Skin lecture notes 1 Lecture objectives: skin 1. Describe the basic histological structure of the skin, identifying the layers of the skin and their embryologic origin. 2. Identify the cell layers that constitute the epidermis and the differences between thick and thin skin. 3. Describe the cellular components of the epidermis and their function: keratinocytes, melanocytes, Langerhans cells and Merkel cells: 4. Describe the structural organization of the dermis and the components of the papillary and reticular layers. 5. Identify other structures present in the skin: vessels, skin sensorial receptors, hair follicles and hairs, nails and glands. 6. Understand the mechanism of skin repair 7. Describe histological findings in common skin diseases. Skin lecture notes 2 HISTOLOGY OF THE SKIN The skin is the heaviest, largest single organ of the body. It protects the body against physical, chemical and biological agents. The skin participates in the maintenance of body temperature and hydration, and in the excretion of metabolites. It also contributes to homeostasis through the production of hormones, cytokines and growth factors. 1. Describe the basic histological structure of the skin, identifying the layers of the skin and their embryologic origin. The skin is composed of the epidermis, an epithelial layer of ectodermal origin and the dermis, a layer of connective tissue of mesodermal origin. The hypodermis or subcutaneous tissue, which is not considered part of the skin proper, lies deep to the dermis and is formed by loose connective tissue that typically contains adipose cells. Skin layers 2. Identify the cell layers that constitute the epidermis and the differences between thick and thin skin. The epidermis is composed of stratified squamous epithelium. Histologically, it is comprised of 4 layers (thin skin) or 5 layers (thick skin). Beginning with the deepest layer, the layers of the epidermis are: • Stratum basale (or stratum germinativum): single layer of basophilic columnar or cuboidal cells which are mitotically active. Cells are connected to the basal membrane by hemidesmosomes, anchoring the epidermis to underlying dermis. • Stratum spinosum: several layers of cells connected by numerous desmosomes (giving the appearance of processes or spines). Skin lecture notes 3 • Stratum granulosum: 3 to 5 layers of flattened polygonal cells filled with basophilic granules called keratohyaline granules. These granules contain filaggrin intermediate filaments and other proteins that associate with keratin in the tonofibrils. Cells of the stratum granulosum also contain lamellar granules filled with lipids only visible with the transmission electron microscopy. The content of the lamellar granules is released to the intercellular spaces and constitutes a major component of the epidermal barrier against the loss of water from skin. The stratum granulosum is less developed in thin skin than in thick skin. • Stratum lucidum: few layers of extremely flattened eosinophilic epidermal cells, present only in thick skin. Skin layers • Stratum corneum: 15-20 layers of flattened, non-nucleated keratinized cells (squames). Thin versus thick skin The thick skin has 5 layers. It is present in palms of the hands and the soles of the feet and it is hairless. The thin skin has 4 layers. It is present elsewhere in the body and it contains hair follicles in all but a few locations. Types of skin Skin lecture notes 4 3. Describe the cellular components of the epidermis and their functions • Keratinocytes: o Predominant cell type in the epidermis o Produce keratin, the major structural protein of the epidermis o Participate in the formation of the epidermal water barrier • Melanocytes: o Derived from neural crest o Round cells with cytoplasmic (dendritic) projections that are scattered among the cells of the stratum basale o Produce and secrete the pigment melanin, which is synthesized from Tyrosine in intracellular organelles called melanosomes o Melanin granules are transferred via cytocrine secretion to keratinocytes where they protect against the damaging effects of non-ionizing ultraviolet radiation • Langerhans cells: Derived from bone marrow Production of melanine by o melanocytes o Star-shaped cells present mainly in the stratum spinosum o Bind, process and present antigens to T lymphocytes, thus mediating immune response • Merkel cells: o Modified epidermal cells located in the stratum basale o Present in thick skin, where sensory perception is acute o Contain dense-cored neurosecretory granules o Closely associates with the expanded terminal bulb of afferent myelinated nerve fibers, forming the Merkel’s corpuscle, a sensitive mechanoreceptor 4. Describe the structural organization of the dermis. The dermis is the connective