Pulmonary PhysiologyEdit
Pulmonary physiology is the study of how the lungs and the respiratory system move air, exchange gases, and deliver oxygen to tissues while removing carbon dioxide. It sits at the intersection of anatomy, physics, chemistry, and neural control, explaining how ventilation, diffusion, perfusion, and metabolism work together to sustain cellular respiration and acid–base balance. In humans, the lungs are a paired organ system housed within the thoracic cavity, protected by the rib cage and powered by the diaphragm and chest wall muscles. The alveolar air–blood interface provides an immense surface area for gas exchange, while the pulmonary circulation brings blood to the site of exchange and the systemic circulation distributes oxygen to the rest of the body. A typical adult lung contains on the order of hundreds of millions of alveoli, yielding a surface area that supports rapid diffusion of oxygen and carbon dioxide under resting conditions and during physical activity. See also lung and alveolus.
The study of pulmonary physiology also encompasses how breathing is controlled, how gas transport is achieved in the blood, and how the system adapts to different environments, from sea level to high altitude, and from sedentary to highly trained exertion. The integration of ventilation with perfusion, the physics of air flow, and the chemistry of gas transport underpins many clinical measurements and interventions, such as arterial blood gases, spirometry, and diffusion capacity testing. See also respiratory physiology.
Anatomy and structure
The respiratory system consists of the conducting airways and the gas-exchanging units. Air enters through the nose or mouth, passes the trachea, and moves through the bronchi and progressively smaller airways to the terminal bronchiole, where gas exchange begins in earnest at the alveolar level. The airways are lined with mucosa and cilia that help filter and condition the air prior to reaching the alveolar space. The lungs contain two lobes on the left and three on the right, adapted to house the alveolar units while accommodating the position and size of the heart.
The primary sites of gas exchange are the alveolar sacs, where the thin alveolar epithelium forms a barrier with the surrounding capillary network. The alveolar epithelium comprises mostly two cell types: type I pneumocytes that cover most of the surface area and type II pneumocytes that secrete surfactant, a substance that reduces surface tension and helps stabilize alveoli during the breathing cycle. The alveolar-capillary membrane—consisting of the alveolar epithelium, the capillary endothelium, and the interstitial space—provides the thin barrier across which gases diffuse. See alveolus, type I pneumocytes, type II pneumocytes, and surfactant.
The chest wall, including the diaphragm and the intercostal muscles, moves to generate the pressure changes that drive ventilation. The pleural membranes create a thin, lubricated space that maintains negative pressure relative to the lungs and prevents collapse during most of the breathing cycle. The pulmonary circulation is a low-pressure, high-capacitance system that brings deoxygenated blood to the alveolar capillaries and returns oxygenated blood to the heart. See pleura and pulmonary circulation.
## Mechanics of breathing
Ventilation, the process of moving air in and out of the lungs, arises from rhythmic changes in intrathoracic pressure created by enlarging and shrinking the chest cavity. During inspiration, the diaphragm contracts and moves downward while the chest wall expands, lowering intrapulmonary pressure and drawing air into the airways. Expiration is usually passive at rest, as the elastic recoil of the lungs and chest wall returns the system to its resting position. At higher respiratory demands, expiratory muscles may actively contract to accelerate air expulsion.
Two key physical properties govern breathing: compliance and elastance. Pulmonary compliance describes how readily the lungs and chest wall expand for a given change in pressure; low compliance means stiffer lungs and greater work to breathe. Elastance is the tendency of the lungs to recoil; high elastance favors faster expiration. The balance of these properties, along with airway resistance, determines the work of breathing and the efficiency of ventilation. Surfactant, produced by type II pneumocytes, lowers surface tension and increases compliance, particularly in small airways. See compliance (physiology), elastance, and surfactant.
Ventilation is also influenced by intrapleural pressure, which becomes more negative during inspiration and less negative during expiration. The pattern of airflow follows physical laws of gas dynamics, including Boyle’s law, which relates pressure and volume in a closed system. See intrapleural pressure and gas laws.
Gas exchange and transport
Gas exchange occurs by diffusion across the thin alveolar-capillary membrane. Oxygen from the air dissolves in the alveolar fluid and diffuses into the blood, where it binds to hemoglobin in red blood cells for transport to tissues. Carbon dioxide, a metabolic waste product, diffuses from the blood into the alveolar air to be exhaled. The rate of diffusion depends on the surface area available (a large surface area in the lungs), the thickness of the membrane, the partial pressure gradient for each gas, and factors that affect diffusion distance and blood flow. See diffusion, hemoglobin, and oxygen.
Oxygen transport in the blood includes dissolved oxygen and oxygen bound to hemoglobin, with the latter providing the major reservoir for arterial oxygen content. The relationship between the partial pressure of oxygen and hemoglobin saturation is described by the oxyhemoglobin dissociation curve, which shifts with temperature, pH, and 2,3-bisphosphoglycerate levels. Carbon dioxide is transported in the blood primarily as bicarbonate after conversion by carbonic anhydrase, with a smaller fraction dissolved in plasma or bound to hemoglobin. See diffusion and carbonic acid-bicarbonate buffer.
