Terminal Bronchioles

1. Overview

Terminal bronchioles are the smallest branches of the conducting portion of the bronchial tree. They mark the end of the conducting zone and the beginning of the respiratory zone, as they give rise to the respiratory bronchioles. Terminal bronchioles play a crucial role in directing air to the regions of the lung where gas exchange occurs. Their structural features allow them to regulate airflow and maintain airway patency in the distal lung.

2. Location

Terminal bronchioles are located:

• Distal to the bronchioles, within each pulmonary lobule

• Proximal to the respiratory bronchioles, forming the final segment of the conducting airway

• Scattered throughout the lung parenchyma, with each one giving rise to multiple respiratory bronchioles

Each lobule in the lung is ventilated by a single terminal bronchiole.

3. Structure

Terminal bronchioles are characterized by:

• Diameter: Typically less than 1 mm

• Epithelium: Lined with simple cuboidal epithelium containing:

  • Ciliated cells: Aid in mucus clearance

  • Club cells (Clara cells): Non-ciliated secretory cells that protect the airway lining

• Wall composition: Lacks cartilage; instead supported by smooth muscle fibers

• No goblet cells: Unlike larger airways, terminal bronchioles do not secrete mucus

This structure ensures a clear, low-resistance pathway to the respiratory zone while protecting the distal lung tissue.

4. Function

Terminal bronchioles perform the following key functions:

• Conduct air: Channel inhaled air from larger airways to the gas-exchanging respiratory bronchioles and alveoli

• Airflow regulation: Smooth muscle in the wall contracts or relaxes to control airflow into the distal lung

• Lung protection: Club cells secrete proteins like CC16 and surfactant-like substances that protect against oxidative and inflammatory damage

5. Physiological Role(s)

Terminal bronchioles play an important role in respiratory physiology:

• Air distribution: Ensure even distribution of air across pulmonary lobules for optimal gas exchange

• Mucociliary clearance: Cilia help move inhaled particles and pathogens out of the distal airways

• Surface tension regulation: Club cells secrete surfactant components that help maintain small airway patency

• Local immune defense: Club cells contribute to immune surveillance and detoxification of inhaled substances

6. Clinical Significance

Bronchiolitis

An acute inflammation of the small airways, particularly terminal and respiratory bronchioles, often seen in infants and young children. Common causes include:

• Respiratory syncytial virus (RSV)

• Influenza

Symptoms: Cough, wheezing, tachypnea, and difficulty breathing.
Treatment is primarily supportive (oxygen, hydration).

Obliterative Bronchiolitis (Constrictive Bronchiolitis)

A chronic condition in which terminal bronchioles are partially or completely obliterated by fibrous tissue. Causes include:

• Post-viral infections

• Graft-versus-host disease

• Toxic exposures (e.g., inhaled fumes like diacetyl)

Symptoms: Progressive dyspnea, cough, and fixed airflow obstruction.
Often irreversible and difficult to treat.

Asthma

Though a disease of the entire bronchial tree, terminal bronchioles can be involved in bronchoconstriction and airway hyperresponsiveness. Inflammation and smooth muscle contraction reduce airway diameter, leading to wheezing and airflow limitation.

COPD and Emphysema

Chronic obstructive pulmonary disease may involve narrowing and destruction of terminal bronchioles, especially in centrilobular emphysema. Results in:

• Air trapping

• Decreased airflow

• Impaired oxygen exchange

Respiratory Bronchiolitis–Associated Interstitial Lung Disease (RB-ILD)

Seen primarily in smokers, this condition features inflammation of terminal and respiratory bronchioles with interstitial changes. Symptoms include chronic cough and exertional dyspnea.

Post-Transplant Bronchiolitis

Terminal bronchiole inflammation is a common feature of chronic lung transplant rejection (bronchiolitis obliterans syndrome), leading to progressive loss of lung function.