Histology of Integumentary System

2 organs: Skin + appendages (derived from epidermis = hair, glands, nails).

Skin = “cutis” covers entire outer surface. Largest organ, 16% body weight, 1.5-2 m^2.

Thickness = .5 mm-4mm. Thickest on dorsal surface. Thickest skin is between shoulder blades.

Mucocutanous junction: where skin meets mucus membranes. Reddish, lacks keratin. See red blood cells in underlying capillaries.

Skin Layers:

Epidermis = stratified squamous keratinized epithelium. Derived from Ectoderm. Is avascular. Has 5 well defined layers.
Dermis = corneum (tough, leatherlike). Thickest layer of skin. Dense irregular connective tissue. Derived from the mesenchyme. Vascular, supplies nutrients. Will supply epidermis via diffusion. Has 2 layers.
- Papillary layer- immediately under epidermis, thinner layer. Has finger like processes (dermal papillae) that stick up into epidermis
- Reticular layer- deeper layer, thicker layer. Contains glands, hair follicles etc.
Hypodermis = not a part of the skin, this lies underneath the skin. Consists of areolar connective tissue = loose sliding layer. Is the subcutaneous fascia / superficial fascia. Allows skin to slide / “give”. Mostly white fat. Panniculus adiposus is abdominal fat region.

Dimple: where dermis is tightly attached to the underlying bone or deep fascia (that covers bones / muscles).

Functions of the skin:

Mechanical protection = against mechanical trauma (abrasion), physical protection against bacterial invasion, blocks UV radiation.
Maintenance of Body Fluids = prevents desiccation, prevents absoption of harmful substances, carries out excretion (sweat glands secrete water, ions, urea, ammonia)
Maintains body temperature = evaporation of sweat cools body, blood vessels bring warm blood to surface to radiate heat, adipose tissue acts as an insulator.
Synthesis of Vitamin D = UV rays cause one precursorà liverà kidneyà Vitamin D. Vitamin D stimulates Ca++ and PO uptake from gut.
Immunity = skin has wandering cells of immune system, and some skin cells interact with immune cells.
Reception of sensory stimuli = receptors in skin for pain, touch, temp, pressure, etc.
Organ of communication = detect embarrassment / nervousness. Clinically important = Cyanosis incidates CV problem like heart attack, Jaundice = liver failure, Age is determined by wrinkling of skin, Nerve damage = loss of sensation in dermatome patterns.
Repair = skin repairs itself to prevent loss of multiple functions, forms scars.

Morphology:

Epidermis: 5 layers:

Stratum Basale (germinativum) = sits on basement membrane, is the deepest layer. Cuboidal / columnar type cell single layer. Mitosis of cells occurs here.
Stratum Spinosum = several layers of irregular shaped cells separated by narrow space. Intercellular bridges / spines connect these cells. Spiny appearance is diagnostic characteristicà is caused by desmosome attachment. Gaps form during tissue processing which leads to shrinkage. Desmosomes don’t detach, thus cell membrane is distended to create spines.
Stratum Granulosum = narrow layer, 3-5 cells thick. Squamous cells with gradually disappearing nuclei. Diagnostic = dark staining granules = keratohyalin granules.
Stratum Lucidum = 2-3 cells thick. Nuclei / cells not very visible, considered a part of the stratum Corneum, only difference is at LM level.
Stratum Corneum = numerous layers of cells (3-30+), no visible nuclei, cells are keritinized and dead. Superficial cells that slough off = Stratum Disjunctivum.

Stratum Malphigi = stratum Basale + Stratum Spinosum. = the living portion.

Thick Skin = Glaborous Skin.

Lacks hair and sebaceous glands.
Refers to thickness of epidermis only, not entire thickness of skin with dermis
Only found on the palms and soles of the feet. Many mm thick.
When include dermis in measurement, the upper back is then considered thickest skin.

Thin Skin = Hairy Skin

Has hair and sebaceous glands
Reduced thickness of strata corneum / lucidum (gone) / granulosum (now single layer) / spinosum. Stratum basale remains the same, one layer thick.
Eyelid is the thinnest skin on the body.

Cell types in epidermis: keratinocytes, melanocytes, langerhans cells, merkel cells.

