BMS Clin Phys 7 PDF

Function Protective barrier Mechanical, chemical or thermal injuries Important barrier to infection Reduces heat, fluid, electrolyte loss Key for regulating body temperature Provides sensory information Limited importance in waste removal and vitamin synthesis (vitamin D) Anatomy & Physiology, 2e....

Function Protective barrier Mechanical, chemical or thermal injuries Important barrier to infection Reduces heat, fluid, electrolyte loss Key for regulating body temperature Provides sensory information Limited importance in waste removal and vitamin synthesis (vitamin D) Anatomy & Physiology, 2e. Chapter 5 https://openstax.org/books/anatomy-and-physiology-2e Micro-Anatomy Of The Skin Largest and heaviest organ 8 lbs, 1.5 - 2 m2 Layers Epidermis Dermis Subcutaneous Thickness varies Thick – palms and soles Epidermis is 0.4 – 1.4 mm thick Thin – everywhere else Epidermis is 0.075 – 0.15 mm Anatomy & Physiology, 2e. Chapter 5 https://openstax.org/books/anatomy-and-physiology-2e Epidermal Layers From outermost to innermost: • Stratum corneum • Stratum lucidum ▪ only in thick skin • Stratum granulosum • Stratum spinosum • Stratum basale Anatomy & Physiology, 2e. Chapter 5 https://openstax.org/books/anatomy-and-physiology-2e Stratum Corneum • Location: most superficial layer • Layer Size: 15-30 cell layers • Function – most important component of the barrier ▪ Prevents penetration of microbes ▪ Prevents dehydration ▪ Mechanical protection • Skin cells here are dead, full of keratin and filaggrin ▪ Held together by tight junctions, desmosomes ▪ Filaggrin helps keratin aggregate into large macrofibrils Anatomy & Physiology, 2e. Chapter 5 https://openstax.org/books/anatomy-and-physiology-2e Stratum Lucidum • Location: immediately below s. corneum ▪ Only found in thick skin of the palms, soles, and digits • Layer Size: 3-5 cell layers • Function ▪ Protection, similar to s. corneum ▪ These cells are dead, just like the s. corneum Anatomy & Physiology, 2e. Chapter 5 https://openstax.org/books/anatomy-and-physiology-2e Stratum Granulosum • Location: between the s. corneum and s. spinosum • Layer Size ▪ 3-5 cell layers, becoming compacted and flattened • Function ▪ Living cells that are re-organizing keratin and associating it with filaggrin and other proteins ▪ Lamellar granules – lipid-rich, layered granules that help reduce water loss Anatomy & Physiology, 2e. Chapter 5 https://openstax.org/books/anatomy-and-physiology-2e Stratum Spinosum • Location: superficial to the s. basale • Layer Size ▪ 8-10 cell layers – in most skin this is the thickest layer ▪ Very thick in thick skin • Function ▪ Very busy synthesizing keratin, proto-filaggrin, and other proteins ▪ Eventually keratin becomes 50% of the cell mass of keratinocytes ▪ Thick bundles of keratin called tonofibrils are linked to desmosomes Anatomy & Physiology, 2e. Chapter 5 https://openstax.org/books/anatomy-and-physiology-2e Stratum Basale • Location: deepest epidermal layer • Layer Size: single layer • Function ▪ Stem cells divide and give rise to all of the layers ▪ Melanocytes: • Synthesize and distribute melanin to keratinocytes ▪ Wide range of sensory receptors • More later this semester ▪ Resident immune cells • Langerhans cells – more next semester Anatomy & Physiology, 2e. Chapter 5 https://openstax.org/books/anatomy-and-physiology-2e Keratin structure • Fibrous protein – strong, often flexible long proteins that have a relatively simple, repeating secondary structure ▪ All have many hydrophobic amino acid residues → insoluble in water • -keratin – alpha-helical protein with many levels of structure: ▪ Single “strand” protein arranged in an alpha helix → ▪ Two strands coiled around each other – “coiled coil” → • The two strands interact with each other at sites of hydrophobic amino acid residues • Rich in alanine, valine, leucine, isoleucine, methionine, phenylalanine (all hydrophobic) Keratin structure • Keratin structure cont… ▪ Protofilament – long chains of two coiled coils ▪ Protofibril – two long chains of protofilaments ▪ Additional levels of structure lead to microfibrils (4 protofibrils, also known as tonofibrils) and macrofibrils (many microfibrils, filaggrin helps formation) • Keratin can be flexible, or can be remarkably hard ▪ Keratin is held together by H-bonds and varying numbers of disulphide bonds • These cross-link individual fibres to each other ▪ “Hardness” depends on the number of disulphide bonds • Rhinoceros horn – 18% of the residues are cysteines (disulphide bonds) Keratin structure • The alpha-helix is a right-handed coil, coiled-coil left-handed ▪ i.e. coiled in opposite directions ▪ Increases strength of the fibre • Hard keratin is “just keratin” with no filaggrin, phospholipids ▪ Hair, nails https://www.labxchange.org/library/pathway/lx-pathway:13a6c8ad-792a-4e89a9ca-84d568afb286/items/lx-pb:13a6c8ad-792a-4e89-a9ca84d568afb286:html:5f9058df Dermal Layers From outermost to innermost: • Papillary Layer • Reticular Layer Note the blood vessels Anatomy & Physiology, 2e. Chapter 5 https://openstax.org/books/anatomy-and-physiology-2e Papillary Layer • Superficial 1/5 • Loose CT ▪ fine elastic fibers, type III and type I collagen • Interlocks dermis and epidermis ▪ Papilla = “fingers” ▪ Dermal papillae are vascularized ▪ Also contains sensory receptors Anatomy & Physiology, 2e. Chapter 5 https://openstax.org/books/anatomy-and-physiology-2e Reticular Layer • Dense irregular CT - type I collagen and elastic fibers ▪ Usually thickest layer of the skin – thickest over the back (4 mm) • Houses ▪ Hair follicles ▪ Nerves, arteries, veins, and lymphatics ▪ Sebaceous and sudoriferous (sweat) glands ▪ Some adipose tissue ▪ Smooth muscle cells ▪ Some sensory receptors Anatomy & Physiology, 2e. Chapter 5 https://openstax.org/books/anatomy-and-physiology-2e Collagen fibres - structure • Type I, II, and III collagen are fibril-forming collagens ▪ Type I collagen forms 90% of the body’s collagen, and has the most structural strength ▪ many cells produce collagens – in the dermis, it is the fibroblast ▪ Final assembly for these fibril-forming collagens actually occurs in the extracellular space • Collagen is a “coiled-coil” structure as well, but is not an -helix ▪ Three collagen -chains (themselves twisted) are coiled around each other – this is called tropocollagen ▪ The tight “twisting” of the -chains is accomplished by a unique amino acid sequence https://commons.wikimedia.org/wiki/File:Tropocollagen.svg Collagen fibres - structure • Amino acid sequence: Gly-X-Y ▪ Often “X” is proline (but not always) ▪ Often “Y” is hydroxyproline (but not always) • The glycine has a very small R-group ▪ It fits well into the tightly-twisted triple helix • Hydroxyproline and proline have rigid, “kinked” structures ▪ These provide the sharp “twists” or “kinks” in the molecule • The hydroxylated proline (and lysine, when it’s there) are ideal for covalent cross-linking of the collagen https://commons.wikimedia.org/wiki/File:Tropocollagen.svg Collagen Vitamin C is crucial to collagen formation and crosslinking of hydroxylated a.a.s More in later Biomedicine classes https://commons.wikimedia.org/wiki/File:Tropocollagen_crosslinkage_lysyl_oxidase_(EN).svg Collagen synthesis… a brief overview • Fibroblasts (or other cells) produce tropocollagen fibres that have some degree of hydroxylation and glycosylation that are secreted into the ECM • Outside of the cell, the tropocollagen molecules are assembled into fibrils and fibres ▪ These fibrils and fibres are also linked to proteoglycans and glycoproteins Junqueira’s Basic Histology, p. 118, fig. 5-20 Hair Follicle What is it? • An epidermal in-growth into the dermis (invagination) that builds a long structure formed from