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The skin is the largest human organ. It covers between 1.5 and 2 m2 , comprising about one sixth of total body

weight.

Function of Skin

The skin performs a complex role in human physiology: serves as a barrier to the environment, and some glands (sebaceous) may have weak anti-infective properties.

acts as a channel for communication to the outside world.

protects us from water loss, friction wounds, and impact wounds.

uses specialized pigment cells to protect us from ultraviolet rays of the sun.

produces vitamin D in the epidermal layer, when it is exposed to the sun's rays.

helps regulate body temperature through sweat glands.

helps regulate metabolism.

has esthetic and beauty qualities.

The skin consists of three functional layers:

- Epidermis

- Dermis or corium

- Subcutis (hypodermis)

In these layers are found the epidermal appendages: nails, hair and glands.

(Note: Sebaceous and sweat glands belong to the exocrine glands. Sebaceous

glands are nearly always connected to hair follicles. Sweat glands deliver

their secretions directly to the skin surface.) The skin performs various

functions such as temperature regulation and insulation, energy storage,

sensory perception and protection from environmental influences such as

fungi, bacteria and (UV) radiation.

The skin is composed of several layers. The lowest layer is called the dermis. This layer is composed of connective

tissue, blood vessels, nerve endings, hair follicles, and sweat and oil glands. (1-Epidermis; 2-Dermis;3-Subcutis;4-

Hair follicle;5-Sebaceous gland;6-Sweat gland)

Skin Cell Types

Keratinocytes

The most abundant cell type of the epidermis is the keratinocyte. These cells produce keratin proteins that

provide some of the rigidity of the outer layers of the skin. Keratinocytes also form the bulk of the material in hair

follicles. Dandruff and hair are dead keratinocytes.

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Fibroblasts

The dermis is produced largely by fibroblasts, which during embryonic development are part of the mesenchyme.

The fibroblasts produce the collagens and elastins that make skin very durable, from within.

Melanocytes

Melanocytes are cells in low abundance in the epidermis that produce the pigment melanin. The pigment made in

melanocytes is transferred to the cells of the hair or epidermis. The melanin granules are injected into (or

ingested by) the keratinocyte cells. There, the melanin granules accumulate around the nucleus of each

keratinocyte.

Melanin absorbs harmful ultraviolet (UV) light before the UV radiation can reach the nucleus. Melanin protects the

DNA in the nucleus from UV radiation damage. When melanin is produced and distributed properly in the skin,

dividing cells are protected from mutations that might otherwise be caused by harmful UV light.

Differences in skin color are due mostly to differences in the types and amount of pigment in our

keratinocytes. Skin darkening (tanning) from sun exposure is caused by the movement of existing melanin into

keratinocytes, and by increased production of melanin by the melanocyte.

During embryonic development these cells migrate from the neural crest into the skin.

Langerhans cells

These are star-shaped resident immune cells, macrophages. A macrophage is a cell that protects your body from

injury or illness. Macrophages break up or destroy (phagocytise) the invading organisms. These macrophages

process the invading organisms and present antigens to the T-lymphocytes. The T-lymphocytes are immune-system

cells which ultimately identify a substance as foreign or dangerous to the body.

Merkel's Cells

Only a few of these cells are present in skin; they are more numerous in the palms and soles (feet). These cells are

probably sensory mechanical receptors that respond to stimulus, such as pressure or touch.

Schematic Drawing of Human Skin



Drawing (transverse section) of human skin

illustrates the epidermis, basement membrane,

dermis, capillaries and major cellular components.

A: Epidermis || B: Dermis || C: Cornified layer of

keratinocytes (stratum corneum) || D: Suprabasal

keratinocytes || E: Basal layer of keratinocytes

(stratum basale) || F: Basement membrane G:

Collagen fibers in dermis || H: Capillary (enclosed

by a single microvascular endothelial cell) || I:

Melanocyte || J: Dermal Fibroblast

The great majority of cells in the epidermis are keratinocytes, which are arranged in stratified layers. At the

dermal-epidermal junction is a single layer of keratinocytes with a small number of interspersed melanocytes

(approximately 1/30) called the stratum basale. This basal layer of keratinocytes is also called the stratum

germinativum, because it is where new keratinocytes are generated by cell proliferation. Three types of

keratinocytes in the stratum basale have been defined by kinetic analysis: stem cells, transient-amplifying cells

and committed cells. Stem cells, which represent ~ 10% of the basal cell population, generate daughter cells from

mitosis that are either stem cells themselves or transient-amplifying cells. Transient-amplifying cells, which

represent ~40% of the basal cell population, replicate with much higher frequency than stem cells, but are capable

of only a few population doublings. Transient-amplifying cells produce daughter cells that are committed to

terminally differentiate. These committed cells detach from the basementmembrane, differentiate, and

ultimately cease to proliferate as they migrate toward the skin surface, where they are sloughed off as dead,

cornified cells called squames.

