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Chapter 6: Integumentary System

Ms. Eddy's BIO210 sec 008
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Organs of the integument system
skin, hair, nails, and skin glands (sweat & sebaceous)
primary function, integument
protection
Primary layers of the integument
2 layers: epidermis and dermis
epidermis
outer, thinner layer of skin
epidermis tissue type
membranous epithelium (stratified squamous epithelium-keratinized)
keratinocytes
protection and waterproofing, most numerous and import cells in the epidermis, filled with (or in the process of becomine filled with) keratin
keratin
strong protein; protects and waterproofs the skin
keratinization
process by which cells in the epidermis become filled with keratin and moved to the skin's surface (cells die in the process) causes both the cell's nucleus and organelles to disintegrate which causes the cell to die
melanocytes
produce and store melanin; have long branching processes and are scatterd among the keratinoctes of the stratum basale; transfer pigment granules called melanosomes into the keratinocytes
functions of melanin
responsible for color of skin, hair, and eyes; filters uv ligh
langerhan's cells
can travel, track down bacterai, provide defense against foreigh invaders (work with immue system) similar to leukocytes)
3 cell types of the epidermis cells
keratinocytes, melanocytes, and langerhan's cells
cell layers of the epidermis
5 layers: stratum corneum, stratum lucidum, stratum granulosum, stratum spinosum, stratum basale
stratum corneum
"hardened layer": cells in this layer are totally filled with keratin (replaces cytoplasm) known as the barrier area, cells at the surface of this layer are dead; what you see when you look at the skin; consists of 20 to 30 layers of deady, scaly interlocking keratinized cells
stratum lucidum
"clear layer" cells in this layer have a clear appearance (keratin precursor/immature form) only present in thick skin within the palms of the hands and the soles of the feet; cells that occupy this layer appear pale and featureless and have indistinct boundaries teh keratinocytes are flattened adn filled with the translucent protein called eleidin
stratum granulosum
"granular layer": cells in this layer are filled with granules (keratin precursor) keratinization begins in this layer
stratum spinosum
"spiny layers": cells in this layer have an irregular shape (plasma membrane modified to hold tighlty together); rich in RNA (preparation for keratinization) each time a keratinocyte stem cell in the stratum basale divides a daugher cell is pushed toward the external surface from the stratum basale
stratum basale
"base layer": the innermost layer of epidermis; mitosis occurs in this layer; is a single layer of cubodial to low columnar cells tightly attached to an underlying basemetn memembrane; have three type of cells: kerationocytes, melanocytes, and tactile cells
turnover (regeneration) time
time required for epithelial cells to form in the stratum basale and migrate to th skin's surface; takes about 35 days on average (maintains a constant skin thickness) application: shortened turnover time results in formation of callus
epidermal proliferating unit (epu)
each group of 8-10 basal cells along with the vertical colums of cells above (up to the skins's surface) epidermis grows in units- not as whole
dermal
epidermal junction; the union between the eidermis and the dermis; a basement membrane
functions of the epidermal junction
tightly "glues" the epidermis to the dermis; provides support for the epidermis; serves as a partial barrier between the epidermis and the dermis
dermis
inner, thicker layer of skin; tissue type: connective tissue called the "true skin" (thicker and gives strength to skin)
structures present in the dermis
sensory receptors, muscle fibers, hair follicles, sweat & sebacous glands, blood vessels
sensory receptors
specialized nerve endgins for hot, cold, pressure, pain, and touch (skin functions as a sene organ)
muscle fibers
two types skeletal and smooth
skeletal muscle fiber
located only in the dermis of the face ans scalp, function: voluntary movement of the face and scalp
smooth muscle fiber
arrector pili muscles, attached to hair follicule, the most abundant of the 2 types of muscle fibers; produces "goose bumps"
hair follicles
tubes that hold hairs
sweat, sebaceous glands
produce oil, skin glands
blood vessels
the derms contains an extensive network of blood vessels that play an important role in regulation of body temperature
layers of the dermis
papillary layer and reticular layer
papillary layer
(dermal papillae/fingerprings) thin superficial layer of the dermis; folded--> folds know as dermal papillae forms fingerprints (thick skin); composed of areolar connective tissue and derives its name from the projections of the dermis called dermal papillae; contains the capillaries that supply nutrients to the cells of the epidermis
reticular layer
