Integument and Epidermis

• The skin (integument) is the largest organ, about 16% of body weight, and covers underlying soft tissues.
• The skin's surface shows grooves and ridges forming dermatoglyphics (fingerprints).
• The skin consists of two layers: the epidermis and the dermis.
• The dermis and epidermis junction is formed by dermal papillae interdigitating with epidermal ridges.
• The hypodermis (subcutaneous tissue) is loose connective tissue with varying fat, binding skin to deep fascia. Its thickness varies with nutritional state, activity, body region, and gender.

Epidermis

• The epidermis is the surface layer of the skin, formed of keratinized stratified squamous epithelium.
• It's ectodermal in origin, avascular, highly innervated, and receives nutrients from dermal blood vessels via diffusion.
• There are four cell types in the epidermis: keratinocytes, melanocytes, Langerhans cells, and Merkel's cells.
• Keratinocytes represent about 85% of the epidermal cell population, producing keratin for protection and shedding.
• Epidermal keratinocytes are arranged in five layers: stratum germinativum, stratum spinosum, stratum granulosum, stratum lucidum, and stratum corneum.
• The basal two layers of the epidermis are together called the malpighian layer.

Stratum Germinativum (Germinal/Basal Layer)

• The stratum germinativum is a single layer of basophilic columnar epithelial cells (rich in ribosomes) resting on a clear wavy basement membrane.
• The nuclei are oval and basal with occasional mitotic figures.
• This layer is continuously undergoing mitotic division for constant renewal of epidermal cells.
• Melanocytes and Merkel's cells are present in the stratum germinativum
• The Cytoplasm is rich in cytokeratin filaments, ribosomes, and few mitochondria.
• Basal cells attach to neighbors by desmosomes and to the basal lamina by hemidesmosomes.

Stratum Spinosum (Prickle Cell Layer)

• The stratum spinosum is formed of 4-6 layers of polyhedral cells, thicker in thick skin (palms and soles).
• It is less basophilic than the basal layer with central nuclei.
• The cells of the stratum spinosum are mitotically active, becoming smaller near the surface.
• Langerhans cells are present in this layer.
• The cells are adherent to each other by desmosomes.
• The cytoplasm is full of tonofilaments, ribosomes, and few mitochondria.
• Superficial layer cells contain membrane-coating granules (lamellar granules) containing lipids and lipoproteins.
• These lipids and lipoproteins are released by exocytosis into intercellular spaces to cement cells, making them impermeable to water and foreign substances.

Stratum Granulosum (Granular Layer)

• The stratum granulosum consists of 3-5 layers of flat cells with flat nuclei.
• It contains intensely basophilic keratohyalin granules (source of the amorphous protein component of soft keratin).
• The cells are full of irregularly shaped non-membranous granules that are small particles and large masses.
• Tonofilaments can be seen within the cells.
• No mitochondria or nuclear envelope (degenerated nuclei) can be seen in the cells.
• Keratohyalin granules and membrane-coated granules are the two types of granules present.
• The non-membranous Keratohyalin granules are present.
• Containing lipids and lipoproteins, the lamellated elongated granules are released in the intercellular spaces to form a protective barrier. These are referred to as membrane-coated granules

Stratum Lucidum (Clear Layer)

• The stratum lucidum is thick in thick skin and appears as a clear unstained or lightly stained homogenous layer.
• It forms of tightly packed flattened cells without nuclei or organelles, but they contain eleidin granules (immature keratin granules) and densely packed keratin filament.
• The cells are extremely flattened.
• No cell organelles can be seen.
• Their plasma membranes are thickened.
• Cells are formed of packed immature keratin.

Stratum Corneum (Horny Layer)

• The stratum corneum is the most superficial layer of the epidermis and is thicker in thick skin.
• It is an acidophilic scaly layer (15-20 layers) of flattened dead non-nucleated keratinocytes.
• It consists of 15-20 layers of flattened dead non-nucleated keratinocytes with no organelles and no nuclei.
• The cytoplasm is replaced by flat keratin scales (tonofilaments).
• Lipid accumulation in the intercellular spaces contributes to the high waterproof properties of this layer.
• These dead cells are continuously shed off and replaced through successive mitotic waves of the deeper cell layers.

