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Biology of the skin
By
Ass. Prof.
Dr. Zena S. Al-Fadhily
/
Department of Medicine
The skin represents the largest organ of the human body. The average adult has
1.75 m2 of skin that contains a variety of complex adnexal structures, including
hair follicles, nails, glands and specialized sensory structures, all of which
function in protection, homeostasis, and the transmission of sensation.
Dermatology is the field of medicine that deals with the macroscopic study of
skin, adjacent mucosa (oral and genital) and cutaneous adnexa, while
dermatopathology deals with the microscopic study of the same structures. The
two fields are closely allied, as they are complementary and requisite to one
another.
Embryology:
The skin is composed of diverse cell types of both ectodermal (keratinocytes,
melanocytes, Merkel cells, neurons) and mesodermal (e.g. fibroblasts,
hematopoietic cells such as Langerhans cells, endothelial cells) lineages.
During the first weeks of life, the fetus is covered by a layer of non-
keratinizing cuboidal cells called the periderm. Later, the periderm is replaced
by a multilayered epidermis. Adnexal structures, particularly follicles and
eccrine sweat units, originate during the third month of fetal life as down
growths from the developing epidermis. Later, apocrine sweat units develop
from the upper portion of the follicular epithelium and sebaceous glands from
the mid region of the follicle.
Adnexal structures appear first in the cephalic portion of the fetus and later in
the caudal portions.
Functions of the skin:
1. Mechanical guard: protection against chemicals, particles .ultraviolet radiation,
antigens and microbes.
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2. Percutaneous absorption: the skin acts as a two way barrier to prevent the inward
or outward passage of water and electrolytes. The barrier is largely situated in the
epidermis within a thin layer of innermost region of stratum corneum.
3. Immunological function: mainly by Langerhans cells which are antigen-presenting
cells and play a role in contact sensitization, immune surveillance against viral
infections and neoplasm and the rejection of skin grafts from other individuals .other
cells take part in the immunological functions are indeterminate dendritic cells and
keratinocytes.
4. Sensory function: a number of sensations are perceived by the skin; like: touch,
pressure warmth, cold and pain.
5. Synthesis of vitamin D: vitamin D3 is essential for skeletal development .It is
synthesized in the skin by keratinocytes as a result of exposure to UVB-radiation.
6. Endocrine function: the tissues of the skin are the producers as well as the target of
hormones.
7. Temperature regulation: by vascular bed dilatation and constriction, eccrine
sweat glands and subcutaneous fat.
8. Lubrication and water proofing: by sebaceous gland secretion.
9. Body odor: by apocrine sweat glands secretion.
10. Shock absorber: by dermis and subcutaneous fat.
Anatomy and physiology:
Skin is composed of three layers: the epidermis, dermis, and subcutaneous
fat (panniculus). The outermost layer, the epidermis, is composed of many
layers of viable keratinocytes that are covered by a layer of keratin, the stratum
corneum. The principal component of the dermis is the fibrillar structural
protein collagen. The dermis lies on the panniculus, which is composed of
lobules of lipocytes separated by collagenous septa that contain the
neurovascular bundles.
There is considerable regional variation in the relative thickness of these layers.
The epidermis is thickest on the palms and soles, measuring approximately 1.5
mm. It is very thin on the eyelid, where it measures less than 0.1 mm. The
dermis is thickest on the back, where it is 30–40 times as thick as the overlying
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epidermis. The amount of subcutaneous fat is generous on the abdomen and
buttocks compared with the nose and sternum.
Epidermis:
The epidermis is formed from many layers of closely packed cells, the most superficial
of which are flattened and filled with keratins, it therefore a stratified squamous
epithelium .It adheres to the dermis partly by the interlocking of its downward
projection (epidermal ridges or rete pegs) with upward projection of the dermis (dermal
papillae).
