The alveolar-capillary membrane represents one of the most remarkable engineering marvels in human physiology. This ultra-thin barrier, measuring only 0.2 to 0.5 micrometers in thickness, serves as the primary site where oxygen enters the bloodstream and carbon dioxide is eliminated from the body.
For respiratory therapists and healthcare professionals working in pulmonary medicine, understanding this structure is fundamental to comprehending gas exchange disorders and implementing effective therapeutic interventions.
What Is the Alveolar-Capillary Membrane?
The alveolar-capillary membrane, also referred to as the respiratory membrane, is a microscopic structure formed by the close contact between the walls of the alveoli (tiny air sacs in the lungs) and the walls of pulmonary capillaries. It serves as the site of gas exchange between the external environment and the circulatory system.
Anatomical Structure and Composition
The alveolar-capillary membrane, also known as the respiratory membrane or blood-gas barrier, consists of three distinct layers that work together to facilitate efficient gas exchange:
- Alveolar Epithelium: The innermost layer facing the alveolar air space is composed primarily of two cell types. Type I pneumocytes form the majority of the alveolar surface area and are extremely thin, allowing for optimal gas diffusion. Type II pneumocytes, while fewer in number, produce surfactant, a crucial substance that reduces surface tension and prevents alveolar collapse.
- Basement Membrane: This middle layer provides structural support and is formed by the fusion of the alveolar and capillary basement membranes. Despite being a shared structure, it maintains the integrity necessary for proper gas exchange while allowing rapid diffusion of respiratory gases.
- Capillary Endothelium: The outermost layer consists of the thin walls of pulmonary capillaries. These endothelial cells are specially adapted to minimize diffusion distance while maintaining the barrier function that prevents fluid from leaking into the alveolar space.
Physiological Function and Gas Exchange
The primary function of the alveolar-capillary membrane is to facilitate the diffusion of oxygen and carbon dioxide between the alveolar air and pulmonary blood circulation. This process occurs through passive diffusion, driven by concentration gradients across the membrane.
Oxygen moves from the alveolar air, where its partial pressure is approximately 100-105 mmHg, into the pulmonary capillary blood, where venous oxygen levels are around 40 mmHg. Simultaneously, carbon dioxide diffuses in the opposite direction, from the blood (where CO2 partial pressure is about 45 mmHg) into the alveolar air (where it’s approximately 40 mmHg).
The efficiency of this gas exchange depends on several factors, including membrane thickness, surface area available for diffusion, and the solubility and molecular weight of the gases involved. The membrane’s remarkable thinness ensures that diffusion occurs rapidly enough to meet the body’s metabolic demands.
Clinical Significance in Respiratory Care
For respiratory therapists, the alveolar-capillary membrane represents both the foundation of normal respiratory function and the primary site of pathology in many pulmonary diseases. Understanding its structure and function is essential for several reasons:
- Assessment and Monitoring: Respiratory therapists regularly evaluate gas exchange efficiency through arterial blood gas analysis, pulse oximetry, and other monitoring techniques. Abnormal values often indicate dysfunction at the alveolar-capillary level, requiring targeted interventions.
- Mechanical Ventilation Management: When providing mechanical ventilatory support, respiratory therapists must consider how different ventilator settings affect the alveolar-capillary membrane. Excessive pressures or volumes can damage this delicate structure, leading to ventilator-induced lung injury.
- Oxygen Therapy Optimization: The membrane’s characteristics directly influence how supplemental oxygen therapy should be administered. Understanding diffusion limitations helps therapists select appropriate oxygen delivery devices and flow rates.
Pathological Conditions Affecting the Membrane
Several disease processes can impair the function of the alveolar-capillary membrane, each requiring specific therapeutic approaches:
- Acute Respiratory Distress Syndrome (ARDS): This condition involves inflammation and damage to the alveolar-capillary membrane, leading to increased permeability, fluid accumulation, and severe gas exchange impairment. Respiratory therapists play a crucial role in managing ARDS patients through lung-protective ventilation strategies.
- Pulmonary Edema: Whether caused by cardiac or non-cardiac factors, pulmonary edema results in fluid accumulation that increases the diffusion distance across the membrane. This requires careful fluid management and often positive pressure ventilation to improve gas exchange.
- Pulmonary Fibrosis: Chronic conditions that cause scarring and thickening of the alveolar-capillary membrane significantly impair gas exchange. Respiratory therapists work with these patients to optimize oxygenation and provide supportive care as the disease progresses.
