Histology of the Skin and its Appendages PDF

(005) HISTOLOGY OF THE SKIN AND ITS APPENDAGES DR. EUGENIO PIPO III| 01/15/21...

(005) HISTOLOGY OF THE SKIN AND ITS APPENDAGES DR. EUGENIO PIPO III| 01/15/21 OUTLINE including mechanical, water loss, biological, ultraviolet I. SKIN light and chemical. A. Functions of the Skin provides moisture control, providing a barrier against B. Three Main Layers both excessive water loss and wetting. It resists II. EPIDERMIS bacterial and fungal invasion A. Cells of the epidermis 1.5- 4.0-mm thick B. Layers of epidermis Appendages: HAIR FOLLICLES, SEBACEOUS AND C. Basement Membrane Zone SWEAT GLANDS, ARRECTORES PILORUM, NAILS D. Clinical Correlation Also known as the integument or cutaneous layer III. DERMIS A. Collagen B. Papillary Dermis A. FUNCTIONS OF THE SKIN C. Reticular Dermis D. Elastic Tissue - These various functions of the skin are mediated by one E. Clinical Correlation or more of its major regions namely the epidermis, IV. SUBCUTANEOUS LAYER dermis, and the hypodermis A. Subcutis/Panniculitis B. Clinical Correlation Physical Barrier V. SKIN APPENDAGES - The epidermis provides a large part of the VI. HAIR physical barrier because of its structural integrity A. Hair Follicle Morphogenesis - It provides a physical barrier against thermal and B. Hair Follicle mechanical insults such as friction C. Anatomy of Hair Follicle Protection from Pathogens D. Hair Shaft - antimicrobial properties are provided by the E. Types of Hair innate immune system F. Stages of Hair Growth Thermoregulation G. Hair Growth - for it provides heat conservation and heat loss H. Hair Shape Sensation I. Hair color - the largest sensory organ in the body containing J. Clinical Correlation a range of different receptors for touch, pressure, VII. SEBACEOUS, ECCRINE AND APROCRINE pain, and temperature - Many types of sensory receptors allow the skin GLANDS to constantly monitor the environment, and A. Sebaceous Glands various skin mechanoreceptors help regulate the B. Sweat Glands body’s interactions with physical objects. 1. Eccrine sweat gland Ultraviolet protection 2. Apocrine sweat gland - the skin pigmentation from melanin protects VIII. NAILS against ultraviolet radiation and exposure A. Nail Structure induces increase skin pigmentation or tanning B. Clinical Correlation Wound repair/ Regeneration IX. BLOOD SUPLY AND INNERVATIION - rapid repair of injuries to the skin is critical to A. Blood Supply minimize infection risk Physical appearance B. Innervation and Nerve Endings - the skin determines the person’s physical X. THICK VS THIN SKIN appearance influenced by pigmentation A. Thick skin provided by melanocytes with body contours, the B. Thin Skin appearance of age and actinic damage. , B. 3 MAIN LAYERS I. SKIN - The three main layers of the skin are the epidermis, largest organ of the body both in weight and surface dermis, and subcutaneous layer. area it shows significant regional variation with the thickest skin being found on the soles of the feet, while the thinnest is on the upper and lower eyelids skin is the external body surface and provides protection against a wide variety of external threats, Page 1 of 27 CMED 1EF  (005) HISTOLOGY OF THE SKIN AND ITS APPENDAGES DR. EUGENIO PIPO III| 01/15/21 - takes place within 28 days The keratinocytes divide, they grow, they migrate up and undergo keratinization or cornification and form the protective epidermal and surface layer of the skin. In the normal skin, this process takes place within 28 days compared with other skin diseases such as psoriasis, keratinization takes place within 3-7 days only. Figure 1. Three Main Layers of the Skin. Showing the Epidermis, Dermis, and Subcutis. Figure 3. Epidermis. A. CELLS OF THE EPIDERMIS 3 Basic cell types - Keratinocytes- most abundant - Melanocytes - Langerhans cells Figure 2. Three Main Layers of the Skin. Showing the Epidermis, Dermis, and Subcutis. Additional cell types - Merkel cells II. EPIDERMIS - Indeterminate dendritic cells The surface layer in contact with the exterior is the epidermis. Avascular stratified squamous keratinizing epithelium (ectodermal in origin) produces a non-living surface layer of the protein keratin, with associated lipid which is in direct contact with the external environment outermost layer keratinized, stratified squamous epithelium composed of cells called keratinocytes 0.4 to 1.5 mm thick Main function of epidermis is Cornification (formation of the outermost dead layer of the skin stratum corneum) - synthesis of lamellar granules & distinctive proteins (keratins, fillagrin, involucrin) - alterations of nuclei, cytoplasmic organelles, Figure 4. Epidermis showing its cell type. plasma membranes, & desmosomes Cornification/keratinization KERATINOCYTES - basal cells divide by mitosis and as they move squamous cells, ectodermal derived cells, and are the upward the cells flatten and nucleus disappears primary cell types in epidermis Page 2 of 27 CMED 1EF  (005) HISTOLOGY OF THE SKIN AND ITS APPENDAGES DR. EUGENIO PIPO III| 01/15/21 accounting for at least 80% of the total cells in aggregates called tonofibrils made up of ectodermal origin bundles of tonofilaments. production of protein keratin that stuff and protective Stratum granulosum surface coat of the epidermis - Granular cells producing many of the structural protein of hair and nails components of the cornified envelope - cells with keratohyalin granules proliferate from the base, move upward, and keratinize to form a non-living protective, abrasion-resistant - consists of three to five layers of flattened cells, waterproofing keratin layer, the stratum corneum now undergoing the terminal