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Anatomical hints: - Functions: Skin is not only a passive protective barrier, but a complex organ with many functions: ● Protects deeper tissues from injury, drying and invasion of microorganisms (through production of protective keratin layer and presence of immune cells like Langerhans cells and T lymphocytes). ● Keratinocytes are sites for the biosynthesis of soluble molecules (cytokines) that regulate adjacent epidermal cells as well as cells in the dermis. ● Has important role in thermoregulation (through sweat glands). ● Absorbs ultraviolet light (by melanin pigments). ● Has cosmetic function ● Metabolizes vitamin D ● Contains peripheral endings of sensory nerves (warn of potentially damaging physical factors in the environment). - Histology: Skin is composed of three main components (epidermis & skin adnexa, melanocytic system, and dermis & subcutis). E p i d e r m i s ● Epidermis is outer layer of skin ● Epidermis forms outer layer of keratin that is protective and waterproof. ● Epidermis is composed of stratified squamous epithelium (keratinocytes) in 4 layers: inner basal, squamous, granular and outer cornified. ● Other cells present include melanocytes, Langerhans’ cells and Merkel cells. ● Skin is thicker in palms and soles, which contain epidermal ridges that prevent slipping and form fingerprints and footprints. ● Keratinization takes 30-45 days; alterations in pattern and speed cause dermatoses, hyperkeratosis or parakeratosis. ● Dermoepidermal junction: thrown into undulating folds of interlocking ridges of epidermis (rete ridges) and dermal papillae. Squamous layer Cornified layer Basal layer Granular layer or Prickle layer Stratum lucidum or Horny layer or Stratum basale or Stratum granulosum or Stratum spinosum or Stratum corneum - Mitotically active, produces - Has several layers of cells, larger than - 1 to 3 layers of flattened - Present only in soles - Basket weave other keratinocytes. basal layer, which become flat and cells with intensely and palms. pattern of multiple - Separated from dermis by eosinophilic as they approach the basophilic keratohyaline - Located between layers of polyhedral continuous basal membrane surface (due to an increase in keratin granules. granular and cornified cells without nuclei. (keratinocytes are attached to and reduction in ribosomes). - These granules contain layer. - Thicker and more this membrane by hemi- - May have clear vacuolated cytoplasm. precursors of filaggrin - Consist of several compact in acral desmosomes). - Cells are attached to each other by protein, which causes layers of dead cells, region (peripheral - Also contains melanocytes. fine spiny bridges with central dot-like aggregation of keratin appear as homogenous body-limbs, fingers, desmosomes (Bizzozero’s nodule). filaments. eosinophilic zone. ears). - Loss of these spiny bridges causes acantholysis. Langerhans cells Merkel cells Melanocytes - Bone marrow derived dendritic cells - Mechanoreceptors concentrated in skin of digits, - Neural crest origin. that present antigens to T cells. finger pads, palms, dorsum of feet, lips, hard palate. - Seen in basal epidermis, hair follicles, most squamous - Scattered in upper squamous layer - Difficult to see with H&E or special stains. mucous membranes, leptomeninges. and in the dermis, but difficult to see - contain neurosecretory granules in its cytoplasm - Produce melanin from tyrosine, transfer it (via cytoplasmic on H&E. (positive for NSE). processes) to adjacent epithelial cells to protect against ultraviolet rays. - Racial skin color is due to amount of melanin in keratinocytes, not number of melanocytes. - Positive for: Fontana-Masson, tyrosinase, S100, MelanA, HMB45. - Negative for: GFAP, neurofilament. Desmosomes (macula adherens) Hemidesmosomes - Definition: - Definition: They are localized spot-like adhesions randomly arranged on the lateral sides Situated at the undersurface of basal keratinocytes, linking them to basement of plasma membranes. They are specialized for cell-to-cell adhesions and membrane. helpful to resist shearing forces. - Structure: - Structure: (1) The hemidesmosome represent half desmosome. (1) Desmosomes are molecular complexes of cell adhesion proteins (2) The hemidesmosome might consist of two proteins: the BPAg1 protein (desmoglein and desmocollin), and linking proteins that attach the cell (located at the intracellular side of the hemidesmosome, bind to keratin surface adhesion proteins to intracellular