INTEGUMENTARY SYSTEM (SKIN) largest single organ of the body 1520% of total body weight Surface area of 2m2

f 2m2 Thickness varies from 0.5 to 4.0mm composed of : epidermis (ectodermal origin) dermis (mesodermal origin) subcutaneous tissue/ hypodermis (a loose connective tissue that may contain pads of adipocytes)

FUNCTIONS: Protective barrier against injury or invasion by microorganisms Sensory pain, touch and pressure Thermoregulatory thorough skins insulating components (fats) and mechanisms for accelerating heat loss (sweat production) Metabolic synthesis of vitamin D3 from UV light Sexual Signaling features of skin (pigmentation and hair)

Two Principal Layers: 1. Epidermis 2. Dermis *hypodermis Beneath the dermis - Layer of looser connective tissue that is not part of the skin but minimizes injury to it by permitting some degree of mobility of skin over underlying structures - In some regions of the body, it may consist mainly of adipose tissue * Mucocutaneous junctions epidermis is continuous with the epithelium lining those structures (lips, nose, eyelids, anus, and vagina.) 1. Epidermis surface epithelium - Stratified squamous epithelium 0.07-0.12mm in thickness (over most of the body), but may reach 0.8mm on palms and 1.4mm on the soles of the feet at birth it is already thicker at these sites than elsewhere, and continuous pressure and friction on these surfaces in postnatal life result in additional thickening.

Layers of the Epidermis: Stratum Basale Single layer of basophilic columnar cells on the basement membrane at the dermal-epidermal junction Sometimes referred to as stratum germinativum deepest layer of the five layers of the epidermis Primarily made up of basal keratinocyte cells, which can be considered the stem cells of the epidermis.

Characterized by mitotic activity and is responsible (in conjunction with the initial portion of the next layer for the production of epidermal cell -All keratinocytes in the stratum basale contain intermediate filament composed of keratins Cells attach to one another by numerous desmosomes, and to basal lamina by numerous hemidesmosomes. o Hemidesmosomes- are very small stud- or rivet-like structures on the inner basal surface of keratinocytes in the epidermis of skin. They connect the basal face to other cells. o Desmosomes-binds the cells of this layer together in their lateral and upper surface. Link two cells together.

Stratum Spinosum layer of the epidermis found between the stratum granulosum and stratum basale. Also referred to as the "spinous" or "prickle-cell" layer. Normally the thickest epidermal layer is about 4-6 rows of cells Consist of polyhedral or slightly flattened cell with their long axis parallel to the surface of the epithelium Have central nuclei with nucleoli and cytoplasm actively synthesizing keratin filament Tonofibrils-are cytoplasmic protein structures in epithelial tissues that converge at desmosomes and hemidesmosomes. Cytoplasm less basophilic is drawn into short cellular extensions around the tonofibrils on the both sides of each desmosomes,leading to the short spine or prickle appearance of the cell surface Lateral surfaces have short processes that interdigitate with those of neighbouring cells. Contain few ribosomes than stratum basale

Presence of bundles of keratin filaments that radiate from perinuclear region and end in the numerous desmosomes along the boundary between adjacent cells (prominent feature)

Stratum Granulosum 3-5 layers of cells that are considerably flatter than those of the stratum spinosum Contain many lamellar bodies (may occupy as much as 15% of the cell volume) Presence of irregularly shaped keratohyalin granules in the cytoplasm, which stain intensely in basic dyes (most distinct feature) Do not have limiting membrane, and bundles of keratin filaments may be incorporated in their periphery, or may pass through them

Stratum Lucidum May be present in the thick skin between stratum granulosum and stratum corneum, but not in thin skin. Appears thin and clear 1 or 2 rows of flat, translucent keratinocytes

Stratum Corneum Latin for 'horned layer outermost layer of the epidermis Consists of 15-20 layers of flattened, non-nucleated keratinized cells Cytoplasm is filled with bifringent filamentous keratins Squames or horny cornified cells-fibrillar and amorphous proteins with thickened plasma membranes form a barrier to protect underlying tissue from infection, dehydration, and chemicals Desquamation-the process of cell shedding from the surface of the stratum corneum, balances proliferating keratinocytes that form in the stratum basale.

