Skin

Epidermal interpapillary pegs interdigitate with dermal papillae. The deeper the interdigitation, the more adaptive the epidermis is to the dermis. Number of differentiating cells projecting into the stratum corneum will be different in the papillae and the pegs --> fingerprints are underlying differential thickness of the height of the epidermis.

Discuss the anchoring of the dermis to the epidermis.

Sulfur-rich keratin that enables disulfide bonds --> hard keratin. No stratum granulosum. Nail matrix = source of proliferating cells under the nail. Eponychium and hyponychium -- block entry of fungi underneath the nail. The cuticle is the thick corneal layer of the eponychium extending on the dorsal surface of the nail plate -- protects the matrix.

Discuss the different parts of the nail. What is the nail composed of?

Fine touch, sensation of heat and cold. Free endings are also found around the base of hair follicles (peritrichial).

Free ends of afferent axons in the skin detect:

Keratinocytes are anchored to each other by desmosomes (cadherins) and intermediate filaments that pass through those desmosomes. Keratinocytes in the basale are anchored to the basal lamine through desmosomes and focal adhesions.

How are keratinocytes held together?

Age decreases melanin production.

How does age affect production by melanocytes?

Every 15-30 days depending on location in the body and external forces (frictional application, signals from underlying connective tissue). Corneal sloughing is about 14 days. Psoriasis causes increased proliferation and epidermal thickening, extension of epidermal pegs into the dermis, and shedding of incompletely keratinized cells as early as 7 days - due to change in cytokines in the area due to migrating cells in the CT.

How often do keratinocytes turnover? What is this dependent on? What causes psoriasis?

Changing of adhesion characteristics -- desmosomal proteins change, intermediate filament complexes change, keratins made by early cells are different from keratins made by later cells.

What allows cells to move through layers in the epidermis?

Keratinocytes are the normal structural components of the epidermis. Differentiate in the stratum basale and die in the stratum granulosum.

What are keratinocytes? Describe their proliferation and keratinization.

Thick skin: >5mm thick and hairless; thick dermis and epidermis; palms and soles of feet; may have stratum lucidum in the epidermis. Thin Skin: 1-2mm thick with hair follicles in most locations and thin epidermis.

What are the differences between thick skin and thin skin?

1. Barrier to infectious, physical, chemical agents, and UV light. 2. Regulates body temperature and water loss. 3. Sensory functions via specialized nerve endings and pressure/touch receptors. 4. Endocrine and signaling factors via hormones (Vitamin D), cytokines, and growth factors. 5. Excretory functions via sweat, sebaceous, and apocrine glands. 6. Immunological functions performed by antigen-processing and presentation.

What are the functions of skin?

Stratum Basale Stratum Spinosum Stratum Granulosum Stratum Lucidum (very thick skin only) Stratum Corneum (Californians like girls in string bikinis)

What are the layers of the epidermis?

Epidermis - stratified squamous epithelium. Dermis - connective tissue (papillary and reticular; reticular is more dense) Hypodermis (subcutaneous fascia) - rich in adipose tissue.

What are the three layers of skin and what are they composed of?

Epidermis -- Stratum basale, stratum spinosum, stratum granulosum, stratum corneum. Keratinocytes are found in all layers of the skin. Stem cells are found in the basal layer. Melanocytes are found between the basal layer with extensions into the spinosum (between keratinocytes). Langerhans cells are antigen processing cells in the basal and spinosum layers. Merkel cells are mechanoreceptors in the basal layer.

What are the various features and cells seen in this image?

Apocrine sweat glands -- secrete by merocrine secretion. Coiled tubular glands with large lumens connected by ducts to hair follicles in axilla, mons pubis, areola, and circumanal areas. Gland secretions are rich in protein, carbohydrates, lipids, and aromatics that vary with location. Secretions may serve as pheromones. In ear contributes to cerumen (earwax).

What are these? Where are they found?

Sebaceous glands, found in the dermis next to hair follicle -- produce oily coating on skin and hair through holocrine secretion. Glands activate at puberty by steroid hormones. Cell proliferation by undifferentiated cells at the basal lamina. Acne vulgaris by overactivity and bacterial growth. Sebaceous cysts by plugging of ducts with thick sebum.

What are these? Where are they found?

Increased melanocyte proliferation and rounding.

What cause nevi/moles?

Melanocytes are deficient in tyrosine uptake or in tyrosinase activity causing lack of melanin production.

What causes albinism?

