Histology of the Respiratory System - Notes

Histology of the Respiratory System

Learning Objectives

• Describe the histological features of the conducting portion of the respiratory system, including the nasal cavity, pharynx, larynx, trachea, and bronchi, and their respective functions.
• Describe the morphology and functional characteristics of the respiratory portion of the system, including the intrapulmonary bronchial tree, bronchioles, and alveoli.
• Outline the function and importance of the blood-air barrier.
• Outline the morphology of the pleura.
• Briefly outline some clinical correlations.

Recommended Reading Material

• Wheater's Functional Histology, 6th Edition, Part 3 “Organ Systems” Ch.12 Respiratory System.
• Histology: A Text and Atlas, with Correlated Cell and Molecular Biology, 8th Edition, 2018, W. Pawlina, Michael H. Ross, Chapter 19 Respiratory System.
• Junqueira's Basic Histology: Text and Atlas, 15th Edition, 2018, Chapter 17 The Respiratory System.

Overview of the Respiratory System

• Air conduction:
  • Nasal cavities
  • Nasopharynx
  • Larynx
  • Trachea
  • Primary Bronchi
• Air Filtration: The conducting system warms, moistens, and removes particulate matter from the air.
• Gas exchange:
  • Respiratory bronchioles
  • Alveolar ducts
  • Alveolar sacs
  • Alveoli
• Production of speech (larynx) and sense of smell (olfactory mucosa in the nasal cavity).
• The conducting system conditions the air before it reaches the respiratory portion (warming, moistening and removal of particulate matter).
• Mucous and serous secretions play an important role in air conditioning.

Nasal Cavities

The nasal cavities are divided into three regions:

• Nasal vestibule: Dilated space inside the nostrils.
• Respiratory region: Largest part (inferior 2/3) lined by respiratory mucosa.
• Olfactory region: Located at the apex of each cavity and is lined by olfactory mucosa.

Nasal Cavity: Respiratory Region

• Respiratory mucosa:
  • Ciliated, pseudostratified columnar epithelium.
  • Goblet cells: tall columnar cells producing mucous.
  • Brush cells: bear short microvilli.
  • Basal cells: stem cells.
  • Covers most of the parts in the conducting system.
  • Warms, moistens and filters inspired air.
• Majority of the nasal cavity is lined by ciliated pseudostratified columnar respiratory epithelium
• Lamina propria contains seromucous glands, which drain to surface via small ducts
• Vessels have muscular walls (contract/dilate) for temperature regulation and secretions

Nasal Cavity: Olfactory Region

• Ciliated, pseudostratified columnar epithelium
• No goblet cells.
• Olfactory epithelium contains:
  • Supporting cells
  • Olfactory cells (bipolar neurons)
  • Basal cells
• Bowman's glands:
  • Serous secretion that serves as trap and solvent for odoriferous substances.

Nasopharynx

• both ciliated respiratory-type epithelium and stratified squamous epithelium

Oropharynx/Hypopharynx

• Non-keratinized stratified squamous epithelium.
• Connective tissue with mucous glands.
• Underlying elastic layer.

Larynx

• Complex tubular region, made up by the "true" and "false" vocal chords.
• Vocal Folds or Vocal Chords:
  • Produce sound
  • Covered by non-keratinized stratified squamous epithelium
  • Underlying skeletal muscle called the vocalis muscles.
• Ventricular folds or "false vocal chords:
  • Create sound resonance.
  • Covered by respiratory mucosa with numerous mucous glands in the underlying connective tissue.

Trachea

• A short flexible tube part of the conducting system of the airways.
• The wall is composed of four definable layers:
  • Mucosa: ciliated, pseudostratified columnar epithelium and elastic-rich lamina propria.
  • Submucosa: serous and mucous glands, blood vessels and nerve fibres
  • Cartilaginous layer: C-shaped hyaline cartilage. The rings are joined posteriorly by bands of smooth muscle known as trachealis muscle (T)
  • Adventitia: Connective tissue that binds the trachea.
• Tracheal epithelium:
  • Ciliated cells
  • Mucous cells (goblet cells)- Identified in H&E by a clear area in the cytoplasm
  • Brush cells
  • Small granule cells- neuroendocrine cells secreting various hormones. Function not well understood. May function in reflexes.
  • Basal cells
  • Thick basement membrane.
• The cartilage and the trachealis muscle divide the submucosa from the adventitia.