Keratinocytes = principle cell type of epidermis, produces keratin, derived from ectoderm
Melanocytes = pigmented cells, gives part of color, only in stratum Basale, derived from Neural Crest Cells.
Langerhans cells = cells of immune system, scattered in stratum spinosum. Are branched / stellate shaped = dendritic cell with branches that run between keratinocytes. Clear cells, no desmosomes to attach it, it can move freely. Monocyte / MAC origin, presents antigens to T helper cells during hypersensitivity reactions such as contact dermatitis.
Merkel Cells = small clear cell in stratum Basale that contain dense core vesicles (not chatecholamines like adrenal medulla). Each is innervated by single nerve axon. Slow adapting cutaneous mechanoreceptor responsible for light touch.

Keratinocytes:

Produce keratin that remains in cell. Will create a protective, water proof barrier.
Produces layers of dense / dead cells that prevent passage of substances.
Continuing renewal of cell population.
Stratum basale undergoes mitosis / proliferationà cells undergo differentiation and maturation as they migrate up and accumulate keratinà process = Cytomorphosis.
Process is 3-4 weeks from bottom to top.
Keratin = fibrous protein, accumulates as cell moves upward. Cells are in either synthesis or degenerative phase of cytomorphosis (can see progress through cytology)
In Stratum basale = function is proliferation, see mitotic figures. Small amounts of keratin here. Have demosomes / hemidesmosomes.

In stratum Spinosum = More keratin fills cytoplasm. Keratin = tonofilaments (cytokeratin). Keratin is an intermediate filament. Tonofibrils are bundles of tonofilaments. See lamellar granules appear (membrane bound granules with glycolipids). Nuclei are still present.

Stratum Granulosum = have karatohyalin granules appear = dark irregular shaped, non membrane bound. Somehow involved in keritinization. Filaggrin = protein that crosslinks tonofilaments to form tonofibrils. Transglutaminase = causes cross linking of involucrin onto cell membrane→ makes membrane thicker, thus lowers diffusion rate.
Lamellar granules secrete glycolipids into extracellular space between cells→increases amount of space between cells→causes hydrophobic ECM to prevent water passage thus decreasing nutrient passage. End result is to kill cells→ nuclei disappear. Needed for waterproof barrier.
Stratum Lucidum and Corneum = keratinocytes are dead / lack nuclei→are now bags of keratin called Squames.

Epidermal Proliferation Unit:

One stem cell of keratinocytes + all of its progeny.
One stem cell will give rise to 10-12 basal cells which move laterally and proliferate again→ moves up about one cell per day, thus it takes 4 weeks for full migration.
Fibronectin in Basment Membrane lamina densa is a glycoprotein that regulates the rate of keratinization. More fibronectin causes more keratinization.
Epidermal Growth Factor stimulates proliferation.

Diseases of epidermis:

Psoriasis: Chronic = characterized by reddish patches with white scales. Unknown cause, probably multifactoral. Due to excess proliferation of keratinocytes. Takes 1 week to migrate to surface rather than 4 weeks. Thus, epidermis is not mature, waterproof barrier is not formed so integrity of epidermis is compromised.
Eczema: Common skin disorder of epidermis. Edema, excudation, crusting, severe itching. Dermis is also affected = edema, infiltration of lymphocytes / eosinophils. Thought to be immunological in origin.
Phemphigus: Potentially fatal disease, autoimmune against demosome proteins→ blistering / loss of fluids / infections.
Basal Cell Carcinoma: Most common skin cancer. Arises from keratinocytes in basale layer→ destroy local tissues, not metastasize readily.
Squamous cell Carcinoma: 2^nd most common. Causes = UV and X rays, chemical agents, arsenic, soot. Readily metastasizes.
DMSO: Dimethyl sulfoxide→ penetrating agent for Arthritis. Potentially can carry other substances (including poisons) into skin. Increases permeability of skin.

Skin color and Melanocytes: 3 pigments responsible for skin color

Melanin – Only one produced by skin, brown color
Carotene– Exogenous plant pigment, Desposted in stratum Corneum and adipose tissue.
Oxyhemaglobin– Located in RBC’s in capillaries of dermis (red)

Melanocytes: only pigment producing cell.

Located in Stratum Basale, is a clear cell. No desmosomesà shinks to small blob with space around it.
High branched, derived from neural crest cells. 10% of the epidermal cells are melanocytes.
In pigmented skin = ¼ of cells are melanocytesà located on face, forehead, areolae, genital skin.
All races have the same # of melanocytes, difference in color is due to rate and number of melanin granules produced.