the deeper, major portion of the dermis that extends from the papillary layer to the underlying subutaneous layer(langer's lines/cleavage lines) inner, thicker layers of dermis; contains many protein fibers; contains many protein fibers (collagenous and elastic) made up of moslty dense irregular connective tissue
collagenous fibers
most of the fibers are this type form langer's/clevage lines (pattern unique to each individual) surgical incisions should be made parallel to langer's lines for better wound healing
elastic fibers
if overstretched and torn, forms stretch marks
subcuatneous layer
(hypodermis; superficial fascia) tissue type: connective tissue (loose areolar and adipose)
skin color primary determinant
amount of melanin produced; primary determinant of skin color is the amount of melanin produces by melanocytes (not hte number of melanocytes)
how melanocytes produce melanin
they convert an amino acit (tyrosine) into melanin (the proces is regulated by an enzyem) they then transfer the melanin to other cells in the epidermis
factors that afffect melanin production
heredity, sunlight, hormones, & age
heredity (DNA)
the most important fator that determine the amount of melanin produced by melanocytes; 4-6 pairs of genes control howmuch melanin melanocytes will produce; however these are several factors that can modifiy the effect of heredity
sunlight
prolonged exposure to sunlight causes melanoctes to increase their production of melanin and skin to darken (a rotective mechanism- melanin protects skin cells from uv light)
hormones
the secretion of certain hormones from the anterior pitutary gland (MSH, ACTH) increases the production of melanin; normally the secretion of these is carefully regulated by genes and negative feedback mechanisms; however, under certain abnormal conditions (diseases) the secretion of these hormones may increase, causing skin to darken
age
increasing age may cause melanocytes to decrese their production of melanin (the converting enzyme becomes less active); responsible for graying hair, blotchy coloring of skin
skin color changes unrelated to melanin production
these changes in skin color tend to be temporary and are best seen in fair-skinned indiviuals: amount of blood flow to skin and amount of oxygen in blood
amount of blood flow to the skin
if some condition causes skin blood vessels to dilate or contract changing the color of the skin ex: excersie
amount of oxygen in the blood
if red blood cells are carryign less oxygen thatn normal (i.e. may ocur in certain respiratory or cardiovascualr diseases) skin may appear bluish in color
melanin
skin pigment produced in response to ultraviolet light exposure
tactile cells
aslo called merkel cells are few in number and foudn scattered among the cells within the stratum baslae, are senstive to touch and when compressed they relesae chemicals that stimualte sensory nerve endings providing information about objects touching the skin
eleidin
an intermediate product in the process of keratin maturation
anucleate
lacking a nucleus
thick skin
found on the palms of the hands, the soles of the feet, and coresponding surfaces of fingers and toes, all five epidermal strata occur here ranges from between 0.4mm to 0.6 mm thick, houses sweat glands but has no hair follicules of sebacous glands
thin skin
covers most of the body, lacks a stratum lucidum only has four layers; conatins hair follicules; sebaceous glands, and sweat glands ranges from 0.075 mm to 0.150mm thick
skin color
normal color results from a combination of the colors of hemoglobin, melanin, and carotene
hemoglobin
an oxygen-binding protein present in red blood cells. exhibits a bright red color upon binding oxygen thus giving blood vessles in teh derms a reddish tint that is seen most easily in lightly pigmented individuals
melanocyte activity
it is not the number of the melanocytes but activity level and the color of the melanin produced by the melanocytes varies among individuals
carotene
a yellow-oragne pigment that is aquired from varoius yellow-orange vegetables, such as carrots, corn and squashes accumulates inside the keratinocytes of the stratum corneum and in the subcutatneous fat, converted into vitamin A
nevus
commonly called a mole is a harmless localized overgrowth of melanin-forming cells on rare occasions can become malignant
freckles
yellowish or brown spots that represent localized areas of increased melanocyte activity
hemangioma
is an anomaly that results in skin discoloration due to blood vessesl that proliferate to form a benign tumor
capillary hemangiomas
strawberry-colored birth-marks, apear in teh skin as bright red to deep purple noduels that are usually present a birth and disapper in childhood
cavernous hemangiomas
also know as port-wine stains, involve larger dremal blood vessels and may last a lifetime
friction ridges
the contours of the skin surface follow ridge patterns varrying from small conical pegs (in the skin) to complex arches, formed from large folds and valleys of both dermis and epidermis, help increase friction on contact four types: arch, whorl, loop, and combination