differentiation process of keratinization. - Also known as a granular layer. Here they acquire dense basophilic, keratohyaline granules which contain proteins rich in Sulphur containing amino acids (cysteine) and proteins such as involucrin basement membrane which interact with the cytokeratin tonofibrils in the final maturation. - they acquire dense basophilic, keratohyaline granules which contain proteins rich in Sulphur containing amino acids (cysteine), and proteins such as involucrin which interact with the cytokeratin tonofibrils in the final maturation. - Stratum lucidum - non-nucleated cells with eleidin granules - palms/soles - found only in thick skin, consists of a thin, translucent layer of flattened eosinophilic keratinocytes held together by desmosomes Stratum corneum - The terminally differentiated keratinocytes shed Figure 5. Slide showing the Keratinocytes. their nuclei and become the stratum corneum, the crosslink network of protein and glycolipids B. LAYERS OF THE EPIDERMIS - layer of dead cornified cells - Because of keratinocytes, different layers of the - consists of 15-20 layers of squamous, epidermis are formed, or the strata of the epidermis. keratinized cells filled with birefringent filamentous keratins. Stratum basale - composed of a compacted cross-linked keratin - Deepest layer consists of basal cells that rest matrix K interspersed with specialised lipids upon the basement membrane of the dermal- epidermal junction - single layer of tall columnar cells - characterized by intense mitotic activity and contains, along with the deepest part of the next layer, progenitor cells for all the epidermal layers. Stratum spinosum - Cells of the spinous layer characterized by abundant desmosomal spines - polyhedral cells with “intercellular bridges” - normally the thickest layer, especially in the epidermal ridges - forms the majority of the epidermis. The stratum spinosum is also known as the prickle cell layer. It is multilayered and composed of polyhedral-shaped keratinocytes with round-oval nuclei, prominent nucleoli and cytoplasm, Figure 6. Layers of the Epidermis. Slide showing stratum basale, forming a pavement-like pattern. stratum spinosum, stratum lucidum, stratum corneum and - these cells synthesize cytoplasmic intermediate stratum granulosum. filaments called cytokeratin which accumulate Page 3 of 27 CMED 1EF  (005) HISTOLOGY OF THE SKIN AND ITS APPENDAGES DR. EUGENIO PIPO III| 01/15/21 2. STRATUM SPINOSUM (Prickle Cell Layer) - As the keratinocytes divide by mitosis, they move upward in the epidermis and formed the second cell layer of keratinocytes known as Stratum Spinosum or Prickle Cell Layer Consists of 4-6 rows of cells numerous cytoplasmic extensions/ spines - represent the sites where desmosomes are anchored to bundles of intermediate keratin filaments or tonofilaments and to neighboring cells - the synthesis of keratin filaments continuous in Figure 7. Layers of the Epidermis. Slide showing stratum this layer and they are assembled into bundles malpighii. of tonofilaments Tonofilaments - The three lower layers, Stratum basale, spinosum and - maintain cell cohesion among cells granulosum are collectively known Stratum malpighii - provide resistance to abrasions of the epidermis. which consists the increted viable epidermis. They terminate at various desmosomes. 1. STRATUM BASALE (Basal Cell Layer) - Deepest in the epidermis Single layer, columnar to cuboidal cells - rests on a basement membrane separating the dermis from epidermis Germinative cells - increased mitotic activity - The cells continually divide and mature as they migrate up toward the superficial layer Desmosomes - These cells are attached to one another by cell junctions called desmosomes Hemidesmosomes - Underlying basement membrane called hemidesmosomes - attachment to the basement membrane zone Figure 9.Stratum Spinosum. Red arrow showing the prickle cell layer (S). Figure 10. Stratum Basale and Stratum Spinosum. This electron micrograph shows cells of the stratum basale and spinosum. Note the bundles of keratin filaments called tonofilaments in the Figure 8. Stratum Basale. Red arrow showing the basal cell layer cytoplasm of cells in the stratum spinosum. Keratin filaments are (B). a form of intermediate filament and connect to desmosomes at the plasma membrane. Page 4 of 27 CMED 1EF  (005) HISTOLOGY OF THE SKIN AND ITS APPENDAGES DR. EUGENIO PIPO III| 01/15/21 Note: the Tonofilaments or Keratin filaments of the Stratum Spinosum that connect to the desmosomes in the Stratum Basale. 3. STRATUM GRANULOSUM (Granular Cell Layer) - Maturing cells that move above stratum spinosum accumulate dense basophilic keratohyaline granules and formed the third layer known as the Stratum granulosum. 3-5 layers of flattened cells surrounded by a membrane consists of protein called filaggrin filled w/ coarse, basophilic (keratohyaline) granules secretory granules not surrounded by a membrane Clinical correlation: The absence or diminished granular layer, you will see Ichthyosis Vulgaris- or fish skin. The skin is hard or rigid. 