Melanin Epidermal Unit:

One melanocyte + all associated keratinocytes (all those that have a branch from melanocyte in contact).
Located in St. Basale and Spinosum. Melanocyte contains unique enzyme Tyrosinase within vesicles called Premelanosomes arising from Golgi.
Melanosomes produce more melanin in vesicles
Melanin granules migrate to tips of processesà ends are pinched off into cytoplasm of keratinocytes after tip pierces into keratinocyte. Considered Cytocrine secretion.
Melanin granules fuse with keratinocyte lysosome to form melanin complexà migrate over to top of nucleus to form a “cap”. Complex degenerates slowly.
Dark skinned races produce more melanosomesà longer lasting complexes, see granules in several layers.

Melanin function:

Protects against UV raysà absorbs it to prevent it from penetrating to chromosomes. Decreases skin cancer risk.

UVA rays = 320 nm, short wave. Increased wrinkling, increases cancer risk. Does not burn skin, thus tanning salons use this. Breaks down collagen and elastic fibers.
UVB rays = 370 nm longer wave. Induces inflammation in Blood vessels of dermis, causes sunburn. Blocked by most sunscreen.

Lack melanin in thick skin (referring to palms / soles of feet).

Clinical Applications

Tanning = Due to immediate darkening of melanin with exposure to sun. See increased tyrosinase activity after several days of exposure
Albino = Lack tyrosinase, still same # of melanocytes.
Vitiligo = Depigmentation disorder, genetically inherited. Scattered white patches in hair / skin due to melanocytes being destroyed. Treatment is cosmetic or hydroquione treatment to reduce formation of melanin to match lighter skin.
Freckle = Patch of skin with slightly higher rate of melanin production.
Malignant carcinoma = Very malignant carcinoma of melanocytes

Dermis

Thick layer of CT:

Papillary layer = areolar CT thin layer under dermis. Contains dermal papillae which project into epidermis. Epidermal-Dermal juction = irregular dermal Papillae interdigitates with epidermal pegs. Helps to absorb shear forces. Shape of papilla differs between thick / thin skin.
In thick skin: primary and secondary ridges of papillae project from ridges. Dermal ridges match epidermal / friction ridges (finger prints). Improve grip. Dermatoglyphics = study of finger prints.
Thin Skin: papillae are just rounded bumps.
Reticular layer = thick layer of Dermis, composed of Dense Irregular CT →rich in collagen fibers with network of elastic fibers running in all directions. Each region of body has predominant orientation of collagen bundles = “Langer Lines”. Very important for surgeons. Make incision parallel to Langer line causes smaller scar, thus wound does not gap open. Striae = stretch marks →region of skin pulled too tight and dermis slowly tears, but not epidermis. Repair is the scar. Occur in pregnancy, obesity, weight lifting.

Blood Supply to Skin: 3 plexuses at different levels.

Subcutaneous plexus = down in hypodermis, deepest level. Gives off branches to:
Cutaenous plexus = at junction of dermis / hypodermis→vessels to:
Subpapillary plexus = located in papillary layer, has capillary loops which run up into each dermal papillae.

Plays a key role in temperature regulation. A-V shunts between cutaneous and subpapillary plexuses. In normal temperature → AV shunts slightly open, mostly closed, some blood flows near surface. In Hot temp → AV shunts closed, forces blood to surface to radiate off heat. Cold Temp → AV shunts open, precapillary sphincter closes to conserve heat. Skin is white due to lack of blood near surface.

Decubitus ulcers = bedsores, compromised circulation

Contusion = bruise

Erythema = redness due to engorged capillaries

Capillary hemangioma = benign tumor of dermal capillaries, appears soon after birth = strawberry mark / port wine stain.

Appendages of the skin:

Hair: Pili → hard, keratinous epithelial fiber protruding from skin.

Hair shaft is anchored in hair follicle = tubular invagination of epidermis that extends into hypodermis and is surrounded by dermal sheath of CT.
External root sheath = a continuation of St. Basale and Spinosum, covered by dermal sheath. Made up of keratinocytes in the 2 layers.
Internal root sheath = extends halfway up follicle from root to hair.

Follicle: 3 parts

Hair shaft = part that is above surface
Root of hair = from middle of follicle downward.
Bulb = where root bulges outward. Enlargement at deep end of follicle that contains dermal papillae of hair composed of CT. Serves as nutrient supply for hair follicle.

Matrix / germativum zone = in bulb→site of proliferation of keratinocytes, equivalent to St. Basale. Keratinocytes move upward and differentiate in the Keratogenous zone→in lower root, where cells become fully keratinized.

