Integumentary system

Question 1

Skin

Answer 1

Skin

• largest single organ of the body (15%-20% of the total body weight)
• integument or cutaneous layer
• elastic & can expand rapidly to cover swollen areas
• self-renewing throughout life
• composed of:
  
  • ​epidermis- epithelial layer of ectodermal origin
  • dermis- layer of mesodermal CT
• ​​subcutaneous tissue(hypodermis)- not part of skin
  
  • beneath the dermis
  • loose CT usually containing pads of adipocytes
  • binds the skin loosely to the underlying tissue
  • superficial fascia of gross anatomy
• dermal-epidermal interdigitations:
  
  • peg-and-socket
  • well-formed ridges & grooves in thick skin of palms & soles
  • dermatoglyphs
    
    • fingerprints & footprints
    • loops, arches, & whorls that form distinctive pattern unique for each individual
• dermal papillae- projections at the irregular junction between dermis & epidermis
• epidermal ridges- invaginations that interdigitate at dermal papillae to strengthen adhesion of 2 layers
• epidermal derivatives: hairs, nails, sebaceous, sweat glands
• functions:
  
  1. Protective
     
     • physical barrier against thermal & mechanical insults such as friction & potential pathogen
     • microorganisms that penetrate skin alert lymphocytes & antigen-presenting cells in skin to mount immune response
     • melanin- dark pigment that protects skin from UV rays
     • permeability barrier against excessive loss of water
     • selective permeability allows lipophilic drugs to be administered via skin patches
  2. Sensory
     
     • allows skin to constantly monitor the environment
     • mechanoreceptors help regulate body’s interaction with physical objects
  3. Thermoregulatory
     
     • insulating components (fatty layers & hair on head)
     • accelerating heat loss (sweat production & dense superficial microvasculature)
  4. Metabolic
     
     • synthesize vitamin D3 for calcium metabolism & proper bone formation through UV light on vitamin’s precursor
     • excess electrolytes can beremoved in sweat & subcutaneous layer stores significant amount of energy in form of fat
  5. Sexual signaling
     
     • pigmentation & hair (visual indicator of health involved in attraction between sexes)
     • effects of sex pheromones produced by apocrine sweat glands

Question 2

Epidermis

Answer 2

Epidermis

• Keratinized stratified squamous epithelium composed of keratinocytes
  
  • lacks microvasculature
  • receives nutrients & O2 by diffusion from the dermis
• renewal about every 15-30 days depending on age, region of the body, & other factors
• 3 less abundant cell types
  
  1. Melanocytes- pigment producing
  2. Langerhan cells- antigen-presenting
  3. Merkel cells- tactile epithelial cells
• thick skin- found on palms and soles (400-1400um or 1.5 mm thick epidermis + dermis)
• thin skin- found elsewhere in the body (75-150um thick epidermis + dermis)
• 4 layers of keratinocytes (from dermis) -> 5 layers for thick skin:
  
  1. Basal layer (stratum basale)
  2. Spinous layer (stratum spinosum)
  3. Granular layer (stratum granulosum)
  4. Stratum Lucidum- found only in thick skin
  5. Stratum Corneum

Question 3

Layers of Keratinocytes in Epidermis

Answer 3

Come Let’s Get Sun Burned (from the top)

Basal Layer (Stratum Basale) -burned:)

• single layer of basophilic cuboidal or columnar cells on the basement membrane at the dermal-epidermal junction
• Hemidesmosomes in basal membrane join cells to basal lamina
• Desmosomes bind cells in cell’s lateral & upper surfaces
• characterized by intense mitotic activity & contains progenitor cells for all epidermal layers
  
  • progenitor cells are also found in hair follicle sheaths that are continuous with the epidermis
• cytoskeletal keratin
  
  • important feature for all keratinocytes in stratum basale
  • intermediated filaments
  • cells move during differentiation-> amount and types of keratin filaments increase until they represent half the total protein in the superficial keratinocytes