4. STRATUM LUCIDUM Only found in the thick skin such as the palms and soles translucent and barely visible flat cells, lies just superior to stratum granulosum and inferior to stratum corneum Figure 11.Stratum Granulosum. Red arrow showing the tightly packed cells in this layer lack nuclei or granular cell layer (G). organelles, meaning they are not viable Keratohyaline granules contains densely packed keratin filaments - Hygroscopic - Responsible for repeated cycles of hydration and dehydration which contribute to the normal desquamation of the stratum corneum - results in the soft and flexible keratin Figure 13. Stratum Lucidum. Red arrow showing stratum Figure 12.Keratohyaline Granules. Showing keratohyaline granules. Page 5 of 27 CMED 1EF  (005) HISTOLOGY OF THE SKIN AND ITS APPENDAGES DR. EUGENIO PIPO III| 01/15/21 5. STRATUM CORNEUM (Cornified Layer) - Most superficial layer of the skin Anucleate- all nuclei and organelles have all disappeared from the cell consists of flattened, dead cells filled with soft keratin filaments keratinized superficial cells from this layer are continuously shedding (desquamation) and replaced by new cells arising from the deep stratum Basale to the stratum corneum. Clinical correlation: Psoriasis vulgaris wherein your keratinocytes are typically produced and differentiate at accelerated rates causing at least light thickening of the epidermal layers and increased keratinization and desquamation. That’s why you see a thick silver scale in patients with psoriasis. Now if you have atypical keratinocytes in the epidermis, your nonmelanoma skin cancer such as squamous cell carcinoma will be formed or developed. Figure 14.Stratum Corneum. Red arrow showing the cornified layer. MELANOCYTES Figure 15.Stratum Corneum. Red arrow showing the cornified Pigment producing cells of the epidermis layer (C). neural crest origin long, irregular cytoplasmic and dendritic extensions that branch into the epidermis located between stratum basale and spinosum of the epidermis Page 6 of 27 CMED 1EF  (005) HISTOLOGY OF THE SKIN AND ITS APPENDAGES DR. EUGENIO PIPO III| 01/15/21 production of MELANIN- the dark brown pigment dendritic cell and its dendrites extend long distance within the epidermis present as separated individual cells in the basal layer of the epidermis and are more numerous in areas which are more exposed to light epidermal melanin unit - 1 melanocyte: in contact with 4 basal keratinocytes (face, shins, genitalia- higher density of melanocytes that’s why they appear darker); together they form the so called epidermal-melanin unit - In normal sun protected trunk epidermis, melanocyte reside in the basal cell layer at a frequency of approximately 1:10 basal cell (limbs) activity of melanocytes increases with exposure to Xrays and UV light they have pale-staining, rounded cell bodies attached by hemidesmosomes to the basal lamina, but lacking attachments to the neighboring keratinocytes. Melanin - synthesized from AA tyrosine by melanocytes - Tyrosinase activity converts tyrosine into Figure 17. Melanocytes. Arrow indicates melanocytes (M). - 3,4-dihydroxyphenylalanine (DOPA), which is then further transformed and polymerized into the different forms of melanin. Melanin pigment is linked to a matrix of structural proteins and accumulates in the vesicles until they form mature elliptical granules about 1-μm long called melanosomes - the formed melanin granules in the melanocytes then migrate to their cytoplasmic extensions from which they are transferred keratinocytes in the basal cell layers of the epidermis - imparts a dark color of the skin in exposure of the skin to sunlight->increases synthesis of melanin - the main function of the melanin is to protects the skin from the damaging effects of UV radiation Figure 18. Melanocytes. Sunlight increases production and changes the chemical characteristics of melanin. Skin Color racial differences in the skin color are caused by number, size and distributionof MELANOSOMES and not by melanocytes. Melanosomes= pigment granules within the keratinocytes vascular pigment (oxyhemoglobin and Figure 16. Epidermal Melanin Unit. Arrow indicates 1 deoxyhemoglobin) melanocyte: 4 basal keratinocytes. dietary pigments (carotene and lycopene) Page 7 of 27 CMED 1EF  (005) HISTOLOGY OF THE SKIN AND ITS APPENDAGES DR. EUGENIO PIPO III| 01/15/21 There are 6 skin types: I, II, III, IV, V, and VI: Figure 19. Fitzpatrick skin type. Skin colors ranging from I-VI. Additional Clinical Correlation Page 8 of 27 CMED 1EF  (005) HISTOLOGY OF THE SKIN AND ITS APPENDAGES DR. EUGENIO PIPO III| 01/15/21 LANGERHAN CELLS EM: possess distinctive electron-dense granules w/in originate from the bone marrow and migrate via the their cytoplasm blood stream and reside in the skin mainly in the Mechanoreceptors- because these cells are associated stratum spinosum in myelinated axons, they function as This dendritic type cells participate in various immune mechanoreceptors for cutaneous perception responses - are sensitive mechanoreceptors essential for -antigen-presenting cells (APCs) called Langerhans light touch sensation. Joined by desmosomes to cells, derived from monocytes, represent 2%-8% of the keratinocytes of the basal epidermal layer, cells in epidermis and are usually most clearly seen in Merkel cells resemble the surrounding cells but the spinous layer. with few, if any, melanosomes. -Langerhans cells bind, process, and present antigens - intra-epidermal touch receptors and contain to T lymphocytes in the same manner as immune neuroendocrine-type membrane-bound vesicles dendritic cells in other organs (dense core granules) in their cytoplasm, star shaped cells with numerous dendritic processes particularly near their base where they make found in stratum spinosum synaptic junctions with myelinated sensory nerve twigs in the upper dermis. by E/M: indented nucleus, well developed RER and Golgi complex, clear cytoplasm with rodlike inclusion: Birbeck granules (Rod/Racquet inclusions) potent stimulators of T-cell mediated immunoreactions because of its location, the skin is continuously in close contact with many antigenic molecules. Various epidermal features participate in both innate and adaptive immunity, providing an important immunologic component