Darkness of skin is not due to changes in number of melanocytes. There are about 1:4 - 1:10 melanocyte:basal cells in everybody, does not vary significantly with race. Darkness of skin is due to the amount of pigment/melanin that is produced by those melanocytes and how it is retained in the skin. Melanin production is in the basal layer and deposition starts in the basal layer. With darker skin and more deposition, it moves up more to neighboring keratinocytes in higher layers of the epidermis.

What causes the difference in pigmentation between light and dark skin? What do the arrows point to?

Patches of skin lose melanocytes due to auto-immune reactions -- lack of melanin in certain areas.

What causes vitiligo?

Cold

What do Krause receptors detect?.

Collagen fiber displacement in the dermis.

What do Ruffini's detect?

Keratinocytes produce lamellar bodies in the spinosum. Lamellar bodies are droplets filled with a variety of fats. These droplets are released in the granulosum and contribute to the water barrier of the skin. Keratinocytes also produce keratohyalin granules that contain cross-linking proteins. These cross-linking proteins will bind to intermediate filaments and stabilize them. When the keratinocyte dies in the granulosum, the intermediate filaments + desmosomes will remain in the corneal layer.

What do keratinocytes produce? What function do they play in the skin?

Bullous pemphigoid antigens 1 and 2 are targets of autoimmune reactions leading to neutrophil/eosinophil release of proteases that digest basal lamina attachments, resulting in blistering.

What does bullous pemphigoid do?

The water barrier is in the stratum granulosum and stratum corneum. Lipid-based oily secretion from granulosum keratinocytes as they die leave an oily coating on the surface -- apoptotic keratinized keratinocytes -- highly insoluble cross-linked proteins deposited on cytoplasmic face of plasma membrane. In addition, tight junctions between cells in the granular layer are imperative. Mutations in the claudins cause death at birth.

What forms the epidermal water barrier? Where is it?

Increased pigmentation -- dysfunction of the adrenal cortex.

What happens to skin pigmentation in Addison's disease?

Clonogenic keratinocytes in bulb can generate hair, sebaceous glands, and even epidermis in the case of wound healing -- source of stem cells.

What is an important feature of hair follicles?

Eccrine sweat glands -- function in thermoregulation and excretion. Sweat produced in the coiled, tubular gland is conducted directly to sweat pore on epidermal surface for evaporative cooling. Duct cells reabsorb NaCl filtrate produced by secretory portion of gland. total weight about 1 kidney, can excrete up to 10 liters/day.

What is seen here?

Melanocyte invasion of dermis in later stage melanoma. From the dermis, the aberrant melanocytes may migrate into vessels and travel to the rest of the body causing a metastasis.

What is seen here?

Radial growth phase of a melanoma - early stage in which melanocytes are dispersed throughout the epidermis. Melanoma causes asymmetric, elevated nodule with irregular borders, varied pigmentation.

What is seen here?

Meissner's corpuscles, found in the dermal papillae in thick skin. Detect touch, detect shape and pressure. Unmyelinated axon enters corpuscle, connections to basal lamina through fibers. When basal lamina shifts, tension on corpuscle -- causes opening of mechanically gated ion channels.

What is seen here? How does it function?

Hair follicle --deep invagination of the epidermis into the dermis/hypodermis. SG is sebaceous glands in the dermis that area associated with the follicle. Apocrine glands may also be associated in certain areas of the body. Sweat glands are not associated. Sensory nerve endings can detect movement of the hair shaft.

What is seen here? What is SG?

Epidermis. Keratinocytes produce lamellar bodies in the stratum spinosum.

What is seen in this image? What do the keratinocytes produce in the SS?

Melanoma

What is shown here?.

Hypotonic solution of water, and varying amounts of NaCl, uric acid, urea, and ammonia.

What is sweat composed of?

L = langerhans cells, which are intra-epidermal antigen presenting cells.

What is the function of "L"?

Merkel's cell - found in basal layer of the epidermis, linked to surrounding cells by hemidesmosomes. Mechanical agitation (touch) will causes exocytosis of vesicles containing neurotransmitters (black dots). This will trigger action of the axon with pseudosynapse nearby (NT).

What is the function of this cell? Where is it found? What is NT?

Sebaceous glands surrounding a hair follicle - holocrine secretion.

What is the method of secretion of these glands?

Micororganisms coat our skin -- not homogenous-- different microbiota in different areas of skin. Create and release many molecules that interact with circulating cells in the dermis, can trigger cytokine response, etc. Balance between microbial population and underlying immune system is very important for normal physiology.

