1. The skin Anatomy and histology

3. The skin (the interface between humans and their environment) is the largest organ in the body. It weighs an average of 4 kg and covers an area of 2 m2. The skin has two layers: 1. The epidermis, outer epithelial layer. 2. The dermis, inner connective tissue. Beneath the dermis is, the subcutis/hypodermis which usually contains abundant fat. The epidermis adheres to the dermis partly by the interlocking of its downward projections ( epidermal ridges or pegs ) with upward projections of the dermis ( dermal papillae ).

4. Epidermis: The epidermis is formed from many layers of closely packed cells called keratinocytes: 1. Basal layer (stratum germinativum). 2. Prickle cell layer (stratum spinosum). 3. Granular layer (stratum ranulosum). 4. Horny layer (stratum corneum) On the palms and soles a pale or pink layer, the stratum lucidum, is noted just above the granular layer. The epidermis varies in thickness from less than 0.1 mm on the eyelids to nearly 1 mm on the palms and soles.

5. 1. The basal layer: Is the deepest layer, rests on basement membrane , which attaches it to the dermis. This layer generate cells of the epidermis. It is a single layer of columnar cells, whose basal surfaces sprout many fine processes and hemidesmosomes, anchoring them to the lamina densa of the basement membrane.

6. 2. The spinous or prickle cell layer: Composed of differentiating cells, contain some tonofibrils and kertohyalin granules, which synthesize keratins. They are larger than basal cells. Keratinocytes are firmly attached to each other by small interlocking cytoplasmic processes, and by abundant desmosomes. Under the light microscope, the desmosomes look like ‘prickles’, they are specialized attachment plaques.

7. 3. Granular layer: Consists of two or three layers of cells that are flatter than those in the spinous layer, and have more tonofibrils. As the name of the layer implies, these cells contain large irregular basophilic granules of keratohyalin, which merge with tonofibrils. As keratinocytes migrate out through the outermost layers, their keratohyalin granules break up and their contents are dispersed throughout the cytoplasm, leading to keratinization and the formation of a thick and tough peripheral protein coating called the horny envelope.

8. 4. The horny layer (stratum corneum): Made of piled-up layers of flattened dead cells (corneocytes). The corneocyte cytoplasm is packed with keratin filaments, embedded in a matrix and enclosed by an envelope derived from the keratohyalin granules. Horny cells normally have no nuclei or intracytoplasmic organelles, these having been destroyed by hydrolytic and degrading enzymes found in lamellar granules and the lysosomes of granular cells.

10. Other cells of the epidermis: 1. Melanocytes. 2. Langerhans cells. 3. Merckle cells

11. Melanocytes: Melanocytes are the only cells that can synthesize melanin. They migrate from the neural crest into the basal layer of the ectoderm where, in human embryos, they are seen as early as the eighth week of gestation. They are also found in hair bulbs, the retina and pia arachnoid.

12. Each dendritic melanocyte associates with a number of keratinocytes, forming an ‘epidermal melanin unit. The dendritic processes of melanocytes wind between the epidermal cells and end as discs in contact with them. Their cytoplasm contains discrete organelles, the melanosomes, containing varying amounts of the pigment melanin .

13. Langerhans cells: The Langerhans cell is a dendritic cell like the melanocyte. It also lacks desmosomes and tonofibrils, but has a lobulated nucleus. The specific granules within the cell look like a tennis racket when seen in two dimensions in an electron micrograph. They are plate-like, with a rounded bleb protruding from the surface.

14. Langerhans cells come from precursors originating in the bone marrow. There are approximately 800 Langerhans cells per mm2. Langerhans cells are alone among epidermal cells in possessing surface receptors for C3b and the Fc portions of IgG and IgE, and in bearing major histocompatibility complex (MHC) Class II antigens (HLA-DR, -DP and -DQ). They are best thought of as specialized macrophages.

