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2011-12-03 19:13:20
F2 Goodlick Skin

F2 4 Goodlick Skin
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  1. ´╗┐Skin Functions
    • Physical Protection
    • Barrier from external agents
    • Prevents dehydration
    • Immune protection
    • Thermoregulation
    • e.g., sweat glands
    • Sensation
    • Pressure, heat, pain
    • Secretion
    • Sweat, other secretions
    • Absorption
    • UV radiation for Vitamin D synthesis
  2. Skin Layers
    • -Epidermis
    • Surface epithelial cell layer
    • Keratin
    • "other cells"
    • -Dermis
    • Middle supporting layer
    • Blood, nerves, connective tissue
    • -Subcutaneous layer
    • Deepest layer
    • Fat, glands, blood vessels
  3. functions of the skin
    • considered a large and extensive organ
    • acts as a physical barrier
    • provides immune protection through being home to resident immune cells
    • control temperature both through sweat glands but also via a plexus of of cutaneous blood vessels
    • number of different types of nerve endings sense pressure, heat, pain, etc.
    • secretes (e.g., sweat, etc)
    • absorbs uv radiation from the sun which is important for vitamin D synthesis
  4. epidermis
    • stratified squamous epithelial layer.
    • The epithelial cells of the skin are called 'keratinocytes'.
    • In addition to the keratinocytes, there are some other cells present in the epidermal layer
  5. keratinocytes
    • The epidermis has 4-5 layers of keratinocytes that have different properties and appearances.
    • Note that the Stratum Lucidum (clear layer) is sometimes difficult to find
    • 4 layers, they are (from the bottom working up):
    • 1. Basal Layer;
    • 2. Spiny layer;
    • 3. Granular layer;
    • 4. Cornified layer.
    • Note that the epidermis is derived embryologically from ectoderm.
  6. Keratinocytes
  7. Basal Layer
    • (aka stratum basale or stratum germinativum).
    • This layer is closest to the dermis and rests on the basement membrane
    • (attached to basement membrane by hemidesmosomes).
    • These cells are also attached to one another via desmosomes.
    • As the name implies, this layer constitutes the stem cell compartment for the skin.
    • That is to say, division of these cells replenishes the skin layer.
    • Division occurs mostly at night.
    • The shape of these cells are cuboidal.
  8. Basal Layer Note
    • Because they are a dividing stem cell population, they are often prone to mutations or other alterations.
    • If such damage is not repaired, cancers can arise.
    • One such malignancies that is thought to be derived from alterations to these cells is called Basal Cell Carcinoma.
  9. Hemidesmosomes
    • Note, not all keratinocytes are attached to the basement membrane; only this lower layer (basal cells) are attached.
    • (This is true for all stratified epithelial layers).
    • This attachment occurs via hemidesmosomes
  10. Spiny layer
    • (also known as stratum spinosum or prickle cell layer).
    • Typically thickest cell layer of epidermis, 4-6 layers of cells
    • Rich in cytokeratin
    • Cytokeratin radiates out - contributes to inerdigitated cell processes which attach one cell to another via desmosomes
    • Can sometimes be mitotically active
    • Cobble-stone, polyhedral appearance; spiny
    • These cells appear cobble-stone shaped and are noted for their "spiny" appearance upon viewing at higher magnification.
    • This spiny appearance, in part is due to numerous cell-cell connections via desmosomes.
    • Recall that cytokeratin intermediate filaments are linked to desmosomes.
    • Such cytokeratin intermediate filaments are sometimes called tonofilaments.
    • On occasion, one can see these cells dividing as well
    • have abundant tonofilaments.
    • have abundant Lamellar granules
    • note mitotic figures
  11. Granular Layer
    • (stratum granulosum)
    • Typically 1-3 layers of keratinocytes
    • They are dying cells
    • Release lipid lamellar granules
    • Important for water-proofing skin
    • Act like glue to hold cells together
    • Contain keratohyaline granules
    • Look like small bluish granules
    • Protein rich (clumps of keratin)
    • Appearance: Flat
  12. Granular layer
    • (also known as stratum granulosum).
    • Appear more flat than basal cells or spiny layer cells.
    • Noted for having small, bluish granules with H&E staining.
    • In the last stages of their life (i.e., they are dying).
    • Release the contents of their lamellar granules.
    • This lipid-rich substance is important for water proofing the skin, but also important for holding dying cells together.
    • These cells also have non-membrane bound clumps of keratin (keratohyalin granules) which appear blue.
  13. lamellar granules
    • (Granular Layer)
    • lipid-rich substance is important for water proofing the skin
    • also important for holding dying cells together
  14. Cornified Layer
    • (stratum corneum)
    • Several layers of dead flat keratinocytes
    • Ghosts with no nuclei or organelles
    • Plasma membrane still present
    • No desmosome connections
    • Heaps o' keratin
    • Ghosts eventually sloughed off (after ~2 weeks)
    • Desquamation
    • Takes ~2 weeks for cells to reach cornified layer
    • Appearance: pink (H&E staining)
  15. Cornified layer
    • (also known as stratum corneum).