lines of clevage
(tension lines) identify the predominant orientation of collagen fiber bundles are surgically significant because any procedure resulting in a cut at right angles to these is pulled open as a result of the recoil resulting from cut elastic fibers, resulting in slow healing and slower healing times
collagen fibers
contribute to the observed physical characteristics of the skin, impart tensile strength
elastic fibers
contribute to the observed physical characteristics of the skin, allow some stretch and recoil in teh dermis during normal movement activities
striae
result as the skin stretches and collagen fibers break, also know as stretch marks
innervation
dermis has an extensive network or ___ which is the distribution of nerve fibers
vasoconstriction
the diameter of the vessles narrows so relatively less blood can travel through them, occurs when the body is trying to conserve heat and is the reason we look paler when exposed to cold temperatures
vasodilation
the diameter of teh vessels increases, so relatively more blood can travel through them. occurs to allow more blood to travel to the body surface and excess heat may be lost if the body is too warm. this is why we become flush when excerting ourselves
subcutaneous layer
deep to the integument, also called the hypodermis or superficial fascia: not part of the integument and consists ofboth areolar connective tissue and adipose connective tissue, helps to bind the dermis to the underlying structures, pads and protects the body, acts as an energy reservoir, and provides thermal insulation, thicker in women
subcutaneous fat
when adipose connective tissue dominates in a subcutaneous layer
why are drugs injected into the subcutaneous layer?
because of the extensive vascular network that promotes rapid absorption
epidermal derivatives
appendages of the integument: nails, hair, and exocrine glands, formed during embryologic development as portions of the epidermis invaginated into the dermis
nails
scalelike modifications of the stratum coreneum layerprotect teh distal tips of the digits and prevent damage or extensive ditorition during jumping, kicking, or catching
free edge
the nails distal whitish part
nail body
pinkish part of the nail
nail root
proximal distal part embedded in the skin
nail plate
the nail body, root, and free edge form this part
nail bed
covered by the nail body, covers a layer of epidermis that contains only teh deeper, living cell layers of teh epidermis
nail matrix
thickened part of the nail bed, the activley growing part of teh nail
lunula
whitish semilunar area of the proximal end of the nail boy, has a whitish apperance becaue a thickened stratum basale obscures teh underlying blood vessels
nail folds
overlap the nail along the lateral and proxmial borders, folds of skin
eponychium
cuticle, narrow band of epidermis extending from the margin of the nail wall onto the nail body
hyponychium
is a region of thickened stratum corenum over which the free nail projects
brittle nails
are proen to vertical splillting and separation of the nail plate layers at the free edge. overexposure to water or to certain household chemicals can cause this
ingrown nail
occurs when teh edge of a nail digs into the skin around it, painful condition is first characterized by pain and inflammation at the site, if left untreated can cause infections. caused by overly tight shoes or improper trimming of nails
onychomycosis
a fungal infection that occurs in nails constantly exposed to warmth and mositure, fungus starts to grow under the nail and eventually causes a yellowish discoloration, a thickened nail, and brittle cracked edges. can result in permanent damage to the nail and a potential spread of infection. treatment is taking oral antifungal medications for 6-12 weeks
yellow nail syndrome
occus when growth and thickening of the nail slows or stops completly as the nail growth slows the nails become yellwoish or soemtiems greenish, can sometimes be an outward sign of respiratory disease
spoon nails
koilonychia, a nila malformation where the outer surface of the anils are concave instead of convex. are frequently a sign of iron deficiancy
beau's lines
run horizontally across the nail and indicate a temporary interference with nail growth at the time this portion of nail was formed. injury or illness can cause this can also be a sign of chronic malnutrition
hair
foudn almso everywehre on teh body except palms of the hands and palmar surface of the finders, the sides of teh soles fo the feet and toes, the lips, and portions of the external genitalia
pilus
a single hair, has the shape of a slender filament it is composed of keratinized cells growing from hair follicles that extend deep intot het dermis, often projecting into the underlying subcutanoues layers
lanugo
a fine, unpigmented, downy hair that first appears on the fetus in the last trimester of development.
