clear”?
4. Where does the inner root sheath terminate?
5. What type of secretion occurs in the sebaceous gland?
SLIDE 51 – NIPPLE
1. Examine the epidermis. Note that the basal layer is deeply pigmented, which accounts
for the darker skin color of the nipple and areola.
2. Examine the dermis. You may be able to identify a few apocrine glands in the deep
reticular dermis.
Questions:
 Does dark skin have more melanocytes and/or more melanosomes?
 What are the occasional deeply eosinophilic bundles with long, ovoid nuclei in the
dermis?
SLIDE 52 – NAIL
Identify the following structures: nail plate, proximal nail fold, nail bed, root, matrix,
eponychium, hyponychium.
Questions:
 What type of keratin is produced by the matrix of the nail? How can you tell that by looking
at this slide (hint – what’s NOT there?)?
 What epidermal layer does the nail plate resemble?
 What is the common name for the eponychium and what is its function?