    • Most superficial layer of the skin
    • Consists of dead keratinocyte ghosts.
    • Lack a nucleus, organelles and desmosomal connections.
    • Ultimately sloughs off.
  16. Thin Skin
    • Most areas of the body contain "thin skin" as defined by the thickness of the cornified layer.
    • Thin Cornified layer
    • A few Layers of spiny cells
  17. Thick Skin
    • areas prone to wear and tear
    • soles of feet, palm of hand
    • No hair
  18. non-epithelial cells in epidermis
    • melanocytes
    • langerhans cells
    • merkel cells
  19. Melanocytes
    • Derived embryologically from neural crest
    • Migrate into epidermis during first 3 months of gestation
    • Responsible for producing melanin
    • Melanin granules in keratinocytes
    • Located in the basal layer of the epidermis
    • Long cellular processes
    • No desmosomes
    • round-ish cells, but they can be recognized in H&E stained sections because of their clear / pale cytoplasm.
    • Note: Cells with melanin are keratinocytes not melanocytes
  20. Melanin
    • Protects DNA from UV Damage
    • Melanocytes contain membrane bound oval granules called melanosomes(contains tyrosinase)
    • Specialized type of lysosome
    • Production -> Tyrosine is converted by tyrosinase to DOPA which polymerizes into melanin
    • Melanin (in melanosomes) are taken up by keratinocytes
    • By basal cells (maintained as cells 'migrate' up) and spiny layer cells
    • Recall, basal cells and spiny layer are mitotically active
    • i.e., most susceptible to UV induced mutations
    • Melanin 'absorbs' non-ionizing UV radiation
  21. Melanin
    • produced by the melanocytes
    • protects keratinocytes from damaging UV radiation.
  22. Melanin production
    • Tyrosinase is produced by melanocytes at the rough ER and packaged by the Golgi into granules called "melanosomes".
    • The amino acid tyrosine is transported in the melanosomes where the enzyme tyrosinase converts it into melanin.
    • Melanosomes are transported to the tips of the long processes of the melanocyte.
    • These processess extend into the spiny layer of the epithelium.
    • The vesicles pinch off, and are taken up by the spiny layer keratinocytes and by basal cells.
    • Therefore, it is these cells that appear pigmented.
    • The melanosome / melanin granules are then localized apical to the nucleus (i.e., to absorb incoming UV rays)
  23. Skin Color
    • All individuals (races) have roughly the same number of melanocytes.
    • Approximately 1 melanocyte per 10 keratinocytes
    • Individuals of darker skin, however, have more active melanocytes.
    • In Caucasians, for example, melanosomes are smaller and fewer and are degraded more rapidly.
    • In addition, sun exposure can increase the activity of melanocytes by increasing tyrosinase activity.
    • This can result in a sun tan.
    • Skin color is determined by the number and size of melanosomes in the keratinocytes (not by the number of melanocytes)
  24. Langerhans (Dendritic) Cells
    • Important in immune responses at the skin
    • Eat then 'present' antigen to immune cells
    • Trigger immune response
    • Present in all layers of epidermis
    • Pale staining cytoplasm
    • Oval nucleus
    • Long cellular/dendritic processes
    • Seen with special stains
    • Cells originate from the bone marrow
    • Travel through blood to skin
  25. Langerhans cells
    • (also called "dendritic cells")
    • immune system
    • present at all layers of the epidermis
    • have a pale staining cytoplasm. Like melanocytes
    • have long cellular processes (however, these are almost impossible to see in typical H&E stained slides).
    • (Note, there are probably some langerhans cells in the dermis as well).
    • These cells are derived from the bone marrow, migrate through the blood, then take up residence in the skin.
    • These cells continually "sample" the environment;
    • if harmful agents get into the skin (like bacteria etc.),
    • langerhans cells "present" this foreign material (antigen) to immune cells to trigger an immune response
  26. Merkel cells
    • derived embryologically from neural crest cells, travel through blood to skin
    • In H&E stained slides, these cells look like (and cannot be distinguished from) melanocytes (however, special stains can distinguish the 2 cells).
    • Oval Nucleus
    • Merkel cells play a sensory function as specialized touch receptors.
    • These are especially abundant in finger tips and oral cavity.
    • Merkel cells synapse with unmyelinated sensory nerve fibers (called the Merkel cell - neurite complex).
    • Merkel cells release neuroendocrine like substances when stimulated, which in turn stimulates this sensory nerve.
  27. Rete Ridges
    • (downward growth of epidermis into dermis)
    • not present everywhere in the skin; they are more pronounced in areas that come under a fair bit of mechanical stress. palm, soles, fingers
  28. Dermal Pegs or Papillae
    • (areas where dermis pushes up into epidermis).