- Pneumonia: Infectious processes cause inflammation and fluid accumulation in the alveoli, disrupting normal gas exchange across the membrane. Treatment involves addressing both the infection and supporting respiratory function.
Therapeutic Interventions and Considerations
Respiratory therapists employ various strategies to support or protect the alveolar-capillary membrane:
- Positive End-Expiratory Pressure (PEEP): This ventilatory technique helps maintain alveolar recruitment and prevents repeated opening and closing of alveoli, which can damage the membrane. Proper PEEP selection requires understanding the membrane’s response to pressure changes.
- Prone Positioning: In patients with severe gas exchange impairment, prone positioning can improve ventilation-perfusion matching and reduce stress on the alveolar-capillary membrane in dependent lung regions.
- Surfactant Replacement Therapy: Particularly in neonatal care, respiratory therapists may administer exogenous surfactant to support the function of type II pneumocytes and maintain membrane stability.
- Pulmonary Rehabilitation: For patients with chronic conditions affecting the membrane, respiratory therapists design exercise programs and breathing techniques to optimize remaining lung function and improve quality of life.
Alveolar-Capillary Membrane Practice Questions
1. What is the function of the alveolar-capillary membrane in the lungs?
To facilitate gas exchange between alveoli and pulmonary capillaries.
2. Approximately how many alveoli are found in the adult human lungs?
Between 300 million and 600 million.
3. What are the three main types of alveolar cells?
Squamous pneumocytes, granular pneumocytes, and wandering macrophages.
4. What role do squamous pneumocytes play in the alveoli?
They allow gases to easily pass through for diffusion during gas exchange.
5. What is the function of granular pneumocytes?
They produce surfactant and assist with alveolar repair.
6. What is the purpose of alveolar surfactant?
It reduces surface tension within the alveoli, preventing their collapse.
7. What do wandering macrophages do in the alveoli?
They remove debris and pathogens to maintain clear airways.
8. What are the pores of Kohn?
Small openings between alveoli that permit macrophage movement and gas exchange between adjacent alveoli.
9. Which four layers make up the alveolar-capillary membrane?
Surfactant layer, alveolar epithelium, interstitial space, and capillary endothelium.
10. What is the role of the alveolar epithelium in the respiratory membrane?
It forms a structural layer through which gases diffuse.
11. What is found in the interstitial space of the alveolar-capillary membrane?
Interstitial fluid that separates the epithelial and capillary basement membranes.
12. What type of cells form the capillary endothelium?
Simple squamous epithelial cells.
13. Through what mechanism do gases cross the alveolar-capillary membrane?
Diffusion.
14. What is the first layer of the respiratory membrane?
The alveolar wall, containing type I and II pneumocytes and macrophages.
15. What forms the second layer of the respiratory membrane?
The epithelial basement membrane.
16. What is unique about the capillary basement membrane in the respiratory membrane?
It is often fused with the epithelial basement membrane.
17. What constitutes the final (fourth) layer of the respiratory membrane?
The endothelial cells of the pulmonary capillary.
18. What are the two types of arteries that supply blood to the lungs?
Pulmonary arteries and bronchial arteries.
19. What do pulmonary arteries carry?
Deoxygenated blood from the right ventricle to the lungs.
20. What do bronchial arteries do?
They deliver oxygenated blood from the aorta to nourish the lung tissue.
21. How do pulmonary vessels respond to localized hypoxia?
They vasoconstrict to redirect blood flow away from poorly ventilated areas.
22. What is the primary site of gas exchange in the lungs?
The alveolar sacs.
23. What percentage of total gas exchange occurs in the alveolar ducts?
Approximately 35%.
24. What percentage of total gas exchange occurs in the alveolar sacs?
Approximately 65%.
25. What structures mark the beginning of the respiratory zone of the lungs?
The respiratory bronchioles.
26. How many generations of respiratory bronchioles are typically present?
Three generations.
27. What follows the respiratory bronchioles in the airway branching?
Three generations of alveolar ducts.
28. What comes after the alveolar ducts in the airway anatomy?
15–20 alveolar sacs arranged in grapelike clusters.
29. What is another name for a primary lobule of the lung?
Acinus, lung parenchyma, or respiratory zone.
30. What is the function of the pores of Kohn besides cell migration?
They allow for collateral ventilation between alveoli.
31. What is the pulmonary interstitium?
A collection of supportive connective tissues in the lungs that contributes to the structure of the alveolar-capillary membrane.