15. Langerhans cells have a key role in many immune reactions. They take up exogenous antigen, process it and present it to T lymphocytes either in the skin or in the local lymph nodes. They probably play a part in immunosurveillance for viral and tumor antigens. In this way, ultraviolet radiation can induce skin tumors both by causing mutations in the epidermal cells, and by decreasing the number of epidermal Langerhans cells. Topical or systemic glucocorticoids also reduce the density of epidermal Langerhans cells.

16. Merkel cells Merkel cells are found in normal epidermis. Act as transducers for fine touch. They are nondendritic cells. Lying in or near the basal layer. Are of the same size as keratinocytes. They are concentrated in localized thickenings of the epidermis near hair follicles (hair discs). Contain membrane bound spherical granules, 80–100 nm in diameter. Sparse desmosomes connect these cells to neighbouring keratinocytes. Fine unmyelinated nerve endings are often associated with Merkel cells.

17. Epidermis—a stratified epithelium

18. The dermo-epidermal junction: The basement membrane lies at the interface between the epidermis and dermis. With light microscopy it can be highlighted using a periodic acid–Schiff (PAS) stain, because of its abundance of neutral mucopolysaccharides.

19. Electron microscopy shows that the basement membrane has 4 componenets: 1.The plasma membrane of basal cells which has hemidesmosomes (containing bullous pemphigoid antigens, collagen XVII and á6 â4 integrin). 2. Electron-lucent area, the lamina lucida which separate lamina densa from the basal cells. The lamina lucida contains laminin-1, laminin-5 and entactin. 3. Lamina densa (rich in type IV collagen). 4. Anchoring fibrils (of type VII collagen), dermal microfibril bundles and single small collagen fibres (types I and III), extend from the papillary dermis to the deep part of the lamina densa.

21. The structures within the dermo-epidermal junction provide mechanical support, encouraging the adhesion, growth, differentiation and migration of the overlying basal cells, and also act as a semipermeable filter that regulates the transfer of nutrients and cells from dermis to epidermis.

22. Dermis: The dermis lies between the epidermis and the subcutaneous fat. It is tow parts: 1. Upper papillary dermis. 2. Lower reticular dermis. Its thickness varies, being greatest in the palms and soles and least in the eyelids and penis. In old age, the dermis thins and loses its elasticity. The dermis interdigitates with the epidermis so that upward projections of the dermis, the dermal papillae, interlock with downward ridges of the epidermis, the rete pegs. This interdigitation is responsible for the ridges seen most readily on the fingertips (as fingerprints). The dermis has three components: cells, fibers and amorphous ground substance.

24. Cells of the dermis: The main cells of the dermis are fibroblasts, but there are also small numbers of resident and transitory mononuclear phagocytes, lymphocytes, Langerhans cells and mast cells. Other blood cells, e.g. polymorphs, are seen during inflammation.

25. Fibres of the dermis: The dermis is largely made up of interwoven fibres, principally of collagen, packed in bundles. Those in the papillary dermis are finer than those in the deeper reticular dermis. When the skin is stretched, collagen, with its high tensile strength, prevents tearing, and the elastic fibres, intermingled with the collagen, later return it to the unstretched state.

26. Collagen fibers: Makes up to 70–80% of the dry weight of the dermis. Its fibres are composed of thinner fibrils, which are in turn made up of microfibrils built from individual collagen molecules. These molecules consist of three polypeptide chains forming a triple helix with a non-helical segment at both ends. Collagen is an unusual protein as it contains a high proportion of proline and hydroxyproline and many glycine residues. Defects in the enzymes needed for collagen synthesis are responsible for some skin diseases, including the Ehlers–Danlos syndrome and osteogenesis imperfecta (fragility of bones).

27. Elastic fibres: Account for about 2% of the dry weight of adult dermis. They have two distinct protein components: an amorphous elastin core and a surrounding ‘elastic tissue microfibrillar component’. Abnormalities in the elastic tissue cause cutis laxa (sagging inelastic skin) and pseudoxanthoma elasticum . Reticulin fibres: Are fine collagen fibres, seen in fetal skin and around the blood vessels and appendages of adult skin.