What is the role of microorganisms on the skin?

Langerhans cell, found in all layers of the epidermis. They are antigen-proessing cells, NOT connected by desmosomes to keratinocytes --> migrate to nearby lymph nodes and interact with T-cells. Derived from the bone-marrow. Important in cutaneous delayed hypersensitivity reactions (contact allergic dermatitis, graft rejection) mediated by T cells. Express MHCI and MHCII, IgG receptors, complement receptors.

What is this cell? Where is it found? What does it do?

Eccrine sweat gland.

What is this?

Eccrine gland -- myoepithelial cells, clear cells (important for moving fluids that escape the vasculature across the epithelia into the lumen), dark cells (secrete proteins into sweat), lumen, intercellular canaliculus.

What is this? What do My, IC, C, D, and L stand for?

Pacinian corpuscles detects deep pressure in the dermis. Multi-layered organization of layers of lamellae (modified Schwann cells) alternating with collagen/fluid. Strong mechanical agitation of the skin causes opening of ion channels. Abundant in dermis, hypodermis of fingertips, CT in general, organs, joints, periosteum.. (not limited to skin). Capscule of fibroblastic cells continuous with endoneurium and separated by fluid spaces surround unmyelinated portion of neuron. Vibration causes depolarization.

What is this? What does it detect?

Stratum spinosum - keratinocyte and connecting desmosomes.

What layer of the epidermis are these cell found?

Stratum basale - keratinocytes and melanocytes are seen.

What layer of the epidermis are these cells found?

Stratum granulosum. ill-defined remnant of the nucleus of a keratinocyte. K - keratohyaline granules.

What layer of the epidermis are these cells found?

At low pH, proteases are secreted that cut the cadherins holding the desmosomes together. Individual structures will flake off.

What occurs with these cells to create the stratum corneum?

Psoriasis -- increased proliferation and epidermal thickening, extension of epidermal pegs into the dermis, shedding of incompletely keratinized cells as early as 7 days.

What pathology is seen in this image?

15-20%

What percentage of body mass is skin?

1. UV light triggers the production of proopiomelanocortin (POMC) in keratinocytes. 2. POMC is cleaved into alpha-melanocyte stimulating hormone (a-MSH) and beta-endorphins. 3. a-MSH acts on melanocytes to trigger pigment production through cAMP dependent process. B-endorphin circulates and has an analgesic effect. 4. Melanocytes produce vesicles containing melanin called melanosomes through TYROSINE --> DOPA --> MELANIN. 5. Melanosomes are pushed towards tips of melanocytes dendritic processes and tips are pinched off to deposit in the keratinocytes. Total accumulation of pigment is dependent on both the rate of production and the rate of removal.

What triggers production of melanin? What are the steops of melanin production? How is melanin deposited in cells?

Melanocytes - found in basal layer - appear as clear cells. Melanocytes produce melanosome vesicles filled with melanin that pigment the skin. The do NOT have desmosomes connecting to keratinocytes -- greater ability to move around in the epidermis.

Where are these cells found? What do they do?

Neural crest cells

Where do melanocytes originate from?

The "clear cells" - melanocytes are producing the melanin. Production is triggered by a-MSH which is released by neighboring keratinocytes after UV light triggers cleavage of POMC.

Which cells are producing "Me"? What triggers the production?

At a low pH proteases (KLK, LETK1) are secreted from keratinocytes that will cut the cadherins forming the desmosomes that hold the individual cells in the stratum corneum together in sheets. This will cause exfoliation. Glycolic acid will artificially create a pH change at lower levels of the corneal level and cause earlier stripping of cells. This process is retinoic acid dependent

Why do exfoliating agents contain glycolic acid and retinoic acid?

UV light is necessary for the production of vitamin D. 1. Photolysis of sterols (ergosterol, 7-dehydrocholesterol) is triggered by UV light. 2. Cleaved products travel to liver where hydroxylation occurs. 3. Further hydroxylation occurs in the kidney, creating vitamin D3/calciferol. (3-hydroxylated) Vitamin D is necessary in gene expression, immune system, and in prevention of certain cancers. Vitamin D deficiency is relatively common in northern hemisphere, about 40-50% deficiency.

Why is UV light necessary for the skin?

Pigmentation shields the keratinocytes and stem cells in the basal layer from DNA damage and mutation.

Why is pigmentation important in the skin?