Keratinocyte stem cells (like stem cells from other tissues) are relatively undifferentiated, both biochemically and

histologically. Although keratinocyte stem cells have a high capacity for cell division, they divide with much lower

frequency than transient-amplifying cells. Thus, when labeled with 3H-thymidine, stem cells retain nuclear label

for long periods of time compared to transient-amplifying cells. Therefore, stem cells have been described as

"label-retaining" cells. Because stem cells are undifferentiated, biochemical markers of stem cells are difficult to

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identify. However, keratin 19 expression has been suggested as a marker of keratinocyte stem cells, based on

localization of keratin 19 expression to 3H-thymidine label-retaining cells. Keratinocyte stem cells may also

express higher amounts of the a2 and a3 integrins, because an approximate 1.5-fold increase in the expression of

these integrins has been observed in keratin 19-expressing cells relative to other epidermal basal cells. The

retention and expansion of keratinocyte stem cells in culture is thought to be essential for using keratinocytes in

ex vivo gene therapy.

The Epidermis

As the outermost skin layer, the epidermis forms the actual protective covering against environmental influences.

Its thickness averages 0.1 mm. On the face it is only 0.02 mm, while on the soles of the feet between 1 and 5 mm.

Though paper thin, the epidermis is composed of many layers of cells. In the basal layer (the living epidermis),

new cells are constantly being reproduced, pushing older cells to the surface. As skin cells move farther away from

their source of nourishment, they flatten and shrink. They lose their nuclei, move out of the basal layer to the

horny layer (the dead epidermis), and turn into a lifeless protein called keratin. After serving a brief protective

function, the keratinocytes are imperceptibly sloughed off. This process of a living cell's evolution, called

keratinization, takes about 4 weeks.

The epidermis consists of up to 90 percent keratinocytes, the actual epidermal cells or dead skin cells, that are

held together by what are called desmosomes. Keratinocytes function as a barrier, keeping harmful substances out

and preventing water and other essential substances from escaping the body. The other 10 percent of epidermal

cells are melanocytes, which manufacture and distribute melanin, the protein that adds pigment to skin and

protects the body from ultraviolet rays. Skin color is determined by the amount of protein produced by these cells,

not by the number of melanocytes, which is fairly constant in all races.

Hair and nails are specialized keratin structures and are considered part of the epidermis. While animals use fur

and claws for protection and defense, these corresponding structures are largely cosmetic in humans. The skin,

however, is uniquely human, since it can betray emotion by blushing (embarrassment), turning red (anger),

blanching (fear), sweating (tension), and forming goosebumps (terror).

On the skin surface are the sweat gland pores (100-200/cm2) and the openings of the sebaceous glands (50-

100/cm2). Their secretions ensure skin moisture and oiliness, and thus maintain the hydrolipid film. The epidermis

itself has no blood vessels, so the nutrients are supplied through the fine blood vessels in the dermal papillae.

The epidermis is differentiated into five layers:

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- Horny layer (stratum corneum)

- Clear layer (stratum lucidum)

- Granular layer (stratum granulosum)

- Prickle-cell layer (stratum spinosum)

- Basal layer (stratum basale)

Differentiation and skin regeneration

Through differentiation, the living, cylindrical

basal cells lose their nuclei and become

flattened cornified cells, changing their shape

and composition in the process. The cells pass

through the barrier zone, the border zone

between the living epidermal layers and the

horny layer, where the epidermal lipids are

released.

Did you know that 90% of household dust is dead skin cells? Keratinocytes contain structural protein (keratin) and

become progressively flattened as they advance upward from the basal layer to the corneal layer. The epidermis

renews itself every 28 days through continual reproduction, differentiation / cornification and desquamation

(mechanical sloughing-off of the uppermost horny cell layer).

The epidermis is a stratified squamous epithelial tissue. This means that it has several layers of epithelial cells and

that its outermost layer is made up of squamous (flat) epithelial cells.

Mitotic Activity: The layer adjacent to the dermis is known as the basal layer. The basal layer is made up of

columnar epithelial cells. Since all of the mitotic (cell-multiplying) activity of the epidermis occurs in the basal

layer, the basal layer is often called the germinative layer. This mitotic activity involves about 4 percent of the

cells in the basal layer at any given time. It occurs primarily between midnight and 0400 hours.

Migration of Cells to the Surface:

Schematic diagram of the

epidermis: the basal cells

change, through

differentiation, into flat

horny skin cells that are

without nuclei.

1 Horny layer / 2 Clear layer

3 Granular layer /4 Prickle-cell layer

5 Basal layer / 6 Basal membrane



Over a period of weeks, new cells gradually migrate from the

basal layer to the surface. During this migration to the surface,

the cells change in shape from the original columnar to

cuboidal and then finally to squamous. As the cells

become squamous in form, they also become hardened, or

cornified, through the development of a special type of

protein. As they approach the surface, they die. Thus, the

outermost layers of the epidermis are dead, horny scales.

Keratinocytes

Keratinocytes are stratified, squamous, epithelial cells which comprise skin and mucosa, including oral,

esophageal, corneal, conjunctival, and genital epithelia. Keratinocytes provide a barrier between the host and the

environment. They prevent the entry of toxic substances from the environment and the loss of important

constituents from the host. Keratinocytes differentiate as they progress from the basal layer to the skin surface.

