Histology of the Integumentary

System
OVERVIEW
 The skin is the heaviest organ, about 16%
of the total body weight.
 It is composed of 2 layers, the epidermis
and dermis, which interdigitate to form an
irregular contour.
 A deeper superficial fascial layer, the
hypodermis, lies under the skin. This
layer, which is not considered part of the
skin, consists of loose connective tissue
that binds skin loosely to the subjacent
tissue.
 The skin contains several appendages
(sweat glands, hair follicles, sebaceous
glands, and nails). The skin and its
appendages are called the integument.
 The skin protects the body against injury,
desiccation, and infection; regulates body
temperature; absorbs ultraviolet (UV)
radiation, which is necessary for synthesis
of vitamin D; and contains receptors for
touch, temperature, and pain stimuli
from the external environment.
EPIDERMIS
Overview
 The epidermis is the superficial
layer of the skin. Primarily of
ectodermal origin, it is classified
as stratified squamous
keratinized epithelium.
epithelium The
epidermis is composed
predominantly of keratinocytes
+ 3 other types of cells:
melanocytes, Langerhans
(Dendritic) cells, and Merkel
cells (sensory receptors).
receptors)
 The epidermis is constantly
being regenerated.
Regeneration, which occurs
approximately every 30 days, is
carried out by the mitotic
activity of keratinocytes, which
normally divide at night.
 The epidermis has deep
down growths called
epidermal ridges or
pegs that interdigitate
with projections of the
dermis (dermal ridges or
papillae), resulting in a
highly irregular
interface. Where the
epidermis overlies the
dermal ridges, surface
ridges are produced. On
the fingertips, these
surface ridges are visible
as finger prints, whose
configuration is epidermal pegs (EP); dermal papillae (DP); dermis
genetically determined (D); stratum basale (B); stratum spinosum (S);
and thus unique to each stratum granulosum (G); and the stratum corneum
individual. (C); X240. H&E.
Layers of the epidermis
1. The stratum basale (stratum
germinativum)
 deepest layer of the epidermis
 composed of keratinocytes that
are cuboidal to columnar in shape.
These mitotically active cells are
attached directly to the basal
lamina of the basement
membrane by hemidesmosomes
and to each other by
desmosomes.
 also contains melanocyte sand
Merkel cells.
2. The stratum spinosum
 consists of a few layers of keratinocytes.
Their extensions, termed “intercellular
bridges” by early histologists, are now
known to terminate in desmosomes.
 also contains Langerhans cells.
 Keratinocytes in the deeper aspects of
the stratum spinosum are also mitotically
active.
 The Malpighian layer (stratum malpighii)
consists of the stratum spinosum +
stratum basale. Nearly all of the mitotic
activity in the epidermis occurs in this
region, and cell division occurs at night.
 In the superficial regions of the stratum
spinosum are keratinocytes that contain
membrane-coating granules. The
contents of these granules are released
into the inter-cellular spaces in the form
of lipid-containing sheets that are
impermeable to water and many foreign
Keratinocytes of the stratum spinosum.
(a): Light micrograph of a section of skin from the sole of the foot (thick skin),
showing only the stratum spinosum, highlights cells with numerous, short
cytoplasmic projections (arrow). X400. PT.
(b): TEMs show a single spinous keratinocyte with arrows marking some
desmosomes at the projections. X8400.
3. The stratum granulosum
 is the most superficial layer in which
nuclei are still present.
 It comprises 3-5 layers of flattened
keratinocytes that contain keratohyalin
granules, and bundles of keratin
filaments (tono filaments).
 Keratohyalin granules contain histidine-
and cystine-rich proteins, which bind the
keratin filaments together.
4. The stratum lucidum
 a clear, homogeneous layer just
superficial to the stratum granulosum; it is
often difficult to distinguish in
histological sections.
 is found only in palmar and plantar skin.
This layer consists of keratinocytes that
have neither nuclei nor organelles but
contain keratin filaments.