Spinous Layer (Stratum Spinosum) Sun:)

• thickest layer especially in the epidermal ridges
• consists of polyhedral cells having central nuclei with nucleoli & cytoplasm actively synthesizing keratins
• stratum germinativum
  
  • layer of dividing cells above the basal layer
  • keratin filaments assemble here into bundles called tonofibrils
    
    • tonofibrils converge & terminate at the numerous desmosomes
• thick skin has thicker stratum spinosum with more tonofibrils & desmosomes

Granular Layer (Stratum Granulosum) Get:)

• 3-5 layers of flattened cells undergoing terminal differentiation (keratinization)
• cytoplasm filled with intensely basophilic masses (keratohyaline granules)
  
  • keratohyaline granules are dense non-membrane bound masses of filaggrin (linking keratins of tonofibrils further into large cytoplasmic structures)
• Golgi-derived lamellar granules
  
  • characteristic feature in cells of the granular layer
  • small ovoid structures with many lamellae continuing lipids & glycolipids
  • undergo exocytosis producing a lipid-rich impermeable layer around the cells (f_orm a major part of the skin’s barrier against water loss_)

Stratum Lucidum Let’s:)

• found only in thick skin
• consists of thin translucent layer of flattened eosinophilic keratinocytes held together by desmosomes
• nucleus or organelles have been lost
• cytoplasm consists most exclusively of pascked keratin filaments embedded in an electron-dense matrix

Stratum Corneum Come:)

• 15-20 layers of keratinized squamous cells filled with filamentous keratins
• keratin filaments contain at least 6 different polypeptides
• squames or cornified cells- fully keratinized or cornified cells shed at the epidermal surface as the desmosomes & lipid-rich cell envelopes break down

Question 4

Friction blisters

Answer 4

Friction blisters

• lymph-filled spaces created between the epidermis & dermis of thick skin by excessive rubbing (example: ill-fitting shoes) - naluthan :)
• corn and calluses (protective thickening and hardening of the outer cornified epidermal layers) develop if rubbing continues

Question 5

Basal cell CA & Squamous cell CA

Answer 5

Basal cell CA & Squamous cell CA

• skin CA derive from cells of the basal and spinous layers
• rarely lethal as early diagnosis & excision is possible
• increased incidence in fair-skinned individuals exposed to high solar radiation

Question 6

Psoriasis

Answer 6

Psoriasis

• chronic skin condition in which keratinocytes are typically produced & differentiate at accelerated rates
• causing slight thickening of epidermal layer & increased keratinization & desquamation
• caused by overactive T-lymphocytes that trigger autoimmune reaction on the skin
• symptoms: inflammation, redness, irritation, itching & scaling with a defective skin barrier

Question 7

Melanocyte

Answer 7

Melanocytes

• specialized cells of the epidermis found among the cells of the basal layer & in hair follicles
• Phelomelanin- similar pigment found in red hair
• several factors that influence skin color
  
  • melanin
  • carotene
  • # of blood vessels in dermis
• Eumelanin- brown or black pigment produced by the melanocytes
• neural crest derivatives that migrate into the embryonic epidermis’ stratum basale (1 melanocyte accumulation for every 5-6 basal keratinocytes)
• pale-staining rounded cell bodies attached by hemidesmosomes to the basal lamina & lacking attachments to the neigboring keratinocytes
• have processes that donate melonosomes to keratinocytes
  
  • long irregular cytoplasmic extension from each melanocyte cell body penetrates the epidermis running between the cells of the basal & spinous layers & terminating in invaginations of keratinocytes
• numerous small mitochondria, short cisternae of RER, well developed Golgi
• Melanin synthesis: Tyrosinase-> converted by tyrosinase (transmembrane Golgi enzyme) to 3,4 dihydroxyphenylalanine (DOPA)-> transformed into different forms of melanin