Thick skin 10-20 layers of cells keratinocytes Keratin cytoskeletal protein synthesizes in large amounts after it enlarge and differentiate in their transit towards the surface Polymerizes into 10 nm intermediate filaments that gradually come to constitute 80%, or more of the cell volume. 20-30 days transit time of keratinocytes from basal layer to surface. Cytomorphosis of keratinocytes sequence of cytological changes the cells undergo in their upward movement.

Stratum Lucidum and Granulosum in Thick Skin In keratinocytes moving upward from the stratum Spinosum 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) only three to five cells thick, where keratin filaments are cross-linked 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). The acidic proteins in the granular, basophilic masses are dispersed through the tonofibril bundles, giving the cells of this new layer an eosinophilic, clear appearance. In the most superficial layers, the stratum corneum (C), the cells are fully differentiated and have lost nuclei and 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).

Melanocytes Skin color is the result of several factors, the most important of which are the keratinocytes' content of melanin and carotene and the number of blood vessels in the dermis. a specialized cell found among the cells of the basal layer and in the hair follicles Eumelanin - brownish black pigment pheomelanin (phaios, dusky, + melas, black) - pigment found in red hair

Melanocytes are neural crest derivatives which migrate into the developing epidermis' stratum basale, where eventually one melanocyte accumulates for every five or six basal keratinocytes (6001200/mm2 of skin). They have rounded cell bodies and form hemidesmosomes with the basal lamina, but no desmosomes with adjacent keratinocytes. Long irregular dendritic extensions from each melanocyte branch into the epidermis, running between the cells of the basal and spinous layers and terminating in invaginations of the neighboring five to ten keratinocytes. A melanocyte is a pale-staining cell with numerous small mitochondria, short cisternae of rough endoplasmic reticulum (RER), and a well-developed Golgi apparatus

Pigmentation 1. Carotene inherent yellowish color (precursor of vitamin A) 2. Hemoglobin - pink tint (oxygenated haemoglobin of blood in the underlying capillary bed of the dermis) 3. Melanin shades of brown to black -produced by melanocytes present in varying numbers in basal lamina of epidermis - synthesized from tyrosine which is transformed into 3-4 dihydrophenylalanine (dopa), and then to dopaquinone, which is converted to melanin. - may be as few as 1000/mm2 on the arms and thighs, and as many as 4000/mm2 on the face and neck 4. Pheomelanin slightly different pigment of red hair

Dendritic (Langerhans)Cell -Antigen presenting dendritic cell -Usually most clearly seen in the spinous layer -2-8% of the epidermal cell -Bone marrow-derived, blood-borne cell -Capable of binding, processing and presenting antigen to T lymphocytes -Immune cells in the dermis Characteristics 1. Solitary cell type widely distributed in the epidermis 2. Stellate in form and has a heterochromatic nucleus of irregular shape, surrounded by pale staining cytoplasm. 3. Contain small membrane bounded granules of unusual type, called Birbeck granules 4. Can be distinguished from keratinocytes by their irregular nuclear shape, their lack of bundles of keratin filaments, and the absence of desmosomes . 5. located in the upper part of the stratum spinosum 6. May number as high as 800/mm2 and make up 3-8% of the cell population of the epithelium. 7. Participate in the bodys immune responses

8. Have surface markers and receptors similar to those T-lymphocytes and macrophages 9. Occur in other stratifies squamous epithelia, including the oral cavity, esophagus and vagina. Tactile(Merkel)Cells -Epithelial tactile cells are mechanoeceptors -Resembles pale-staining keratinocytes with keratin filament in their cytoplasm and few, if any, melanosomes -Characteristic feature: small, Golgi-derived dense-core neurosecretory granules containing peptides like those of neuroendocrine cells -Derived from neural crest cells -Located at the basal epidermal layer in areas of high tactile sensitivity and at the bases of hair follicles -Basolateral surfaces of the cells contact expanded terminal disc of unmyelinated sensory fibers that penetrate the basal lamina Characteristics 1. Small numbers are found in the basal layer of the epidermis over the entire body. 2. More abundant in fingertips, which have an important role in sensory reception. 3. Nucleus is deeply invaginated and the cytoplasm contains may dense cored granules 80-130nm in diameter and intermediate filaments 4. Have mechanoreceptor function sensing pressure 5. Also occur in the epithelium of the oral mucosa Function: -related to the diffuse neuroendocrine system -contribution as mechanoreceptors in the sense of touch 2. DERMIS Is the connective tissue that supports the epidermis and binds it to the subcutaneous (hypodermis). immediately beneath the epidermis Makes up the greater part of the thickness of the skin Ranges in thickness from 0.6mm, in the thin skin of the eyelids, to 3mm or more, on the palms and soles of the feet. Usually thinner in female than in men The surface is very irregular and has many projections (dermal papillae) that interdigitate with projections (epidermal pegs or ridges) of the epidermis.