28. Ground substance of the dermis: The ground substance of the dermis consists largely of two glycosaminoglycans (hyaluronic acid and dermatan sulphate) with smaller amounts of heparan sulphate and chondroitin sulphate. The ground substance has several important functions: • it binds water, allowing nutrients, hormones and waste products to pass through the dermis; • it acts as a lubricant between the collagen and elastic fibre networks during skin movement; and • it provides bulk, allowing the dermis to act as a shock absorber.

29. Muscles: Both smooth and striated muscle are found in the skin. The smooth arrector pili muscles are used by animals to raise their fur and so protect them from the cold. They are vestigial in humans, but may help to express sebum. Smooth muscle is also responsible for ‘goose pimples’ (bumps) from cold, nipple erection, and the raising of the scrotum by the dartos muscle. Striated fibres (e.g. the platysma) and some of the muscles of facial expression, are also found in the dermis.

30. Blood vessels: Although the skin consumes little oxygen, its abundant blood supply regulates body temperature. The blood vessels lie in two main horizontal layers: 1. The deep plexus is just above the subcutaneous fat, and its arterioles supply the sweat glands and hair papillae. 2. The superficial plexus is in the papillary dermis and arterioles from it become capillary loops in the dermal papillae. The blood vessels in the skin are important in thermoregulation.

31. Cutaneous lymphatics: Afferent lymphatics begin as blind-ended capillaries in the dermal papilla and pass to a superficial lymphatic plexus in the papillary dermis. There are also two deeper horizontal plexuses, and collecting lymphatics from the deeper one run with the veins in the superficial fascia.

33. Nerves: The skin is supplied with an estimated one million nerve fibres. Most are found in the face and extremities. Their cell bodies lie in the dorsal root ganglia. Both myelinated and non-myelinated fibres exist, with the latter making up an increasing proportion peripherally. Most free sensory nerves end in the dermis; however, a few non-myelinated nerve endings penetrate into the epidermis. Some of these are associated with Merkel cells .

34. Free nerve endings detect stimuli of heat and pain (nocioceptors), while specialized end organs in the dermis, Pacinian and Meissner corpuscles, detect pressure (mechanoreceptors), vibration and touch. Autonomic nerves supply the blood vessels, sweat glands and arrector pili muscles. Itching is an important feature of many skin diseases. It follows the stimulation of fine free nerve endings lying close to the dermo-epidermal junction. Impulses from these free endings pass centrally in two ways: quickly along myelinated A fibres, and more slowly along non-myelinated C fibres. In itchy skin diseases, pruritogenic chemicals such as histamine and proteolytic enzymes are liberated close to the dermoepidermal junction.

35. The nail: The hard keratin of the nail plate is formed in the nail matrix, which lies in an invagination of the epidermis (the nail fold) on the back of the terminal phalanx of each digit. The matrix runs from the proximal end of the floor of the nail fold to the distal margin of the lunula. From this area the nail plate grows forward over the nail bed, ending in a free margin at the tip of the digit.

36. The nail bed is capable of producing small amounts of keratin which contribute to the nail and which are responsible for the ‘false nail’ formed when the nail matrix is obliterated by surgery or injury. The cuticle acts as a seal to protect the potential space of the nail fold from chemicals and from infection. The nails provide strength and protection for the terminal phalanx. Their presence helps with fine touch and with the handling of small objects.

37. The rate at which nails grow varies from person to person: fingernails average between 0.5 and 1.2 mm per week, while toenails grow more slowly. Nails grow faster in the summer, if they are bitten, and in youth. They change with ageing from the thin, occasionally spooned nails of early childhood to the duller, paler and more opaque nails of the very old.

40. Hair unit: Cosists of 2 parts: 1. Hair follicle, include: inner root sheath and outer rot sheath 2. Hair shaft, consists of: hair cuticle, cortex and medulla. Hair shaft and hair follicle are produced by the matrix portion of hair bulb. Along one side, the sebaceous gland open to the upper part of the hair follicle, arrector pili muscle attach to the lower part. Apocrine gland also open to the hair follicle from the opposite side. From the surface opening of the hair follicle to the enterance of the sebaceous duct is called infundibular segment. The portion between the sebaceous duct and insertion of arrector pili muscle is isthmus. The lowest portion is hair bulb.