    • not present everywhere in the skin; they are more pronounced in areas that come under a fair bit of mechanical stress. palm, soles, fingers
  29. Psoriasis
    • Common skin disorder
    • Increased (but controlled) proliferation of basal cells and
    • Incomplete keratinization of the upper layer of cells
    • This layer is shed quicker than normal (a week rather than several weeks)
  30. Carcinoma
    • Malignancies of epithelial cells typically referred to as "Carcinomas"
    • Malignancies of Epidermis layer
    • Basal cell carcinoma
    • Squamous cell carcinoma
    • Melanoma
  31. Basal Cell Carcinoma
    • Common slow growing tumors that rarely metastasize
    • Chronic sun exposure
    • Increase risk with immuno-suppression and DNA repair deficits
  32. Squamous Cell Carcinoma
    • Exposure to UV light
    • Increase risk with immuno-suppression and DNA repair deficits
  33. Melanoma
    • Relatively common
    • Highly invasive and metastatic
    • Deadly (if not caught early)
    • Sun exposure a risk factor
    • Other hereditary factors
  34. Dermis
    • Middle Supporting Layer
    • Blood, Nerves, Connective Tissue
    • below the epidermis
    • completely composed different from the epidermis
    • blood vessels, nerves and specialized nerve endings,
    • abundant connective tissue (including cells, fibers and ground substance), and glands and ducts
  35. inhabitants of the dermis
    • Blood, nerves, glands, lymphatics, lymphocytes, extracellular matrix
    • Note, that many of the cells are derived embryologically from mesoderm.
    • The extracellular fibers are mostly collagen (type I and type III; some type VII) and elastic fibers.
    • Also, some glands are present in the Dermis as well as a down-growth of the epidermis which results in the hair follicle.
  36. Meissner's Corpuscles
    • Located at dermal papillae i.e., junction of epidermis - dermis
    • Numerous at tips of fingers, lips, eyelids
    • Mechano-receptors
  37. Pacinian Corpuscles
    • Located in dermis and subcutaneous region
    • Large onion-like structure
    • Central core axon
    • Detects pressure and vibration
  38. subcutaneous layer
    • (also known as the hypodermis).
    • This has a lot of loose connective tissue and fat (and is equivalent to superficial fascia studied in anatomy course).
    • The subcutaneous region is home to some of the glands, some Pacinian corpuscles, and larger blood vessels.
  39. Eccrine glands
    • type of sweat gland located deep in the dermis
    • important for thermoregulation of the skin
    • distinct in size and structure from apocrine glands
    • secretory section is made up of simple cuboidal epithelial cells.
    • single layer, cuboidal cells, narrow lumen
    • Surrounding them are myoepithelium (to help squeeze out the content).
    • The ducts are composed of (2 layers) stratified cuboidal epithelium.
    • Duct goes through epidermis
    • Duct goes through keratin layer
  40. Cystic Fibrosis
    • Cystic fibrosis, is a genetic disorder of epithelial transport of chloride by the channel protein CFTR.
    • These channel proteins are located in the eccrine sweat gland ducts.
    • When not functioning properly, the sweat that is released onto the surface of the skin has an increased concentration of chloride and sodium. The skin is salty.
  41. Sebaceous Glands
    • Secrete oily / waxy substance (sebum)
    • This secretion is called "holocrine" referring to the fact that the glandular cell often dies and becomes part of the secretion.
    • Cholesterol, triglycerides, cellular debris
    • Near hair follicle, typically release into hair shaft
    • Located in dermis and subcutaneous region
    • Present everywhere except palms, soles of feet
    • Appearance: Round, plump, lipid-filled, fluffy cells
    • Active at puberty
    • Cells are large, plump and fluffy - the cytoplasm is relatively clear (or pale) due to the lipid content.
  42. Apocrine sweat glands
    • also located deep in the dermis or subcutaneous regions.
    • These glands are only present at a few specific locations in the body -- namely the arm pit, groin area, and areola region of the nipple.
    • These too are more active after puberty, and they secrete a viscous milky substance which is often smelly when metabolized by skin bacteria.
    • The exact reason for these glands is unknown.
    • Produces viscous, milky secretion
    • Smells when metabolized by skin bacteria
    • Release of product tied to nervous system
    • Secreted when nervous
    • Secretory portion: simple cuboidal
    • Myoepithelium around gland
    • These glands look distinctly different from eccrine and subaceous glands.
    • They have a wide dilated lumen. T
    • he secretory portion is composed of simple cuboidal epithelium.
    • Myoepithelial cells surround the gland to help squeeze out content.
    • They always secrete near (and into) hair follicle shaft.
  43. Hair Follicle
    • Derived from epithelium of epidermis
    • Landmarks
    • Hair bulb (part of hair papilla)
    • Dermis
    • Blood vessels and nerve endings
    • Germ cells
    • Fibrocollagen follicle sheath
    • Erector Pili muscle
    • Goose bumps
    • Sweat glands nearby