Melanocytes

• Melanocytes are ectodermal in origin (derived from the neural crest) and located between cells of the stratum germinativum.
• The number of melanocytes in the skin varies in different areas from 800-2300/mm2.
• They have rounded cell bodies with central nuclei and long cytoplasmic processes passing between neighboring keratinocytes.
• Melanocytes are not well demonstrated in H&E stained sections.
• Melanocytes exhibits abundant RER, mitochondria, prominent Golgi apparatus, and membrane-bound granules (melanosomes).
• Intermediate filaments are present.
• These granules are transferred from one melanocyte to adjacent keratinocytes, forming "epidermal melanin unit".
• Their nuclei are pale (euchromatic).
• No desmosomes are present between melanocytes and keratinocytes.
• Function: They synthesize melanin pigments to protect the skin against ultraviolet rays and determine skin color.
• Important to note that melanin granules are present in the supranuclear region for optimum cellular protection against UV rays.
• Melanin synthesis starts in the RER, which has the tyrosinase enzyme which converts tyrosine into DOPA, then into dopaquinone and then into melanin.
• Melanin is concentrated, accumulated, stored, and completed in the Golgi apparatus.
• Melanin pigment is found in secretory vesicles called melanosomes.
• Melanocytes transfer or inject melanin granules into keratinocytes by way of their processes (cytocrine secretion).
• They are degraded by lysosomes in keratinocytes.
• Both negros and white people have the same number of melanocytes in the different regions of the body, so skin color is dependent mainly on the amount of the released melanin and the number of melanocytes.
• Factors affecting melanin synthesis are increased in prolonged exposure to the sun and excess production of melanocyte-stimulating hormone from the pituitary gland.
• Factors decreasing Melanin synthesis includes a genetic condition called albinism and in application of some compounds like hydroquinones "whitening compounds".
• If fresh skin sections are incubated with DOPA, the tyrosinase enzyme (within the melanocytes) converts DOPA into melanin, so the black pigment can be identified with melanocytes. This is called DOPA reaction.
• The color of the skin is due to three major pigments: melanin (black) formed by melanocytes, hemoglobin (red) in blood vessels, and carotene (yellow).

Melanophores

• Melanophores are CT phagocytic cells that phagocytose melanin pigments formed by melanocytes.
• They are mesodermal in origin and are present in the dermis.
• They have no tyrosinase enzyme, so they are DOPA negative.

Langerhans Cells

• Langerhans cells are mesodermal in origin and distributed between stratum spinosum cells.
• They cannot be well identified with H&E.
• Using supravital stains or gold chloride, they are identified as star-shaped cells.
• They display pale cytoplasm and dense nuclei.
• Their long slender processes extend between keratinocytes in the intercellular spaces.
• Their cytoplasm is low electron density with Golgi apparatus, little endoplasmic reticulum, lysosomes, and multivesicular bodies.
• Their nuclei are polymorphic and irregular.
• The most characteristic and unique feature are their membrane-bound tennis paddle-shaped granules (Birbeck granules), probably formed by clathrin-assisted endocytosis.
• They may contain hydrolytic enzymes; however, their exact function is not yet known.
• They have no desmosomes, no keratin filaments, and no melanosomes.
• Langerhans cells are antigen-presenting cells (dendritic cells) and play a role in immunity.
• Keep in mind that Langerhans cells are found in other stratified squamous epithelia as oral cavity, esophagus and vagina.

Merkel Cells

• Merkel cells are derived from the neural crest (ectodermal in origin).
• They are present in the stratum germinativum near well-vascularized, richly innervated connective tissue.
• Naked terminals of myelinated nerve fibers enter the epidermis and form disc-shaped expansions at the base of Merkel cells.
• They are distributed all over the body, notably in fingertips, oral mucosa, and hair follicle bases.
• Merkel cells are found as single cells parallel to the basal lamina.
• They extend their processes between adjacent keratinocytes to which they are attached by desmosomes.
• The cytoplasm contains perinuclear small dense cored granules, and intermediate filaments.
• Their nuclei are deep and indented.
• They function in touch sensation (mechanoreceptors) and may be APUD cells.