The normal turnover time for keratinocytes is around 30 days but epidermal turnover may be accelerated in some

skin diseases such as psoriasis.

Keratinocyte stem cells reside in the basal layer. These cells have a low rate of mitosis and give rise to a

population of transient amplifying cells. (Figure 1) Transient amplifying cells go through a limited number of

divisions, differentiate, and move up in the epidermis. The cells above the basal layer are known as the spinous

layer. Under routine microscopy small bridges, resembling spines, can be seen between the keratinocytes which

represent intercellular adhesion complexes known as desmosomes. As the cells further differentiate, they

Scanning electron microscope image of

scaling horny skin cells.

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synthesize keratohyaline granules, a prominent feature of cells in the granular layer. Proteins synthesized in the

granular layer are important in the final stages of epidermal differentiation and include profilagrin, loricrin,

involucrin, and cornifin. These molecules are important in the formation of the stratum corneum, the outer most

layer of the epidermis.

Keratin

Electron microscopical examination of cells from all tissues reveals that they contain a complex, heterogenous,

intracytoplasmic system of filaments. The components of this system include actin, myosin, and tubulin, whose

diameters average approximately 60A°, 150A°, and 250A°, respectively. In addition, other intracytoplasmic

filaments were noted, and since the diameter of these latter structures was found to be between 70 and 100A°,

they were called intermediate filaments.

Intermediate filaments form a major part of the cytoskeleton of most cells and fulfill a variety of roles related to

cell shape, spatial organization, and perhaps informational transfer. The nucleus contains structures related to

these intermediate filaments and many intracellular components including polyribosomes, mitochondria, nucleic

acids, enzymes, and cyclic nucleotides are attached to the cytoskeleton.

Based on their biochemical, biophysical, and antigenic properties, a number of classes of intermediate filaments

can be recognized in different cell types: desmin (skeletin) in muscle cells, glial fibrillary acidic filaments in glial

cells, neurofilaments in neurons, vimentin in mesenchymal cells, and keratin in epithelial cells. In cultured

epidermal cells, keratins account for up to 30% of the cellular protein, while in stratum corneum, keratin accounts

for up to 85% of the cellular protein.

At least 19 keratin proteins can be identified ranging in molecular weight from approximately 40,000 to 68,000

micrograms. Moll and his coworkers published their human keratin catalogue in 1982. According to this catalogue,

there are two keratin subfamilies. The molecular weight of the members of one (the basic subfamily) is relatively

larger than that of the members of the other (the acidic subfamily). Each of the keratins is the product of a unique

gene and, in essentially all situations, the keratins are expressed as pairs containing one member of each

subfamily. The two members of each pair are in the same size rank order within their respective family, e.g., the

largest acidic keratin is expressed with the largest basic.

The type of keratin differs in different tissues, i.e, there are different types of keratin for keratinized epidermis,

hyperproliferative epidermis of palms and soles, corneal epithelium, stratified epithelium of the esophagus and



cervix, and simple epithelium of the epidermal glands. As mentioned before, keratin is the main structural protein

of the epidermis.

The Subcutis (Hypodermis)

The subcutis (sub = under; cutis = skin/Lat.) refers to the fat tissue below the skin. It consists of spongy connective

tissue interspersed with energy-storing adipocytes (fat cells).

Fat cell clusters

Fat cells are grouped together in large cushion-like clusters held in place by collagen fibres called connective

tissue septa or sheaths.

Nourishment, insulation and padding

The subcutis is heavily interlaced with blood vessels, ensuring a quick delivery of

stored nutrients as needed. The functions carried out by the subcutaneous fatty

tissue, beside the storage of nutrients in the form of liquid fats, include the

insulation of the body from cold and shock absorption. On the palms of the hand,

the soles of the feet and the buttocks, fat padding serves almost exclusively for shock absorption. (Note: Fats, also

triglycerides or acylglycerins, are the most plentiful and simplest fatty acid-containing lipids. They are esters of

the triol alcohol, glycerine with three saturated and/or unsaturated fatty acids. Fats make up the main component

of the fat depots.)

Fat distribution in men and women

The fat content of the subcutis is not the same in all body regions. Also men and women differ in the distribution

of subcutaneous fat. An example is cellulite - it is characterized by a special arrangement of the subcutaneous fat

tissue septa and predisposes to fat deposition on the hips, thighs and buttocks - which occurs mostly in women.

Men on the other hand tend to store fat on the torso.

Functions of the Skin

The skin protects the body. The skin protects the body from water loss. The skin isinvolved in the production of vitamin D from precursors with the aid of sunlight.There are many sensory receptors in the skin: pain, pressure, fine touch. The skinis also involved in heat regulation.

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Types of Skin

Thick skin is found on the palms of the hand and the sole of the feet. Thin skin isfound everywhere else.

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Layers of the Skin

The skin is composed of two layers: the epidermis and the dermis. Underneaththese layers lies the hypodermis (subcutaneous tissue). The hypodermis is a layerof loose connective tissue.