The layers of epidermis from innermost to outer most are:
1. Basal cell layer:
The basal cells form a single layer. They are columnar and have a deeply basophilic
cytoplasm and a dark- staining nucleus. The basal cell layer is the germinal layer of the
skin .It is the precursor of other layers and its cells proliferated and ascend upward to
form the other layers of epidermis .In normal skin 30% of basal cells are preparing for
divisions. As moving up, these cells lose their organelles, the nuclei and other
structures and get flattened till they reach the outermost horny layer. The process of
maturation of these cells is called Epidermopoisis and the time taken for it, is called
Epidermal turnover or transit time which is about 60 days.
2. Prickle cell layer (Malpighian layer; stratum spinosum)
Consists of polyhedral cells about 5-10 layers thickness .They become flattened
toward the surface with their long axis arranged parallel to the skin surface.
3. Granular cell layer (Stratum granulosum):
The cells are flattened and their cytoplasm is filled with keratohyaline granules that
are deeply basophilic and irregular in size and shape.
The thickness of the granular layer in normal skin is generally proportional to the
thickness of the horny layer above .It is only 1-3 cell layer thick in areas in which the
horny layer is thin ,but measures up to 10 layers in areas with a thick horny layer such
as the palms and soles.
4. Horny layer (Stratum corneum):
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Unlike the nucleated cells of the other epidermal layers, the cells of the normal stratum
corneum are non-nucleated thus the horny layer stains eosinophilic as a result of
omission of basophilic nuclei in hematoxylin and eosin (H&E) stain.
In certain formalin-fixed sections, the lower portion of the stratum corneum appears
after processing and staining as thin homogenous eosinophilic zone referred to as the
stratum lucidum. This zone is most pronounced in areas in which the horny layer is
thick especially on the palms and soles.
The epidermis contains different types of cells, the main 3 are:
1.
Keratinocytes:
The keratinocyte or squamous cell is the principle cell of the epidermis .It is a cell of
ectodermal origin that has the specialized function of producing keratin, a complex
filamentous protein that not only form the surface coat (Stratum corneum) of the
epidermis but also is the structural protein of hair and nails.
A proportion of basal cells proliferate, differentiate and move in a step wise fashion
through the full thickness of the epidermis. As the cells move upward through the
epidermis, they changed morphologically; they flattened out and the nuclei disappear.
The keratinocytes accumulate within its cytoplasm intermediate filaments called
tonofilaments which terminate at the plasma membrane of the cells where they end in
specialized attached plates called: desmosomes. The keratinocytes are separated by
spaces that are traversed by intercellular bridges (desmosomes).
Keratinocytes also play a role in the immune function of the skin. They secrete a
variety of cytokines and inflammatory mediators.
2.
Melanocytes:
Melanocytes are the only cells which can synthesize melanin. They migrate into the
basal layer of the ectoderm form the neural crest. Their cytoplasm contains discrete
organelles ,the melanosomes, containing varying amounts of the pigment melanin .
In histological section of skin routinely stained by (H&E), the melanocyte appears as
a clear cell in the basal layer of the epidermis (approximately 1 melanocyte for every
10 basal keratinocytes). When using silver stain, melanocyte appears as dendritic
cell .It's dendrites extend for long distance within the epidermis and any 1 melanocyte
is therefore in contact with a large number of keratinocytes, together they form the so
called epidermal melanin unit.
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Fully melanized organelles pass into the dendritic processes of melanocytes and are
then inject into neighboring keratinocytes, Once there melanosomes are distributed
throughout the cytoplasm. Negros are black, not because they have more melanocytes,
but because their melanocytes produce more and larger melanosomes which are broken
down less rapidly than those of Caucasoid. The larger melanosomes of dark skin are
individually dispersed within the cytoplasm of keratinocyte; the smaller melanosomes
of light skin are packaged in membrane-bound complexes within the keratinocytes.
3. Langerhans' cells:
They are bone marrow-derived cells that are normally found scattered among
keratinocytes of prickle cell layer of epidermis .They constitute 3-5 % of the cells in
this layer .Like the melanocytes, they are not connected to adjacent keratinocytes by
the desmosomes. Langerhans' cells are seen in histological sections stained with H&E
as clear cells in the supra basal epidermis. They appear as dendritic cells in sections
impregnated with gold chloride, a stain specific for Langerhans
'
cells.