vellus
the primary human hair adn si foudn on hte upper and lower limbs, is fine and unpigmented to lightly pigmented and replaces lanugo
terminal hair
usually coarser, pigmented, and longer than vellus, grows on the scalp and it is also the hair of teh eyebrows and eyelashes, during puberty replaces vellus hair in the armpits, pubic regions and in men the hair of the beard
what are the three parts of a hair
hair bulb, root and shaft
hair bulb
consists of epithelial cells adn is a swelling at the base where the hair originates in the dermis
hair bulb
surrounded by epithelium at the base of the hair bulb, composed of a small amount of connective tissue containing tiny blood vessels and nerves, living epithelial cells
root
the portion of the hair deep to the skin surface, consist of dead epithelial cell
shaft
portion of the hair that extends beyond the skin surface, consist of dead epithelial cells
hair matrix
a specialized type of keratinization occurs here, part of hair production. it is a structure at teh base of the hair bulb. epithelial cells near its center divide producing new cells that are gradually pushed toward the surface
medulla
not found in all hair types is a remant of the soft core of the matrix is composed of loosely arranged cells and air spaces, and contains flexible soft keratin.
cortex
serveral layers of flattend cells closer to the outer surface of the developing hair form the this relatively hard_____
cuticle
single cell layer around the cortex, coats the hair
hair follicle
an oblique tube that surrounds the hair root, extends into teh dermis and sometimes into the subcutaneous layer
connective tissue root sheath
the outer layer of the follicle wall, originates from the dermis
epithelial tissue root sheath
the innner layer of the follicle wall, originates from the epidermis
arrector pili
thin ribbons of smooth muscle, stimulation of this is usually a result of an emotional state, such as fear or rage, or a sa response to exposure to cold temperatures, produces goose bumps
Functions of hair
protection, heat retention, sensory reception, visual identification, and chemical signal dispersal
protection function of hair
the hair on the head protects the scalp from sunburnand injury, within the nostrils it traps particles before they enter the respiratory tract, protect against particles and insects entering the ear canal, eyelashes protect the eyes and eyebrows prevent sweat on the forehead from entering the eye
heat retention function of hair
hair on the head prevents the loss of conducted heat from the scalp to the surrounding air.
sensory reception function of hair
hair has associated tactile receptors (hair root plexuses) that detect light touch
visual identification function of hair
hair characteristics are important in determining age and sex, and identifying individuals
chemical signal dispersal
hairs help disperse pheromones, which ar echemical signals involved in attracting members of the opposite sex and in sex recognition
hair color
a result of the synthesis of melanin in the matrix adjacent to the hair papillae, variations in this are genetically determiend differences in the structure of melanin. environmental and hormonal factors can also effect this
hair growth
about one-third of a millimeter per day for 2 to 5 years, may attaina lenght of about a meter
hair dormant pahse
3 to 4 months after its growth phase
normal daily hair loss
10-100 strands daily, more than than can indicate a possible health problem or exposur to drugs, dietar factors, radiation, high fever or stress
alopecia
thinning of the hair, can occur in both sexes, usually as a resultof aging
diffuse hair loss
condition where hair is shed from all parts of the scalp, women primariy suffer from this condition which may be due to hormones, medications, or iron deficiency
male pattern baldness
loss of hair form only some regions of the scalp rather han uniformly, typically in men, caused by a combination of genetic and hormonal influences, relevant gene hs two alleles, expressed in the presence of high testosterone levels
skin's two type of glands
sweat (sudoriferous) glands, and sebaceous glands
sweat glands
two types, meocrine and apocrine: have a coiled, tubular, secretory portion that is located in the reticular layer of the dermis; contain myoepithelial cells
sweat gland duct
carries the secretion to the surface of the epidermis (in a meocrine gland) or into a hair follicle (in an apocrine gland)
sweat pore
the opening of the sweat gland duct on the epidermal surface, is an indented region
merocrine sweat glands
are the most numerous and widely dstruitubted seat glands, adult integument contains between 304 million; simple coiled tubular glands tht discharge tier secretions directly onto the surface of the skin; primary function thermoregulation
sweat
clear secretion released by merocrine sweat glands by exocytosis, consisits of approximately 99%water adn 1% other chemicals that include electrolytes
thermoregulation
regulation of body temperature by evaportaion of fluid form teh skin