hard keratin = a hair ▪ All hair follicles, although found in the dermis, are derived from the epidermis ▪ Specialized keratinocytes Are there areas of the skin completely without hair? • Palms and soles • Lips, genital structures (glans penis, labia minora, clitoris) The face has a lot of hair – 600 hairs/cm2; most other areas have around 60/cm2 ▪ Roughly 5 million hairs total Anatomy & Physiology, 2e. Chapter 5 https://openstax.org/books/anatomy-and-physiology-2e Hair - structure Hair bulb – bulbous part at the base of the follicle • Dermal papilla “contacts” the bulb, supplying a capillary network • Keratinocytes at the papilla are very similar to the stratum granulosum and spinosum (hair matrix) – site of active cell division ▪ Only found in the bulb • Melanocytes in the bulb transfer melanosomes to keratinocytes • Hair shaft itself has 3 layers: ▪ Medulla ▪ Cortex ▪ Cuticle Anatomy & Physiology, 2e. Chapter 5 https://openstax.org/books/anatomy-and-physiology-2e Hair Histology Hair shaft: • Medulla: lightly keratinized • Cortex: filled with hard keratin • Cuticle: the structure of the keratinocytes is more easily seen – looks like “tiles” or “shingles” • Technically, not called the hair shaft until it passes beyond the epidermis Mescher, A. Junqueira’s Basic Histology Text and Atlas 15th ed. Fig 18-14, p. 385 Hair Structure Arrector pili – a bundle of smooth muscle cells that pull the shaft into a more erect position ▪ Why? ▪ Innervated by the sympathetic nervous system, found on same side as the sebaceous gland Hair root plexus – very sensitive mechanoreceptors ▪ Myelinated nerves ▪ Desensitize rapidly Anatomy & Physiology, 2e. Chapter 5 https://openstax.org/books/anatomy-and-physiology-2e Hair Growth • Three phases ▪ Anagen – longer period of mitotic activity and growth ▪ Catagen – arrested growth and regression of the hair bulb ▪ Telogen – cellular inactivity, often → hair shedding • At the beginning of the next anagen phase, epidermal stem cells produce progenitors ▪ The progenitors give rise to the matrix of the new hair bulb ▪ Stem cells are located in the outer layer of the follicle, the external root sheath, near the attachment points of the arrector pili Anatomy & Physiology, 2e. Chapter 5 https://openstax.org/books/anatomy-and-physiology-2e Hypodermis/subcutaneous tissue/superficial fascia • Lower most layer • Contains loose areolar and adipose tissue • Important in stabilizing the position of the skin in relation to underlying tissues • Fat storage area, insulates against excessive heat loss • Superficial region contains vessels Anatomy & Physiology, 2e. Chapter 5 https://openstax.org/books/anatomy-and-physiology-2e Pigmentation Skin colouration: Hemoglobin: red blood cells in vasculature below epidermis If deoxygenation occurs (hypoxia) then the skin looks relatively “blue” cyanosis Carotene: yellow pigment from plants in the diet Melanin: pale yellow to black pigment produced by melanocytes Anatomy & Physiology, 2e. Chapter 5 https://openstax.org/books/anatomy-and-physiology-2e For future dermatology lectures: • Function and regulation of sebaceous glands • Function and regulation of suderiferous (sweat glands) • More disorders! Physical Exam: Recalling The Skin Exam How would you describe a skin lesion? What are the important things to note? Morphology: general shape, size, color and appearance Distribution: Is there a pattern? What area of the body does it affect? Inspection – How do you describe a skin lesion? Description <5mm >5mm Flat Lesion Macule Patch Flat + Raised Papule Plaque Solid Bump (Round-topped, no fluid) Papule Nodule round, solid, no fluid in it Serous fluid filled Vesicle Bulla(e) Pustule (cyst) Abscess or also a cyst Depends on the structure - has to be epithelial lining Pus-filled Inspection – How do you describe a skin lesion? Some extras… Cyst: any pocket of fluid (infected or