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components of skin?
cell types of each?
- epidermis - keratinized startified squamous epithelium
- dermis -dense connective tissue
- hypodermis (actually not part of skin) - fat, loose connective tissue, contains panniculus adiposus, binds skin loosely to subjacent tissue
specialized derivatives of skin?
- •Protection -
- barrier against UV light and protection against mechanical, chemical and
- thermal insults
- •Barrier -
- relatively impermeable; prevents dehydration and acts as physical barrier to
- invasion by microorganisms
- immunologic information during antigen
- •Thermoregulation -
- insulated against heat loss (hairs and subcutaneous adipose tissue; heat loss
- facilitated by evaporation of sweat and increased blood flow (dermis)
- •Sensation -
- contains a variety of receptors for touch, pressure, pain and temperature
- functions - secretes hormones - ex. Vit. D
- functions - sweat, sebaceous, and apocrine
classification of skin?
- thick - hairless, locations subject to abrasion (palms, soles)
- thin- contains hair follicles
adipose tissue beneath the dermis
5 layers of skin starting deep?
- stratum basal - mitotically active cells, stem cells, single layer of columnar or cuboidal cells, desmosomes and hemidesmosomes (lots of cell junctions), contain melanin
- stratum spinosum (prickle layer), at least several cells thick, cytoplasmic processes (or spines) which give it its name, cells transform through out layers here - become more flattened and squamous, cuboidal or slightly flattened cells w central nucleus, cells are in process of growth and keratin synthesis, thicker in tissue subjected to continous friction and pressure (soles of feet)
- stratum granulosum - most superficial layer of non keratinized portion of epidermis, intense basophilia (bc of protein in granules), 1-5 layres of flattened polygonal cells, charachterized by cytoplasm full of basophilic granules which contribute to keratinizaition
- stratum lucidum (only in thick skin)
- stratum corneum (keratinized cells) - flattened, fused and anucleated keratinized cells, cytoplasm filled almost entirely with keratin, pakced together in matrix of keratohyalin granules, these cells are dead
trend as you move to the surface?
- more keratin
- become larger and more flattened
what are 2 hypothesies of psoriasis?
1) autoimmune disease, immune system cells signals to increase mitosis (activation of t cells that secrete cytokines)
2) fault of skin cells
how often does human epidermis get renewed?
what layer is thicker in soles of feet?
tonofibrils - form many small cellular extensions which terminates with desmosomes located at tips of spiny projections
maintains cohesion and resists the effects of abrasion
what are tonofibrils?
where are they?
- bundles of keratin filaments that converge
- stratum spinosum
what are granules in stratum granulosum? aka.. keratohyalin granules?
histadine rich and cysteine rich proteins that are precursers to filagrin and trichohyalin
what is fx of filagrin?
aggregates keratin filaments so ultimately... conversion of granular cells into cornified cells of stratum corneum
in which layer is typical apoptotic nuclear morpholog (DNA fragmentation)
what enzyme plays a role in disappearance of organelles?
what layer is this?
- stratum corneum
whats up with the thick plamsa membrane on the stratum corneum?
coated with layer of lipids - water barrier
which layer of the epidermis is the thickest?
which one determines whether skin is thick or thin?
stratum corneum for both
what is desquamination?
- continous exfoliation
- degradation of cells' desmosomes
how does pH aid in desquamation?
pH decreases as you approach surface - activates (through freeing from inhibitor) a peptidase that cleaves desmosomes
deeper stratum corneum?
- cornified cells retain desmosomal
- junctions and intracellular keratin has an ordered pattern
what in stratum corneum that precedes desquamation?
- the desmosomes and internal structure of the cells
- become completely disrupted - precedes desquamation
Which layer is only in thick skin? and what does it do?
- stratum lucidum
- more eosinophilic, process of keratinization is advanced, nuc and organelles are disappearing
describe the junction between the dermis and epidermis
what are the projections of the dermis?
what is evagination of epidermis?
what appendages does the epidermis contain?
