Integument

__**Integument**__
Skin consists of two organs: Skin and Appendages of skin. Skin= cutis. Covers entire outer surface, largest organ of body. 16% of our body weight, 2 square meters area. From .5-4mm thick. Typically thicker on dorsal surface.
 * Mucocutaneous junctions**- reddish, lack keratin. Where mucous meets dermis. Appears red because of hemoglobin.

__Composed of two layers: Dermis and Epidermis.__
 * Epidermis-** Stratified squamous keratinized epithelium. Avascular, 5 layers.
 * Dermis:** thickest layer of the skin, consists of dense irregular CT.
 * 1) Papillary layer- superficial, finger like projections (dermal papillae)


 * 1) Reticular Layer- Dense irregular CT, has hair follicles, sebaceous glands, vascular capillaries etc.


 * Hypodermis-** NOT part of the skin. Beneath the dermis, aureolar connective tissue, lots of fat, slides a lot. Subcutaneous Fascia(superficial fascia).

Dimple= place where the dermis of the skin is tightly adhered to an underlying structure, like bone.

__**Skin has 8 functions:**__
 * 1) Mechanical trauma protection- abrasion, bacterial invasion, UV light
 * 2) Maintenance of body fluids- prevent dehydration, waterproof, prevents absorption of harmful substances. Allows excretion of water/ions/urea/ammonia, etc.
 * 3) Maintenance of Body Temperature- Sweat glands/BV allow blood to cool, adipose tissue insulates warmth.
 * 4) Synthesis of Vitamin D- Allows precursors to be exposed to UV light to convert it to another precursor (cholecaciferol).
 * 5) Immunity- Skin contains wandering cells of immune system
 * 6) Reception of Sensory Stimuli- pain, touch, pressure, temperature
 * 7) Organ of Communication- Color and texture of skin tells a lot about internal systems status, and skin can indicate embarassment, etc.
 * 8) Repair- must be able to repair itself.

__**Structure of Epidermis:**__ -Composed of stratified squamous keratinized epidermis. -Avascular, gets nutrients from dermis. 5 Layers:
 * 1) Stratum Basale (Germinativum)- Sits on basement membran, cuboidal and columnar in shape
 * 2) Stratum Spinosum- Several layers of irregularly shaped cells. Spines are diagnostic feature, caused by desmosome attachments that hold when cells shrink.
 * 3) Stratum Granulosum- Narrow layer, 3-5 cells thick. Flattened cells, with disappearing nuclei. Diagnostic feature is the darker staining, due to presence of Keratohyalin granules.
 * 4) Stratum Lucidum- Layer is 2-3 cells thick. Cells and Nuclei NOT visible. Part of stratum corneum.
 * 5) Stratum Corneum- Many layers of dead cells, no visible nuclei. Cells filled with Keratin. Cells sloughing off known as Stratum Disjunctivum, at the external border.
 * 6) Stratum Malphigi (Mal-piggy-eye): Strata basale+ Stratum Spinosum.

__Thick Skin:__ AKA Glabrous skin. -Diagnostic feature is the lack of hair and sebaceous glands. -"Thick" refers only to the thickness of the epidermis (more than a mm thick). Found on palms of hands and soles of feet.

__Thin Skin:__ AKA Hairy Skin (Nonglabrous) -reduced thickness of epidermis. Diagnostic feature is presence of hair and sebaceous glands. -reduced thickness of the stratum corneum, granulosum and spinosum. -Stratum Lucidum is absent. -Found on rest of body that is not glabrous skin (ex. Eyelids).


 * Classification of skin depends on two things: thickness of EPIdermis, and presence/absence of hair and sebaceous glands.

__Cell Types of Epidermis:__** AKA Dendritic Cells. Have no desmosomes attaching to keratinocytes, and can move around. Macrophage/Monocyte system origin. Will present antigens to T-helper cells.
 * 1) Keratinocyte: Principal cell type of the epidermis. They produce keratin. Stratified Squamous Keratinized epithelium, deriving from ectoderm.
 * 2) Melanocytes: Pigmented cells, found in stratum basale, wedged in between keratinocytes. Responsible for skin coloration. Derived from Neural Crest cells.
 * 3) Langerhans Cells: Cell of the immune system, scattered around Stratum Spinosum. Branched stellate cells, extend between keratinocytes.
 * 1) Merkel cells: Innervated by a single nerve axon, acts as a slow adapting-mechanocutaneous receptor, involved with the sensation of light touch. Small, clear, located in stratum basale. Contain dense core vesicles like adrenal medulla cells, but no catchecolamines!

__Keratinocytes__- more detail:
 * 1) Most common cell
 * 2) Function of epidermis is to create a watertight barrier, through a layer of dead, dense cells.
 * 3) Population is continually renewed by cells in the stratum basale, which undergo mitosis and proliferation.
 * 4) Cells will differentiate and mature as they move towards the surface, known as Cytomorphogenesis.
 * 5) From stratum basale to sloughing off is about 4 weeks.
 * 6) Keratin is a fibrous protein, weighing 40-70k kD. The amount of keratin in a cell will increase as the cell migrates towards the surface.
 * 7) Cells are either in Synthesis Phase, or Degeneration Phase.