apocrine sweat glands
are coiled, tubular glands that release thier secretion into hair follicles in the axillae, aroudn the nipples, in the pubic region, and in the anal region; the secretion they produce is viscous and cloudy and it contains both proteins and lipids that are acted upon by bacteria to produce a distinct, noticeable odor, begin workign around puberty
sebaceous glands
holocrien glands that produce sebum
sebum
an oily, waxy secretion, acts as a lubricant to keep the skin and hair from becoming dry, brittle, and cracked, has some bactericidal properties,simulated by puberty
ceruminous glands
modifited apocrein sweat glands located only in the external acoustic meatus (ear canal)
cerumen
secreted by ceruminous glands a waterproof earwax, help trap foreign particles or small insects and keeps them from reachign teh eardrum
mammary glands
modified apocrine sweat glands, both males and females have them but these glands oly become functional in pregnant and lactating femals when they produce milke
epidermis protection function
acts as a physical barrier that protects the entier body from physicla injury and trauma, protects against harmful chemicals, toxins, microbes, and excesive heat or cold, protects deeper layers from UV rays
prevention of water loss
the epidermis is water resistant and helps prevent unnecessary water loss, water cannot easily exit the skin, unless it is specifiically secreted by the sweat glands
Vitamin D3
also called cholecalciferol, is synthesized from a steroid precursor by the keratinocytes whn they are exposed to ultraviolet radioation, released ino the blood and transported to the liver where it is convereted to antoehr intermediate molecule adn then transported to the kidney where it is converetd to calcitriol
calcitriol
is the active form of vitamin D and is considered a hormone it increases the absorption of calcium and phosphate from the small intestine into the blood
acne
term used to describe plugged sebaceoisu ducts, typically becomes abundant beginnign at puberty because increase in hormone levels stimulate sebaceous gland secretion making the pores more prone to blockage
comedo
a sebaceous gland plugged with sebum
blackhead
open comedo because the plugged material has a dark blackish apperane
whitehead
closed comedo called this because the top surface is whitish in color
papule
dome shaped lesions are fluid-filled form red elevations on the skin and do not contain pus
pustule
dome shaped lesions which are filled with a mixture of white blood cells, dead skin cells, and bacteria called pus
nodule
similar to a pustule, but extending into the deeper skin layers and usually rupturing the hair follicle wall, prone to scarring
cyst
a large, fluid-filled nodule that can become severly inflamed and painful and can lead to scarring of the skin
secretion and absorption
skin exhibits a secretory function when it discharges substances from teh body during sweating, which occurs when the bod needs to cool itself off
selectively permeable
some materials are able to pass through it, while others are effectively blocked
transdermal administration
drugs that are soluble eith rin oils or lipid-soluble carries may be administered transdermally by an adhesive patch that keeps the drug in contact with the skin surface. drugs adminstered in this way slowly penetrate the epidermis an can be absorbed into the blood vessels fo th dermis
immune function
small population of immune cells within the stratum spinosum called the epidermal dendritic cells: play an important role in initiating an immune response against pathogens that have penetrated the skin
temperature regulation
influenced by teh vast capillary networks and sweat glands in the dermis
to dissipate heat
the blood vessels in the dermis vasodialate allowing for more flow and helping to release heat, sweat glands release fluid onto the skin's surface, and the body cools off due to evaporation of the sweat
to conserve heat
blood vessels in the dermis vasoconstrict so more blood is shunted to deeper body tissues conserving the warmth from teh blood, the face and exposed skin surfaces become flush
sensory receptors
are located primarily in the dermis (some in the epidermis) and detect heat, cold, touch, pressure, adn vibration has different sensory receptors types to detect, distringuish and interpret these stimuli
regeneration
the replacement of damaged or dead cells with the same cell type, restores organ function
fibrosis
when the damage to the organ is to extensive and the cells are no longer able to divide, the body fills the gap with scar tissue, binds the damaged parts back together, produced by fibroblasts and composed primarily of collagen fibers
step 1 in wound healing
cut blood vessles initiate bleeidn into the wound. The blood brings clotting proteins,numerous leukocytes, and antibodies
step 2 in wound healing
a blood clot forms, temporarily patchign teh edges of the wound together and acting as a barrier to prevent teh entry of pathogetns into the body. Internal to the clot macrophanges and neutrophils clean the wound of cellular debris
