What are the different epithelial linings of the human airway from the oropharynx to the terminal bronchioles?

Epithelial Lining of the Human Airway from Oropharynx to Terminal Bronchioles

The human airway transitions from stratified squamous epithelium in the oropharynx to pseudostratified ciliated columnar epithelium with goblet cells in the trachea and bronchi, then to simple cuboidal epithelium with Clara cells in the bronchioles, and finally to simple cuboidal/low columnar epithelium in terminal bronchioles.

Oropharynx and Upper Airway

• The oropharynx is lined with stratified squamous epithelium adapted to withstand mechanical stress from both respiration and deglutition 1
• This region forms part of the common aerodigestive tract where the airway and alimentary canal cross 1

Trachea and Large Bronchi

• The trachea and large bronchi are lined with pseudostratified ciliated columnar epithelium 2, 3

• This epithelium contains multiple cell types including:

  • Ciliated cells that propel mucus toward the hypopharynx 3
  • Goblet cells (mucous cells) that secrete gel-like mucus to trap particles and pathogens 4, 5, 3
  • Basal cells that serve as progenitor cells and do not reach the luminal surface 3
  • Neuroendocrine cells (Kulchitsky cells) arranged in small clusters called neuroendocrine bodies 4, 3
  • Indifferent cells showing early signs of differentiation 3

• The epithelium progressively thins as it extends from upper to lower trachea 2

• Goblet cells are normally present in these large central airways but comprise less than 1% of total epithelial cells in healthy airways 5, 2

Small Bronchi and Bronchioles

• As airways become smaller, the epithelium transitions from pseudostratified to simple columnar or cuboidal 2, 6
• Clara cells (nonciliated secretory cells) become increasingly prominent and are found as far proximally as the hilum, not just in terminal bronchioles 2, 6
• Clara cells are dome-shaped, protrude into the lumen, contain numerous mitochondria and secretory granules, and produce Clara cell protein (CC10) 4, 6
• These cells serve as stem cells for bronchiolar ciliated cells 4
• Ciliated cells increase in concentration progressively toward the periphery 2

Terminal Bronchioles

• Terminal bronchioles are lined with simple cuboidal epithelium consisting primarily of two cell types 6:

  • Ciliated cells that are cuboidal with long thin microvilli 6
  • Clara cells (nonciliated cells) that are the predominant cell type 4, 6

• The depth of the ciliary layer decreases progressively from central to peripheral airways 2

• At all airway levels, 40-50% of cells are non-ciliated 2

Critical Pathological Considerations

• Goblet cells are normally absent in small airways and terminal bronchioles 4, 5
• The appearance of goblet cells in small airways (mucous metaplasia) is a pathological hallmark of chronic bronchitis and COPD, contributing significantly to airway obstruction 4, 5
• In disease states, there is increased size and number of goblet cells in large airways, plus their abnormal appearance in small airways where they should not exist 4, 5
• A common progenitor cell likely exists at the junction between terminal bronchioles and alveoli, though this has not been definitively identified 4

Human airways differ significantly from rodent models, as mice lack bronchial submucosal glands and goblet cells entirely 4, making direct extrapolation from animal studies problematic for understanding human airway epithelial pathology.