Stratum Basale: Small bundles of keratin first appear in this layer (10nm diameter intermediate filaments). Numerous desomosomes and hemidesmosomes for attachment to the extracellular matrix. Mitotic figures present, proliferation is main function.

Stratum Spinosum: Lamellar granules first appear in cytoplasm: Membrane bound granules rich in glycolipids. Acts as a waterproof substance between the cells. Associated with a 1-30% increase in intercellular space. Cells begin to die as a result of lack of nutrients to the nucelus. Membrane bound packets of light and dark bands, extruded as the cells approach Stratum Granulosum. Tonofilaments create bundles called Tonofibrils.

Stratum Granulosum: Keratohyalin granules appear. Irregular, dense-staining inclusions, not membrane bound. Tonofilaments may pass through them. Not sure how they are involved in keratinization. Filaggrin is a protein that crosslinks tonofilaments. Involucrin is first produced in stratum spinosum, associated with increased levels of transglutaminase. Creates water impermeable cell membranes, leading to cell death.

Stratum Lucidum: All Keratinocytes in this layer are dead. Cells are full of keratin in various forms: Eliden is a transformed keratohyalin granule.

Stratum Corneum: Consists of flattened squamous cells called Squames. Nuclei are gone, cells all dead. No granules remaining. Note: cells MUST be dead to create the waterproof barrier.

Epidermal Proliferation Unit(EPU): One stem cell in center of unit gives rise to 10-12 basal cells that migrate upward. Move up at the rate of about 1 cell layer per day. Takes 4 weeks to go from Stratum basale to top. -Fibronectin is a glycoprotein molecule that helps regulate the rate of keratinization. Epidermal growth factor also stimulates regulation of growth sites.

Squames are the most efficient packing mechanism of the cells. (They look like packed stacks of to-go boxes).

__Diseases of Epidermis:__ Psoriasis- Unknown causes (likely multifactorial). Due to excess proliferation of keratinocytes. Chronic condition characterized by patches of red-brown area with whitish scales on skin. Cells reach surface after 1 week rather than 4, and surface is not fully keratinized, not waterproofed. Integrity of epidermis compromised,

Eczema: Characterized by edema, exudation, and crusting. Also itching (pruritis). Dermis and Epidermis affected, infiltration and edema with lymphocytes, monocytes and eosinophils. Thought to be immunological in origin.

Phemphigus -Potentially fatal skin disease, autoimmune isease against desmosome proteins in epidermis. Severe blistering and loss of fluids, infections.

Basal Cell Carcinoma: Most common skin cancer Affects keratinocytes Destroys local tissue but does not readily metastasize

Squamous cell Carcinoma: Second most common Can be caused by UV, Xray, Chemical agents, arsenic Readily metastasizes

DMSO: Dimethyl Sulfoxide, a penetrating agent commonly used as an arthritis treatment -Can carry other substances with it when it goes through glycolipids-- like poisons

Skin Color: Comes from Melanocytes. Skin has 3 pigments that are responsible for its color.
 * 1) Melanin is the only pigment produced by the skin (brown).
 * 2) Carotene is an exogenous plant pigment deposited in stratum corneum or adipose cells (yellow)
 * 3) Oxyhemoglobin located in RBCs turn dermis red.

__MELANOCYTES:__ -Only pigment producing cell in epidermis. -Located in Stratum Basale. -AKA "Clear Cell" at the light microscopy level. Lack of desmosomes allows it to shrink and create clear space around it. -Highly branched--dendrites. -Derived from Neural Crest. Skin distribution is constant. Normal skin has 800-1000 melanocytes per square millimeter. Pigmented skin has 2000 melanocytes per square mm. Ratio to epidermal cells 1:4. Pigmented skin is located on face, forehead, nipples, genitals. Racial skin color difference is based on the rate of melanin granules produced, NOT on the number of melanocytes.

__Melanin Epidermal Unit:__ Composed of a melanocyte and associated keratinocytes. Located in stratum basale and spinosum. Melanocytes have tyrosinase, which converts tyrosine to melanin in the vesicles, forming premelanosomes, which arise from golgi. Melanosomes then form by addition of melanin, until Melanin Granules are formed. Melanin granules migrate out to the ends of the branches, where the process is pinched off into the keratinocyte cytoplasm, also known as cytocrine secretion. Once in keratinocyte, melanin granules fuse with lysosomes to form melanosome complex, which forms cap of complexes over nucleus. Dark skin= increased number of melanosomes, longer lasting complexes, and granules in all layers.

Function of Melanin is to protect against UV radiation. Two types:
 * 1) UVA radiation(320nm)- causes increased wrinkling and sagging of skin, also causes increased cancer risk. DOES NOT burn skin; used in most tanning salons.
 * 2) UVB (370nm)- induces inflammation of BV's in dermis. Causes sunburning, most sun screens block this wavelength. Does not cause cancer.