Stratum granulosum and stratum lucidum: thick skin.
skin
In keratinocytes moving upward from the stratum spinosum (S) (S differentiation proceeds with
the cells becoming filled with numerous large, amorphous masses of protein called
keratohyaline granules which are highly basophilic. Cells that contain such granules form a
stratum granulosum (G) (G only three to five cells thick, where keratin filaments are crosslinked
with filaggrin and other proteins from these granules to produce tight bundles filling the
cytoplasm and flattening the cells. Smaller organelles called lamellar granules undergo
exocytosis in this layer, secreting a lipid-rich layer around the cells which makes the
epidermis impermeable to water. Together the lipid envelope and the keratin-filled cells
determine
most of the physical properties of the epidermis. The cells leaving the stratum granulosum, still
bound together by desmosomes, undergo terminal differentiation and in thick skin appear as
a dense, thin layer called the stratum lucidum (L). In the most superficial layers, the stratum
corneum (C), the cells are fully differentiated and have lost nuclei and cytoplasm.
cytoplasm They
consist only of flattened, keratinized structures called squames bound by hydrophobic, lipid-rich
intercellular cement and at the surface they are worn away (thick skin) or flake off (thin skin). X560.
5. The stratum corneum
 the most superficial layer of the
epidermis.
 may consist of as many as 15 to 20 layers
of flattened, non-nucleated dead “cells”
filled with keratin. These nonviable scale
like structures are called squames (or
horny cells). The outermost layer of
squames is continuously shed by
desquamation.
Nonkeratinocytes in the epidermis
1. Melanocytes
o are present in the stratum basale and originate from neural crest.
o synthesize a dark brown pigment (melanin) in oval-shaped organelles
(melanosomes). Melanosomes contain tyrosinase, a UV-sensitive enzyme directly
involved in melanin synthesis.
o the number of melanocytes per unit area of skin appears to be the same in dark-
and light-skinned people. Pigmentation differences are due to the rate of
melanin synthesis, melanosome size, content, rate of transfer, and degradation
patterns.
o melanin protects against tissue damage caused by UV radiation.
o Long melanosome-containing processes of the melanocytes extend between the
cells of the stratum basale and stratum spinosum. Melanin is transferred via a
unique mechanism known as cytocrine secretion from these melanosome-filled
tips into keratinocytes of these layers.
2. Langerhans cells
o are dendritic cells (so named because of their long processes) that originate in the
bone marrow.
o are located primarily in the stratum spinosum, contain characteristic paddle-
shaped Birbeck granules, and function as antigen-presenting cells in immune
responses to contact antigens (contact allergies) and some skin grafts.
Melanocytes.
(a): Micrograph showing melanocytes (M) in the epidermal
basal layer which synthesize melanin granules and
transfer them into neighboring keratinocytes of the basal
and spinous layers.
layers Typically melanocytes are pale-
staining cells on the basement membrane,
membrane with lower total
melanin content than the keratinocytes. X400. H&E.
(b): Diagram of a melanocyte.
melanocyte It sends irregular dendritic
processes between neighboring keratinocytes for transfer
of melanin to those cells.
cells
(c): Ultrastructurally, a melanocyte is located on the basal
lamina (BL) and has well-developed Golgi complexes (G)
producing the vesicles in which melanin is synthesized. As
they fill, these vesicles become melanin granules (MG), which
accumulate at the tips of the dendritic cytoplasmic
extensions (CE) before transfer to keratinocytes (K).
X14,000.
3. Merkel cells
o are present in small numbers in the stratum basale, near areas of well-
vascularized, richly innervated connective tissue.
o possess desmosomes and keratin filaments, suggesting an epithelial origin.
o their pale cytoplasm contains small, dense-cored granules that are similar in
appearance to those in some cells of the diffuse neuroendocrine system (DNES).
o receive afferent nerve terminals and are believed to function as sensory
mechanoreceptors.

Thick and thin skin

 are distinguished on the basis of the thickness of the epidermis.
 thick skin has an epidermis that is 400 to 600 µm thick. It is characterized by a
prominent stratum corneum, a well-developed stratum granulosum, and often a
distinct stratum lucidum. It lines the palms of the hands and the soles of the feet.
