Alveoli

1. Overview

Alveoli are tiny, air-filled sacs in the lungs where gas exchange occurs between the air and blood. They represent the functional units of the respiratory system, enabling oxygen to diffuse into the blood and carbon dioxide to diffuse out. Each human lung contains approximately 300 million alveoli, which collectively provide an enormous surface area (~70–100 m²) critical for efficient respiration.

2. Location

Alveoli are located at the terminal ends of the respiratory tree, within the lung parenchyma. Their position in the respiratory pathway is:

• Distal to the respiratory bronchioles

• Opening off the walls of alveolar ducts

• Grouped in clusters called alveolar sacs

Alveoli are most numerous in the peripheral regions of the lungs, especially within the pulmonary lobules, and are enveloped by a rich network of capillaries.

3. Structure

Each alveolus is a thin-walled, balloon-like sac designed to facilitate rapid gas exchange. Key structural features include:

• Alveolar wall (alveolar septum): Extremely thin (0.2–0.5 microns), consisting of epithelial cells, basement membrane, and adjacent capillary endothelium.

• Cell types:

  • Type I pneumocytes: Flat, squamous cells covering ~95% of the alveolar surface, specialized for gas exchange.

  • Type II pneumocytes: Cuboidal cells that secrete pulmonary surfactant and serve as progenitor cells for Type I pneumocytes.

  • Alveolar macrophages (dust cells): Patrol the alveolar surface, removing debris and pathogens.

• Capillary network: Densely packed pulmonary capillaries surround each alveolus, separated by a thin interstitial space.

• Alveolar pores (of Kohn): Small openings that allow collateral airflow and pressure equalization between adjacent alveoli.

4. Function

The alveoli are specialized for efficient gas exchange, serving several essential functions:

• Oxygen uptake: Oxygen diffuses from inhaled air across the alveolar wall into pulmonary capillaries.

• Carbon dioxide elimination: CO₂ diffuses from the blood into alveolar air to be exhaled.

• Surfactant production: Type II cells reduce surface tension to prevent alveolar collapse during exhalation.

5. Physiological Role(s)

Alveoli play a central role in maintaining homeostasis by supporting respiratory physiology:

• Large surface area: Enhances diffusion efficiency due to a high surface-to-volume ratio.

• Minimal diffusion distance: The thin barrier between alveolar air and blood allows rapid gas transfer.

• Elastic recoil: Alveolar walls contain elastic fibers that help with passive exhalation.

• Ventilation-perfusion coupling: Blood flow is matched to ventilation in alveolar units to optimize gas exchange.

• Defense mechanisms: Macrophages and epithelial secretions provide local immune protection.

6. Clinical Significance

Emphysema

A form of chronic obstructive pulmonary disease (COPD) characterized by the destruction of alveolar walls and airspace enlargement. This results in:

• Loss of surface area for gas exchange

• Reduced elasticity and air trapping

• Hypoxia and respiratory distress

Commonly caused by smoking and long-term air pollutant exposure.

Pulmonary Fibrosis

Chronic inflammation leads to scarring and thickening of the alveolar septa, impairing diffusion. Associated with:

• Dyspnea on exertion

• Restrictive lung patterns on spirometry

• Progressive respiratory failure

Acute Respiratory Distress Syndrome (ARDS)

A life-threatening condition where inflammation and capillary leakage flood alveoli with proteinaceous fluid. This leads to:

• Impaired gas exchange

• Decreased lung compliance

• Severe hypoxemia

Causes include sepsis, trauma, and pneumonia.

Neonatal Respiratory Distress Syndrome (NRDS)

Due to surfactant deficiency in premature infants, alveoli collapse after exhalation. Symptoms include:

• Grunting, retractions, cyanosis

• Ground-glass appearance on chest X-ray

Treated with exogenous surfactant and respiratory support.

Pneumonia

Infection causes inflammation and consolidation of alveoli. Common symptoms include:

• Fever, cough, purulent sputum

• Pleuritic chest pain

• Crackles and bronchial breath sounds

COVID-19 Pneumonitis

SARS-CoV-2 affects alveolar epithelial cells, especially type II pneumocytes, leading to:

• Diffuse alveolar damage

• Microvascular thrombosis

• Respiratory failure in severe cases