The diffusion capacity of the lungs for carbon monoxide (DLCO) is a clinical measure of the ability of gases to diffuse across the alveolar-capillary membrane and reflects the combined effect of membrane thickness, surface area, and pulmonary capillary blood volume. DLCO testing, along with arterial blood gas analysis and spirometry, helps characterize ventilatory and gas-exchange defects. See DLCO and arterial blood gas.
Ventilation-perfusion balance is critical for efficient gas exchange. Regions of the lung with high ventilation but low perfusion, or vice versa, create mismatches that limit gas exchange. The body can adapt through mechanisms such as hypoxic pulmonary vasoconstriction and local regulation of perfusion to optimize the match. See ventilation-perfusion ratio and hypoxic pulmonary vasoconstriction.
Regulation of breathing
Breathing is regulated by neural and chemical feedback mechanisms. The respiratory center in the brainstem integrates sensory input and drives rhythmic ventilation. Chemoreceptors in the carotid bodies and the aortic bodies monitor arterial partial pressures of oxygen and carbon dioxide, and pH, providing critical information that modulates respiratory drive. Central chemoreceptors in the brain respond primarily to CO2 levels, while peripheral chemoreceptors respond to changes in O2. The system adjusts tidal volume and respiratory rate to meet metabolic demands during rest and activity. See respiratory center, carotid body, and aortic body.
During exercise or illness, the system adapts by increasing ventilation to maintain arterial gas tensions, facilitating higher oxygen delivery and CO2 removal. In certain pathological states, such as chronic lung disease, the regulatory system may operate under altered set-points, with implications for symptom burden and exercise tolerance. See exercise physiology and chronic obstructive pulmonary disease.
Pulmonary circulation and gas transport interplay
The lungs operate in concert with the cardiovascular system to optimize gas exchange. Blood is routed to well-ventilated alveolar regions to maximize oxygen uptake and carbon dioxide elimination. The concept of ventilation-perfusion (V/Q) matching describes how air flow and blood flow are coordinated to support efficient gas exchange. Abnormal V/Q relationships can contribute to hypoxemia even when the lungs appear structurally normal on imaging. See ventilation-perfusion ratio and blood gas.
Hypoxic regions trigger local vasoconstriction in the pulmonary circulation, a response known as hypoxic pulmonary vasoconstriction, which helps redirect blood flow to better-ventilated regions. This mechanism is important for maintaining systemic oxygen delivery but can contribute to pathophysiology in chronic lung disease or high-altitude exposure. See hypoxic pulmonary vasoconstriction.
Pathophysiology and clinical relevance
Pulmonary physiology underpins the understanding of common respiratory diseases and their management. Obstructive diseases (such as Chronic obstructive pulmonary disease and asthma) feature airflow limitation and changes in airway resistance, while restrictive diseases (such as interstitial lung disease and pulmonary fibrosis) involve reduced lung volumes and altered mechanics. Gas-exchange defects can arise from diffusion impairment, V/Q mismatch, or shunting, affecting arterial oxygen and carbon dioxide tensions. Clinically, pulmonary function is assessed with tools such as spirometry, plethysmography (body plethysmography), and DLCO testing, complemented by arterial blood gas analysis. See asthma, interstitial lung disease, pulmonary hypertension.
The study of pulmonary physiology also informs therapeutic and public-health decisions, including oxygen therapy, mechanical ventilation strategies, and exposure risk management. Research continues to refine our understanding of how best to optimize gas exchange, prevent ventilator-induced lung injury, and tailor interventions to individual physiology and activity patterns. See oxygen therapy and mechanical ventilation.
Controversies and debates
In clinical practice, several areas remain subject to debate and evolving evidence. For example, the optimal targets for oxygen therapy in hypoxemic patients are debated, balancing the hazards of hypoxia against potential oxygen toxicity from excessive oxygen administration. In acute respiratory failure and ARDS, ventilatory strategies—such as low tidal volume ventilation versus higher PEEP levels—have been refined over time, with ongoing trials assessing the best balance between lung protection and gas exchange. The adoption of high-flow nasal oxygen, noninvasive ventilation, and varying approaches to weaning from mechanical support also reflect competing interpretations of patient physiology and outcome data. See oxygen therapy, acute respiratory distress syndrome, and mechanical ventilation.
Another area of discussion concerns the interpretation of gas-exchange measurements in heterogeneous diseases. Diffusion capacity measurements (DLCO) can be influenced by multiple factors, including alveolar-capillary membrane thickness, capillary blood volume, and even body position during testing. As such, DLCO must be considered in the broader clinical and physiological context, not in isolation. See DLCO.
In public-health and policy spaces, debates about access to care, timely diagnosis, and the allocation of resources for respiratory screening and treatment intersect with pulmonary physiology in complex ways. A careful, evidence-based approach emphasizes understanding physiological limits while recognizing real-world constraints and patient-centered outcomes. See public health and health policy.