32. What are the two major compartments of the pulmonary interstitium?
The tight space and the loose space.
33. What are the three cell types found in the alveolar epithelium?
Type I (squamous pneumocytes), Type II (granular pneumocytes), and Type III (alveolar macrophages).
34. What is the primary function of Type III alveolar cells?
To remove bacteria and foreign particles from the alveoli.
35. What percentage of the alveolar surface is formed by Type I cells?
Approximately 95%.
36. What is the main function of Type I alveolar cells?
They provide structural support and form the thin surface for gas exchange.
37. What percentage of the alveolar surface is covered by Type II cells?
Approximately 5%.
38. What is the primary role of Type II alveolar cells?
They produce and secrete pulmonary surfactant.
39. What is surface tension in the context of the alveoli?
It is the inward force created by liquid molecules attracting each other, which can lead to alveolar collapse.
40. How does surfactant affect surface tension in the lungs?
It reduces surface tension, preventing alveolar collapse.
41. What happens to surface tension as alveolar volume increases or decreases?
It increases with alveolar expansion and decreases with alveolar contraction.
42. What does Laplace’s law explain in lung physiology?
That smaller alveoli with equal surface tension are more prone to collapse into larger ones unless surfactant is present.
43. What is pulmonary surfactant made of?
A mixture of phospholipids and proteins.
44. What is the function of pulmonary surfactant?
To coat the alveoli and reduce surface tension, allowing them to stay open during exhalation.
45. What important lung component is lacking in premature infants?
Pulmonary surfactant.
46. What lung volumes are made possible by pulmonary surfactant?
Expiratory reserve volume and residual volume.
47. What is amniocentesis used for in relation to lung maturity?
To sample amniotic fluid and assess fetal lung development and surfactant levels.
48. When does surfactant production begin in fetal development?
Around the 23rd week of gestation.
49. At what gestational age do the lungs typically become capable of retaining air?
After 28 weeks of gestation.
50. At what gestational age is surfactant production typically sufficient for normal lung function?
Around 34–35 weeks of gestation.
51. What does an L/S (lecithin-to-sphingomyelin) ratio greater than 2:1 indicate?
That fetal lungs are mature and surfactant production is stable.
52. What does an L/S ratio of ≤1 indicate?
The fetus likely has immature lungs with insufficient surfactant, increasing the risk of respiratory distress.
53. What condition is caused by insufficient surfactant in newborns?
Infant Respiratory Distress Syndrome (IRDS).
54. What treatment can help manage IRDS in neonates?
Administration of biological or artificial surfactant.
55. What are some general causes of pulmonary surfactant deficiency?
Acidosis, hypoxia, hyperoxia, atelectasis, and pulmonary vascular congestion.
56. What are two specific clinical conditions linked to surfactant deficiency?
Acute Respiratory Distress Syndrome (ARDS) and Infant Respiratory Distress Syndrome (IRDS).
57. What is the role of the alveolar-capillary (A/C) membrane?
It allows for gas exchange by diffusion between alveoli and pulmonary capillaries.
58. What is diffusion in respiratory physiology?
The passive movement of gas molecules from areas of higher concentration to areas of lower concentration.
59. What is the normal capillary transit time for red blood cells in the lungs?
Approximately 0.25 to 0.75 seconds.
60. What does Henry’s Law state regarding gas exchange in the lungs?
The amount of gas that dissolves in a liquid is proportional to its partial pressure and solubility.
61. Which gas is more soluble in blood: CO₂ or O₂?
Carbon dioxide (CO₂) is more soluble than oxygen (O₂).
62. How much faster does carbon dioxide (CO₂) diffuse across the alveolar-capillary membrane compared to oxygen (O₂)?
Approximately 20 times faster.
63. What is the respiratory exchange ratio (RER)?
The ratio of carbon dioxide production to oxygen consumption, typically 200 mL/min to 250 mL/min, or 0.8.
64. What is the alveolar air equation used to estimate?
It estimates the partial pressure of oxygen in the alveoli (PAO₂) using the formula: PAO₂ = (PB – PH₂O) × FiO₂ – (PaCO₂ / R).
65. What is a typical value for the respiratory quotient (R) in the alveolar air equation?
0.8
66. What is polycythemia, and which patients commonly have it?
A condition with an abnormally high red blood cell count; it’s common in COPD patients.