to the skin’s overall protective function. Figure 21. Merkel cells. Merkel cell-neurite complex. C. BASEMENT MEMBRANE ZONE (BMZ) junction between epidermis & dermis Figure 20. Langerhan cells. Black arrows showing the langerhan Dermo-epidermal junction (DEJ) cells (L). FUNCTIONS: - attaches the epidermis to the dermis MERKEL CELLS - separates components of the epidermis and found in stratum germinativum (or stratum basale and dermis are most abundant in the fingertips in association with - provides resistance against external shearing intraepithelial nerve endings forces - palms, soles, infundibula, epithelium of nail - maintains tissue architecture during remodeling beds, oral mucosa, genital regions and repair Page 9 of 27 CMED 1EF  (005) HISTOLOGY OF THE SKIN AND ITS APPENDAGES DR. EUGENIO PIPO III| 01/15/21 Figure 22. Basement Membrane Zone. Shows the BMZ. Figure 24. Basement Membrane Zone. Components of the dermal-epidermal basement membrane. 4 ZONES 1. Hemidesmosomes - plasma membrane of the basal keratinocytes that constitute the upper boundary of the interface 2. Lamina lucida - electron-lucent region that lies beneath basal keratinocytes - portion of papillary dermis 3. Lamina densa - electron-dense plate below lamina lucida & above papillary dermis - a.k.a basal lamina 4. Sublamina densa - below the lamina densa - fibrous components: anchoring fibrils, dermal microfibrils, and collagen fibers Figure 25. Basement Membrane Zone. Components of the dermal-epidermal basement membrane. Types of Collagen Type IV Collagen – major component of the basal lamina Type VII Collagen – major component of the anchoring fibrils 2 Major Hemidesmosomal Proteins: BP230 (Bullous Pemphigoid Antigen 2) BP180 (Bullous Pemphigoid Antigen 1 or Type XVII Figure 23. Basement Membrane Zone. Shows the 4 zones of the BMZ. Collagen) Page 10 of 27 CMED 1EF  (005) HISTOLOGY OF THE SKIN AND ITS APPENDAGES DR. EUGENIO PIPO III| 01/15/21 2. EPIDERMOLYSIS BULLOSA ACQUISITA – antibodies against collagen VII Figure 28 Epidermolysis Bullosa Acquisita III. DERMIS Figure 26. Basement Membrane Zone. Shows the Type IV and Inferior to the epidermis, characterized by dense Type VII collagen. irregular connective tissue, blood vessel, nerves and different glands. D. CLINICAL CORRELATION Mesodermal in origin derived from mesenchyme 1. BULLOUS PEMPHIGOID –antibodies against BP230 composition: Mostly collagen (70%), elastin, ground and BP180 – an autoimmune bullous disease substance (proteoglycans) contains sweat glands, sebaceous glands and hair follicles consists of fibrous and fibroadipose tissue which supports the epidermis, both physically and metabolically. It contains blood vessels, nerves and sensory receptors. The Dermis is responsible for the tone and texture of the skin, it also contains the skin appendages, the vascular supply to the skin and nerves and sensory nerve endings highly vascular 2 Parts/Regions: - Upper Papillary dermis - Deeper Reticular dermis A. COLLAGEN The principal component of the dermis A family of fibrous proteins consisting of 15 types in human skin Figure 27. Bullous Pemphigoid major structural protein for the entire body found in tendons, ligaments and in the dermis synthesized by fibroblasts Type 1 Collagen - major component of the dermis FUNCTION: - stress-resistant material of the skin - integrity, firmness, elasticity Page 11 of 27 CMED 1EF  (005) HISTOLOGY OF THE SKIN AND ITS APPENDAGES DR. EUGENIO PIPO III| 01/15/21 collagen fibers have parallel orientation (Cleavage lines or Langer’s lines) Characterize by dense irregular connective tissue fibers mainly Type I collagen elastic fibers course along collagen bundles fewer fibrocytes, blood vessels & ground substance Figure 29. Collagen B. PAPILLARY DERMIS Figure 31. Cleavage lines or Langer’s lines thin zone immediately beneath/below the epidermis D. ELASTIC TISSUE haphazardly arranged collagen bundles highly irregular it contains loose irregular connective tissue fibers, blood vessels, fibroblast, macrophages Minority of the dermis is made of elastic tissue and other loose connective tisues 2 - 4% of dermis accounts for the whorls, loops and arches that Elastin for retractile properties of the skin constitute fingerprints also synthesized by fibroblasts delicate branching elastic fibers ELASTIN – amorphous protein; fiber matrix plentiful fibrocytes Component abundant ground substance Papillary dermis: thin and run at right angles to the skin highly developed circulation made up mostly of surface capillaries Reticular dermis: thicker and oriented parallel to skin surface Demonstrated/ Appreciated by van-Gieson stain Figure 32 Plastic-embedded section showing Collagen (C) and Elastin (E) Figure 30. Papillary Dermis and Reticular Dermis under microscope C. RETICULAR DERMIS The deeper layer of the dermis thick collagen bundles arranged in orthogonal pattern. Therefore, thicker than the papillary bulbous Page 12 of 27 CMED 1EF  (005) HISTOLOGY OF THE SKIN AND ITS APPENDAGES DR. EUGENIO PIPO III| 01/15/21 E. CLINICAL CORRELATION 4. SKIN AGING (Dermatoheliosis) – loss of collagen (wrinkling) and elastin (sagging) 1. KELOID – excessive collagen deposition Figure 33. Keloid 2. STRIAE (stretched marks) – decreased expression of collagen Figure 36. Skin Aging IV. SUBCUTANEOUS LAYER A. SUBCUTIS/PANNICULUS Beneath the dermis is the subcutis or hypodermis or panniculus Layer rich of adipose tissues deepest layer, derived from mesenchyme lobules of adipocytes separated by fibrous SEPTA Figure 34. Striae - collagen - blood vessels 3. CUTIS LAXA – decreased elastin synthesis consists of adipose tissue, blood vessels & nerves also contains sweat glands & bases