Question 8

Melanosomes

Answer 8

Melanosomes

• mature elliptical granules formed from vesicle accumulation of melanin pigment to a matrix of structural proteins
• transported via kinesin to the tips of cytoplasmic extension-> neighboring keratinocytes phagocytose tips of these dendrites to take in the melanosome-> transport them by dynein toward their nuclei
• accumulate in keratinocytes as a supranuclear cap that prior to keratinization absorbs & scatters sunlight protecting DNA of the living cells from the ionizing mutagenic effects of UV radiation
• Epidermal-melanin unit- 1 Melanocyte + Keratinocytes (depending how mamy processes of the 1 Melanocyte to transfer melanosomes)
  
  • Keratinocytes will have more melanosomes than Melanocytes as Melanocytes distribute the melanosomes to neighboring Keratinocytes
  • Keratinocytes are melanin depot
• high need of sun protection= high need of melanin granules
• 2 step processes of skin darkening or tanning:
  
  1. physiochemical reaction darkens preexisting melanin
  2. paracrine factors secreted by keratinocytes experiencing increased UV radiation accelerate melanin synthesis & accumulation in epidermis

Question 9

Albinism

Answer 9

Albinism

• congenital disorder producing skin hypopigmentation due to a defect in tyrosinase or other component of the melanin-producing pathway

Question 10

Vitiligo

Answer 10

Vitiligo

• acquired condition involving skin depigmentation only in affected patches due to loss or decreased activity of melanocytes
• may be environmental, genetic, or autoimmune

Question 11

Langerhans cells

Answer 11

Langerhans cells

• Antigen-presenting cells
• derived from monocytes
• represent 2-8% of cells in epidermis
• most clearly seen in Stratum Spinosum
• cytoplasmic processes extend from these dendritic cells between keratinocytes of all the layers
• bind, process, & present antigen to T-lymphocytes in the same manner as immune dendritic cells in other organs (comprise a major component of the skin’s adaptive immunity)

Question 12

Merkel cells

Answer 12

Merkel cells

• epithelial tactile cells
• sensitive mechanoreceptors essential for light touch sensation
• joined by desmosomes to keratinocytes of the basal epidermal layer
• abundant in highly senstive skin like in fingertips and bases of hair follicles
• originate from the same stem cells as keratinocytes
• characterized by small golgi-derived dense core neurosecretory granules containing peptides near the basolateral cell membrane-> direct contact with the expanded disc-like ending of an unmyelinated sensory fibers

Question 13

Merkel cell CA

Answer 13

Merkel cell CA

• 40X less common than malignant melanoma but has 2X the mortality

Question 14

Dermis

Answer 14

Dermis

• layer of CT that supports the epidermis & binds it to the subcutaneous tissue
• thickness varies with the region of the body (max 4mm on back)
• surface is very irregular & has many projections (dermal papillae) that interdigitate with projections (epidermal pegs or ridges) of the epidermis
• basement membrane occurs between stratum basale & dermis (nutrient diffuses from dermal vasculature-> basement membrane->avascular epidermis)
• tattoo is injected at dermis where bleeding is the proof
• Autonomic effector nerves to dermal sweat glands & smooth muscle fibers in the skin of some areas (Sympathetic ganglion)
• 2 sublayer & indistinct boundaries- both contains rich network of bood & lymphatic vessels:
  
  • nutritive function (plexus)
  • thermoregulatory function (arteriovenous anastomoses or shunts- located between plexuses)
  1. thin Papillary layer
     
     • includes dermal papillae
     • consists for Loose CT with type I & III collagen fibers, fibroblasts, scattered mast cells, dendritic cells, leukocytes
     • anchoring fibrils of type VII collagen insert into a basal lamina helping to bind the dermis to the epidermis
     • one of sensory afferent fibers form a network here
  2. underlying Reticular layer
     
