section name header

Info


A. Role of Skin

  1. Barrier
  2. Thermoregulation
  3. Sensation
  4. Immunity
  5. Vitamin D synthesis
  6. Social/Sexual

B. Layers of Skin

  1. Stratum Corneum
  2. Epidermis
    1. Keratinocytes
    2. Melanocytes
    3. Langerhans Cell
    4. Merkel Cell
  3. Basement Membrane Zone
    1. Lamina lucida, densa, and anchoring region
    2. Support and attachment for epidermis, filtration and permeability
    3. Hemidesmosome (Basal Cells) - Lamina Lucida / Densa attachments
    4. Diseases: Bullous Pemphigoid, Herpes Gestationes, Systemic Lupus Erythematosus (SLE)
  4. Dermis
    1. Loose connective tissue with collagen, elastin, reticulin
    2. Cells include fibroblasts, macorphages (M_), mast cells, lymphocytes
    3. Vasculature, lymphatics and nerves are present
    4. Sweat glands: eccrine (thermal), apocrine, sebaceous (lipids)
    5. Diseases: solar elastosis, pseudoxanthoma elasticum, urticaria, scleroderma, sarcoid
  5. Adipose Tissue
    1. Underlies dermis, overlies muscle
    2. Main function is thermal barrier, energy storage
    3. Diseases: panniculitis, erythema nodosum

C. Stratum Corneum

  1. Dried, flattened (dead) keratinocytes (corneocytes)
  2. Protective layer, permeability barrier
  3. Cornification and desquamation
  4. Diseases: psoriasis, exfoliative dermatitis, Ichthyosis vulgaris

D. Epidermis

  1. Keratinocytes
    1. Progression from Baseal to Spinous to Granular Layers (~80% of epidermis)
    2. No blood vessels or nerves
    3. Synthesis of keratin precursors, etc.
    4. Diseases: ichthyosiform dermatoses, keratosis follicularis, psoriasis
  2. Normal Keratinocyte Maturation
    1. Basal keratinocytes progress to Spinous Layer to Granular Layer, then desquamate
    2. Normal Completion of Transit 30-40 days
    3. Rate of basal cell division: altered in disease or normal
    4. Dishesion of cornified cells - breakdown of adhesive molecules
  3. Sequential expression of specific proteins correlated with 4 histological strata
    1. Keratin filaments
    2. Desmosomes
    3. Cell envelope
  4. Diseases of Keratinocytes
    1. Non-Hyperproliferative: Ichthyosis vulgaris, Recess X linked Ichthyosis (R-XLI)
    2. Benign Hyperproliferative: Psoriasis, Actinic Keratosis
    3. Malignant: Basal Cell CA, Squamous Cell CA
  5. Melanocytes (5-10% of cells)
    1. Synthesis of melanin, skin color
    2. Protection against damaging UV, heat absorption for body temperature
    3. Diseases: albinism (reduced), Addison's Disease (increased), vitiligo (abnormal)
  6. Langerhans Cell (5%)
    1. Antigen recognition, processing, presentation
    2. Disease: contact eczematous dermatitis, Histiocytosis X
  7. Merkel Cells (<1%) [2]
    1. Slowly adapting mechanoreceptor in basal layer of skin and outer root sheath of hair follicle
    2. Possibly APUD (neuroendocrine) cell type
    3. Cytokeratin 20 perinuclear dot-like pattern