of hair follicles Figure 37. Lobules composed of adipocytes separated by fibrous septa Figure 35. Cutis Laxa Page 13 of 27 CMED 1EF  (005) HISTOLOGY OF THE SKIN AND ITS APPENDAGES DR. EUGENIO PIPO III| 01/15/21 B. CLINICAL CORRELATION 1. LOBULAR & SEPTAL PANNICULITIS - inflammation of the adipose tissue. Figure 38. Lobules composed of adipocytes separated by fibrous septa Figure 41. Lobular and Septal Panniculitis FUNCTIONS: 2. LIPODYSTROPHY – selective loss of body fat repository of energy endocrine organ - LEPTIN (body weight regulation) - conversion of androstenedione into estrone by aromatase this ayer produces leptin a hormone that regulates body weight via the hypothalamus. Figure 42. Lipodystrophy V. SKIN APPENDAGES Skin appendages first developed during the 2 nd trimester of intrauterine development as simple down the roots of the surface simple epithelium into the developing subepithelial layers of mesoderm which will eventually become the dermis and epidermis. Figure 39. Subcutis/Panniculus - functions in repository of 1. Hair Follicles energy 2. Sebaceous glands 3. Sweat glands 4. Apocrine glands 5. Nails FUNCTIONS: reserve epidermis in the re-epithelialization after skin injury to the surface epidermis by migration of keratinocytes from the adnexal epithelium to the skin surface - E.g., a wound on face and scalp which contains abundant hallow sebaceous unit, it would heal more rapidly than a wound a non-hairy area re- Figure 40. Subcutis/Panniculus functions in an endocrine organ epithelializes more rapidly than the bac. which aids in body weight regulation Page 14 of 27 CMED 1EF  (005) HISTOLOGY OF THE SKIN AND ITS APPENDAGES DR. EUGENIO PIPO III| 01/15/21 A. HAIR FOLLICE MORPHOGENESIS During the embryogenesis Mesenchymal cells in the fetal dermis collect immediately below the basal layer of the epidermis. Epidermal buds grow down into the dermis Developing follicle forms at an angle to the skin surface and continues its downward growth. At the base, the column of cells widens forming the bulb and surrounds small collections of mesenchymal cells. The pilosebaceous gland or the sebaceous gland and the arrector pili muscle together with the hair follicle is collectively known as the PILOSEBACEOUS UNIT Figure 43. Diagram of an eccrine sweat gland, a sebaceous Figure 45. Morphogenesis of hair follicle gland, and their constituent cells. B. HAIR FOLLICLE VI. HAIR Along one side of the FETAL FOLLICLE, 2 buds are formed: - Present almost all over the part of the body and plays - UPPER = develops into sebaceous gland an important role in: - LOWER =becomes attachment for the arrector HAIRS - regulate body temperature pili muscle - elongated keratinized structures formed within - PILOSEBACEOUS UNIT (hair follicle, epidermal invaginations sebaceous gland and arrector pili muscle) HAIR FOLLICLE - hair production and growth Opposite side of the follicle (3rd bud) - tubular structure formed of formed of specialized Gives rise to the eccrine gland peri-follicular connective tissue and epithelium. HAIR BULB - stem cells- which will then eventually undergo differentiation of various cell types that will make up the hair. - A bulbous expansion that encloses the hair papilla Figure 46. Pilosebaceous unit Figure 44. Parts of the Hair Page 15 of 27 CMED 1EF  (005) HISTOLOGY OF THE SKIN AND ITS APPENDAGES DR. EUGENIO PIPO III| 01/15/21 3 VERTICAL SEGMENTS: INFUNDIBULUM C. ANATOMY OF THE HAIR FOLLICLE - uppermost portion - surface opening to the entrance of the sebaceous duct ISTHMUS - between the sebaceous duct and the insertion of arrector pili muscle - IRS fully keratinizes and sheds within this portion INFERIOR SEGMENT – it is where the hair bulb is located HAIR BULB base, bulbous expansion highly vascularized & contains melanocytes Matrix cell - produce the hair shaft, IRS and ERS Undergoes cycles of involution and regeneration throughout life Figure 48. Anatomy of the hair follicle As hair follicles grow, they are pushed towards the skin surface from the hair bulb and 5 epithelial layers are formed. The 3 inner layers undergo keratinization to form the hair shaft or the hair, while the 2 outer layers form an internal and external root sheath. Normal hair growth is approximately.37mm/day or approximately 1 cm/month. Tubular structure - formed of perifollicular CT and epithelium - invagination of the epidermis Surrounded by external and internal root sheaths (ERS and IRS) Figure 47. Parts of the hair follicle Figure 49. Hair follicle Page 16 of 27 CMED 1EF  (005) HISTOLOGY OF THE SKIN AND ITS APPENDAGES DR. EUGENIO PIPO III| 01/15/21 External root sheath (ERS) - separated from the CT tissue sheath by the glassy membrane passing inwards the uppermost cells - homogenous appearance - covers the internal root sheath and extends all the way to the epidermis where it is continuous with the basal and spinous layers - external epithelial layer and merges with the epidermis of the sebaceous gland. Internal root sheath (IRS) - Recognized by its prominent pores, Eosinophilic (keratohyaline) granules - Completely surrounds the initial part of the hair root but degenerates above the level of the sebaceous glands - Lightly keratinized and locked with developing cuticle, keeping the developing hair as a solid Figure 51. Transverse section of the hair Shaft showing cuticle, unit as it matures. cortex and medulla. - Internal root sheath (IRS) LAYERS: ▪ Henle layer - thin, pale epithelial stratum ▪ Huxley layer - thin, granular epithelial stratum - However, these 2 cells become indistinguishable as their cells merge with the cells in the expanded part of the hair, called the hair bulb. Figure 52. Microscopical view of the