Thick skin lacks hair follicles, sebaceous glands, and arrector pili muscles.
 thin skin has an epidermis that is 75 to 150 µm thick. It has a less prominent
stratum corneum than thick skin and generally lacks a stratum granulosum and
stratum lucidum. Thin skin covers most of the body and contains hair follicles,
sebaceous glands, and arrector pili muscles.
Tactile (Merkel) cell.
Epithelial tactile cells in the
basal epidermal layer of skin
with high tactile sensitivity are
neural crest-derived cells
that function as
mechanoreceptors.
TEM of a tactile cell from the
finger epidermis of a 21-
week fetus shows a mass of
dense-core cytoplasmic
granules (G) near the
basolateral cell membrane,
which is in direct contact
with the expanded ending of
a nerve (N). X14,000.
X14,000
Inset: Granules are similar in
morphology and content to
the granules of many
neuroendocrine cells.
X61,500.
Clinical Considerations
 Exposure of unprotected skin to UV light can cause harmful effects to the cells,
even in the absence of sunburn. Studies have shown that UVA may be an
important factor in the development of skin cancer (especially basal cell
carcinoma and melanoma) later in life. Skin cancers commonly originate from cells
in the epidermis. These cancers usually can be treated successfully if they are
diagnosed early and surgically removed. Basal cell carcinoma arises from basal
keratinocytes. Squamous cell carcinoma arises from cells of the stratum
spinosum. Malignant melanoma is a form of skin cancer that can be life-
threatening. This form of cancer originates from melanocytes that divide,
transform, and invade the dermis and then enter the lymphatic and circulatory
systems, metastasizing to a wide variety of organs.
 Psoriasis is a condition in which reddened, inflamed patches of skin, having a
whitish, flaky layer on top, appear almost anywhere on the body. It is caused by an
increase in mitotic activity of cells in the malpighian layer of the epidermis
(stratum basale and stratum spinosum) that have a shorter than normal cell cycle.
 Warts may occur anywhere on the skin or on the oral mucosa but are most
common on the dorsal surfaces of the hands, often close to the nails. Histological
features of warts include marked epidermal hyperplasia, eosinophilic cytoplasm
icinclusions, and deeply basophilic nuclei. By electron microscopy, many
intranuclear viral particles can be observed in the keratinocytes.
DERMIS
 The dermis is of mesodermal origin and is composed of dense, irregular
connective tissue that contains many type I collagen fibers and networks of thick
elastic fibers.
 Although it is divided into a superficial papillary layer and a deeper, more
extensive reticular layer, no distinct boundary exists between these layers.
 The dermal papillary layer is uneven and forms dermal ridges (dermal papillae),
which interdigitate with the epidermal down growths (epidermal ridges). This
layer is composed of thin, loosely arranged fibers and cells, and contains capillary
loops and Meissner corpuscles,
corpuscles which are fine-touch receptors (i.e., making it
possible to specifically identify two different coins in your pocket simply by
feeling them).
 The dermal reticular layer constitutes the major portion of the dermis. It is
composed of dense bundles of collagen fibers and thick elastic fibers. In its
deeper aspects, it may contain Pacinian corpuscles,
corpuscles which are pressure receptors,
as well as Krause end-bulbs (formerly thought to be cold receptors, but their
function is uncertain).
Clinical Considerations
Keloids are swellings in the skin that result from increased collagen formation in
hyperplastic scar tissue. They are most prevalent in African Americans.
Elastic fibers of dermis.
Section of thin skin stained for
elastic fibers shows the extensive
distribution of darkly stained elastic
fibers among the eosinophilic
collagen bundles. In the dermal
papillary layer, the diameter of fibers
decreases as they approach the
epidermis and insert into the
basement membrane. X100.
Weigert elastic stain.
Tactile receptors.
Skin contains several types of sensory receptors, primarily involved in the sense of touch. In the
epidermis are free nerve endings and tactile discs on nerve fibers associated with
tactile (Merkel) cells of the basal layer.
layer Both have unencapsulated nerve fibers,
fibers like does the
root hair plexus around the bases of hair follicles in the dermis. They detect light touch or
movement of hair, although epidermal free nerve endings also detect pain and temperature
extremes. More complex tactile receptors encapsulated with connective tissue layers are
all in the dermis and include: tactile (Meissner) receptors (light touch), lamellated (Pacinian)
corpuscles (pressure and high-frequency vibration), Krause bulbs (pressure and low
frequency vibrations), and Ruffini corpuscles (continuous pressure and tissue distortion).