     • much thicker
     • consists of dense irregular CT (mainly bundles of type I collagen)
     • more fibers and fewer cells than papillary layer
     • elastic fibers are also presnet providing elasticity to the skin
     • proteoglycans rich in dermatan sulfate are abundant between collagen and elastic fibers

Question 15

2 Plexuses in dermal layer

Answer 15

Lymphatic vessels begin in dermal papillae & converge to form 2 plexuses:

1. Subpapillary plexuses

• lies between papillary and reticular layers
• capillary branches extend into dermal papillae & form a rich nutritive capillary network just below the epidermis

2. Deep plexus & larger blood & lymphatic vessels
   * lies near the interface of the deris & subcutaneous layer

Question 16

Bullous pemphigoid & Pemphigus vulgaris

Answer 16

Bullous pemphigoid

• blistering disorder d/t abnormalities of dermal-epidermal junction
• (bull sitting :)

Pemphigus vulgaris

• blistering disorder caused by autoimmune damage to intercellular junctions between keratinocytes
• occurs in Stratum Spinosum (presence of desmosomes)

Question 17

Subcutaneous Tissue

Answer 17

Subcutaneous tissue

• consists of Loose CT that binds the skin loosely to the subjacent organs making it possible for the skin to slide over them
• also called hypodermis or superficial fascia
• contains adipocytes that vary in number in different body regions
• extensive vascular supply at this layer promotes rapid uptake of insulin or drug injected into this tissue

Question 18

Sensory Receptors

Answer 18

UNencapsulated Receptors:

1. Merkel cells
   
   • expanded nerve endings
   • tonic receptors for sustained light touch & for sensing an object’s texture
2. Free nerve endings
   
   • in papillary dermis & extending into lower epidermal layer
   • respond to high & low temperatures, pain, & itching
   • also function as tactile receptors
3. Root hair plexus
   
   • web of sensory fibers surrounding the bases of hair follicles in the reticular dermis
   • detect movements of hairs

Encapsulated Receptors (phasic mechanoreceptors responding rapidly to stimuli on the skin):

1. Meissner corpuscle
   
   • elliptical structures
   • consisting of sensory axons winding among flattened Schwann cells arranged perpendicular to the epidermis in the dermal papillae
   • initiate impulse when light touch or low frequency stimuli against skin temporarily deform their shape
   • numerous in fingertips, palms, soles but decline slowly after puberty
   • also detected in scleroderma & other CT disroders that lead to sclerosis (hardening of dermis & tightening of skin)
   • density can be determined approximately by two-point discrimination test
   • can be IDd in H&E
2. Lamellated (Pacinian) corpuscle
   
   • large oval structure with an outer capsule & concentric lamellae of flattened Schwann cells & collagen surrounding a highly branched unmeylinated axon
   • onion-shaped
   • found deep in reticular dermis & hypodermis
   • specialized for sensory coarse touch, pressure (sustained touch) & vibrations with distortion of the capsule amplifying a mechanical stimulus to the axonal core where an impulse is initiated
   • found in CT of organs located deep in the body including wall of rectum & urinary bladder (sensation of pressure)
3. Krause end bulbs
   
   • simpler encapsulated ovoid structures with extremely thin collagenous capsules penetrated by a sensory fiber
   • found in skin of penis, clitoris (sense low frequency vibrations)
4. Ruffini corpuscles
   
   • collagenous fusiform capsules anchored firmly to the surrounding CT with sensory axons stimulated by stretch (tension) or twisting (torgue) in the skin
   • can’t ID in slide

Question 19

Hair

Answer 19

Hair

• elongated keratinized structures that form within epidermal invaginations (hair follicles)
• no hair on skin of palms, soles, lips, glans penis, clitoris, labia minora
• Hair bulb
  