not) lined by epithelium Abscess: a pocket of purulent fluid (bigger than a pustule) – not lined by epithelium Ulcer: a defect in the epidermis, down at least to dermis level, usually due to impairment of healing/re-epithelialization Vascular lesions : include telangiectasias (dilated arterioles, venules that one can see with the naked eye) and hemangiomas (many different types of vessel-rich, red or violet growths) Scale – accumulation or excess shedding of the stratum corneum – can be dry or waxy-feeling. Remember atopic dermatitis from Monday? Defects in the moisture barrier (filaggrin) and/or tight junctions → antigens “getting past” the epidermal barrier over and over → recruitment of immune cells repetitive episodes of itchy, erythematous, edematous macular-papular rash Distribution: extensor surfaces, face, scalp https://commons.wikimedia.org/wiki/File:Atopic_dermatitis_child.JPG Atopic dermatitis (eczema) under the microscope Early → late Note the edema in the epidermis (1), the lymphocytes and mast cells (2), and eventually the hyperkeratotic skin (from scratching it so much) (3) 1 1,2 Kumar et. al., Robbins and Cotran Pathologic Basis of Disease 9th ed. Fig 25-22, p. 1155 3 3 1 1 2 2 2 2 2 2 Psoriasis Extremely common Pathogenesis is not well understood: Chronic inflammatory condition that appears to have an autoimmune basis Epidermal hyperproliferation – they divide really quickly Abnormal differentiation of epidermal keratinocytes What is this?! Kumar et. al., Robbins and Cotran Pathologic Basis of Disease 9th ed. Fig 25-25, p 1157 Psoriasis What does it look like? Morphology? Distribution? Vitiligo Pathogenesis is not well understood: disorder of skin pigmentation Immune system attacks the cells that produce melanin (what were those again?) Anatomy & Physiology, 2e. Chapter 5 https://openstax.org/books/anatomy-and-physiology-2e Vitiligo What does it look like? Morphology? Distribution? The Hair Cycle - reminder Anatomy & Physiology, 2e. Chapter 5 https://openstax.org/books/anatomy-and-physiology-2e Alopecia areata Prevalence is 0.1-0.2% lifetime risk of developing 1.7% 0.7-3% of patients seen by dermatologists M:F = 1:1, affects Any age Pathophysiology NK cells and cytotoxic T-cells attack the hair follicle (adaptive immune system) More likely in those that are genetically susceptible ~ 20% associated with stressful events Severe infection, trauma Severe psychologic stress Alopecia areata Clinical Features Patchy hair loss that does not scar – hair will re-grow Stressful event tends to predate hair loss by 1 – 6 months 80-90% have only 1 patch of hair loss Most often affects scalp, can affect beard Re-growth tends to occur about 1 year later Androgenetic Alopecia Prevalence – 50% of men at least 13% of women premenopause, > 50% women older than 65 Usually begins to be detectable at age 40 Pathophysiology Gradual conversion of terminal hairs to vellus hairs - inherited Greatly dependent on androgen exposure over time in men Androgens may be less responsible in women Androgenetic Alopecia Clinical features: Hair loss over the crown for both sexes For men: Posterior and lateral scalp are spared See next slide For women: Mid-frontal hair loss Vertex, temporal regions spared; often frontal hair-line preserved If rapid, should check for diseases → androgen excess Often larger psychosocial impact on women AGA in males Acute Telogen Effluvium Common disorder, but no good epidemiologic studies Nonscarring alopecia characterized by acute - subacute diffuse hair shedding caused by a metabolic or hormonal stress or by medications => hair loss occurs 2-3 months later Stressor causes anagen hair to enter telogen – remember that? Generally, recovery is spontaneous and occurs within 6 months, unless a background of pattern alopecia is present A chronic form with a more insidious onset and a longer duration also exists