Keratinization — expanded notes
Keratinocyte differentiation
Keratinocytes originate from stem and progenitor cells in the basal layer. They proliferate, leave the basement membrane, differentiate through the spinous and granular layers and ultimately become corneocytes. Differentiation involves changes in keratin expression, cytoskeletal organisation, cell shape, lipid secretion and programmed destruction of the nucleus and organelles.
Molecular components
Keratin: intermediate filament proteins provide mechanical resilience. Basal K5/K14 pairs are replaced by suprabasal K1/K10 during differentiation.
Filaggrin: derived from profilaggrin in keratohyalin granules; aggregates keratin filaments and contributes to natural moisturising factor after degradation.
Involucrin and loricrin: major cornified-envelope proteins cross-linked by transglutaminases.
Lamellar bodies: secretory organelles that release lipid precursors and enzymes into extracellular spaces of the upper epidermis.
Corneodesmosomes: specialised adhesive structures between corneocytes; their controlled breakdown allows desquamation.
Barrier function
The stratum corneum is often described as a brick-and-mortar structure: corneocytes are the bricks and extracellular lipid lamellae are the mortar. Ceramides, cholesterol and free fatty acids are essential for the water barrier. Natural moisturising factor binds water within corneocytes. An acidic skin surface supports enzymes involved in barrier maintenance and discourages pathogen growth.
Disorders of cornification
Hyperkeratosis: thickening of stratum corneum; may be due to friction, inflammation or inherited keratinisation disorders.
Parakeratosis: retained nuclei in stratum corneum, commonly due to accelerated epidermal turnover or abnormal maturation.
Dyskeratosis: premature keratinisation of individual cells, seen in selected inflammatory, viral and neoplastic disorders.
Ichthyoses: inherited or acquired disorders with abnormal scaling due to defects in epidermal differentiation, lipid processing or desquamation.
Psoriasis: cytokine-driven keratinocyte hyperproliferation with incomplete maturation, parakeratosis, reduced granular layer and neutrophils in the stratum corneum.
Clinical relevance
Barrier impairment increases transepidermal water loss and penetration of irritants and allergens. This contributes to xerosis and atopic dermatitis. Repeated friction stimulates protective hyperkeratosis, producing calluses and corns. Follicular keratin plugging contributes to comedone formation in acne.