In hair→hard keratin = more sulfur covalent bonds and more cross links.

Internal root sheath→produces soft keratin such as that in epidermis.

Derived from outside region of the matrix as cells move upwards
Contains soft keratin
This layer disappears half way up follicle near opening of sebaceous gland duct into the follicle.

Hair Shaft: 3 layers

Cuticle of hair = hard keratin
Cortex = hard keratin, bulk of hair
Medulla = few cells with soft keratin

All derived from matrix keratinocytes.

Basement membrane separates the external root sheath from the dermal sheath. Internal root sheath is right adjacent to hair. Stratum malphigi forms the external root sheath.

Hair color: melanocytes in matrix of bulb granules transferred to melanocytesà produce 2 types of melanin.

Pheomelanin = red – yellow, developed from tryptophan
Eumelanin– brown-black, developed from tyrosine

Gray hair comes from loss of tyrosinase.

White hair comes from loss of tyrosinase plus gap formation in follicle which reflects light.

Arrector pili muscle: Smooth muscle, inserts on basement membrane of dermal papilla and dermal sheath at base of follicle, functions to stand hair upright (goosebumps) which is for thermoregulation.

Sebaceous glands: usually at acute angle close to arrector pili.

Oil gland
Empties into upper part of follicle

Hair cycle: does not grow continuously. It is cyclic with 3 phases:

Growth phase →proliferation of matrix, grows at .5 mm per day. Different regions have different length of growth. Terminal hair on scalp has 2-6 year cycle, eyebrow hair has 2-3 month cycle.
Transitional phase→growth stops, hair is in follicle, usually short
Resting phase→hair shaft falls out of follicle and bulb involutes.

All individual hairs are in different phases of cycle.

Glands: 3 kinds

Sebaceous– Acute angle, associated with hair follicle. Simple / branched alveolar gland, secretes oil sebum via holocrine secretion. These get infected with bacteria to give rise to acne. Sex hormones stimulate increases secretions of sebaceous gland causing bulging to allow greater infection.
Eccrine sweat– Sudiferous gland. Most common sweat gland in body, 3-4 million on body. Forehead, palms, sole of foot. Not associated with hair follicles. Are serous secretion, 10 L per day (includes ions, water, urea, NH3, PO). Are simple coiled tubular with serious secretion via merocrine secretion. 3 cell types within gland secretory region. Dark, Clear, myoepithelial cells (help force secretions from secretory portion). Ducts open at top of friction ridges on hands and feet. Function for temp regulation and excretion.
Apocrine sweat– 2^nd type of sudiferous gland. In axillary, mons pubis, areola, circumanal regionsà always with hair follicle, duct empties into hair follicle. Simple coiled tubular, serous secretion via merocrine secretion. Not function till puberty, odor comes from bacteria that invade the gland.

Three other glands of skin:

Meibomian glands = Modified sebaceous glands, inner surface of eyelid, secrete oily substance which prevents evaporation of tears, keeps cornea moist.
Ceruminous glands = Modified apocrine sweat glands, secretes waxy substance, in extermal meatus of ear canal.
Mammary glands = Modified apocrine sweat glands, secrete milk, apocrine / merocrine secretion.

Nails: Composed of keratinocytes with hard keratin, replaces st. corneum.

White crescent at root of nail = lunula, is the distal most extent of nail matrix.

Lateral nail groove = Where lateral edge of nail plate, where ingrown nails occur.

Nail root = Proximal portion where nail begins growth, hidden by skin.

Nail Bed = Beneath nail plate, portion of epidermis, composed of St. Basale / spinosum of epidermis.

Nail Matrix = Where proliferaton of keratinocytes occurs→differentiate via cytomorphosis (keratin builds up)à becomes nail plate. Normal growth is .5mm per week. Fingernails grow faster than toenails. If lose nail matrix, nail wont grow back.

Eponychium = Cuticle of nail, epidermis that hangs over nail plate at root.

Hyponychium = Excess epidermis under free edge of nail.

Sensory receptors:

Receptor is a transducer that turns energy stimulus into an afferent nerve impulse that the brain can interpret. They are afferent nerve endings that are surrounded by associated cells. Classified either

Functionally:

Mechanoreceptor- touch, pressure, stretch
Thermoreceptor – temp changes
Nocireceptor – pain, itch, noxious agents

Morphological receptors = the 6 different receptors based on structure.