Contains two layers: Papillary layer o Outermost o Thin in diameter o Constitutes the major part of the dermal papillae o Composed of loose connective tissue with fibroblast and other connective tissue cells such as mast cells and macrophages o Extravasated leukocytes are also seen in this layer o From this layer, anchoring fibrils of type VII collagen insert into the basal lamina and bind the dermis to the epidermis

Reticular layer o deeper layer o thicker in diameter o composed of irregular dense connective tissue (mainly bundles of type I collagen), and has more fibers and fewer cells than the papillary layer o a network of elastic fibers is also present, providing elasticity to the skin

BASEMENT MEMBRANE Is always found between the stratum basale and the papillary layer of the dermis and follows the contour of the interdigitations between these layers. The basement membrane is a composite structure consisting of the basal lamina and the reticular lamina and can usually be seen with the light microscope. Nutrients from keratinocytes must diffuse into the avascular epidermis from the dermis vasculature through this basement membrane.

Basement membranes. This section of kidney shows the typical basement membranes (arrows) of several tubules and of structures within the single glomerulus included here. In renal glomeruli the basement membrane, besides having a supporting function, has an important role as a filter.

SUBCUTANEOUS TISSUE SUBCUTANEOUS LAYER o Also known as hypodermis or superficial fascia contains fat cells that vary in number in different regions of the body and vary in size according to nutritional state o Consists of loose connective tissue that binds the skin loosely to the subjacent organs, making it possible for the skin to slide over them o Adipose cell tend to accumulate in the hypodermis of the abdomen and buttocks, and may reach a thickness of 3cm or more. o Panniculus adiposus subcutaneous layer of adipose cells.

VESSELS AND SENSORY RECEPTORS Connective tissue of the skin contains a rich network of blood and lymphatic vessels Blood vessels that nourish the cells of the skin form two major plexuses: Deep at the interface between hypodermis and dermis Superficially between the papillary and reticular dermal layers A variety of sensory receptors are present in skin, including bot hsimple nerve endings with no glial or collagenous covering and more complex structures with sensory fibers enclosed by glia and delicate connective tissue capsules. The unencapsulated receptors include the following: Tactile discs o Associated with the epidermal tactile cells, which function as receptors for light touch. Tactile (Merkel) cell Epithelial tactile cells in the basal epidermal layer of skin with high tactile sensitivity are neural crestderived cells that function as mechanoreceptors. TEM of a tactile cell from the finger epidermis of a 21week fetus shows a mass of densecore cytoplasmic granules (G) near the basolateral cell membrane, which is in direct contact with the expanded ending of a nerve (N). X14,000. Inset: Granules are similar in morphology and content to the granules of many neuroendocrine cells. Free nerve endings o Found in the papillary dermis and extending into lower epidermal layers, which respond primarily to high and low temperatures, pain, and itching o Also functions as tactile receptors Root hair plexuses o Is a web of sensory fibers surrounding the bases of hair follicles in the reticular dermis that detects the movements of the hairs. The following encapsulated receptors are tactile mechanoreceptors: Tactile corpuscles (Meissners corpuscles) o Elliptical structures o About 30 75 m o Perpendicular to the epidermis in the dermal papillae and papillary layer of the fingertips, palms and soles o They detect light touch Lamellated (Pacinian) corpuscles o Large oval structures o Approximately 0.5 mm by 1 mm a) Tactile corpuscle b) Lamellated corpuscle

Found deep in the reticular dermis or hypodermis with an outer capsule and 15 to 50 thin, concentric lamellae of flat Schwann-type cells and collagen surrounding a highly branched, unmyelinated axon. Specialized for sensing coarse touch, pressure (sustained touch), and vibrations with distortion of capsule amplifying a mechanical stimulus to the axonal core where an impulse is initiated.