By electron microscopy examination, Langerhans' cells are characterized by a folded
nucleus and a distinct intra cytoplasmic organelles called Langerhans
'
or Birbeck
granules. In their fully developed form, the organelles are rod shaped with a vacuole at
one end resemble a tennis racquet.
Langerhan's cells play a role in induction of graft rejection, primary contact
sensitization and immune surveillance of viral and tumor antigens. They can recognize,
uptake, process and present antigens to sensitize T-lymphocytes.
* Additional 2 cells:
1) Indeterminate dendrite cells:
They have the ultra-structural features of Langerhan's cells but lack Birbeck granules.
2) Merkel cells:
They found in normal epidermis and probably act as transducers for fine touch. These
non -dendritic cells lying in or near the basal layer, are the same size as keratinocytes
and are concentrated in localized thickenings of the epidermis near hair follicles. Fine
unmyelinated nerve endings are often associated with Merkel cells which express
immunoreactivity for various neuropeptides.
Dermo- epidermal junction:
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The junction of epidermis and dermis is formed by the basement membrane zone
(BMZ). Ultra-structurally, this zone is composed of 4 components:
1. the plasma membrane of basal cells with the specialized attachment plates
(hemidesmosomes).
2. an electron lucent zone called the lamina lucida .
3. the basal lamina (lamina densa)
4. the fibrous components associated with the basal lamina including : Anchoring
fibrils, dermal micro fibrils and collagen fibers.
The BMZ is considered to be a porous semi permeable filter which permit exchange of
cells and fluid between the epidermis and dermis. It serves as a structural support for
the epidermis and holds the epidermis and dermis together.
Epidermal Appendages (Adnexia):
These include hair follicles, nails, eccrine and apocrine glands, sebaceous
glands.
Eccrinesweatglands: The eccrine sweat unit is composed of 3sections:
1. the intra epidermal eccrine duct: which opens directly into the skin surface .It is a
spiral duct derived from dermal duct cells through mitosis and upward migration .
2. the straight intradermal eccrine duct.
3. the secretary portion of the eccrine gland :is found within the panniculus near the
junction of the dermis and subcutaneous fat .It is composed of inner layer of epithelial
cells surrounded by a layer of flattened myoepithelial cells.
Eccrine glands are found in greatest abundance in the palms, soles and axillae.
They play an important role in temperature control .Up to 10 liters of sweat may be
excreted per day. The eccrine sweat gland are innervated by cholinergic fibers of the
sympathetic nervous system, mediator is Acetyl choline.
Apocrine sweat glands:
They are tubular glands, the secretory cells of which pass through various stages.
During secretion, part of the cells was pinched off and released into the lumen, this is
called decapitation secretion. Apocrine glands like eccrine glands, are composed of 3
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segments: The intraepithelial duct, the intradermal duct and the secretary portion. The
duct of an apocrine gland usually leads to a pilosebaceous follicle, entering it in the
infundibulum above the entrance of the sebaceous duct.
Apocrine glands are encountered in only a few areas: axillae, anogenital region and as
a modified glands in the external ear canal (ceruminous glands), in the eyelids (moll's
glands) and in the breast (mammary glands).
The secretion of apocrine glands appear milky and is odorless until it reaches the skin
surface where it is altered by bacteria which make it odoriferous .Apocrine gland
secretion in human serves no function known .In other species ,it has a protective as
well as a sexual function and in some species ,it is important in thermoregulation as
well. Apocrine glands are innervated by adrenergic fibers of sympathetic nervous
system. The mediators are catecholamine of adreno-medullary origin.
Sebaceous glands:
The sebaceous gland is formed embryologically as an outgrowth from the upper
portion of the hair follicle .It is composed of lobules of pale-staining cells with
abundant lipid in their cytoplasm. Sebaceous glands are found in greatest abundance
on the face and scalp, though they are distributed throughout all skin sites except the
palms and soles .They are always associated with hair follicle, except at the
following sites (free sebaceous glands):
1. the eyelids (Meibomian glands).
2. the buccal mucosa and vermilion border of the lip (Fordyce's spots).
3. the prepuce (Tyson's gland)
,
4. the female areolas (Montgomery's tubercles).