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Histology of the Epidermis

The epidermis is formed by stratified squamous epithelium. Keratinization is seen inthe epidermis. Keratinocytes, melanocytes Merkel cells and Langerhans cells are allfound in the epidermis. The keratinocyte is the most abundant cell in the epidermis.The melanocyte produces melanin, which is responsible for skin pigmentation. TheMerkel cell is a mechanoreceptor. The Langerhans cell is a phagocyte. Langerhanscells are macrophages seen in the skin.

The epidermis is divided into five layers: stratum basale, stratum spinosum,stratum granulosum, stratum lucidum, and stratum corneum.

Stratum Basale

The stratum basale contains the dividing cells. This layer is also called the stratumgerminativum.

Stratum Spinosum

The stratum spinosum consists of a layer several cells deep. The cells have pointyor spiny processes on them.

Stratum Granulosum

The cells in the stratum granulosum contain keratohyaline granules.

Stratum Lucidum

The stratum lucidum is present only in thick skin.

Stratum Corneum










The stratum corneum is the outermost layer. It is also called the horny layer. Thecells in this layer are essentially bags of keratin. They contain no nuclei ororganelles.

Histology hint from Sarah Bellham: The epithelium is classified as "squamous"based on the cells of the surface layer.

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Histology of the Dermis

Beneath the epidermis is the dermis. The dermis is composed of a papillary layerand a reticular layer. The reticular layer of the dermis is made up of dense irregularconnective tissue. Fibroblasts are found in the dermis. Fibroblasts producescollagen.

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Histology of the Subcutaneous Layer

The subcutaneous tissue layer (hypodermis) is the loose connective tissue layerunderneath the dermis.

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Receptors in the Skin

There are several different sensory receptors in the skin.

Ruffini endings, pacinian corpuscles, meissner's corpuscles, and merkel cells are allencapsulated sensory receptors. Free nerve endings are not encapsulated.

The most abundant sensory receptor are the free nerve endings. Free nerveendings respond to pain and temperature. Ruffini's corpuscles respond tocontinuous pressure. Pacinian corpuscles respond to vibration and rapidly changingpressure. Krause's end bulbs are a receptor for fine touch which are located inmucous membranes and the tongue. Meissner's corpuscles are also a receptor forfine touch but they are located in the dermis. Pacinian corpuscles are pressurereceptors in the skin.

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Skin Appendages

Sweat glands, hair, nails and sebaceous glands are all considered epidermalappendages.

Nails

The lunula is the half moon shaped white area on a nail. The anatomical term forthe cuticle is the eponychium. The matrix is the region of the nails where there aredividing cells and nail growth. The nail plate rests on the nail bed. The nail root isthe proximal portion of the nail that is underneath skin.

Ceruminous Glands

The ceruminous glands of the ear are apocrine sweat glands.

Glands of Moll

The glands of Moll in the eyelid are apocrine sweat glands.

Histology of Sweat Glands

Sweat gland are also called sudoriferous glands.
















Classification of Sweat Glands

Sweat glands are divided into apocrine and eccrine. Apocrine sweat glands arefound on the areola, external genitalia, axilla, and curcumanal region. Eccrine sweatglands are distributed over most of the body.

Innervation of Sweat Glands

Eccrine sweat glands are innervated by the sympathetic nervous system. Theneurotransmitter for the eccrine sweat glands is acetylcholine. Thus, it ischolinergic.

Histology hint from Sarah Bellham: For most postganglionic sympathetic neurons,

the neurotransmitter isnorepinephrine. Eccrine sweat glands are an exception to this generalization, as theinnervation for eccrine sweat glands is cholinergic sympathetic.

Apocrine sweat glands are innervated by the sympathetic nervous system. Theneurotransmitter for theapocrine sweat glands is norepinephrine. Thus, it is adrenergic.

Hair

Hair is present over most of the body. It is not found on the palms of the hand,soles of the feet, urogenital openings, and lips. Huxley's layer is a layer in the hairfollicle. Henle's layer is a layer in the hair follicle.

-Human skin is considered the largest organ of the body and form about 16% of

the body weight (1) with a surface area somewhat less than 1.5 m2 (2).

-The skin form the external surface of the human body.At the orifices of the

mouth,nose and the anal canal, the skin join the mucous membrane at the muco-

cutaneous junction (3).



-Types of human skin (1):-

1. Thick skin (Non-Hairy) which has thick epidermis and found only in the

palms and soles as they are the most sites subjected to abrasions and

trauma and thick skin shows characteristic parallel ridges and grooves

which are called "Finger prints".

2. Thin skin (Hairy) which has thin epidermis and covers the rest of the body.

-Histological structure of the skin :-

skin is composed of 3 layers

1. Epidermis

2. Dermis

3. Hypodermis (Subcutaneous fatty layer)

1- Epidermis:-

It is the outer superficial epithelial layer of skin.

It is composed of Stratified squamous keratinized epithelium.

The thickness of the epidermis varies in different types of skin. It is the

thinnest on the eyelids and the thickest on the palms(0.8mm) and

soles(1.4mm).

The epidermis is ectodermal in origin.

The epidermis is devoid of blood vessels and gets its nutrition through

diffusion.