Dermis

• The dermis forms a connective tissue layer under the epidermis.
• It is mesodermal in origin.
• It contains sweat glands, sebaceous glands, and hair follicles.
• Dermal thickness varies in different regions, thickest at the back.
• It is formed of a superficial papillary layer and a deeper reticular layer.
• The papillary layer is the superficial layer of loose connective tissue, forming dermal papillae interdigitating with epidermal ridges.
• The cells found in the papillary layer of the dermis are connective tissue cells especially fibroblasts, macrophages, and plasma cells.
• It contains type III and VII collagen fibers, elastic fibers that form anchoring fibrils, blood capillaries, and nerve receptors (Meissner's corpuscle and Krause end bulb).
• The papillary layer forms the dermo-epidermal junction, enhancing fixation and surface area for epithelial nutrition.
• The epidermis is fixed to the dermis through the basement membrane, dermal papillae, and hemidesmosomes.
• The reticular layer is the deeper dermal layer formed of dense irregular connective tissue fibers running in different directions.
• It contains type I collagen fibers and a network of thick elastic fibers.
• It contains a rich network of blood (regulating body temperature) and lymph vessels, with arteriovenous anastomoses.
• The reticular layer is richly supplied by nerves and nerve endings (Pacinian corpuscles and Krause end bulbs).

Thick and Thin Skin

• Thick skin covers the palms and soles.
• It lacks hairs and sebaceous glands.
• It has many sweat glands and a thick epidermis.
• Thin skin covers the rest of the body, except for the palms and the soles.
• Thin skin has variable thickness and is usually hairy.

Skin Appendages

• Skin appendages include skin glands (sweat and sebaceous) and keratinous appendages (hair and nails).

Eccrine Sweat Glands

• Eccrine sweat glands are present in the dermis of both thick and thin skin.
• They are simple coiled tubular glands that are merocrine.
• The secretory portion lies in the dermis and contains dark cells, clear cells, and myoepithelial cells.
• Dark cells are pyramidal small cells with narrow bases and wide apices (like an inverted cone) that line the lumen and contain many apical mucinogen granules. These secretions are mucus.
• Clear cells are more numerous than dark cells, with broad bases and narrow apices. They surround dark cells and have pale cytoplasm, folded basal cell membranes, no secretory granules, and abundant glycogen granules.
• The clear cell secrete watery fluids.
• Myoepithelial cells are present between secretory cells and their basement membrane, containing actin and myosin filaments, and aid in expressing gland secretion.
• The conducting portion is continuous with the secretory unit, forming a spiral duct to reach the epithelium, lined by 2-3 layers of cuboidal cells, running upwards in the dermis to open in a sweat pore.
• Function: conducts secreted sweat, and duct cells excrete ions, urea, lactic acid, and some drugs.
• The epidermis has no epithelial duct wall; sweat makes its own pathway.

Apocrine Sweat Glands

• Apocrine sweat glands differ from eccrine glands.
• They are present only in the axilla, breast, pubic, and perineal regions.
• Their ducts open into hair follicles.
• These glands function after puberty under hormonal control.
• Apocrine glands secrete a cloudy viscous odorless fluid by merocrine action, acquiring a distinctive odor from bacterial degradation.
• They have cerminous (wax) glands of the external ear and glands of Moll in the eyelids that are modified apocrine sweat glands.
• The secretory portion is coiled and embedded in the dermis, lined by a cuboidal or columnar cell layer, enveloped by a basal lamina with myoepithelial cells in-between.
• The conducting portion is coiled, lined with cuboidal cells, and opens into hair follicles superficial to the sebaceous gland duct entry.

Sebaceous Glands

• Sebaceous glands are skin appendages present mainly in the dermis of thin skin.
• They are simple alveolar excretory glands of which produce the entire cell becomes a part of the secretion (holocrine glands).
• They secrete sebum: a complex oily material and degenerated epithelium, keeping thin skin and hairs soft and waterproof.
• The secretory portion is a compound acinar gland lined with stratified cuboidal cells that secrete sebum; each acinus is composed of peripherally located basal cells surrounding larger round cells filling the central part.
• The central cells degenerate and die to release their lipid content.
• The conducting portion has clustered acini opening into a single short duct that converges to open in a large short duct.
• The opening is located in the upper part of the hair follicle.
• Sebaceous glands are embedded in the dermis close to the hair follicle.
• They are lined by stratified squamous epithelium.
• They secrete sebum, a complex oily material containing degenerated epithelium that helps keep the hair and skin soft.
• Note on acne: acne is the most common disease involving the sebaceous glands and hair follicles and obstruction of the duct.
• Acne is is usually seen in teenagers with increased sex hormones in which results accumulated secretions followed by bacterial infection.