Hair cuticle Figure 50. Transverse section of the hair follicle showing the external and internal sheaths. H&E. D. HAIR SHAFT extending beyond the surface of the skin is composed of cuticle, cortex and medulla HAIR CUTICLE - thin, pale-stained Figure 53. Cuticle surrounding the cortex and medulla - surrounds the pigmented CORTEX and pale MEDULLA Page 17 of 27 CMED 1EF  (005) HISTOLOGY OF THE SKIN AND ITS APPENDAGES DR. EUGENIO PIPO III| 01/15/21 E. TYPES OF HAIR LANUGO - fetal/ newborn hair - Fine hair present in the body of the fetus/newborn VELLUS - fine, light-colored - narrow hair shaft - thin inner root sheath - rooted in papillary or upper reticular dermis TERMINAL HAIRS - Coarse - Thick - dark (except blondes) - extends into the dermis and sometimes even subcutis Figure 56. Terminal hairs F. STAGES OF HAIR GROWTH Occurs in cyclical manner each follicle is an independent unit (humans do not shed synchronously) 3 STAGES: ANAGEN - Active growth phase - 2-6 years - generally, a long period of mitotic activity and growth CATAGEN - Transition phase - 1-2 weeks - a brief period of arrested growth and regression of the hair bulb Figure 54. Lanugo TELOGEN - Resting phase - 2-4 months - Dermal papilla separated from follicle - a final long period of inactivity during which the hair may shed **Returns to Anagen – hair matrix forming new hair Figure 55. Vellus Figure 57. Stages of hair growth Page 18 of 27 CMED 1EF  (005) HISTOLOGY OF THE SKIN AND ITS APPENDAGES DR. EUGENIO PIPO III| 01/15/21 G. HAIR GROWTH ANAGEN HAIRS: - active growth phase, - scalp: 0.37 mm/day - pigmented bulb in IRS CATAGEN HAIRS: - involution - many apoptotic cells in the ORS TELOGEN HAIRS: - resting phase - eyelashes: short anagen, long telogen - nonpigmented bulb with a shaggy lower border Figure 60. Hair shape I. HAIR COLOUR degree of melanization distribution of melanosomes within the hair shaft hair bulb contains melanocytes that synthesizes melanosomes and transfer them to keratinocytes of the bulb matrix Figure 58. Hair growth Figure 61. Hair colour Figure 59. Stages of Hair Growth J. CLINICAL CORRELATION H. HAIR SHAPE ALOPECIA AREATA – common autoimmune, dimensions and curvature of the inner root sheath peribulbar lymphocytic infiltrates; arrest in anagen determine the shape of the hair phase scalp hairs of people of African decent is oval causing their hair to be curly Figure 62. Alopecia areata Page 19 of 27 CMED 1EF  (005) HISTOLOGY OF THE SKIN AND ITS APPENDAGES DR. EUGENIO PIPO III| 01/15/21 This gland occurs in two forms, majority are associated TELOGEN EFFLUVIUM –premature termination of with hair follicle and develop as a lateral protrusion from anagen phase, increase in telogen phase the hair follicle near the junction between its upper thirds and lower two thirds. Figure 65. Sebaceous Gland SEBUM Figure 63. Telogen effluvium mixture of lipids (wax esters, squalene, cholesterol and triglycerides) VII. SEBACEOUS, ECCRINE & APOCRINE GLANDS - increases at puberty - stimulated by androgens - helps maintain the stratum corneum and hair shaft - weak antibacterial and antifungal properties - gradually covers the surfaces of the epidermis and hair shaft Figure 64. Sebaceous, eccrine & apocrine glands - The skin includes 3 types of exocrine glands: the sebaceous, eccrine sweat gland and the apocrine sweat gland. A. SEBACEOUS GLANDS Figure 66. Sebum Majority assoc. with hair follicles lateral protrusions from the hair follicle Sebaceous glands are not found in palms and soles, but can also be found in other non-hairy sites including simple or branched alveolar in morphology appearing eyelids, nipples, lips and around the genitals like a bunch of grapes The ducts of these glands open directly into the Holocrine gland-total disintegration of secretory cells epidermal surface with sebum (the acini of these glands are classic found everywhere on the body except the palms and examples of holocrine secretion) soles basal layer of flattened epithelial cells on the basal lamina which proliferates centrally and undergo more abundant in the scalp, face, midline of the back, terminal differentiation perineum and orifices of the body eyelids: Meibomianglands Sebocytes –filled with small fat droplets Near the duct the cells disintegrate releasing the main buccal mucosa & vermilion of lip: Fordyce spots secretory product, the sebum. areola of women: Montgomery glands. Secretions increases at puberty, stimulated primarily labia minora & glans: Tyson glands by testosterone in male and by ovarian and adrenal androgens in female. Page 20 of 27 CMED 1EF  (005) HISTOLOGY OF THE SKIN AND ITS APPENDAGES DR. EUGENIO PIPO III| 01/15/21 CLINICAL CORRELATION: ACNE VULGARIS – inflammation of the pilosebaceous unit Figure 67. Acne vulgaris Figure 69. Arrector pili muscle histology SEBORRHEIC DERMATITIS–found in areas rich in sebaceous glands Figure 70. Arrector pili muscle B. SWEAT GLANDS Figure 68. Seborrheic dermatitis ARRECTOR PILI MUSCLE part of the pilosebaceous unit each hair follicle has an arrector pili muscle consisting of a bundle of smooth muscle fibers. This muscle inserts at one end into the sheath of the follicle just below the sebaceous glands, on the other hand, at the dermal papillary area beneath the epidermis oblique bands of smooth muscle inserted into middle of hair follicle controlled by the autonomic nervous system contraction erects the hair shaft, depresses the skin for inserts and produces small bumps into the skin surface: Figure 71. Sweat glands “goose flesh appearance” or goosebumps a small bundle of smooth muscle cells that extend from the midpoint of the fibrous sheath to the dermal ECCRINE/ sweat source papillary layer