-It consists of :-

Keratinocytes (85% of cells) which are responsible for formation of keratin,

Dendertic cells which are (melanocyte and the Langerhans cell)

Merkel cells which until recently, were not consistently identified as the

third dendritic cell in human epidermis, because light microscopy and low

power electron microscopy did not readily allow the differentiation of

merkel cells from the other two dendritic cells of the epidermis.

-Keratinocytes are arranged in 5 layers from above downward:-

Stratum basale (basal cell layer)(The stratum germinatum):- which is single

layer of columnar cells with basal oval nuclei,cells of this layer are resting

on basement membrane and attached to each other and with the overlying



cells by inter-cellular bridges called "desmosomes" these basal cells

continue to divide throughout the life so they are called mother cells of

epidermis.

Stratum spinosum (prickle cell layer):- formed of 5-7 layers of nucleated

polygonal cells attached to each other by desmosomes which are like spines

hence its name.

Stratum granulosum (Granular cell layer):- formed of 2-3 layers of

nucleated spindle shaped cells which accumlate dense basophilic

keratohyalin granules,these granules contain lipids, which along with the

desmosomal connections, help to form a waterproof barrier that functions

to prevent fluid loss from the body.

Stratum licidum (Clear layer):- only well seen in thick epidermis and

represents a transition from the stratum granulosum to the stratum

corneum and formed of dead clear non nucleated containing eleidin

granules.

Stratum corneum (horny layer):- formed of flattened non nucleated cellscalled "squames" condensed in linear manner and containing Keratin which

derived from eleidin granules.These squames are continuously shed from

the surface and replaced from the deeper layer by new ones.

-Melanocytes:- they form melanin from tyrosine under the effect of tyrosinase

enzyme and lie just under and in between basal cells and in hair matrix.

-The Langerhans' cells:- present in Stratum spinosum,they act as macrophages.

-The Merkel's cell's:- present in Stratum basale and they act as receptors for touch

sensation.

2- Dermis:-

The dermis is typically subdivided into two zones, a papillary layer and a

reticular layer.

It is 15-40 more thicker than epidermis.

Function:- act as frame work and supports for nerves,lymphatics,hair

follicles,sweat glands,Sebaceous glands and blood vessels to supply the

avascular epidermis with nutrients.

The dermis contains mostly fibroblasts which are responsible for secreting

collagen, elastin and ground substance that give the support and elasticity

of the skin. Also present are immune cells that are involved in defense

against foreign invaders passing through the epidermis.

The dermis is mesodermal in origin.



The papillary layer lies below and interdigitates with the epidermal rete

ridges,papillary layer is formed of loose C.T with fine collagenous fibers type

II,reticular and elastic fibers . and contains the free sensory nerve endings

and structures called Meissner's corpuscles in highly sensitive areas.

The reticular layer lies below papillary layer and is formed of dense C.T

with coarse collagenous fibers type I and some elastic fibers the fibers are

irregularly arranged,this layer contain Pacinian corpuscles.

3- Hypodermis:-

- Contains adipose tissue and this layer is rich in adipose tissue except in scrotum

and eyelids.

- Skin has 4 appendages :-

Hair. Nails.

Sweat Glands.

Sebaceous glands.

INTEGUMENTARY SYSTEM

The skin or cutis covers the entire outer surface of the body. Structurally, the skin

consists of two layers which differ in function, histological appearance and theirembryological origin. The outer layer orepidermis is formed by an epithelium and is of

ectodermal origin. The underlying thicker layer, the dermis , consists of connective tissue

and develops from the mesoderm. Beneath the two layers we find a subcutaneous layer

of loose connective tissue, the hypodermis or subcutis , which binds the skin to

underlying structures. Hair, nails and sweat and sebaceous glands are of epithelial

origin and collectively called the appendages of the skin .

The skin and its appendages together are called the integumentary system .

Suitable Slides

sections of skin - H&E, trichrome or van Gieson



Epidermis

The epidermis is a keratinised stratified squamous epithelium . The main function of the

epidermis is to protect the body from harmful influences from the environment and

against fluid loss. Five structurally different layers can be identified:

1. The stratum basale is the deepest layer of the epidermis (closest to the dermis). It consists of a

single layer of columnar or cuboidal cells which rest on the basement membrane.

Basal cells are the stem cells of the epidermis. Their mitotic activity replenishes

the cells in more superficial layers as these are eventually shed from the



epidermis. The renewal of the human epidermis takes about 3 to 4 weeks.

2. In the stratum spinosum,

the cells become irregularly polygonal. The cells are often separated by narrow, translucent clefts

These clefts are spanned by spine-like cytoplasmatic extensions of the cells (hence the name of

the layer and of its cells: spinous cells), which interconnect the cells of this layer. Spines of cells

meet end-to-end or side-to-side and are attached to each other by desmosomes. In addition to the

usual organelles of cells, EM shows membrane-boundlamellar granules in the cytoplasm of the

spinous cells.

3. The stratum granulosum

consists, in thick skin, of a few layers of flattened cells. Only one layer may be

visible in thin skin. The cytoplasm of the cells contains numerous fine

grains, keratohyalin granules . The keratohyalin is not located in membrane-

bound organelles but forms "free" accumulations in the cytoplasm of the cells.