keratin cytoskeletal filaments. intermediate filaments), and the BPAg2 protein (transmembranous protein (2) Desmoglein and desmocollin (members of the cadherin family) that contains an intracellular domain bonded to BPAg1, a transmembranous are transmembrane proteins that bridge the space between segment, and an extracellular domain that projects into the lamina lucida of adjacent epithelial cells by way of homophilic binding of their extracellular basement membrane). domains to other desmogleins and desmocollins on the adjacent cell. (4) Other proteins that either form or stabilize hemidesmosomes are also (3) On the cytoplasmic side of the plasma membrane, there are two dense present. For example intracellular plectin protein (that binds to keratin structures (outer and inner dense Plaques), spanned by filaments) is bonded to a single-pass transmembrane adhesion molecule the Desmoplakin protein. The Outer Dense Plaque is where the cytoplasmic (α6β4 integrin). The integrin might then attach to one of many multi-adhesive domains of the cadherins attach to desmoplakin (via plakoglobin and proteins such as laminin & collageb VII (anchoring filaments & fibrils), that plakophillin). The Inner Dense Plaque is where desmoplakin attaches to resident within the basement membrane. intracellular keratin cytoskeletal filaments. S k i n A d n e x a e Hair Sebaceous glands Sweat glands - Most of the skin is haired although the hair in - Lobulated structures which develop as a lateral - Sweat glands are either eccrine (regulate body most areas is short, fine and only lightly pigmented. protrusion from the outer root sheath of hair temperature), apocrine or mixed. This type of hair is called vellus hair. follicles. Eccrine Apocrine - Truly hairless parts are: the palms and soles, the - Can also be found in some of the areas where no - Tubular glands with - Concentrated in distal phalanges and sides of fingers and toes, and hair is present (e.g. lips, oral surfaces of the cheeks secretory and axilla, groin and parts of the external genitalia. and external genitalia). excretory portions. perineum; also in face, - The free part of each hair is called the shaft. The - The secretory part (alveoli) have outer basal cells - Secretory coil is in external auditory root of each hair is anchored in a tubular that are mitotically active, move inward and deep dermis or meatus, eyelid and invagination of the epidermis (the hair follicle), accumulate intracytoplasmic lipid droplets, causing subcutis, has inner areola. which extends down into the dermis and, usually, a multivacuolation and multiple indentations of secretory and outer - Have secretory and short distance into the hypodermis. nuclei myoepithelial cells. excretory components - Excretory ducts of these glands empty into - Hair follicles form hair via cyclic process of (a) - Excretory portion - The secretory portion infundibulum of hair follicle. anagen or growing phase, (b) catagen or involuting open directly onto skin has an outer phase and (c) telogen or resting phase. - The lipid secretion of the sebaceous glands has no surface, and has discontinuous layer of softening effect on the skin, and it has only very - The deepest end of the hair follicle forms an dermal (straight) and myoepithelial cells and limited antibacterial and antifungal activity. Its enlargement, called the bulb. Matrix (regenerative) intraepidermal (spiral, an inner secretory importance in humans is unclear. Clinically the cells are cells of the bulb that line the dermal also called cells. sebaceous glands are important in that they are papillae, they are mitotically active, give rise to hair acrosyringium) - The excretory duct of liable to infections (e.g. with the development of shaft and inner root sheath. portions. apocrine sweat glands acne). - Inner root sheath is surrounded by layer of large does not open directly clear cells called outer root sheath. onto the skin surface, but into the upper part - Outer root sheath cells undergo abrupt of the hair follicle. keratinization without a granular layer, at level of isthmus (mid hair follicle, extends from arrector pili - Pilosebaceous unit: complex of hair follicle, insertion to sebaceous duct), this is called sebaceous gland, erector pili muscle, and if present, trichilemmal keratinization. apocrine sweat glands. - Outer root sheath cells undergo usual keratinization (as epidermis) at level of infundibulum (upper hair follicle). D e r m i s & S u b c u t i s
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