E. Wound Healing [1]

  1. Critical for responses to:
    1. Traumatic wounds
    2. Burns
    3. Skin Ulcers: pressure, venous stasis, diabetes mellitus
    4. Impairment of wound healing leads to chronic skin ulceration
    5. Skin ulcers lack barrier function of skin and complications are very common
  2. Stages of Wound Healing
    1. Clotting and Inflammation
    2. Epithelialization
    3. Granulation
    4. Neovascularization
  3. Clotting
    1. Blood cut establishes hemostasis
    2. Damage to vessels leads to exposure of tissue factor (TF, Factor III)
    3. TF stimulates extrinsic clotting cascade, binds to Factor VIIa
    4. Activates fibrinogen to fibrin conversion and formation of clot matrix
    5. Release of bioactive molecules attracts platelets and activates them
    6. Forms platelet plug with clot matrix
  4. Inflammation
    1. Platelets secrete several mediators of wound healing
    2. Platelet derived growth factor (PDGF) is one key factor
    3. However, platelets are not absolutely essential for wound healing
    4. Coagulation and activated complement pathways stimulate inflammation
    5. Infiltrating neutrophils are the first leukocytes to infiltrate the wound area
    6. These cells cleanse area of bacteria and foreign particles
    7. Monocytes infiltrate site next in response to chemoattractants
    8. Monocytes are activated to macrophages and secrete TNFa, CSF-1, PDGF and others
    9. Monocytes also secrete TGFa, TGFß, IGF-1 and IL-1
    10. PDGF, TGFß, and IGF-1 are highly stimulatory for fibroblasts
    11. Fibroblasts are important for laying down an extracellular matrix for epithelia
  5. Re-epithelialization
    1. Replacement of damaged epithelium begins within hours of wound formation
    2. Undamaged epithelial cells near wound aid in removal of debris
    3. These adjacent epithelial cells retract tonofilaments and desmosomal proteins
    4. Thus, epithelial (and dermal) cells no longer adhere to each other
    5. Migratory epithelia express integrin receptors and can bind to dermal collagen and other extracellular matrix proteins (vitronectin, fibronectin)
    6. Lateral migration of epithelia permit some initial closure of wound
    7. Migratory epithelia also secrete collagenase and other matrix degrading enzymes
    8. Epidermal cells also secrete plasminogen activator, which produces plasmin
    9. This permits new layers of skin to be built and the fibrous scar to be dissolved
    10. One to two days after wound occurs, epithelial cells proliferate vigorously
    11. Basement membrane proteins are produced from edge of the wound inward
    12. Once the basement membrane is in place, epithelial cells bind to it and reform adhesion
  6. Granulation Tissue
    1. New stroma overlying the wound is often called granulation tissue
    2. This is present ~4 days into wound healing
    3. Many new capillaries cause this stroma to be highly vascular, giving it a red appearance
    4. Macrophages are critical for producing growth factors for fibroblasts and angiogenesis
    5. The process of angiogensis is discussed below
    6. TGFß1 and PDGF are important for stimulating fibroblasts
    7. The new stroma is composed of fibrin, fibronectin and hyaloronic acid
    8. This stromal matrix fascilitates migration of wound healing cells
    9. Fibroblasts are most important for synthesis of new extracellular matrix
    10. Fibroblasts use proteases including stromelysin, plasmin, collagenase, and others
    11. Fibroblasts lay down collagen matrix which is a relatively avascular "scar"
    12. Normally, once the matrix is complete, collagen synthesis stops and cells in the matrix undergo apoptosis (including apoptosis of new blood vessels)
    13. This process is abnormal in keloids, morphea and scleroderma
  7. Neovascularization
    1. Formation of new blood vessels is required to support the new collagen matrix
    2. Low oxygen tension and lactate as well as growth factors stimulate angiogenesis
    3. FGFa, FGFb, VEGF, TGFß, angiogenin, angiotropin, angiopoietin 1 stimulate angiogenesis
    4. Many of these stimulate VEGF and FGFb production by macrophages and endothelial cells
    5. Extracellular matrix must also be layed down before angiogensis can occur
    6. Endothelial cells "grow into" this extracellular matrix
    7. Once the wound is filled, blood vessels within the wound undergo apoptosis
    8. Thrombospondins 1 and 2, endostatin and others are important for this apoptosis
  8. Wound Contraction (Scar)
    1. Contraction and extracellular matrix reorganization then occurs
    2. During the second week of wound healing, fibroblasts assume "myofibroblast" form
    3. These myofibroblasts appear to mediate contraction of the wound
    4. Collagen remodelling occurs as the granulation tissue becomes a scar
    5. Wounds gain ~20% of their strength in the first three weeks
    6. Wounds attain a maximum of ~70% of the strength of normal skin

References

  1. Singer AJ and Clark RAF. 1999. NEJM. 341(10):738 abstract
  2. Busse PM, Clark JR, Muse VV, Liu V. 2008. 2008. NEJM. 358(25):2717 (Case Record) abstract