Krause corpuscles and Ruffini corpuscles o Pressure-sensing mechanoreceptors in the dermis o Are more poorly characterized structurally

The encapsulated, lamellated, mechanoreceptors are also found in the connective tissue of organs located deep in the body, including the wall of the rectum and urinary bladder, where they also produce the sensation of pressure when the surrounding tissue is distorted.

HAIR: Tactile Elongated keratinized structures derived from invaginations of the epidermal epithelium called hair follicles. receptor Extends downward to the dermis, and sometimes a short distance into the subcutaneous tissue Hairs are absent only on the palms and soles, the lateral aspect of the feet, the glans penis, clitoris, and the labia minora There are about 800hairs/mm2 on the face, but on the rest of the body they number only about 60hairs/mm2 On eyelids, no hairs other than the eyelashes project beyond their follicle, but on the head, hairs may grow to well over 1m in length. The color, size, shape, and texture of hair vary according to age, genetic background, and region of the body.

Parts of hair 1. Hair follicle the point from which the hair grows. It is a tiny cup-shaped pit buried in the fat of the scalp. 2. Hair bulb A terminal dilation of the hair follicle during anagen. Made up of epithelial cells (keratinocytes) similar to those in the basal and spinous layers of epidermis. They divide constantly and then undergo keratinization, differentiating into specific cell types. Dermal Papilla- inserts into the base of the hair bulb and contains a capillary network required to sustain the hair follicle. Hair root- the epidermal cells covering the dermal papilla. Internal root sheath- completely surrounds the initial part of the hair shaft but degenerates above the level of the attached sebaceous glands.

 External root sheath- covers the internal sheath and extends all the way to epidermis, where it is continuous with the basal and spinous layers. 3. Hair shaft. The part of the hair seen above the skin It is made up of dead cells that have turned into keratin and binding material, together with small amounts of water. This structure explains why we do not feel any pain while our hair is being cut. Medulla of the hair - A large, vacuolated, and moderately keratinized cells. It is the innermost layer of the hair shaft and is seen only in large and thick hairs. Hair cortex- A heavily keratinized, compactly grouped fusiform cells. It is the middle layer of the hair shaft made of keratin fibers. Hair cuticle- A thin layer of heavily keratinized, shingle-like cells covering the cortex. The outermost layer of the hair shaft. Glassy membrane- An acellular hyaline layer with thickened basement membrane separating the hair follicle from the dermis. Arrector pili muscle- A small bundle of smooth muscle cells running from a midpoint on the connective tissue sheath (surrounding dermis) to the dermal papillary layer. Contraction of these muscles pulls the hair shaft to a more erect position producing tiny bumps on the skin surface called the goose bumps where each contracting muscle distorts the attached dermis.

Nail - hard, flexible plates of keratin on the dorsal surface of each distal phalanx *Parts* Nail Plate The hard part of the nail. Made of keratin. Protects the nail bed

Free edge The very hardest part of the nail. The extension of the nail plate. Protects the fingertip.

Lunula Half-moon part of the nail. No real function. Creates the shape of the nail. The white color indicates the transition stage of the nail from live to dead.

Nail Grooves The two runners that keep the nail growing in a straight line.

Nail Walls or Nail Fold Sides of the nails, the fleshy parts. Protects the edges of the nail plate.

Cuticle Protects the matrix. The cuticle is dead skin.

Matrix The only living part of the nail. Any damage to the matrix is irreparable. The matrix is where the nail grows from, and where new nail cells are formed.

Nail Bed This lies below the nail plate. It contains the blood vessels and nerve endings. The nail bed supplies nutrients to the matrix.

Hyponychium The top part of the nail seal. Protects against infection of the nail bed.

Dermatoglyphs alternating ridges and grooves on the finger pads o Distinct pattern of arches, loop, whorl basis of the individuality of fingertips.