APOCRINE/ the smell source Page 21 of 27 CMED 1EF  (005) HISTOLOGY OF THE SKIN AND ITS APPENDAGES DR. EUGENIO PIPO III| 01/15/21 1. ECCRINE SWEAT GLANDS: Dark cells (mucoid) - the secretion is primarily mucus filled with eosinophilic granules at the lumen and undergo merocrine secretion to release mixture of glycoprotein Myoepithelialcells at the basal lamina contract to move watery substance to the duct Figure 72. Eccrine sweat glands Dermal duct: found in palms, soles and foreheads double layer (2 layers of acidophilic cells). merocrine /eccrine in type It opens on the epidermis as a sweat form and is biochemically active as it modifies the composition of secretion discharged by exocytosis sweat because its cell membrane is rich with sodium, simple coiled tubular in morphology potassium, ATPase thus reabsorbing sodium ions to stimulus is heat, under control of hypothalamic prevent excessive loss of these electrolytes. thermostat: SWEAT eosinophilic lumen duct opens into epidermis as sweat pore, re-absorb Na+ reabsorption sodium without water merges with the stratum basale to form the SWEAT collectively the 3 million eccrine sweat glands of the PORE average person approximately equals the mass of a kidney and produce as much 10 L/d. 2. APOCRINE/ ODORIFEROUS SWEAT GLAND: Figure 74. Apocrine/ odoriferous sweat gland found in axilla, mammary areola, labia majora and circumanal region Figure 73. Secretory coil & Dermal duct larger than eccrine glands Secretory coil: opens into a hair follicle secretory portion is coiled and tubular shows only one distinct layer composed of secretory wider and dilated lumen cells myoepithelial cells more numerous 3 distinct cell types: non-functional until puberty Clear cells (secretory) viscous secretion - produce sweat which contains water and initially odorless à unpleasant odor (bacterial electrolytes decomposition) - transports interstitial fluid from the stimuli: emotional stress, sympathetic discharge capillary rich dermis around the gland (adrenergic nerve endings vs. cholinergic fibers in - found on basal lamina and is abundant of eccrine) mitochondria and microvilli to provide development depends on sex hormones and is not large surface area complete and functional until after puberty connects to the follicular infundilum and have a possible function in producing odor. Page 22 of 27 CMED 1EF  (005) HISTOLOGY OF THE SKIN AND ITS APPENDAGES DR. EUGENIO PIPO III| 01/15/21 VIII. NAILS Figure 75. Apocrine/ odoriferous sweat gland Comparison Between Eccrine and Apocrine Glands: Figure 78. Nails - Dorsal surfaces of terminal phalanges A. NAIL STRUCTURE Nail apparatus: - Nail plate - Specialized epithelia: a) Proximal Nail Fold b) Nail Matrix Figure 76. Eccrine and Apocrine sweat gland c) Nail Bed Both glands are coiled and tubular d) Hyponychium Apocrine glands are less coiled, wider lumen, Nail root: more numerous myoepithelial cells and opens - proximal part of the nails into a hair follicle - covered by a fold of skin (PROXIMAL NAIL FOLD) from which the epidermal stratum CLINICAL CORRELATION: corneum extends as the CUTICLE/ EPONYCHIUM HYPERHYDROSIS– excessive sweating (eccrine - forms the nail matrix glands) Figure 77. Hyperhydrosis BROMHIROSIS –offensive odor from apocrine gland secretions and bacterial flora Figure 79. Nail root Nail matrix: - nail growth and distal movement by proliferation and differentiation of the epithelium Page 23 of 27 CMED 1EF  (005) HISTOLOGY OF THE SKIN AND ITS APPENDAGES DR. EUGENIO PIPO III| 01/15/21 - a semilunar area of proliferative cells on proximal - (hypo=below); a thickened region of stratum ventral surface of nail groove corneum that secures the nail to the fingertip, - 3 mm/month (fingernails) and 1 mm/month and lies below the nail plate. (toenails) - In which cells divide more distally and become keratinized in the process similar to hair formation but without keratohyaline granules Figure 82. Nail plate, Nail bed &Hyponychium B. CLINICAL CORRELATION NAIL PITTING –abnormal keratinization of the nail matrix Figure 80. Nail matrix Lunula: - crescent-shaped white area - derived its color from opaque nail matrix and immature nail plate below it - normal nail growth 3.5mm/month - complete nail replacement of fingernail requires 6 months, while the toenail is 12-18 months - white because the underlying epithelium is thicker Figure 83. Nail pitting MELANONYCHIA –melanin production in the nail matrix Figure 81. Lunula Nail plate: - continuous growth in the matrix pushes the nail plate forward over the nail bed and the nail plate is a dense keratinized appendage - the nail root matures and hardens to form the nail Figure 84. Melanonychia plate which is composed of hard keratin - rests on a stratified squamous epithelium, the NAIL BED Nail bed: - contains only last 2 layers, basal and spinous epidermal layers Hyponychium: - distal end of the plate Page 24 of 27 CMED 1EF  (005) HISTOLOGY OF THE SKIN AND ITS APPENDAGES DR. EUGENIO PIPO III| 01/15/21 IX. BLOOD SUPPLY AND INNERVATION Figure 86. Arteries and veins B. INNERVATION AND NERVE ENDINGS both efferent and afferent nerve supplies free nerve endings Figure 85. Blood supply and innervation - pain, itch and temperature - maybe myelinated or non-myelinated A. BLOOD SUPPLY specialized encapsulated nerve endings - Meissner: rapidly adapting mechanoreceptors, Cutaneous plexus: between the dermis and subcutis responsible for touch sensation. They are § larger blood vessels particularly prominent in the papillary dermis of Subpapillaryor superficial plexus: between the fingers, toes, soles and palms. papillary and reticular dermis - Pacinian: deep pressure and vibration. In the §capillaries, end