67. How does the affinity of carbon monoxide (CO) for hemoglobin compare to oxygen (O₂)?
CO has 245 times greater affinity for hemoglobin than O₂.
68. What happens to pulmonary vessels when PaO₂ levels are low?
They constrict, helping to redirect blood flow to better-oxygenated areas of the lung.
69. What is the visceral pleura?
A membrane that covers the outer surface of the lungs and extends into the interlobular fissures.
70. What is the parietal pleura?
The membrane that lines the inner surface of the thoracic cavity.
71. What is the pleural cavity?
The potential space between the visceral and parietal pleurae.
72. What is the function of serous fluid in the pleural cavity?
It reduces friction and holds the pleural membranes together during breathing.
73. What is the natural tendency of the lungs?
To collapse inward due to their elastic recoil.
74. What is the natural tendency of the chest wall?
To expand outward.
75. Where is negative intrapleural pressure normally found?
In the space between the parietal and visceral pleurae.
76. What is thoracentesis?
A surgical procedure to remove fluid from the pleural space.
77. What is driving pressure in the context of respiratory physiology?
The pressure difference between two points in a tube or vessel that drives the movement of gas or fluid.
78. What is pleurodesis?
A medical procedure that eliminates the pleural space by causing adhesion between the pleural layers.
79. What does the transairway pressure gradient represent?
The pressure difference from the mouth to the alveoli.
80. What does transpleural pressure measure?
The pressure difference between the alveoli and the pleural space.
81. What does transthoracic pressure represent?
The pressure difference between the alveoli and the body surface.
82. What is transairway pressure (Pta) and how is it calculated?
Pta = Pm – Palv; it’s the pressure difference between the mouth and the alveoli.
83. What is transpulmonary pressure (Ptp) and how is it calculated?
Ptp = Palv – Ppl; it’s the difference between alveolar and pleural pressure.
84. What is transthoracic pressure (Ptt) and how is it calculated?
Ptt = Palv – Pbs; the difference between alveolar and body surface pressure.
85. What vital structures are protected by the thorax?
The heart, lungs, and spinal cord.
86. What is the manubrium?
The upper portion of the sternum.
87. What is the body of the sternum?
The middle and largest part of the sternum.
88. What is the xiphoid process?
The small, cartilaginous lower portion of the sternum.
89. How many thoracic vertebrae are in the human body, and what do they form?
There are 12 thoracic vertebrae, forming the posterior midline border of the thoracic cage.
90. How many intercostal spaces are there between the ribs?
There are 11 intercostal spaces.
91. What is empyema?
A condition characterized by a collection of pus in the pleural cavity.
92. What is flail chest?
A serious condition where multiple adjacent ribs are fractured in multiple places, resulting in chest wall instability.
93. What is the hallmark clinical sign of flail chest?
Paradoxical motion of the chest wall during breathing.
94. What are the accessory muscles of inspiration?
Scalene, sternocleidomastoid, pectoralis major, trapezius, and external intercostals.
95. What is the function of the scalene muscles in respiration?
They flex the neck and elevate the first and second ribs during inspiration.
96. What does the sternocleidomastoid muscle do during breathing?
It helps flex and rotate the head and elevate the sternum.
97. How does the pectoralis major assist in breathing?
It elevates the chest during labored breathing.
98. What role does the trapezius muscle play in respiration?
It helps raise the shoulders and assists in thoracic cage elevation.
99. What happens to the diaphragm during inspiration?
It contracts and flattens to increase thoracic volume.
100. What happens to the diaphragm during expiration?
It relaxes and moves upward into the thoracic cavity.
Final Thoughts
The alveolar-capillary membrane stands as a testament to the elegant efficiency of human respiratory physiology. For respiratory therapists, mastering the intricacies of this structure is not merely an academic endeavor—it forms the foundation for evidence-based practice and optimal patient care.
Every breath depends on the proper functioning of millions of these microscopic barriers, each working silently to sustain life. For respiratory care professionals, recognizing the critical importance of the alveolar-capillary membrane ensures that interventions are designed not just to treat symptoms, but to protect and support the fundamental processes that make breathing possible.
Written by:
John Landry is a registered respiratory therapist from Memphis, TN, and has a bachelor's degree in kinesiology. He enjoys using evidence-based research to help others breathe easier and live a healthier life.
References
- Powers KA, Dhamoon AS. Physiology, Pulmonary Ventilation and Perfusion. [Updated 2023 Jan 23]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2025.