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STRATUM CORNEUM (10-20 microns)
| • | the primary compartment that limits the percutaneous absorption of compounds |
| • | it can be accurately characterized as “bricks” of bundled proteins embedded in “mortar” of intercellular lipid |
| • | (mucous membranes lack a stratum corneum) |
“bricks” (corneocytes)
| • | a core of keratins surrounded by an envelope made up of cross-linked proteins |
“mortar” (intercellular lipid)
| • | roughly equimolar amounts of ceramides, cholesterol, and long-chain free fatty acids |
| • | the intercellular lipids of the stratum corneum, in contrast to almost all other biomembranes, include no phospholipids |
| • | the rate limiting step for permeation includes a hydrophobic barrier – i.e. the intercellular lipid |
| • | the only continuous domain within the stratum corneum is formed by the intercellular lipid space; a tortuous path |
Keratinocyte:
Two types of granules:
1 - Odland bodies:
| • | AKA lamellated oval membrane-coating granules |
| • | present in prickle cells, and to a greater extent, cells of granular layer |
| • | bound by a double layered membrane |
| • | contain parallel lamellae (like stacks of pennies) |
| • | contain a mixture of lipids: phospholipids, sphingolipids, cholesterol |
| • | release their lipid contents by exocytosis into the intercellular space of the stratum corneum, this forms a highly efficient water barrier |
| • | also contains a mixture of hydrolytic enzymes (important in natural desquamation) |
2 - Keratohyalin granules:
| • | = the “granules” in cells of the granular layer |
| • | not membrane bound; contain profillagrin/ filagrin |
| • | often appear to be intimately associated with tonofibrils |
cell envelope:
| • | the corneocyte has a highly insoluble cornified envelope its formation represents an expression of terminal differentiation of the keratinocyte within the plasma membrane, formed by the cross-linking of the soluble protein precursor involucrin (Greek = envelope) |
| • | envelope precursors (e.g. involucrin, loricrin) are synthesized late in stratification and then cross-linked by the action of transglutaminase enzymes, which are synthesized in the granular layer |
| • | major cell envelope constituents = involucrin, filaggrin and loricrin |
| • | defect in ichthyosis vulgaris – filaggrin |
| • | defect in Vohlwinkel’s syndrome – loricrin |
| • | defect in lamellar ichthyosis - transglutaminase |
basement membrane
| • | “basement membrane material” = PAS positive, diastase negative, stains with antibodies to type IV collagen |
| • | deposited around papillary dermal vessels in cutaneous porphyrias |
| • | thickened BM in lupus and dermatomyositis |
| • | thickened dermal capillary basement membranes in diabetic skin |
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