Day 7: Skin

Question 1

keratinocytes (+ functions)

Answer 1

• arise from embryonic ectoderm
• functions:__​​​​
  
  • epidermal structural integrity + strength
    
    • ​migrating outward from stratum basale, keratinocytes gradually fill with keratin + nucleus degenerates
    • in SG: keratin filaments bundle into tonofilaments (with help of filaggrin, constituent of keratohyalin granules)
    • tonofilaments attach to desmosomes, strengthen cytoskeleton
    • involucrin, loricrin, etc?
  • protecting against abrasion/shearing
    
    • keratinocytes are joined together by desmosomes
      
      • joined to the basal lamina by hemidesmosomes
    • pemphigus: body makes antibodies against desmoglein (protein in desmosomes)
      
      • blisters and skin sloughing
  • protecting against dehydration
    
    • ​produce lipids and lipoproteins (lamellar bodies)
    • released as cells die and fill intercellular spaces
    • insoluble structural proteins like involucrin and loricrin contribute to the waterproof barrier
  • protecting against pathogens
    
    • ​physical barrier
    • produce antimicrobial peptides and proteins
  • synthesis of vitamin D
    
    • ​plasmalemma contains precursor of Vitamin D
    • UV radiation transforms/activates

Question 2

fetal development of skin

Answer 2

• 6 weeks into pregnancy
  
  • 2 layers; periderm & basal layer
• 2nd trimester
  
  • periderm sloughs off, 4 layers of epidermis develop
• stratum basal contains stem cells, but only one cell in ~10 in the basal layer produce daughter stem cells, other cells in this pack can divide, but differentiate into keratinocytes (proliferative unit)
• ​when stem cells divde:
  
  • ​metaphase plate perpendicular to basement membrane:
    
    • ​division results in 2 cells that remain in stratum basale
    • other cell may leave to become keratinocyte–> delamination
  • metaphase plate parallel to basement membrane:
    
    • ​one daughter cell remains in the stratum basale
    • other commits to becoming a keratinocyte in the stratum spinosum
  • during early embryonic develpment, most divisions occurs perpendicular, so daughter cells remain in stratum basale to increase surface are of skin
  • during maturation + skin thickening, more stem cells divide parallel to increase production of cells that differentiate into keratinocytes

Question 3

adult homeostasis

stem cell division in the epidermis

Answer 3

• maintenance of layers
• division parallel and perpendicular to BM
• renewal of the epidermis every 28-40 days

Question 4

Langerhans cells

Answer 4

• occur among keratinocytes in all layers, but are most common in the stratum spinosum
• arise from common myeloid progenitors in BM
  
  • component of mononuclear phagocytic system
• antigen-presenting cells: phagocytose antigens, migrate to lymph nodes, and present the antigen to T-helper lymphocytes
• may also play a role in immune tolerance
• originate from yolk sac/fetal liver

Question 5

melanocytes

Answer 5

• arise from the neural crest of the developing embryo
• protect the integument and underlying tissues against UV radiation
• large cells, cytoplasm appears empty and unpigmented
  
  • their intracellular immature melanosomes (where pigment melanin is stored) do not become dark until they mature and transfer to keratinocytes
  • cytocrine secretion: transfer pigment through tips of their melanosome-containing dendrites that fuse with neighboring keratinocytes
  • melanin granules concentrate near the nucleus, which helps protect the dividing cells from UV damage
• differences in skin color are not due to differences in melanocytes but in the amount of melanin the melanocytes produce.
  
  • dark skinned individuals: more melanin, more melanosomes are larger, and there is an increase in the transfer of melanin from melanocytes to keratinocytes

Question 6

synthesis of melanin

Answer 6

• synthesized from the amino acid tyrosine, which requires the activity of the catalytic enzyme tyrosinase

Question 7

eccrine sweat glands

Answer 7

• simple coiled tubular glands in the dermis
• primary function: regulation of body temperature

Question 8

means of regulating temperature - skin

Answer 8

• sweat glands
• balanced vasodilation and vasoconstriction of networks of small blood vessels in the dermis also regulate body temperature
• skin in the extremities contains arterio-venous anastomoses that modulate the flow of blood to and from the surface of the body and thus the amount of heat exhange

Question 9

merkel cells

Answer 9

• cells specialized in the sense of (gentle) touch
• located in the stratum basale of the epidermis
• innervated by myelinated sensory nerve fibers that become unmyelinated as they cross the basement membrane and form expanded endings that contact the surface

Question 10

Meissner’s corpuscles

Answer 10

• spiraled unmyelinated axon surrounded by modified Schwann cells that are flattened and arranged as encircling horizontal lamellae
• most abundant in the dermal papillae in the fingertips, palms, soles of the feet, lips, face
  
  • areas that are sensitive to light touch

Question 11

Pacinian corpuscles

Answer 11

• central sensory axon located in a fluid-filled cavity surrounded by 20 to 60 concentric lamellae of thin, flat, modified Schwann cells
• detect deep pressure and high frequency vibration
• less frequent in the skin than Merkel cells or Meissner’s corpuscles

Question 12

free nerve endings

Answer 12

• unencapsulated sensory axons that penetrate the epidermis and end in the stratum granulosum
• detect polymodal receptors and are thought to detect hot/cold, pain, pressure, and itch