- hair follicles
- sweat glands
- sebaceous glands
what will happen isf the skin is under a lot of pressure?
lots of dermal papilla
what are the two layers in the dermis?
- papillary layer - delicate collagen network, most superficial, LCT, fibroblasts, mast cells, macrophages, contains epidermal serving blood vessels, nerves
- reticular layer - thicker and less cellular (irregular DCT), thick collagen and elastic fibers not randomly arranged - regular lines of tension (langer's lines), less scarring if incisions follow this line
what is psoriasis?
- a common skin disease, increase in the number of proliferating cells in stratum basale and stratum spinosum
- also decrease in cycle time
what happens to collagen?
epidermis thins (very thin at the bottom of a wrinkle)
collagen fibers get thicker and synthesis ceases
elastin content decreases
crosslinking of collagen fibers, loss of elastic fibers, sun exposure --> wrinkles (more fragile skin)
dermis and hypodermis atrophy (reduced collagen and Gags)
oxtalin fibers disappear in papillary dermis
describe the process that leads to wrinkles
sunlight damages collagen fibers - accumulation of abnormal elastin (causes tissues to stretch), metalloproteinases are produced (which are supposed to reform collagen but sometimes they overact and degrade collagen - solar scars
what are solar scars?
disorganized collagen fibers caused by the sun
what are the 4 cells of the epidermis and what is their function?
- keratinocytes - produce keratin and form the epidermal water barrier
- melanocytes - pigment producing cells
- langerhans' cells - involved in signalling in the immune system
- merkel's cells - associated with sensory nerve endings
what is the process of keratinization and where does it occur?
start in the basal layer - as they move through the stratum spinosum synthesize keratin filaments (tonofilaments) which begin to bundle into tonofibrils - in the upper part of the stratum spinosum keratohyalin granules are synthesized (these are discrete in the granulosum layer) - contain 2 proteins gilaggrin and trichohyalin that promote aggregation into tonofibrils which convert granular cells into cornified cells (keratinization) - the surface is fully keratinized (contains a thickened plasma membrane with tons of lipids and bundles of tonofilaments in specialized matrix
what and where is the change in pH?
7.17 in stratum granulosum --> 5 in stratum corneum
what is the process of exfoliation of keratinized cells from the stratum corneum? and what is it called?
- desquamation - happens from degradation of desmosomes
- KLK's cleave desmosomes in a pH dependent manner, at acidic pH LEKT1 releases KLK
what is inhibitor of KLK?
where is the epidermal water barrier?
what are the 2 main factors that contribute to it?
between stratum granulosum and stratum corneum
- 1) deposition of insoluble proteins on the inner surface of the PM
- 2) lipid layer that is attached to the outer surface of the PM
how does the epidermal water barrier form?
keratinocytes in stratum spinosum layer also produce lamellar bodies (contain proteases and other lipid enzymes) - contents of granules secreted by exocytosis into intercellular spaces between the stratum granulosum and strat corn
check out page 495!
what structure of skin is important for mammalian evolution?
epidermal water barrier
structural elements of water barrier:
- cell envelope
- insoluble proteins on the inner surface of PM, undergoes mechanical stress - from crosslinking proteins
- lipid envelope lipids attached to cell surface by ester bonds
what his major problem if you get burned?
loss of epidermal barrier - life threatening
functions of melanocytes?
- responsible for synthesis and release of melanin
- skin coloration (protection)
structure of melanocytes?
dendritic cell bc cell body near basal membrane but extends processes up into strat spinosum in between the keratinocytes
reside close to the basal lamina and connect via hemidesmosomes
how is skin pigment produced?
where does it occur?
tyrosinase enzyme oxidizes tyrosine -> DOPA -> melanin
premelanosomes - basal lamina then mature into melanosomes when produce lots of melanin (ends of the processes)
what is fx of melanin?
how do they do it?
protect organism against damaging effects of nonionizing ultrviolet irradiation
melanin granules collect in supranuclear region of cytoplasm
what causes albinism?
absence of tyrosinase activity or inability of cells to take up tyrosine
what is vitiligo
degeneration and disappearance of entire melanocyte
what is pigment donation?
melanosomes and melanin content are phagocytosed at the tip of melanocyte - transferred to neighboring keratinocytes
small amount of cytoplasm surrounding hte mlanosome is also phagocytosed
why do you get darker skin?
melanosomes last longer, melanin is degraded slowly
how does melanin disappear in upper epithelial cells?
within keratinocytes, melanocytes granules fuse with lysosomes
why is thigh lighter than scrotum?
greater number of melanocytes
how is skin color determined?