The cells begin to release the contents of the lamellar granules. The lipids

contained in the granules come to fill the entire interstitial space, which is

important for the function of the epidermis as a barrier towards the external

environment.

4. The stratum lucidum

consists of several layers of flattened dead cells. Nuclei already begin to

degenerate in the outer part of the stratum granulosum. In the stratum lucidum,

faint nuclear outlines are visible in only a few of the cells. The stratum lucidum

can usually not be identified in thin skin.

5. In the stratum corneum ,

cells are completely filled with keratin filaments (horny cells) which are

embedded in a dense matrix of proteins. Individual cells are difficult to observe

because (1) nuclei can no longer be identified, (2) the cells are very flat and (3)

the space between the cells has been filled with lipids, which cement the cells



together into a continuous membrane. In the EM, the cell membranes appear

thickened and interdigitate with those of neighbouring cells. Closest to the

surface of the epidermis, the stratum corneum has a somewhat looser

appearance. Horny cells are constantly shed from this part of the stratum

corneum.

The protection of the body by the epidermis is essentially due to the functional

features of the stratum corneum .

Variations in the thickness of the epidermis (~0.1 mm in thin skin, 1 mm or more in thick skin) are

mainly the result of variations in the thickness of the stratum corneum, although the

other layers also vary in thickness. Cells of the epidermis of the skin will at some time of

their life keratinise and are collectively also called keratinocytes .

Keratinisation should not be used as a synonym for the formation of the stratum corneum: other stratified squamous

epithelia may become keratinised but may not form a stratum corneum in which cells join to form a horny cell

membrane.

Suitable Slides

sections of skin - H&E, trichrome or van Gieson

Skin, thin - H&E and Skin, thick, trichrome

The most superficial part of the epidermis is formed by the stratum corneum. Nuclei are

not visible in this layer. Cell outlines may be visible at high magnification or, in the form

of artefacts, as cracks or clefts in the stratum corneum. The stratum granulosum is

formed by a single layer of very dark and flattened cells in thin skin. Several layers of

cells containing keratohyalin granules are visible in thick skin. Polyhedral cells with clear

outlines form the stratum spinosum. The stratum basale is formed by a single layer of

cuboidal or columnar cells and delimits the epidermis from the dermis.

At high magnification, the basal cytoplasm of the basal cells seem to interdigitate with the underlying dermis. Similar

to the dermal papilla, this irregular border at the cellular level, the dermal-epidermal junction , anchors individual basal

cells firmly to the underlying dermis.

Identify and draw the epithelium in thick and thin skin. Identify in your drawing as

many of the layers of the epidermis as possible.



Other Cells of the Epidermis

The red and yellow hues of the skin are due to haemoglobin in the red blood cells,

which pass through the capillaries beneath the epidermis, and carotene, which

accumulates in fat cells found in the dermis and hypodermis.

Melanocytes

The brown colour component is due to melanin , which is produced in the skin

itself in cells called melanocytes (typically 1000-2000 / sqr. mm). These cells are

located in the epidermis and send fine processes between the other cells. In the

melanocytes, the melanin is located in membrane-bound organelles

called melanosomes . The cell bodies of melanocytes are difficult to distinguish in



ordinary LM preparations, because the melanosomes are located mainly in the

processes of the cells.

Melanocytes can transfer melanin to keratinocytes - mainly to the basal cells. The fine processes o

melanocytes may invade keratinocytes and bud-off part of the melanocyte cytoplasm, including t

melanosomes, within the keratinocytes. Melanin protects the chromosomes of mitotically active b

cells against light-induced damage.

Pigmentation is not just under the control of light. Hormones produced by the pituitary and the ad

glands also affect pigmentation. Diseases of these two endocrine organs often result in changes o

pigmentation of the skin.

Although melanocytes are also ectodermal in origin, they are derived exclusively from the neural crest of the embryo, from where

migrate to all other parts of the body.

Langerhans Cells

are another cell type found within the epidermis. Morphologically they are not

unlike melanocytes, but functionally they are more closely related to

macrophages. They are important in immune reactions of the epidermis. Their

fine processes form a network between the cells of the epidermis and

phagocytose antigens which have entered the epidermis. Langerhans cells may

only be temporary residents of the skin. If they have come into contact with anantigen, they can migrate to regional lymph nodes, where they initiate an immune

response.

T-lymphocytes

are, like Langerhans cells, a group of cells functioning in the immune system. Some of them will be present

in the epidermis. Together with Langerhans cells they are sometimes referred to as SALT, i.e. skin-

associated lymphoid tissue.

Dermis

The dermis is the thick layer of connective tissue to which the epidermis is attached. Its

deepest part continues into the subcutaneous tissue without a sharply defined



boundary. Its thickness is for this reason difficult to determine but 1-2 mm is a good

guestimate for "average" skin. The dermis may be divided into two sublayers (again without

a sharp boundary):

The papillary layer consists of loose, comparatively cell-rich connective tissue,which fills the hollows at the deep surface (dermal papillae ) of the epidermis.