tissue that supports the epidermis and binds it to the subcutaneous tissue (hypodermis). It is composed of 2 layers: • Papillary layer: most superficial layer formed by loose connective tissue immediately beneath the epidermis. It is composed of a network of delicate type I collagen and elastic fibers, and anchoring fibrils of type VII collagen that insert into the basal lamina and bind the dermis to the epidermis. The papillary layer contains nerve processes and blood vessels that supply but do not penetrate the epidermis. • Reticular layer: lies deep to the papillary layer. Its thickness varies in different parts of the body, but it is always thicker and less cellular than the papillary layer. It is Skin lecture notes 5 formed by type I collagen and elastic fibers regularly oriented forming lines of tension in the skin (Langer’s lines). Dermatoglyphics (fingerprints): Certain areas of the human skin show ridges and grooves arranges in distinctive patterns, which are unique for each individual (they even differ in identical twins). Vessels: the skin is nourished by a rich network of blood and lymphatic vessels. The arterial and the lymphatic vessels form 2 plexuses, one is located between the papillary and reticular layer and the other is located between the dermis and the subcutaneous tissue. Veins are disposed in 3 plexuses, 2 that accompany the arterial plexuses and a third in the middle of the dermis. Arteriovenous anastomoses (connection between arteries and veins) are frequent in the skin and regulate body temperature. Vessel organization in the skin 5. Identify other structures present in the skin • Skin sensorial receptors: the skin is the most extensive sensory receptor. It contains free nerve endings (without connective tissue or Schwann cell investment) that terminate in the stratum granulosum in the epidermis and allow multiple sensations including Pacinian corpuscles Meissner’s fine touch, heat and cold. corpuscles Skin lecture notes 6 Other nerve endings are encapsulated by connective tissue, including: o Pacinian corpuscles: large ovoid structures found in the deeper dermis and the hypodermis, composed of a myelinated nerve ending surrounded by a capsule structure. Pacinian corpuscles respond to pressure and vibration. o Meissner’s corpuscles: tapered cylinders oriented perpendicular to the skin surface in the papillary layer of hairless skin. Meissner’s corpuscles are touch receptors responsive to low-frequency stimuli. o Ruffini‘s corpuscles: elongated fusiform structures that function as mechanoreceptors. • Hair follicles and hairs: hair follicles are epidermal invaginations responsible for the production and growth of a hair. An acellular hyaline layer formed by thickened basement membrane, the glassy membrane, separates the hair follicle from the dermis. During the growing period hair follicles have a terminal dilation called the hair bulb. At the base of the hair bulb is the dermal papilla containing a capillary network that irrigates the hair follicle. Hair color is produced by melanocytes located between the papilla and the epithelial cells of the hair root. Sebaceous glands are associated with the hair follicles and release their content (sebum) into the infundibulum, a pilosebaceous canal that surrounds the hair. Hairs are elongated keratinized filamentous structures that consist of three layers: o Medulla: central part of the shaft containing large vacuolated and moderately keratinized cells o Cortex: located peripheral to the medulla, containing cuboidal cells that undergo differentiation into keratin- filled cells o Cuticle: outermost layer of the hair that contains Hair follicle and sweat and sebaceous glands squamous cells Phases of hair development Anagen: active phase Skin lecture notes 7 Catagen: apoptosis (cell death)-driven involution, end of active growing phase of the life cycle of the hair, between growing phase (anagen) and resting stage (telogen). Telogen: hair follicle resting phase Phases of hair development • Nails: plates of keratinized cells containing hard keratin. Nails are composed of the following parts: o Nail root: proximal part of the nail, hidden in the nail groove. The constant addition of cells in this area and their keratinization accounts for nail growth. o Nail matrix: formed by dividing cells that eventually cornify forming the proximal part of the nail plate. The matrix contains a variety of cells including stem cells, melanocytes, Merkel cells and Langerhans cells. o Nail plate: highly specialized stratum corneum. Constitutes Nails what it is commonly referred to as the nail. Contain hard keratin which, unlike the soft keratin of the epidermis, does not desquamate. Skin lecture notes 8 o Nail bed: area of the skin where the nails rest; formed by stratum