Tactile and lamellated corpuscles.
Micrographs showing the two most commonly seen sensory receptors of skin. skin
(a): Tactile (Meissner) corpuscle. X400. H&E.
(b): Lamellated (Pacinian) corpuscle. X40. H&E.
Tactile corpuscles (TC) are specialized to detect light touch and are frequently located
in dermal papillae (DP), very close to the epidermis (E).
GLANDS IN THE SKIN
Eccrine sweat glands
 are simple coiled tubular glands consisting of a
secretory unit and a single duct.
 present in skin throughout the body.
 the secretory unit of eccrine sweat glands is
embedded in the dermis and is composed of 3 cell
types: Dark cells line the lumen of the gland and
contain many mucinogen-rich secretory granules.
Clear cells underlie the dark cells, are rich in
mitochondria and glycogen, and contain
intercellular canaliculi that extend to the lumen of
the gland. These cells secrete a watery,
electrolyte-rich material. Myoepithelial cells lie
scattered in an incomplete layer beneath the clear
cells. They contract and aid in expressing the
gland’s secretions into the duct.
(a): Micrograph of an eccrine sweat gland which plays an important
thermoregulatory function in production of fluid which evaporates on the
body surface, thereby cooling that surface. Histologically eccrine glands have
small lumens in the secretory portions (S) and the ducts (D), both of which
have an irregular stratified cuboidal appearance.
 The duct of eccrine sweat glands is
narrow and lined by stratified
cuboidal epithelial cells, which
contain many keratin filaments and
have a prominent terminal web. The
cells forming the external (basal)
layer of the duct have many
mitochondria and a prominent
nucleus. The duct leads from the
secretory unit through the superficial
portions of the dermis to penetrate
an interpapillary peg of the
epidermis and spiral through all of its
layers to deliver sweat to the
outside. As the secreted material
passes through the duct, its cells
reabsorb some electrolytes and
excrete other substances (such as
urea, lactic acid, ions, and certain
drugs).
(a): Micrograph of an eccrine sweat gland which plays an important
thermoregulatory function in production of fluid which evaporates on the
body surface, thereby cooling that surface. Histologically eccrine glands have
small lumens in the secretory portions (S) and the ducts (D), both of which
have an irregular stratified cuboidal appearance.
Apocrine sweat glands
 include the large, specialized sweat glands
in various areas of the body (e.g., axilla,
areola of the nipple, perianal region) and
the ceruminous (wax) glands of the
external auditory canal.
 do not begin to function until puberty and
are responsive to hormonal influences.
 their large coiled secretory units are
enveloped by scattered myoepithelial
cells.
 empty their viscous, odorless secretions
into hair follicles at a location superficial
to the entry of sebaceous gland ducts.
(b): Apocrine sweat glands are restricted
Bacteria act on these secretions to pro- mainly to the axillae and perineum and
duce odors that are somewhat specific to produce a more protein-rich secretion with
each individual. pheromonal properties. The lumens of
 although the term apocrine implies that a apocrine gland secretory portion
portion of the cytoplasm becomes part of (S) are much larger than those of eccrine
the secretion, electron micrographs have glands and their ducts open into hair follicles
(H) rather than to the epidermal surface. Both
shown that the cytoplasm does not X200. Mallory trichrome.
become part of the secretions of apocrine
sweat glands.
Sebaceous glands
are branched acinar glands having a lobular
appearance. The clustered acini of one sebaceous
gland empty into a single short duct. The duct
empties into the neck of a hair follicle.
are embedded in the dermis over most of the
body’s surface but are absent from the palms
and soles. They are most abundant on the face,
forehead, and scalp.
holocrine glands that release sebum
(composed of an oily secretion + degenerating
epithelial cells).
Sebaceous glands.