Tanning: Immediate darkening of melanin due to UV exposure, and increased tyrosinase activity after several days of exposure.

Albinism: Lack tyrosinase, but have the same number of melanocytes.

Vitiligo: Depigmentation disorder, genetically inherited defect. Scattered patches of white skin and hair where melanocytes are destroyed. Treatment is hydroquinone treatment to reduce melanin formation in normal areas.

Freckle: Patch of skin with slightly higher melanin granule concentration.

Nevus: Benign localized overgrowth of melanocytes, arising in early life.

Malignant Melanoma: carcinoma of the melanocytes, extremely malignant.


 * Melanin absorbs both UVA and UVB radiation.

DERMIS: -Cornium L (for leather) -Thick layer of connective tissue to which epidermis is attached. Two layers: -thinner of the two layers -located immediately subadjacent to epidermis -Composed of modified AUREOLAR CT -Contains Dermal papillae, finger like projections protruding into epidermis.
 * 1) Papillary Layer:

Epidermal-dermal junction is irregular because of dermal papillae,which interdigitate with the pegs or ridges. Helps prevent side/shearing forces from separating the two layers. Shape is different for thick vs thin skin. Thick Skin: Has interpapillary peg(rete peg) of epidermis, dividing the primary dermal ridge into two secondary ridges. Primary dermal ridges correspond to Epidermal ridge (friction ridges). Thin Skin: simply rounded bumps or mounds of connective tissue, no fingerprints

Cleavage Lines of Langer: predominant direction of the collagen fiber bundles in a region of the body. Cutting along langer line allows minimal scarring and easy healing, Cutting across it causes a wide, gaping wound. Very important for plastic surgery.
 * 1) Reticular Layer- thickest layer of dermis, composed of DENSE IRREGULAR CT, rich in collagen and elastic fibers.

Striae= stretch marks, region where skin was pulled too tight. -Underlying dermis slowly tears, but the epidermis is not broken Gap is repaired with scar tissue--- pregnancy, obesity, weight lifters.

Blood Supply: Deepest is the
 * 1) Subcutaneous Plexus, located in the Subcutaneous fascia.
 * 2) Cutaneous Plexus is located at the dermal-subcutaneous junction.
 * 3) Subpapillary Plexus is located in the papillary layer, has capillary loops running up to dermal papillae.

__Vasculature: Printed handout Notes are incorrect!__ Correct version: In skin, you have A-V shunts(Glomus) that run parallel to the capillaries-- a coil of small vessels running from arteriole to venuole. When partially closed, blood will run up near the surface. In high temperatures, partial dilation occurs so blood can reach the surface and release heat. Cold temperatures cause sympathetic innervation that clamps down on AV shunts so the blood cannot reach the surface. Apical skin: Covers ears, nose, etc. Process above occurs. In Non-Apical skin, there are no A-V shunts. Sympathetic Nervous System causes release of norepinephrine, which prevents blood from reaching surface. In warm temperatures, acetylcholine release causes vasodilation.

__Clinical Application:__
 * 1) Decubitus Ulcers (Bedsores) - caused by compromised circulation in an area of the skin.
 * 2) Contusion (Bruise)
 * 3) Erythema-Redness of the skin due to engorged capillaries.
 * 4) Capillary Hemangioma- Birthmarks. Benign vascular tumor of dermal capillaries appearing soon after birth (strawberry birth mark, port wine stain), can be treated with lasers.

__Skin Appendages:__ __Hair: (Pili)__ -A hard, keratinized epithelial fiber protruding from the skin. Hair shaft is composed of keratinocytes, a shaft of cells anchored in hair follicle. Runs through dermis down to hypodermis, at an oblique angle. -Surrounded by a connective tissue sheath called Dermal Sheath.
 * External Root Sheath continuous with Stratum Basale and Stratum Spinosum
 * Internal Root Sheath extends about halfway up follice and comes from the root of the hair. It is derived from the outside region of the matrix as the cells move upwards. This layer contains soft keratin, and disappears halfway up near opening of sebaceous gland duct.
 * Three main portions:
 * 1) Hair Shaft
 * 2) Root of Hair
 * 3) Bulb of Hair- enlargement at the end of the follicle, contains dermal papillae of the hair (NOT the same as normal dermal papillae)

Matrix or Germativum zone: where proliferation of keratinocytes occurs at the base of the follicle. Keratogenous Zone: Where cells become fully keratinized. Hard keratin is formed in hair, not soft keratin. Hard keratin has more sulfur (more crosslinks).

Hair Shaft has three layers:
 * 1) Cuticle of hair- outside of hair shaft
 * 2) Cortex- Makes up bulk of shaft
 * 3) Medulla- Located in center, difficult to find. Made of soft keratin.

Matrix contains melanocytes, that produce pigments responsible for hair color. -Pheomelanin: Yellow, develops from tryptophan -Eumelanin: Black or brown, develops from tyrosine -Gray hair- lack tyrosinase in melanocytes -White Hair- tyrosinase lacking but now air pockets in hair which reflect white light.