Keratinous Structures - Hair

• Hair is a keratinized filamentous structure projecting from the epidermis with varying color, size, and distribution based on race, sex, and body region.
• Hair growth is optimal between ages 16-46 and diminishes after age 50.
• The types of hair are vellous (fine and short), terminal (coarse and long), and lanugo (very fine, present all over the fetus).
• Each hair is formed of the shaft (projecting above the surface of the skin), the root (embedded in the skin), and the hair follicle.

Shaft of Hair

• The shaft is the part of the hair projecting above the skin's surface, formed of four layers: medulla, cortex, cuticle, and hair matrix.
• The medulla is the central core of the shaft and contains poorly keratinized vacuolated cells (soft keratin) separated by air space.
• The cortex surrounds the medulla and is composed of keratinized fusiform cells rich in pigment (giving color to the hair).
• The cuticle is the outermost layer of the shaft (hard keratin), composed of scale-like non-nucleated cells.
• The hair matrix is a mass of cells inside the hair bulb around the dermal papilla.

Root of Hair

• The root is the expanded terminal part of the hair in the dermis, indented to fit the dermal papilla shape, and surrounded by the hair follicle.

Hair Follicle

• The hair follicle is a tubular invagination of the epidermis extending into the dermis and surrounding the hair, formed of two sheaths.
• The internal root sheath (soft keratin) has three layers: cuticle cells, Huxley's layer, and Henle's layer.
• The cuticle layer consists of flat overlapping scaly cells of soft keratin in contact with the hair.
• The transparent Huxley's layer has two or three cell layers.
• Henle's layer shows one layer of elongated cells rich in hyaline granules.
• The external root sheath surrounds the internal root sheath and is continuous with the epidermis; above the sebaceous gland duct, it contains all layers of the epidermis otherwise it is formed by Malpighian and spinous layers.
• The epithelium of the external root sheath is separated from the dermis by a non-cellular glassy membrane, and the dermis surrounding the hair follicle forms the connective tissue dermal sheath.

Arrector Pili Muscle

• The smooth muscle fibers that originates in the papillary layer of the dermis is defined as arrector pili muscle.
• It extends superficially to underlie the sebaceous gland and inserts at an oblique angle to the dermal sheath surrounding the hair follicle.
• Sympathetic stimulation causes contraction, elevating the hair and depressing the skin, forming "goosebumps."

Nails

• Nails are located on the distal phalanx of each finger and toe.
• Nails are hard keratinized plates (nail plate) on a bed of epidermis (nail bed).
• Nails consist of the nail root, nail plate, and free edge.
• The nail root is the proximal hidden part of the nail, covered by the proximal nail fold.
• The nail matrix is a region of the nail root located beneath the proximal nail fold.
• The stratum corneum of the proximal nail fold forms the eponychium, which extends over the nail.
• The nail plate is the attached uncovered part, resting on the epidermis nail bed, occupying the stratum corneum.
• The crescent-shaped area at the base of the nail plate is called the lunula.
• Nail growth, referred to as the growth of the nail plate, occurs by proliferation of the cells of the matrix.
• The free edge is the unattached extension of the nail.

Function of the Skin

• Protection: protecting the body against trauma, microorganisms, ultraviolet radiation (melanin), and dehydration (keratin).
• Formation of vitamin D3 by the absorption of ultraviolet radiation acting on 7-dehydrocholesterol.
• Sensation: sensory receptors in the epidermis receive touch, temperature, and pain.
• Secretion: secretion of sweat and sebum.
• Regulation of blood pressure with this highly vascular organ.
• Regulation of body temperature with high vascularity and sweat secretion.
• The dermatoglyphs (fingerprints) are unique for personal identification.

Blood Supply of the Skin

• The skin is a very vascular organ and stores a large volume of blood.
• Subcutaneous arteries and veins in the hypodermis supply the dermis.
• The two plexuses are the cutaneous plexus (dermis and hypodermis) and the subpapillary plexus (papillary and reticular layers).

Arteriovenous Anastomosis (A-V Shunts)

• Direct connections (shunts) between arteries and veins exist within the dermal papillae plexuses.
• Arteriovenous anastomosis (shunt) is present for regulation of blood pressure and body temperature.
• In some sites like nail beds and auricle of the ear A-V anastomoses are branched and tortuous, forming a specialized organ called the glomus.