Sebaceous glands secrete a complex mixture of lipids called
sebum into short ducts which generally open into hair
follicles
(a): Micrograph shows small cells near the connective
tissue capsule which proliferate and give rise to an acinus
composed of large sebocytes (S), which undergo terminal
differentiation by filling with small lipid droplets and then
disintegrating at the ducts (D) near the hair (H) shaft, with the
loss of nuclei and other organelles. X122. H&E.
(b): Micrograph showing the gland's capsule and
differentiating sebocytes at higher magnification X400. H&E.
Sebum production is the classic example of holocrine
secretion, in which the entire cell dies and contributes to
the secretory product.
Clinical Consideration
 Hyperhidrosisis a disorder of excessive sweating caused by over perspi-
ration from secretion by eccrine sweat glands in the skin. Treatment
with drugs have been unsatisfactorily in alleviating the symptoms of this
condition, but injecting a highly diluted form of Botox directly into the
skin on the palms of the hands, soles of the feet, or of the axillae offers
relief. The toxin blocks sympathetic nerve impulses to the cells of the
eccrine sweat glands and decreases their ability to secrete. A single
injection of Botox may provide months of relief, and the injections can be
repeated when excessive sweating resumes.
HAIR FOLLICLE AND ARRECTOR
PILI MUSCLE
Hair follicle
 is an invagination of the epidermis
extending deep into the dermis.
 the hair shaft is a long, slender
filament in the center of the follicle
that extends above the surface of
the epidermis. It consists of an inner
medulla, cortex, and outer cuticle of
the hair. At its deep end, it is
continuous with the hair root.
 the hair bulb is the terminal
expanded region of the hair follicle
in which the hair is rooted. It is
deeply indented by a dermal papilla,
which contains a capillary network
necessary for sustaining the follicle.
The hair bulb contains cells that
form the internal root sheath and
medulla of the hair shaft.
 the internal root sheath lies deep to
the entrance of the sebaceous
gland. It is composed of the Henle
layer, the Huxley layer, and the
cuticle.
 the external root sheath is a direct
continuation of the stratum
malpighii of the epidermis.
 the glassy membrane is a non-
cellular layer, a thickening of the
basement membrane. It separates
the hair follicle from the
surrounding dermal sheath.
Arrector pili muscle
 attaches at an oblique angle to the
dermal sheath surrounding a hair
follicle.
 extends superficially to underlie
sebaceous glands, passing through
the reticular layer of the dermis and
inserting into the papillary layer of
the dermis.
 contraction of this smooth muscle
elevates the hair and is responsible
for formation of goose bumps,
caused by depressions of the skin
where the muscle attaches to the
papillary layer of the dermis.
Layers of a hair and its follicle.
(a): The base of a hair follicle sectioned obliquely
obliquel shows the vascularized dermal papilla (DP)
continuous with the surrounding connective tissue sheath (CTS). The papilla is surrounded
by the deepest part of the epithelial sheath, which is continuous with both the internal root sheath
(IRS)
(IRS and external root sheath (ERS). Both of these layers are in turn continuous with the stratified
epidermis. Just outside the ERS is the glassy membrane (G) which is continuous with the
basement membrane of the epidermis. The epithelial cells (keratinocytes) around the papilla
proliferate and differentiate as the root of the hair itself. Above the papilla only the cortex (CO)
of the hair is clearly seen in this section. X140. H&E.
(b): A hair root sectioned more transversely shows the same layers of the follicular sheath,
but the layers of the hair root are now seen to include the medulla (M), cortex (CO), and
cuticle (CU). X140. H&E.
NAILS
 are located on the distal
phalanx of each finger and toe.
 are hard keratinized plates
that rest on the nail bed of the
epidermis.
 at the proximal end, each is
covered by a fold of epidermis,
called the cuticle or
eponychium, which
corresponds to the stratum
corneum. The cuticle overlies
the crescent-shaped whitish
lunula.
 at the distal (free) edge, each is
underlain by the hyponychium,
which is also composed of
stratum corneum.
 grow as the result of mitoses of
cells in the matrix of the nail
root.
eponychium

A: Fold
B: Plate
C: Bed
D: Dermis

hyponychium