Free nerve endings – no associated cells, only the end of a nerve
Encapsulated receptor – free ending has cells that are associated with it

Free nerve ending:

Single nerve ending between keratinocytes, lack schwann cells / myelin, thought to be thermoreceptors or nociceptors.

Merkel cell ending:

In St. Basale
Single nerve fiber forms terminal disc on cell. Mechanoreceptor for light touch

Pacinian corpuscle:

Largest receptor, encapsulated receptor (onion like).
Located in deep dermis / hypodermis, respond to deep pressure / vibration

Meissner’s Corpuscle:

Encapsulated receptor in dermal papillae of papillary layer of thick skin, mechanoreceptor for light touch.

Ruffini corpuscle:

Encapsulated receptor located in deep dermis / hypodermis.
Lie parallel to E-D junction.
Collagen fibers run through surrounding capsule
Mechanoreceptor for tension

Krause end bulb:

Encapsulated, has delicate capsule. Similar to pacinian but without onion shape.
Branching nerve inside located in conjunctiva of eye and oral cavity mucosa.

Skin embryology:

3 weeks into gestationà embryonic skin = single layer of ectoderm cells on layer of mesenchyme. Epidermis comes from ectoderm, dermis is derived from mesenchyme.

4-5 weeksà surface ectoderm proliferates into 2 layer structure = periderm (surface layer) + basal germativum layer (basal layer).

11 weeksà intermediate layer forms between periderm and basal germativum layer. After 21 weeks, periderm stops sloughing and forms the normal St. Corneum (get normal cytomorphosis). Thus, epidermis is formed at 21 weeks.

Periderm secretes amniotic fluid via microvilli on surface. The Vernix Caseosa covers the fetus, consists of soughed off periderm cells and sebum from forming sebaceous glands. Slippery greasy coating. The function is to protect fetus from the amniotic fluid (urine etc.) and gives slippery coat to ease delivery.

Development of skin is based on keratin production by keratinocytes. Differentiation of periderm cells into keratinocytes is based on growth factors and interactions between forming epidermis and dermis.

Epidermal growth factor, keratin growth factor, fibronectin, calcium, retinoic acid.

Genetic disorders: Result of defect in keratinization (usally too much)

Lamellar icthyosis = hyperkeritinization, dry fish-like scales, lack hair and sweat glands. Problems with thermoregulation. Always have fissures / cracks / dehydration. Control temperature.
Harlequin fetus = extreme hyperkeratinization = alligator skin, deeply fissured epidermis, fatal, usually still born.

Epidermal ridges (finger prints) for @ 10 wksà due to interaction between dermis and epidermis, complete by 17 weeks.

6 weeks→ Neural crest cells migrate from Neuroectoderm into dermis and differentiate to become melanocytes.

10-11 weeks = Melanoctyes migrate into epidermis and continue proliferation. Reach peak at third month, then slowly degenerate until reach normal amount for birth.

Langerhans cells = Arise from bone marrow, migrate into epidermis by 4^th week, fully differentiated by 12-14 weeks.

Merkel cells = appear in basal layer by 8 weeks in basal layerà differentiate and hook up with nerve processes later.

Hair development:

Starts at 9-12 week of gestation (starts at head goes to feet). 3 stages:

Stage 1 = 9-12 weeks. Have slight invagination of epidermis into dermis = called Hair Germ.
Stage 2 = Elongation of Hair Germ into Hair Bud. Occurs 13-15 weeks.
Stage 3 = Club shaped Hair Bulb forms. Have matrix present in bulb and dermal papillae form.

Sebaceous and apocrine sweat glands dump into hair follicle, and are outgrowths of it. They are formed during the formation of the follicle.

Apocrine sweat gland – Begins as outgrowth from side of follicle 4 weeks after follicle starts to appear.

Sebaceous gland – starts forming during 16^th week. This is the second gland down, thus it forms second.

The hair shaft first passes through the epidermis at about 18 weeks (still have periderm).

Hair Development stages:

Lanugo hair: the first hair formed during development
Very fine hair, covers entire body by 5-6 months
Falls out and is replaced by Vellus hair = downy hair on body. 65% of adult female body is covered with vellus hair.
Last type of hair formed = terminal hair = coarse hair of scalp , eye brows, pubic hair. Makes up 95% of body hair on male due to testosterone influence.