Bronchi

• Trachea bifurcates into two main or primary bronchi, later divided into segmental bronchi. A characteristic component is the presence of cartilage chips, rather than the C-shape of the trachea.
• Bronchial layers:
  • Mucosa- respiratory epithelium
  • Muscularis- smooth muscle cells
  • Submucosa-glands, CT
  • Cartilage layer (chips)
  • Adventitia - CT

From Bronchi to Bronchioles

• Conducting zone
  • Trachea
  • Bronchi
    • Pseudostratified ciliated columnar epithelium
      • Basal cell
      • Goblet cell
      • Ciliated cell
    • Smooth muscle
    • Cartilage
  • Bronchioles
    • Simple ciliated columnar epithelium
      • Club cell
      • Ciliated cell
    • Smooth muscle
  • Terminal bronchioles

Bronchioles

• Large bronchioles branch off the bronchi. They give rise to terminal bronchioles that finally result in respiratory bronchioles.
• No cartilage plates and glands.
• Goblet cells disappear at the terminal bronchioles (except in smokers).
• Epithelial layer: simple ciliated columnar/cuboidal epithelium.
• Thick layer of smooth muscle cell that causes folding of the mucosa.

Bronchioles - Clara cells

• Goblet cells are replaced by Clara cells.
• Clara cells: non-ciliated cells embedded in the epithelium, which secrete:
  • a watery surface-active lipoprotein, that prevents luminal adhesion if the wall of the airway collapses during expiration.
  • a secretory protein C16, associated with pathologies such as COPD/asthma.
  • a detoxifying compound, cytochrome p450: regenerates the epithelium of small airways when damaged.

Respiratory Bronchioles

• Part of the respiratory region.
• Involved in both air conduction and gas exchange.
• Lined by simple cuboidal epithelium.
• Will give rise to alveolar ducts.

Alveoli

• Sites of gas exchange, each alveolus is surrounded by a network of capillaries that bring blood to close proximity to the inhaled air.
• Surface of all the alveoli is roughly the size of a tennis court.
• Alveolar ducts: elongated airways with almost no walls only alveoli.
• Alveolar sacs: Are spaces surrounded by clusters of alveoli

Alveoli - Pneumocytes

• Type I and II alveolar cells (pneumocytes).
• Pneumocytes I:
  • Flat squamous cells.
  • Line 95% of the surface of alveoli.
  • Do not divide.
• Pneumocytes II:
  • Cuboidal cells
  • Cover only 5% of the alveoli surface.
  • Synthesize surfactant that decreases alveoli surface tension preventing lung collapse.
  • Stem cell like properties and replace type I cells after injury.

Alveoli - Macrophages

• Pulmonary macrophages in the alveoli, but not within the walls.

Alveoli-Gas Exchange

• 4 layers exist between the blood and inspired air in the blood-air barrier:
  • capillary endothelium (continuous, no fenestrations)
  • fused basal lamina
  • alveolar epithelium (type I pneumocyte)
  • surfactant

Summary of the Histological Features of the Respiratory Airways

Pleura

• Thin, continuous membranous lining within thoracic cavity (visceral pleura invests lungs, parietal pleura lines outer surface of thoracic cavity)
• Thin layer of mesothelial cells (flat-cuboidal cells, no nucleoli) upon thin basement membrane overlying fibroelastic CT.
• Reactive mesothelial cells: larger, more conspicuous cells, enlarged nucleus and prominent central nucleoli (in normal mesothelium often non visible)
• Submesothelium: spindled fibroblastic cells, collagen, elastin

Respiratory Pathology: Asthma

• Mucous plugging of the airways.
• Pseudostratified columnar epithelium with goblet cell hyperplasia.
• Eosinophils in lamina propria and epithelium.
• Thickened basement membrane.
• Smooth muscle hypertrophy.

Respiratory Pathology Bronchitis

• Goblet cell metaplasia, mucous plugging.
• Inflammation (lymphocytes and macrophages mainly) and fibrosis
• Enlargement of the mucus secreting glands