Question 13

proliferative unit

Answer 13

• a stem cell surrounded by about 10 committed cells in the stratum basale

Question 14

hair growth occurs in 3 phases

Answer 14

Anagen: phase of active growth; this usually lasts 2 to 6 years for scalp hair (length of hair is dependent upon the duration of this cycle (90% of scalp hair)

Catagen: brief phase of reduced hair growth in which the length of the hair follcle shortens (3 weeks) (about 1% of scalp hairs)

Telogen: resting phase that lasts 2 to 4 months. At the end, hair is shed from the follicle, cycle begins anew (10-15% of scalp hair)

Question 15

components of hair follicle

Answer 15

• bulge
  
  • location of stem cells
  • re-populate hair bulb after telogen phase
  • SC can migrate to epidermis
• matrix
  
  • dividing epithelial cells responsible for hair growth

Question 16

transport in epidermis

Answer 16

• modes of transport:
  
  • intercellular
  • transcellular
  • intracellular
• favorable transport:
  
  • low MW
  • moderately lipophilic

Question 17

differentiation of keratinocytes through skin layers

Answer 17

Question 18

keratinocytes & production of vitamin D

Answer 18

• keratinocyte
  
  • 7-dehydrocholesterol –> UV exposure–>
    
    • pre-vitamin D3
      
      • VD3 (in blood vessel)
        
        • 25-OH VD (liver)
          
          • 1,25 (OH)2D3 (calcitriol) (kidney)
            
            • stimulates:
              
              • calcium absorption by GI tract
              • calcium re-absorption by kidney
              • bone resorption by osteoclasts
• associated with Vitamin D defiency:
  
  • osteomalacia
  • rickets
  • others

Question 19

three major steps involved in tanning

Answer 19

1. photo-oxidation of melanin
2. re-distribution of melanin granules to upper layers
3. increased number of melanin granules

Question 20

ruffini endings

Answer 20

skin stretch and joint deformation

Question 21

pemphigus vulgaris

Answer 21

• chronic autoimmune blistering skin disease with the formation of antibodies against desmosomes

Question 22

Stevens Johnson syndrome

Answer 22

• a type of severe skin and mucous membrane reaction characterized by blisters and peeling

Question 23

first-degree burn

Answer 23

involves the epidermis only, appears red and dry without blisters

Question 24

superficial second-degree burn

Answer 24

• extends into the papillary layer/upper dermis, appears red and blistered

Question 25

deep second-degree burn

Answer 25

* extends into the reticular / deep dermis, appears yellow or white, may be blistered

Question 26

third-degree burn

Answer 26

* extends through entire dermis, can involve the hypodermis, appear white/brown may be blistered

Question 27

fourth-degree burn

Answer 27

* extends beyond hypodermis into underlying tissue, appears black, dry, and charred

Question 28

melanoma in-situ

Answer 28

* cancer of pigment-containing cells (melanocytes) limited to the epidermis

Question 29

Breslow depth

Answer 29

* refers to the thickness of an invasive melanoma measured from the top of the epidermis to the deepest invasive cells

Question 30

Clark's level

Answer 30

* a melanoma staining system that describes the level of anatomical invasion based on the layers of the skin

Question 31

squamous cell carcinoma

Answer 31

* skin cancer that forms from the squamouse cells of the epidermis (the uppermost epidermal cells)

Question 32

basal cell carcinoma

Answer 32

* skin cancer that forms from the basal cells of the epidermis * (the lowermost epidermal cells)

Question 33

epidermis

Answer 33

* stratified squamous keratinized epithelium

Question 34

dermis

Answer 34

*dense irregular connective tissue* * **papillary layer** * knob-like papillae (projections) of connective tissue protrude into the epidermis to assist in binding these two tissues together * downward projections of the epidermis are known as interpapillary pegs * composed of tightly woven mesh of thin collagen and elastic fibers with some reticular fibers * network of capillaries beneath the epidermis * **reticular layer** * coarse, densely interwoven collagen, parallel to skin * hair follicles, sebaceous and sweat glands, Pacinian corpuscles, and smooth muscle (arrector pili muscle) are located in this layer

Question 35

stratum basale

Answer 35

## Footnote somwhat columnar cells attached to the basement membrane, with added binding strength of hemidesmosomes

Question 36

stratum corneum

Answer 36

* thick layer of tightly packed, flattened, highly modified keratinocytes * keratinocyte nucleus is absent and a homogenous filamentous substance, keratin, is deposited on the inside of the plasma membrane, forming a cornified cell envelope

Question 37

stratum lucidum

Answer 37

* layer 3 to 5 cells thick; keratinocytes are flattened and stain feebly, they have lost their nuclei and cytoplasmic organelles

Question 38

stratum granulosum

Answer 38

* keratinocytes are flattened, cytoplasm contains irregularly-shaped **keratohyalin granules** associated with tonofilaments * **Lamellar bodies** (pale, intracellular) increase in number, and lamellar product is released into the extracellular space when the cells die

Question 39

stratum spinosum

Answer 39

* keratinocytes are "prickle cells" * unique spiny intercellular bridges / projections * cytoplasmic extensions containing tonofilaments (keratin bundles) attached to an intercellular *desmosome* * *​*keratinocytes develop lamellar bodies in this layer