*Importance* - The fingernail acts as a protective plate and enhances sensation of the fingertip. - The nail acts as a counterforce to the fingertip providing even more sensory input when an object is touched. Sebaceous gland Sebum secretion that is composed of mixture of triglycerides, cholesterol, and waxes. Maintain soft texture of thin skin and flexibility of the hairs Eccrine sweat glands Widely distributed throughout the skin Coiled tubular glands, with their secretory portion deep in the dermis, or in the hypodermis. Slender ducts ascends through these layers to open at a sweat pore on the surface of the skin Secretory portion is lined by cuboidal, or low columnar, epithelium containing 2 cell types, designated light cell (clear cells), and dark cells, on the basis of their appearance in stained histological sections. Appendages of the hair follicles and are found throughout the dermis, except where hairs are lacking (palms, soles, and sides of feet) 1 or 2 are associated with each hair follicle Numbers 400-800/cm2 on the face, forehead, and scalp, but over the rest of the body their numbers are very much lower. It is 0.2-2.0mm in diameter and are located above the origin of the arrector pilli muscle Ducts open into the follicular canal around the hair shaft.

Light cell pyramidal in form Base in contact with the basal lamina between myepithelial cells Plasmalemma at cell base is elaborately infolded Egress of their secretion is via intercellular canaliculi that open into the duct Cytoplasm is rich in glycogen, but contains no secretory granules

Dark cell inverted pyramid in form

With a broad adlumenal end tapering down to a small adlumenal end, that does not reach the basal lamina. Small , dark staining nucleus, a prominent Golgi complex, long mitochondria, and a few cisternae of rER Apical cytoplasm contains many moderately dense secretory granules Contains glycoprotein Long duct of the gland is line by and epithelium consisting of two layers of cuboidal cells.

Myoepihelial cell between epithelium and its basal lamina. Contract to press the secretion out of the gland. Number between 3 million and 4 million, and their aggregate weight is roughly equivalent to that of a kidney. Innervated by cholinergic nerves

Apocrine sweat glands Second kind of sweat Found in the skin of axilla, mons pubis, and in the circumanal region Located deep in the dermis Larger than the eccrine sweat glands

Merocrine - mode of secretion Nerves Free endings Penetrate the epidermis and terminate in the stratum granulosum Sense of pain or temperature Axons of other myelinated nerves end in disk-like expansions, called Merkel endings, that are in contact with Merkel cells at the base of the epitheliuim. Function is still unknown Encapsulated endings Duct opens in the canal of the hair follicle Secretory portion of the tubular gland is lined by cells that are usually cuboidal, but they may be squamous if the gland is distended with secretion. Apical cytoplasm contains large secretory granules Slightly viscous fluid that is oderless when secreted, after modification by bacteria residing on the skin, it acquires an odor. Secretory activity does not begin until puberty In women, there is an enlargement of the cells, and of the lumen of axillary apocrine sweat glands, during premenstrual phase of the cycle, followed by regression during menses. Innervated by adrenergic nerves

Pacinian corpuscles in the dermis and hypodermis are ovoid structures up to 1mm in length. The axon of the myelinated nerve penetrates into the core of the corpuscles, where it is surrounded by 20-60 concentric lamellae consisting of very thin, flat cells separated by narrow spaces that are filled with gelatinous material. Resembles an onion in cross section

Meissners corpuscles pear shaped structures made up of flattened cell oriented transversely, resulting in a ladder-like appearance in section. The nerve axons loses it sheath, enters one pole of the corpuscle, and pursues a spiral or zigzag course among the flat cells in its interior. Meissnrs corpuscles are found in occasional dermal papillae. Such ending are probably mechanoreceptor sensing slight deformation of the skin.

Krauss end bulbs small spheroidal bodies in the papillary layer of the dermis. They bear a superficial resemblance to Pacician corpuscles, but are much smaller and lack concentric lamellae. Their sensory modality is unclear.

Medical Applications Skin cancer - shows an increased incidence in fair-skinned individuals residing in regions with high amounts of solar radiation.

Psoriasis - greater epidermal thickness and more rapid renewal of epidermis -- abnormal keratinization with a defective skin barrier.

Malignant melanoma is an invasive tumor of melanocytes.

Addison disease - lack of cortisol from the adrenal cortex -- increase the pigmentation of the skin. Albinism - a hereditary inability of the melanocytes to synthesize melanin

Vitiligo - causes a patchy loss of pigment in the skin bullous pemphigoid - blistering disorder

pemphigus - blistering disorder caused by autoimmune damage to intercellular junctions between keratinocytes.

acne - a chronic inflammation of obstructed sebaceous glands common during and after puberty.