The sebaceous glands are holocrine glands form their secretions by decomposition
of their cells. The secretion (sebum) is a complicated material of lipid, triglycerides,
cholesterol esters, waxes and squalene. The sebum has antifungal and antibacterial
properties.
Dermis:
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The constituent of the dermis are mesodermal in origin except for nerves which like
melanocytes, derived from neural crest. The extracellular matrix of the dermis consists of
collagen and elastic fibers embedded into the ground substance. All the 3 components are
formed by fibroblasts .The dermis consists of 2 parts, the upper part is the papillary dermis
and the lower part is the reticular dermis.
Collagen fibers: are the most abundant constituent of the connective tissue of the dermis .On
light microscopy: collagen consists of fibers, the diameter of which ranging from 2-15Mm.
The collagen fibers are present either as a finely woven network (loose pattern) or as thick
bundles.
Finely woven meshwork of collagen fibers is found in the papillary layer of the dermis.
Biochemically, the papillary dermis is composed primarily of type III collagen. The rest of the
dermis constituting by far the largest portion ,referred to as the reticular dermis ,shows the
collagen fibers united into thick bundles .Biochemically, reticular dermal collagen is composed
primarily of type I collagen .
Collagen serves as the major structural protein of the entire body .It is found in
tendons .ligaments and the lining of bones as well as in the dermis .It represents 70% of the dry
weight of the skin.
Elastic fibers: Are thin in comparison with collagen bundles measuring from 1-3 Mm in
diameter and are wavy. The elastic fibers are thickest in the lower portion of the dermis
where they are arranged like collagen bundles, chiefly parallel to the surface of the skin. They
become thinner as they approach the epidermis.
Elastic fibers undergo significant changes during life .One change representing aging. The
other change, elastotic degeneration, which is the result of chronic sun exposure.
Reticular fibers: Represent a special type of thin collagen fibers that measure from 0.2-1 Mm
in diameter. They are first -formed fibers during embryonic life and in various pathological
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conditions that associated with increase fibroblast activity. They are found normally in the
BMZ, around blood vessels and around fat cells.
Ground substance: The extracellular matrix or ground substance of the dermis is composed of
acid mucopolysaccharides principally hyaluronic acid, chondroitin sulfate and dermatan
sulfate; neutral mucopolysaccharides and electrolytes.
Dermal vasculature: Consist principally of 2 important intercommunicating plexuses:
1. the subpapillary plexus or upper horizontal network, courses within the papillary portion of
the dermis parallel to the epidermis and furnishes a rich supply of capillaries , end -arterioles
and venules to the dermal papillae .
2. the deeper , lower horizontal plexus is found at the dermal -subcutaneous interface and is
composed of large blood vessels than those of the superficial plexus . Between these 2
horizontal plexuses, there are ascending arterioles and descending venules. There is always
dermal lymphatics associated with the vascular plexus.
Muscles: Smooth muscles occur in the skin as: arrectors pilorum (arrector of the hair), as
tunica dartos of the scrotum and in the areolas around the nipples. The arrectors pilorum are
attached to the hair follicles below the sebaceous glands and in contraction, pull the hair
follicle upward producing goose flesh.
Striated (voluntary) muscles occur in the skin of the neck as the platysma muscle and in the
skin of the face as the muscles of expression.
Nerves: Touch and pressure are mediated by Meissner corpuscle in the dermal papillae
particularly on the palms and soles, and by vater –pacini corpuscles located in the deeper
portion of the dermis of weight -bearing surfaces. Mucocutaneous end - organs are found in
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the papillary dermis of modified hairless skin at the mucocutaneous junction, namely the glans,
prepuce, clitoris labia minora, perianal region and the vermilion border of the lips.
Temperature, pain
and itching sensation are transmitted by un-myelinated nerve fibers which
terminated in the papillary dermis and around hair follicles.
Autonomic nervous system: Postganglionic
adrenergic
fibers
mediate
vasoconstriction
,
apocrine gland secretion and contraction of arrector pili muscles of hair
follicle. Cholinergic fibers mediate eccrine sweat secretion.
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