terminal bronchiole

**Location and function** - The terminal bronchiole is the last segment of the conducting zone (generations ~0-16). The conducting zone runs from the trachea to the terminal bronchioles. - It is the smallest airway without alveoli, so it takes no part in gas exchange. This makes it part of anatomic dead space. - Distal to it are the respiratory bronchioles, then alveolar ducts, alveolar sacs, and alveoli. These make up the respiratory zone (generations ~17-23).

**Histology (high-yield)** - Epithelium: simple ciliated cuboidal. Proximal airways have pseudostratified columnar epithelium, which becomes cuboidal distally. - No cartilage, no submucosal glands, and no goblet cells. - Club (Clara) cells are abundant. They are nonciliated, dome-shaped secretory cells that: - Secrete a surfactant-like, protective component (club cell secretory protein, CC16). - Detoxify xenobiotics via cytochrome P450. - Act as progenitor cells that regenerate bronchiolar epithelium (and type II pneumocytes). - Secrete glycosaminoglycans and some immunomodulatory proteins. - A relatively thick smooth muscle layer is present. Airway patency depends on radial traction from surrounding lung parenchyma (elastic recoil), not cartilage.

**Physiology** - Airway resistance is highest in the medium-sized bronchi (generations ~4-8). The terminal bronchioles contribute little to total resistance despite their small size, because their total cross-sectional area is very large (the airways are arranged in parallel). - Smooth muscle tone is controlled by the autonomic nervous system: - β2 stimulation causes bronchodilation. - Muscarinic M3 (parasympathetic) stimulation causes bronchoconstriction. - Total cross-sectional area increases greatly toward the periphery, so airflow velocity is very low in the small airways. This allows gas to move by diffusion at the respiratory zone.

**Clinical correlations** - **Asthma:** reversible bronchoconstriction, smooth muscle hypertrophy, mucus plugging, and eosinophilic inflammation (Th2, IL-4/5/13). Curschmann spirals and Charcot-Leyden crystals may be seen in sputum. - **COPD:** - Chronic bronchitis: Reid index >50%, with mucus gland hyperplasia in larger airways. - Emphysema: destruction of alveolar walls distal to the terminal bronchiole. Centriacinar emphysema (smoking) affects the respiratory bronchioles and is typically in the upper lobes. Panacinar emphysema (α1-antitrypsin deficiency) affects the entire acinus and is typically in the lower lobes. - **Small airway disease:** the small airways (<2 mm) are an early site of obstruction in smokers. Examples include bronchiolitis obliterans (post-transplant, toxic fume inhalation, or viral infection), RSV bronchiolitis in infants, and respiratory bronchiolitis-ILD in smokers. - **Neonatal RDS:** relates to the respiratory zone, not the bronchioles. Surfactant is made by type II pneumocytes, not Club cells. - **Terminology:** the acinus is the unit distal to a terminal bronchiole. The lobule or secondary pulmonary lobule is a larger unit made up of several acini.

**Mnemonic:** "Terminal = last Tube, no Trade of gas." Gas exchange begins at the respiratory bronchiole.