Type II Alveolar Cells

1. Overview

Type II alveolar cells, also known as Type II pneumocytes or granular pneumocytes, are specialized epithelial cells located in the alveoli of the lungs. Unlike the flat Type I cells responsible for gas exchange, Type II cells are cuboidal in shape and serve primarily as the source of pulmonary surfactant. They also act as progenitor cells for Type I pneumocytes and play a significant role in alveolar repair and immune modulation.

2. Location

Type II alveolar cells are found:

• Scattered among the Type I alveolar cells within the alveolar walls

• Located mostly at the alveolar corners, where they occupy junctions between adjacent alveoli

Though they make up only about 5%–10% of the alveolar surface area, they are more numerous than Type I cells and serve multiple essential functions.

3. Structure

Type II alveolar cells exhibit distinct histological and ultrastructural features:

• Shape: Cuboidal with a central nucleus

• Cytoplasm: Rich in mitochondria, endoplasmic reticulum, and lamellar bodies

• Lamellar bodies: Membrane-bound organelles containing surfactant components ready for secretion

• Microvilli: Short microvilli on the apical surface increase surface area for secretion

They are equipped for active protein synthesis and secretion, as well as cell division and differentiation into Type I cells following injury.

4. Function

Type II alveolar cells perform several vital functions:

• Surfactant production: Synthesize and secrete pulmonary surfactant, which reduces alveolar surface tension and prevents collapse (atelectasis)

• Alveolar repair: Serve as stem cells capable of proliferating and differentiating into Type I cells after lung injury

• Immune function: Release cytokines and antimicrobial peptides to modulate immune responses

5. Physiological Role(s)

In pulmonary physiology, Type II alveolar cells are essential for:

• Maintaining alveolar stability: Surfactant ensures that alveoli remain open, especially during expiration

• Enhancing lung compliance: Lower surface tension reduces the work of breathing

• Host defense: Act as immune sentinels and interact with alveolar macrophages

• Lung regeneration: Capable of re-epithelializing damaged alveolar surfaces, making them vital in recovery from respiratory injury

6. Clinical Significance

Neonatal Respiratory Distress Syndrome (NRDS)

In premature infants, underdeveloped Type II cells lead to insufficient surfactant production, causing alveolar collapse and impaired gas exchange. Managed with:

• Exogenous surfactant therapy

• Corticosteroids antenatally

• Mechanical ventilation or CPAP

Acute Respiratory Distress Syndrome (ARDS)

Type II pneumocytes are damaged in ARDS due to infection, trauma, or inflammation. This impairs surfactant secretion and increases alveolar permeability, leading to:

• Non-cardiogenic pulmonary edema

• Hypoxemia

• Respiratory failure

Pulmonary Fibrosis

Persistent alveolar injury can trigger maladaptive repair, where Type II cells excessively proliferate and promote fibrotic remodeling instead of regenerating Type I cells. Seen in conditions like:

• Idiopathic pulmonary fibrosis (IPF)

• Post-COVID fibrosis

Surfactant Protein Mutations

Mutations in genes like SFTPB, SFTPC, and ABCA3 affect surfactant production or secretion by Type II cells, leading to:

• Chronic interstitial lung disease

• Neonatal respiratory failure

COVID-19 and Viral Injury

SARS-CoV-2 infects Type II alveolar cells via the ACE2 receptor, leading to:

• Inflammation

• Alveolar damage

• Surfactant deficiency

This contributes to severe hypoxia and ARDS in COVID pneumonia.