arterioles, venules skin they are found in the subcutaneous layer in Glomusbodies: special type of AV anastomosis for small clusters particularly numerous in the palms temperature regulation; fingers, toes and nails and soles. Small arteries (deep vascular plexus) and arterioles (dermis) possess three layers: - Intima - composed of endothelial cells and an internal elastic lamina - Media– contains collagen, elastic fibers, & several concentric layers of smooth muscle cells bounded by an external elastic lamina (in arteries) - Adventitia– composed of fibrocytes, collagen, & elastic fibers Arteries have narrow lumens and thicker walls Walls of veins generally are thinner than those of arteries and less clearly divided into the three classic Figure 87. Nerve endings layers. x. THICK SKIN vs THIN SKIN A. THICK SKIN palms of hands, fingers, soles, toes thickness of epidermis considerable abundant sweat glands no pilosebaceous follicles grooves and ridges prominent because of tall dermal papillae numerous arterio-venous anastomosis Page 25 of 27 CMED 1EF  (005) HISTOLOGY OF THE SKIN AND ITS APPENDAGES DR. EUGENIO PIPO III| 01/15/21 consist of 5 distinct cell layers QUESTION AND ANSWER 1.) People with albinism have a defect in tyrosinase, an oxidase that helps to control skin pigment production. In what epidermal layer is tyrosinase active? a. S. lucidum b. S. granulosom c. S. basale d. S. spinosum 2.) Which of the following is NOT a feature of the stratum granulosum? a. Cells in this layer contain keratohyaline granules b. There are 3-5 layers of cells in this layer Figure 88. Thick skin c. Cytokeratin is produced in this layer 3.) Which structures contain connective tissue, B. THIN SKIN blood vessels, and nerves? Other regions except palms, soles, fingers, toes a. Papillary dermis only thin epidermis b. Papillary and reticular dermis small number of sweat glands c. Epidermis, papillary dermis, and presence of pilosebaceous follicles reticular dermis lacks ridges and grooves with checkered network of d. Reticular dermis only lines 4.) the phenomenon known as “goosebumps” is absent or few arterio-venous anastomosis often combined with shivering to reduce heat where wear and tear are minimal loss. What integumentary layer is most directly related to this reflex? a. Papillary dermis b. Epidermis c. Hypodermis d. Reticular dermis 5.) Hyperhidrosis is characterized by excessive sweating, especially at the palms of the hands and soles of the feet. Which of the following could cause this disorder? a. Increased sweat at the base of hair follicles b. Apocrine gland activation with puberty c. Higher density of holocrine glands Figure 89. Thin skin d. Increased stimulation of merocrine glands 6.) A second degree burn can result in a loss of sensation, but do not necessarily affect motor control of arrector pili muscles. Which of the following are damaged in a second degree burn? a. Pacinian’s corpuscles b. Meissner corpuscles c. Hair follicle receptors d. Ruffini’s endings Page 26 of 27 CMED 1EF  (005) HISTOLOGY OF THE SKIN AND ITS APPENDAGES DR. EUGENIO PIPO III| 01/15/21 a. Molecules in the pepper trigger vasodilation through endothelial 7.) Scientists are measuring mechanoreceptor receptors in blood vessels reactions to a variety of stimuli. What stimuli b. Molecules in the pepper destroy cells, would you expect to generate the following which triggers a pain response that response? follows the same pathway as the heat response c. Molecules in the pepper bind the same receptors responsible for thermoregulation d. Molecules in the pepper stimulate the posterior pituitary, like the heat response True or False 11.) Myoepithelial cells form a continuous layer a. Constantly changing deep touch on between the secretory cells and the basement hairy skin membrane b. Sustained deep touch on hairy skin 12.) Thin skin is where wear and tear are minimal c. Sustained light touch on hairy skin 13.) Meisner corpuscle are for deep pressure d. Constantly changing light touch on 14.) Glomus bodies is special type of AV hairy skin anastomosis for temperature regulation. 8.) Scientists are measuring mechanoreceptor 15.) Eccrine glands are glands that arise as upgrowth reactions to a variety of stimuli. What stimuli from the epidermis during the second trimester would you expect to generate the following of the intrauterine life response? 16.) Arrector pili muscle insert at one end into the sheath of the follicle just below the eccrine glands 17.) Thick skin has no pilosebaceous follicles 18.) Nail root is the distal part of the nail 19.) Clear cells found on basal lamina and is abundant of mitochondria and microvilli to provide large surface area 20.) Sebaceous glands develop as a lateral protrusion from the hair follicle near the junction between its upper thirds and lower two thirds. a. Constantly changing deep touch on 19.T 20. T hairy skin 1.C 2.C 3.B 4. D 5.D 6.B 7.D 8.D 9.A 10.C 11.F 12.T 13.F 14.T 15.F 16.F 17.T 18.F b. Sustained deep touch on hairy skin ANSWERS: c. Sustained light touch on hairy skin d. Constantly changing light touch on hairy skin REFERENCE 9.) Which of the following allows for an almost instantaneous response to painful stimuli? a. The extensive myelination of A-delta WHEATER’S FUNCTIONAL HISTOLOGY –A fibers, leading to increased TEXT AND COLOUR ATLAS, 6th edition conductance JUNQUEIRA’S BASIC HISTOLOGY, 15th b. The small radius of C fibers, leading to edition increased conductance ANDREW’S DISEASES OF THE SKIN: c. The high density of A-delta fibers in the CLINICAL DERMATOLOGY, 10th edition stimulated area d. The high sensitivity of the TrpVI receptor 10.) Why does eating jalapeno peppers feel “hot”?