  • terminal dilations of a growing hair follicle
  • dermal papillae inserts into the base of the hair bulb & contains a capillary network required to sustain the hair follicles
  • keratinocytes continuous with basal epidermis covers the dermal papilla ( form the matrix of elongating hair root)
  • similar to those in basal & spinous layers of epidermis
  • undergo keratinization, melanin accumulation, & terminal differentiation
  • keratin of hair is harder and more compact that that of the stratum corneum maintaining its structure at the hair shaft much longer
• Hair shaft
  
  • part of hair extending beyond the skin surface
• Central medulla of hair root
  
  • formed by large vacuolated & moderately keratinized cells in most thick hairs
• Cortex around the medulla
  
  • made up of heavily keratinized densely packed cells
• Cuticle
  
  • thin layer of heavily keratinized squamous cells covering the cortex
• 2 layers of epithelial root sheath (can see keratinocytes)
  
  1. internal root sheath- completely surrounds the initial part of the hair root but degenerates above the level of tge attached sebaceous glands
  2. external root sheath- covers the internal sheath & extends all the way to the epidermis continuous with the basal & spinous layers
• Glassy membrane
  
  • thickened basement membrane of acellular hyaline layer that separates the hair follicle from the dermis
  • composed of collagen
• Arrector pili muscle
  
  • small bundle of smooth muscle fibers
  • extends from the midpoint of the fibrous sheath to the dermal papillary layer
  • contraction pulls hair to a more erect position usually when cold to trap layer of warm air near the skin
    
    • for fine hair-> contraction is seen to produce timy bumps on surface (goosebumps)

Question 20

3 major phases of hair growth cycle

Answer 20

3 major phases of hair growth cycle:

1. Anagen

• long period of mitotic activity & growth
• epidermis stem cells located in small bulges of the external root sheath near the arrector pili muscle produce progenitor cells for new hair bulb
• hair growth on face & pubis is strongly influenced by androgen & begins at puberty

2. Catagen
   * brief period of arrested growth & regression of hair bulb
3. Telogen

• final long period of inactivity
• hair may be shed

Question 21

Alopecia or Baldess and effects of Chemotherapy in hair

Answer 21

Alopecia or Baldness

• loss of hair
• genetic & hormonal factors

Chemotherapy

• arrests mitotic activity in the hair matrix

Question 22

Nails

Answer 22

Nails

• hard plates of keratin on the dorsal surface of each distal phalanx
• Nail root
  
  • proximal part of the nail
  • covered by a fold of skin from which the epidermal stratus corneum extends as the cuticle or eponychium
• Nail plate
  
  • bound to a bed of epidermis (nail bed which contains only basal & spinous epidermal layers)
  • useful window on amount of O2 in blood in dermal vessels
• Nail matrix
  
  • formed from the nail root in which cells divide more distally & become keratinized
  • process similar to hair fomation but without keratohyaline granules
  • continuous growth pushes the nail plate forward over the nail bed
    
    • rate of 3mm/mo for fingernails
    • rate of 1mm/mo for toenails
• Hyponychium
  
  • distal end of the plate that free of nail bed at the epidermal fold

Question 23

Sebaceous glands

Answer 23

Sebaceous glands

• embedded in the dermal over most of the body except in the skin of palms and soles
• Simple branched acinar exocrine gland
  
  • acini converging a short duct & empties into the upper portion of a hair follicle
  • acini of sebaceous gland is an example of holocrine secretion
  • secretion increase greatly at puberty stimulated by testosterone, ovarian, & adrenal androgens
  • acini is basal layer of flattened epithelial cells in the basal lamina-> proliferate & are displaced centrally undergoing terminal differentiation as large lipid sebocytes (filled with small fat droplets)
    
    • sebocytes nuclei shrink & undergo autophagy along with other organelles & the cells disintegrate releasing sebum near the duct
      