Capillaries are frequent. Collagen fibres appear finer than in the reticular layer.

The reticular layer appears denser and contains fewer cells. Thick collagen

fibres (5-10 µm) often aggregate into bundles (up to 100 µm thick). The fibres form an

interlacing network, although their predominant direction is parallel to the surface

of the skin. A preferred orientation of the collagen fibres is not visible in the

sections, but the main orientation of the fibres differs in skin from different parts

of the body. Usually, their main orientation will follow the " lines of greatest

tension " in the skin (Kraissl lines). This is of some surgical importance since

incisions parallel to these lines will heal faster and with less formation of scar

tissue.

Kraissl lines have been defined in living humans. They not always coincide with the cleavage lines, which

Langer defined (Langer's cleavage lines ) about a century before Kraissl in cadavers.

Elastic fibres are found in both the papillary (fine fibres) and reticular (coarse fibres)

layers.

They can not be identified in H&E stained sections.

Suitable Slides

sections of skin - H&E, van Gieson

Van Gieson stained sections are particularly nice if the van Gieson stain has been combined with an elastin

stain.

Skin, thin - H&E and Skin, thick - van Gieson & elastin How easy it is to differentiate between the papillary and reticular layer of the dermis

depends on the preparation - you may have to look at several preparations. Immediately

beneath the epidermis you should see a layer which at low magnification appears rather

evenly stained. At high magnification the stain should resolve into a fine network of

collagen fibres, which blend with equally fine elastic fibres. Cells are more numerous in



the papillary layer and you should see more nuclei in this area than in the deeper

reticular layer. Also, the papillary layer contains the capillary network which supplies the

epidermis, The reticular layer contains coarse collagen and elastic fibres and the larger

vessels which feed into the capillary network of the papillary layer..

Draw part of the epidermis and the underlying dermis. Label the layers of the

dermis and structures contained within them.

Appendages of the Skin

Hair

A characteristic feature of the human skin is the apparent lack of hair (pili ) on most of

the body surface. This is actually not quite true. Most of the skin is haired although the



hair in most areas is short, fine and only lightly pigmented. This type of hair is

called vellus hair .

Truly hairless are only the palms of hands and soles of feet, the distal phalanges and

sides of fingers and toes and parts of the external genitalia.

In those parts of the skin which we perceive as "hairy" we find terminal hairs . The free

part of each hair is called the shaft . The root of each hair is anchored in a tubular

invagination of the epidermis, the hair follicle , which extends down into the dermis and,

usually, a short distance into the hypodermis. The deepest end of the hair follicle forms

an enlargement, the bulb . Cells in the bulb are mitotically active. Their progeny

differentiates into the cell types which form the hair and the cells that surround its root,

the root sheath . Hair cells keratinise within the lower one-third of the hair follicle. Above

this level it is not possible to identify individual cells within the hair. Each hair follicle has

an associated bundle of smooth muscle, the arrector pili muscle . This muscle inserts

with one end to the papillary layer of the dermis and with the other end to the dermal

sheath of the hair follicle.

Hair growth is discontinuous . Hairs are lost and replaced by new ones. The hair follicle

goes through different stages that reflect the discontinuous hair growth. Anagen is the

phase of growth. The resting stage is called telogen . The length of the anagen is

variable in different regions of the body - lasting only a few months for hair of the

eyebrows and eyelashes but 2 to 5 years for hair of the scalp. Hair growth is controlled

by a number of hormonal and hereditary factors and their interactions.

Suitable Slides

Sections of hairy skin or scalp - H&E

With a few exceptions (thick skin and skin covering parts of the external genitalia), all skin sections should

contain a few hair follicles.

Skin, hairy - H&E

Hair follicles of terminal hair span the entire dermis and usually extend deep into the

hypodermis. Most of them will be cut at odd angles and only a few good longitudinally or

transversely cut profiles are visible. The hair may have been lost during the preparation

of the specimen and not all hair follicles will contain hairs. Although it is often possible to



see the attachment of the arrector pili muscle into the hair follicle or the papillary layer of

the dermis, both attachments are hardly ever visible in the same section.

Draw a hair follicle at low magnification. Try to draw a composite from several

hair follicles and associated structures, which captures their appearance from the

bulb to the epidermis.

Sebaceous Glands

Sebaceous glands empty their secretory product into the upper parts of the hair follicles.

They are therefore found in parts of the skin where hair is present. The hair follicle and

its associated sebaceous gland form a pilosebaceous unit .



Sebaceous glands are also found in some of the areas where no hair is present, for

example, lips, oral surfaces of the cheeks and external genitalia.

Sebaceous glands are as a rule simple and branched (Remember the nomenclature of

glands!). The secretory portion consists of alveoli . Basal cells in the outermost layer of thealveolus are flattened. Basal cells are mitotically active. Some of the new cells will

replenish the pool of basal cells, while the remaining cells are displaced towards the

centre of the alveolus as more cells are generated by the basal cells. The secretory

cells will gradullay accumulate lipids and grow in size. Finally their nuclei disintegrate,

and the cells rupture. The resulting secretory product of lipids and the constituents of

the disintegrating cell is aholocrine secretion .