step 3 in wound healing
the cut blood vessles regenerate and grow in the wound. A soft mass deep in the wournd becomes granulation tissue; macrophanges within the woudn begin to remove the clotted blodd, fibroblast produce new collagen fibers in teh region
granulation tissue
vascular connective tissue that initially forms in a healing wound
step 4 in wound healing
epithelial regeneration of the epidermis occurs due to division of epithelial cells at the edge of the wound. These new epithelial cells migrate over the wound, creping internally to the now superficial remains of the clot (the scab). The connective tissue is replaced by fibrosis
psoriasis
a chronic autoimmune skin disease that has periods of flare-ups and remission throught a person's lifeteime, T-lymphocyte mistakenly attacks teh kerationocytes causing rapid overgrowth of and overproduction of new skin cells. the normal sloughing off is thrown out of balance and whitish scaly skin patches develop on the skin: can cause itchign pain, and skin cracking and bleeding
burns
a major cause of accidental death and ar usually causd by heat, radiation, harmful chemiclas, sunlight or electrical shock, immediate threat to life results primarily form fluid loss, infection and the effects of burned dead tissue
first degree burns
involve only the epiderms and are characterized by redness, pain, and slight edema. ex: mild sunburn. treatemetn involves immersing the burned area in cool water or applying cool, wet compresses, possibly followed by covering the burn with sterile, nonadhesive bandages healing time 3-5 days
second degree burns
involve the epidermisand part of the dermis. the skin appears red, tan or white. the skin is blistred adn painful. ex: severe sunburns, scalding from hot liquids or chemicals: treatment: immersing the burned area in cool water, or appling cool wet compresses, possibly followed by covering the burn with sterile, non adheavise bandages being careful not to burst the blisters. takes 2-4 weeks to heal
third degree burns
involve teh epidermis, dermis, and subcutanerous layer, which often are destroyed. caused by contact with corrosive chemicals or fire, or prolonged contat with extremely hot water. dehydration is a major concern due to the entire portion of skin has been lsot, adn water cannot be retained in the area. patients are treated with anitbiotics to prevent infection, most require hospitalizatoin, skin grafting
skin graft
is a piece of skin transplanted from one part of the body to anotehr to cover a destroyed area
rule of nines
used to estimate surface area of a burn most major body areas approximatley accoutn for some factor of 9%
adult percentages for burns
head and neck 9%, right upper limb 9%, left upper limb 9%, anterior trunk 18%, posterior trunk 18%, right lower limb 18%, left lower limb 18%, perineum 1%
child percentages for burns
head and neck 18%, righ upper limb 9%, left upper limb 9%, anterior trunk 18%, posterior trunk 18%, right lower limb 14%, left lower limb 14%, perineum 1%
when are burns considered critical
1. over 25% of the body ahs second-degree burns. 2 over 10% of the body ahs third-degree burns 3. third-degree burns are present on the hands, feet, face or perineum
escharotomy
an incision is made in the dermis to lessens the constriction caused by swelling
periderm
at the end of seventh week of development, the ectoderm forms a layer of squamos epithelium that flattens and becomes this layer
vernix caseosa
during the fetal period the perderm is sloughed off and cells mix with sebum secreted by the sebaceous glands, producing this waterproof protective coating, that coats the skin of the fetus
mesenchyme
during the embryonic period the mesoderm becomes this, it begins to form the components of the dermis at about eleven weeks
basal cell carcinoma
most common type of skin cancer, least dangerous type as it seldom metastasizes, orginates in stratum basale, first appears as small, shiny elevation, elevatin enlarges, develops central depression wiht "pearly" edge, usually occurs on the face, treated by surgical removal of lesion
squamous cell carcinoma
arises from kerationocytes of stratum spinosum, lesions usually appear on scalp, ears, lower lip, or dorsum of hand, early lesions are raised, reddend, scaly, later lesion form concave ulcers with elevated edges; may metastasize to othe rparts of the body; treated by early detection and surgical removal of lesion
malignant melanoma
most deadly type of skin cancer due to aggressive growth and metastasis; arises from melanocytes, usually in a preexisting moe; individuals at increased risk include those who have had severe sunburns, especially in childrn; characterized by change in mole diameter, color, shape of border and asymmetry; survival rate improved by early detection and surgical removal of lesion; advanced cases (metastasis of disease) difficult to cure and are treated with chemotherapy, interform therapy, and radiation therapy