      • sebum- complex mixture of lipids that includes wax esters, squalene, cholesterol & triglycerides
      • hydrolyzed by bacterial enzymes after secretion
      • helps maintain stratum corneum & hair shafts
      • exerts weak antibacterial & antifungal properties
• pilosebaceous unit-> hair follicle & its associated sebaceous gland
• hairless regions such as penis, clitoris, eyelids, & nipples-> sebaceous ducts open directly into the epidermal surface

Question 24

Acne Vulgaris

Answer 24

Acne Vulgaris

• inflammatory disorder of the philosebaceous unit
• occurring during adolescence
• excessive keratinization & excess sebum production-> blocks follicular ducts
• Propionibacterium acnes- grow in accumulated sebum leading to localized inflammation & neutrophil infiltration
• comedone- enlarged follicle

Question 25

Sweat glands

Answer 25

Sweat glands

• develop as long epidermal invaginations embedded in the dermis
• 2 types (both Merocrine secretion through exocytosis from secretory cells):
  
  1. Eccrine sweat glands
     
     • widely distributed in the skin & most numerous on foot soles
     • innervated by cholinergic fibers (ACh parasympathetic)
     • auxiliary excretory organ eliminating small amounts of nitrogenous wastes & excess salts
     • sweating
       
       • physiologic response to increased body temperature during physical exercise or thermal stress
       • most effective means of temperature regulation
     • both secretory components and ducts are coiled & have small lumens
     • secretory components are/does/have:
       
       • pale-staining than ducts
       • consist of stratified cuboidal epithelium
       • 3 cell types:
         
         1. Clear cells
            
            • pale-staining
            • located in the basal lamina
            • produces the sweat
            • abundant mitochondria & microvilli (provide large surface area)
            • interstitial fluid is transported through clear cells
         2. Dark cells
            
            • filled with strongly eosinophilic granules
            • line most of the lumen
            • do not contract the basal lamina
            • granules undergo merocrine secretion
         3. Myeloepithelial cells- on basal lamina contract to move the watery secretion unto the duct
     • Ducts:
       • have 2 layers of more acidophilic cells filled with mitochondria & having cell membranes rich in Na+, K+-ATPase
       • duct cells absorb Na+ ions from secreted water to prevent excessive electrolyte loss
       • At epidermis, each duct merges with stratum basale & sweat flow continues in a spiraling channel to excretory sweat pore which sweat quickly evaporates cooling the skin and blood
  2. Apocrine sweat glands
     
     • confined to skin of axillary & perineal regions
     • development depends on sex hormones & completed after puberty
     • secretory components have much larger lumens than those of eccrine glands
     • Simple cuboidal eosinphilic cells with numerous secretory granules that undergoes exocytosis
     • ducts usually open into hair follicles at the epidermis & contains protein-rich product
     • viscous secretion is initially odorless but acquire a distinctive odor as a results of bacterial activity
     • involved in production of pheromones
     • innvervated by adrenergic nerve endings (NE sympathetic)
     • misnomer d/t merocrine secretion

Question 26

Skin repair

Answer 26

Skin repair

• cutaneous wound healing (surgically or accidentally)
• 1st phase
  
  • events of inflammation
    
    • Blood from cut vessesl coagulates in the wound
    • Releases polypeptide growth factors & chemokines from disintegrating platelets
    • Neutrophils & macrophages undergo diapedesis locally & remove bacteria & debris from wound
  • epithelialization
    
    • cells of epidermal basal layer remove their desmosomes & hemidesmosomes & migrate laterally beneath the blood clot (facilitated by matrix metalloproteinases & other proteases)
• 2nd phase
  
  • Proliferating fibroblasts & newly sprouted capillaries produce new collagen-rich well vascularized tissue in the dermis (granulation tissue)-> gradually replaces blood clot
• Final phase
  
  • epidermis reestablish continuity but has lost the ability to form new hairs or glands
  • Remodeling by the granulation tissue & a normal vasculature is reestablished
  • Scar tissue (disorganized abundance of collagen bundles & fibroblast) at wound site