- differences in number of melanin granules
- increase in basal level of malanogenesis
2 forms of melanin?
- eumelanin - dark brown
- pheomelanin - reddish brown
- - after exposure to solar radiation (290-320 nm) result of
- two step process:
- -Physicochemical reaction darkens prexisting melanin and releases it rapidly
- -Rate of melanin synthesis accelerates
- - damages DNA, increases MSH (melanin stimulating hormone)
skin cancer types
- -Basal cell carcinoma = the most common, slow growing,
- noninvasive, cells look like stratum basal cells (that’s where gets its name),
- often come from cells from the hair, treat it easily by cutting it out
- -Squamous cell carcinoma – faster growing, more in vasive but it
- is not always invasive, 2nd most
- common, inflammation, highly atypical, all levels of epidermis, if it disrupts
- the basement membrane then it can mestasticize
- melanoma – the most serious, very fast growing, very invasive, very fatal
what is their fx? mechanism of action?
what do they express?
start in bone marrow, enter blood, travel to epidermis, interacts with antigens, phagocytoses it, presents it, then migrates to lymphnodes where it interacts with t cells
express MHC1 and MHC2 as well as Fc receptors
what special type of derm problem are langerhans' cells involved in?
where? what type? fxn?
- found in thick skin of palms and soles
- stratum basale
- attached via desmosomes to keratinocytes
- acute sensory perception (touch, heat, cold, pressure)
what is a Merkel's corpuscle?
- complex of afferent nerve fiber and merkel's cell.
- it is a mechanorecptor
- as the nerve endings penetrate through the basal lamina they lose their myelin sheath, the bulb of the nerve ending lies right next to the merkel's cell
free nerve endings?
what makes them free?
- mainly around hair follicles, specifically attach to the outer root sheath - mechanorecptors
- there are tons!
no shwann cells around them
what are the 3 types of encapsulated nerve endings and their functions?
- pacinian corpuscles - detect pressure changes and vibrations, in the dermis and hypodermis, myelinated nerve ending covered by capsule, concentric layers of endoneurial cells around nerve terminal, space betwen diff lamellae filled with fluid, mechanical pressure displaces lamellae which depolarizes axon
- meissners corpuscles - sensitivity to light touch - located in dermal papillae in hairless skin, consists of coil of endoneurial cells around a nerve terminal, unmyelinated endings of nerve fibers spiral into corpuscle
- ruffini's corpuscles - sensitive to skin stretch and torque, thin connective tissue capsule that encloses a fluid filled space, displacement of collagen fibers cause stretch
where else are pacini and ruffini endings found?
in CT of deep organs, probably sensitive to movement of internal organs
basal cell carcinoma?
- occurs around hair follicles
- stratum basal
squamous cell carcinom
- inflammatory ring because immune system is
- trying to attack these cells
- more atypical
- all levels of epidermis (can start anywhere)
if basement membrane disrupts… then it becomes melanoma
- most serious, fast growing, invasive
- migratory, metastatic
- come from neuralcrest cell (make a lot in your
- body!) à
- why its so invasive and nasty
- neural crest cells are melanocytes (they migrate
- around the body – that’s why cats have white feet, white stomachs
want to get rid of this right away!
2 different types of skin cancer growht:
- 1) radial growth stage -grows in all directions , up down sideways
- 2) vertical growth stage - most likely to metastasize
how to recognize melanoma?
assymetry, borders uneven, colors - two or more shades, diameter - larger than 6 mm, evolution- changes
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