The lipid secretion of the sebaceous glands has no softening effect on the skin, and it

has only very limited antibacterial and antifungoid activity. Its importance in humans is

unclear. Clinically the sebaceous glands are important in that they are liable to

infections (e.g. with the development of acne).

Suitable Slides

slides of hairy skin or thin skin - H&E, trichrome, van Gieson

Skin, hairy - trichrome, H&E

Sebaceous glands will be present in all types of skin other than thick skin. Their numbers should correlate with the

number of hair follicles. If your section does not contain hair follicles you are unlikely to see a good sebaceous

gland. Sebaceous glands are usually embedded in the dermis. Although they empty into

the hair canal of the hair follicle, this point will only be visible for a few of them because

of the thinness of the sections. It should however be possible to follow the fate of the

secretory cells. Deep in the sebaceous glands cells are smaller with intact nuclei. Cell

size increases with the accumulation of sebum as the cells are gradually displaced

towards the opening of the gland into the hair follicle. The nuclei condense, becomedarker and irregularly shaped.

Draw a sebaceous gland. Emphasise the appearance of the secretory cells in

different parts of the gland. If possible include part of the associated hair follicle.



Sweat Glands

Two types of sweat glands are present in humans. They are

distinguished by their secretory mechanism into merocrine

(~eccrine) sweat glands and apocrine sweat glands. In

addition, they differ in their detailed histological appearance

and in the composition of the sweat they secrete.

Merocrine sweat glands are the only glands of the skin with a

clearly defined biological function. They are of critical

importance for the regulation of body temperature. The skin

contains ~3,000,000 sweat gland which are found all over the

body - with the exception of, once again, parts of the external genitalia .

Sweat glands are simple tubular glands. The secretory

tubulus and the initial part of the excretory duct are

coiled into a roughly spherical ball at the border

between the dermis and hypodermis.

The secretory epithelium is cuboidal or low columnar.

Two types of cells may be distinguished: a light type,

which secretes the watery eccrine sweat, and a dark

type, which may produce a mucin-like secretion. The

cells have slightly different shapes and, as a result of

the different shapes, the epithelium may appear

pseudostratified.

A layer of myoepithelial cells is found between the

secretory cells of the epithelium and the basement

membrane.

The excretory duct has a stratified cuboidal epithelium

(two layers of cells).

The excretory ducts of merocrine sweat glands empty directly

onto the surface of the skin.

unusually thick, haematoxylin stainedsection of the skin



Apocrine sweat glands occur in, for example, the axilla. They are stimulated by sexual

hormones and are not fully developed or functional before puberty. Apocrine sweat is a

milky, proteinaceous and odourless secretion. The odour is a result of bacterial

decomposition and is, at least in mammals other than humans, of importance for sexual

attraction.

The histological structure of apocrine sweat glands is similar to that of merocrine sweat

glands, but the lumen of the secretory tubulus is much larger and the secretory

epithelium consists of only one major cell type, which looks cuboidal or low columnar.

Apocrine sweat glands as such are also much larger than merocrine sweat glands.

The excretory duct of apocrine sweat glands does not open directly onto the surface of

the skin. Instead, the excretory duct empties the sweat into the upper part of the hair

follicle . Apocrine sweat glands are therefore part of the pilosebaceous unit.

Some texts argue that the apocrine sweat glands use a merocrine or a combined merocrine / apocrine secretory

mechanism.

Suitable Slides

merocrine sweat glands: sections of thick skin or thin skin - H&E

apocrine sweat glands: sections of skin from the areolae (pigmented skin surrounding the nipples), the

axilla (arm pit) or skin covering the external genitalia - H&E

Skin, thick - H&E

Scan along the border between dermis and hypodermis and locate a sweat gland. The

secretory tubulus and the initial segment of the duct usually form a cluster of round or

irregularly shaped profiles, which stain darker than the surrounding connective tissue.

The structural preservation of the sweat glands may vary quite a bit in the different

preparations. The different cell types in the secretory epithelium of merocrine sweat

glands are only visible in well preserved glands. The red rim around the secretory

tubulus is formed by the cytoplasm of myoepithelial cells. Their small, dark nuclei may

be visible close to the periphery of the tubulus.

Draw a small schematic illustrating the relative position of the sweat gland in the

skin. Identify and draw the secretory tubulus and excretory duct. Label as many

features as can be identified.



Nipple - H&E

Like merocrine sweat gland, the

secretory tubulus of apocrine

sweat glands will coil close to

the border between the dermis

and the hypodermis. Only one

type of secretory cell is present,

and the lining of the secretory

tubulus looks more uniform than

that of merocrine sweat glands.

The key feature though is the

very wide lumen of the

secretory tubulus. The secretorycells are surrounded by a layer

of myoepithelial cells. Their

cytoplasm forms the slightly

darker outline of the secretory

tubulus.

raw the secretory tubulus of

an apocrine seat gland -

referably next to your drawing

of the merocrine sweat gland.

Label the structures included in

our drawing.

kat skin grp 8

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