Stratified epithelium

Introduction

• Definition and overview of stratified epithelium
• Comparison with simple and pseudostratified epithelia
• Historical perspective and nomenclature
• Clinical relevance in protective barriers and disease

Embryology and Development

Germ Layer Origins

• Ectodermal derivatives (e.g., epidermis)
• Endodermal derivatives (e.g., distal anal canal)
• Mesodermal contributions in specialized sites

Ontogeny of Stratification

• Basal progenitors and commitment
• Layer acquisition and terminal differentiation
• Parakeratosis vs orthokeratosis during development

Gross and Microscopic Anatomy

Layer Architecture

• Basal (germinativum) layer
• Spinous and granular layers
• Superficial (keratinized or non-keratinized) layer

Ultrastructure

• Desmosomes, hemidesmosomes, and intermediate filaments
• Basement membrane (lamina lucida, densa) and anchoring fibrils
• Electron microscopy features (TEM/SEM)

Classification

Stratified Squamous Epithelium

• Keratinized: skin, vermilion border
• Non-keratinized: oral cavity, esophagus, vagina
• Special patterns: parakeratinized, orthokeratinized

Stratified Cuboidal Epithelium

• Typical two-cell layers in ducts (sweat, salivary, mammary)
• Functional implications in secretion and protection

Stratified Columnar Epithelium

• Locations: conjunctiva, large glandular ducts, male urethra
• Transition zones and mixed phenotypes

Transitional Epithelium (Urothelium)

• Umbrella cells and asymmetric unit membrane
• Plasticity with distension (relaxed vs stretched states)

Topographic Distribution

• Integumentary system: epidermis, nail bed
• Alimentary tract: oral cavity, oropharynx, esophagus, anal canal
• Genitourinary tract: vagina, ectocervix, distal urethra
• Ocular structures: corneal epithelium, palpebral conjunctiva
• Exocrine ducts: salivary, sweat, mammary, pancreatic accessory ducts
• Urinary tract: renal pelvis, ureter, bladder (urothelium)

Cellular Composition and Renewal

Stem and Progenitor Cells

• Basal layer stem cell niches
• Transit-amplifying populations

Differentiation Programs

• Keratin expression switching (e.g., K5/K14 to K1/K10)
• Cornified envelope formation and filaggrin

Turnover Kinetics

• Site-specific renewal rates
• Regulation by growth factors and mechanical stress

Molecular and Immunohistochemical Profile

Cytokeratin Panels

• Basal markers: CK5/6, CK14, p63
• Differentiation markers: CK1, CK10, involucrin
• Urothelial markers: GATA3, uroplakins, CK7/20 patterns

Cell Junction and Adhesion Molecules

• Desmogleins, desmocollins, plakoglobin
• Integrins and laminins (α6β4, laminin-332)

Barrier and Stress Proteins

• Claudins, occludin, ZO proteins
• Filaggrin, loricrin, small proline-rich proteins

Physiology and Biomechanics

Protective Functions

• Resistance to abrasion and shear
• Barrier to pathogens and toxins

Hydration and Permeability

• Natural moisturizing factors and lipid lamellae
• Transepithelial water and solute transport

Mechanical Testing and Metrics

• TEER, permeability assays
• Elasticity and viscoelastic properties

Pathology

Non-neoplastic Disorders

• Dyskeratosis, hyperkeratosis, parakeratosis
• Inflammatory conditions: esophagitis, vaginitis, keratitis
• Infectious diseases: candidiasis, HPV-related lesions
• Autoimmune blistering diseases: pemphigus, pemphigoid

Metaplasia and Dysplasia

• Squamous metaplasia (respiratory, cervical)
• Grading of epithelial dysplasia

Neoplasia

• Squamous cell carcinoma (cutaneous, oral, esophageal, cervical)
• Carcinoma in situ vs invasive carcinoma
• Urothelial neoplasia: papilloma to high-grade carcinoma

Diagnostics

Histopathology

• Biopsy techniques and site selection
• Routine stains and special stains

Immunohistochemistry and Molecular Testing

• Marker panels for site and lineage determination
• Genomic alterations and risk stratification

Differential Diagnosis

• Distinguishing stratified from pseudostratified and transitional epithelia
• Mimickers: reactive atypia vs dysplasia

Clinical Management and Therapeutics

Medical Management

• Topical and systemic therapies for inflammatory and infectious conditions
• Barrier-restoring strategies and wound care

Surgical and Procedural Approaches

• Excision, Mohs surgery, ablative therapies
• Endoscopic management in mucosal sites

Surveillance and Follow-up

• Screening protocols (e.g., cervical, oral potentially malignant disorders)
• Recurrence risk and long-term monitoring

Special Topics

Transition Zones and Junctional Epithelium

• Anatomy of squamocolumnar junctions
• Cancer risk at epithelial interfaces

Pediatric and Geriatric Variations

• Developmental differences in thickness and turnover
• Age-related barrier decline and comorbidities

Occupational and Environmental Exposures

• Chemical irritants, heat, radiation
• Protective measures and regulations

Research and Emerging Directions

Stem Cell Biology and Regeneration

• Basal stem cell markers and lineage tracing
• Organoids and ex vivo culture models

Tissue Engineering

• Bioengineered skin and mucosal substitutes
• Scaffolds, bioprinting, and integration

Systems Biology and Omics

• Transcriptomics and proteomics of stratification
• Microbiome–epithelium interactions

Public Health and Preventive Medicine

• HPV vaccination and screening impact
• Tobacco, alcohol, and carcinogen exposure reduction
• Health disparities in epithelial cancers

References

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5. Alberts B, Johnson A, Lewis J, Morgan D, Raff M, Roberts K, et al. Molecular Biology of the Cell. 7th ed. New York: Garland Science; 2022.
6. Fuchs E. Keratins and the skin. Annu Rev Cell Dev Biol. 1995;11:123-53.
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