Hypertrichosis: Excess hairiness due to excess formation of hair follicles during development or persistence of follicles that normally disappear.

Hirsutism: Unusual hairiness of women / children à develop same terminal hair pattern as males due to androgen overproduction or receptor malfunction.

Development of Eccrine sweat glands:

Not associated with hair follicle. Begins at 18-20 weeks when epidermal bud forms elongation down into forming dermisà cord forms coil at end.
The central cells in the cord degenerate to form lumen, the outer cells differentiate into Clear, Dark, and myoepithelial cells by 22 weeks (Clear and Dark are secretory portion).
No more glands are formed after birth.

Nail Formation:

Finger nails start at 10 weeks, toenails at 14 weeks.
Starts on palmer or plantar surface of digità thickened epidermis migrates around to dorsal surface and carries innervation with it.
Primary nail field = epidermis that forms the nail bed. NF flattens on suface and drives a wedge deep into dermisà forms nail matrix that produces the nail plate.
11-12 weeks, nails are delineated by lateral and proximal folds.
14 weeks, nail plate is visible but covered by periderm / epidermis cells that degenerate by birth.
Nail plate reaches end of digit by 32 weeks.
Prematurity is indicated if nail plates don’t reach the ends of the fingers by birth.

Wound healing:

Any break must be rapidly and efficiently repaired. Temporary repair is formed by blood clot.

Next steps are for regeneration of missing parts, for skin- lesions heal in 1-2 weesks.

Two types of wound healing:

Epidermal wound healing: occurs with slight scratches, burns, abrasiona, chemical trauma. Only epidermis is affected and is scraped away to basement membrane.
- Clot formation – platelets embedded in mesh of crosslinked fibrin and fibronectinà matrix (scab) for keratinocytes and MACs to migrate through resevoir of cytokines and growth factors to kick start closure process.
- Activation / proliferation – chemotactic factors released by initial interaction draw neutrophils / monocytes (extravasation occurs). Neutrophils arrive within minutes and produce CKs and growth factors that stimulate proliferation of keratinocytes at wound edges. Proliferation occurs within 24 hours of injury. Growth factors increase 100 x at wound sites within 24 hours.
- Migration – keratinocytes migrate on basement membrane toward center of wound. Occurs through or beneath clot. Diapedesis occurs through clot. Must lose cell junctional complexes and hemidesmosomes with metalloproteases. Plasmin (fibrolytic) produced by keratinocytes works to break through. Integrins changed and upregulated for making focal contact at wound site.
- Maturation – when Kcytes meet in centerà induce contact inhibition to stop migration and proliferation at cell edge. Process shifts to build up thickness of epidermis. Focal attachment integrin and metalloprotease production down regulated. Scab is sloughed off as epidermis is filled in.
Deep wound healing: trauma extends into dermis: 4 steps

- Inflammation – blood clot forms and unites wound edges, vasodilation of capillaries due to histaime release causes influx of neutrophils / MACs that are responding to cytokines and chemotaxic factors via extravasation.
- Proliferative phase – under influence of growth factors, Kcytes and fibroblasts are stimulated to proliferate. In dermis, fibroblasts secrete matrix to form granulation tissue (delicate connective tissue).
- Migratory phase – K cytes and fibroblasts enter blood clot 3 days after injury. Blood vessels follow into granulation tissue. Within 7 days, fibroblasts have entered into clot. Fibroblasts at edge transform into Myofibroblasts which cause contraction of the wound (contain contractile elements).
- Maturation phase – granulation tissue becomes dense irregular CT. epidermis returns to normal thickness, scab released.

Burns: 3 levels of burns

First degree burn: only epidermis is affected, but on part of the thickness, not entire layer. Have redness and mild pain such as a mild sunburn without blisters.
Second degree burn: all the epidermis and upper part of dermis is affected. Have blisters, pain, and edema such as with burn from picking up hot object. Edema causes separation of layers of St. Corneum from Spinosum = blister.
Third degree burn: full thickness of skin affected.

- Destruction of both epidermis and dermis
- Have charred skin
- No pain in the center of the burn, only at the periphery where the pain receptors are still in tact. Have loss of many skin functions.
- Systemic effects are a greater threat to life than local effects:
- Dehydration – water loss and plasma protein loss. Can lead to shock due to loss of blood volume.
- Bacterial infection – barrier function of skin is lost
- Blood circulation is reduced due to loss of fluid, low blood volume reduces urine production and thus renal shut down may cause uremic poisoning.