43. Classification of hairs: 1. Lanugo hairs . Fine long hairs covering the fetus, but shed about 1 month before birth. 2. Vellus hairs . Fine short unmedullated hairs covering much of the body surface. They replace the lanugo hairs just before birth. 3. Terminal hairs . Long coarse medullated hairs seen, for example, in the scalp or pubic regions. Their growth is often influenced by circulating androgen levels.

44. The hair cycle There are three phases of follicular activity: 1. Anagen . The active phase of hair production. 2. Catagen . A short phase of conversion from active growth to the resting phase. Growth stops, and the end of the hair becomes club-shaped. 3. Telogen . A resting phase at the end of which the club hair is shed.

45. The scalp contain an average of 100 000 hairs, anagen lasts for up to 5 years, catagen for about 2 weeks, and telogen for about 3 months. As many as 100 hairs may be shed from the normal scalp every day as a normal consequence of cycling. On the scalp, about 85% are normally in anagen and 15% in the telogen phase.

48. Sebaceous glands: They are associated with hair follicle, lie in the obtuse angle between the follicle and the epidermis. They are multilobed and contain cells full of lipid, which are shed whole (holocrene secretion) during secretion into the upper part of the hair follicle. Sebum contains a mixture of triglycerides, fatty acids, waxy esters, squalene and cholesterol. It lubricates and waterproofs the skin and protects it from drying. Free sebaceous glands may be found in the eye lids (meibomian glands), mucous membranes (Fordyce spots), nipples, peri-anal region and genetalia. Androgen hormones, especially dihydrotestosterone stimulate sebaceous gland activity.

49. Eccrine sweat glands: There are 2-3 million sweat glands distributed all over the body surface but they are most numerous on the palms, soles and axillae. The tightly coiled glands lie deep in the dermis, and the emerging duct passes to the surface by penetrating the epidermis in a corkscrew fashion. Initially sweat is isotonic like plasma but, under normal conditions, it becomes hypotonic by the time it discharged at the surface, after the tubular resorption of electrolytes and water under the influence of aldosterone and antidiuretic hormones.

50. The PH of sweat is between 4.0 and 6.8; it contains sodium, potassium chloride, lactate, urea and ammonia. Sweat glands have an important role in temperature control, the skin surface being cooled by evaporation. Up to 10 L/day of sweat can be excreted. The sweat glands are innervated by cholinergic fibers of the sympathetic nervous system. Sweating can therefore be induced by cholinergic and blocked by anticholenergic drugs. Central control of sweating resides in the preoptic hypothalamic sweat centre.

51. Apocrine sweat glands : They are limited to the axillae, nipples, peri-umbilical area, perineum and genitalia. The coiled tubular glands (larger than sweat glands) lie deep in the dermis, and during sweating the luminal part of their cells is lost (decapitation secretion). Apocrine sweat passes via the duct into the mid-portion of the hair follicle. The action of bacteria on apocrine sweat is responsible for body odour. The glands are innervated by adrenergic fibres of the sympathetic nervous system.

52. Functions of the skin: 1. protection against: *chemicals, particles-------------------------horny layer *ultraviolet light radiation-------------------melanocytes *antigens--------------------------------------langerhans cells *microbes-------------------------------------langerhans cells 2. preservation of a balanced------------------horny layer internal environment 3. prevents loss of water,-----------------------horny layer electrolytes and macromolecules

53. 4. Shock absorber---------------------dermis & subcutaneous fat 5. Temperature regulation------------blood vessels eccrine sweat glands 6. Sensation-----------------------------specialized nerve ends 7. Lubrication---------------------------sebaceous glands 8. Protection and prising--------------nails 9. Calorie reserve----------------------subcutaneous fat 10. Vitamin D synthesis---------------keratinocytes 11. Psychosocial, display--------------skin, lips, hair and nails

54. Thanks