Seminars in respiratory and critical care medicine最新文献

Gas exchange in the lung depends on tidal breathing, which brings new oxygen to and removes carbon dioxide from alveolar gas. This maintains alveolar partial pressures that promote passive diffusion to add oxygen and remove carbon dioxide from blood in alveolar capillaries. In a lung model without ventilation and perfusion (V̇_AQ̇) mismatch, alveolar partial pressures of oxygen and carbon dioxide are primarily determined by inspiratory pressures and alveolar ventilation. Regions with shunt or low ratios worsen arterial oxygenation while alveolar dead space and high lung units lessen CO₂ elimination efficiency. Although less common, diffusion limitation might cause hypoxemia in some situations. This review covers the principles of lung gas exchange and therefore mechanisms of hypoxemia or hypercapnia. In addition, we discuss different metrics that quantify the deviation from ideal gas exchange.

The pulmonary circulation is a low-pressure, low-resistance circuit whose primary function is to deliver deoxygenated blood to, and oxygenated blood from, the pulmonary capillary bed enabling gas exchange. The distribution of pulmonary blood flow is regulated by several factors including effects of vascular branching structure, large-scale forces related to gravity, and finer scale factors related to local control. Hypoxic pulmonary vasoconstriction is one such important regulatory mechanism. In the face of local hypoxia, vascular smooth muscle constriction of precapillary arterioles increases local resistance by up to 250%. This has the effect of diverting blood toward better oxygenated regions of the lung and optimizing ventilation-perfusion matching. However, in the face of global hypoxia, the net effect is an increase in pulmonary arterial pressure and vascular resistance. Pulmonary vascular resistance describes the flow-resistive properties of the pulmonary circulation and arises from both precapillary and postcapillary resistances. The pulmonary circulation is also distensible in response to an increase in transmural pressure and this distention, in addition to recruitment, moderates pulmonary arterial pressure and vascular resistance. This article reviews the physiology of the pulmonary vasculature and briefly discusses how this physiology is altered by common circumstances.

Pulmonary physiology is significantly altered during underwater exposure, as immersion of the body and increased ambient pressure elicit profound effects on both the cardiovascular and respiratory systems. Thoracic blood pooling, increased breathing gas pressures, and variations in gas volumes alongside ambient pressure changes put the heart and lungs under stress. Normal physiologic function and fitness of the cardiovascular and respiratory systems are prerequisites to safely cope with the challenges of the underwater environment when freediving, or diving with underwater breathing apparatus. Few physicians are trained to understand the physiology and medicine of diving and how to recognize or manage diving injuries. This article provides an overview of the physiologic challenges to the respiratory system during diving, with or without breathing apparatus, and outlines possible health risks and hazards unique to the underwater environment. The underlying pathologic mechanisms of dive-related injuries are reviewed, with an emphasis on pulmonary physiology and pathophysiology.

This article provides an overview of the journey of inspired oxygen after its uptake across the alveolar-capillary interface, and the interplay among tissue perfusion, diffusion, and cellular respiration in the transport and utilization of oxygen. The critical interactions between oxygen and its facilitative carriers (hemoglobin in red blood cells and myoglobin in muscle cells), and with other respiratory and vasoactive molecules (carbon dioxide, nitric oxide, and carbon monoxide), are emphasized to illustrate how this versatile system dynamically optimizes regional convective transport and diffusive gas exchange. The rates of reciprocal gas exchange in the lung and the periphery must be well-matched and sufficient for meeting the range of energy demands from rest to maximal stress but not excessive as to become toxic. The mobile red blood cells play a vital role in matching tissue perfusion and gas exchange by dynamically regulating the controlled uptake of oxygen and communicating regional metabolic signals across different organs. Intracellular oxygen diffusion and facilitation via myoglobin into the mitochondria, and utilization via electron transport chain and oxidative phosphorylation, are summarized. Physiological and pathophysiological adaptations are briefly described. Dysfunction of any component across this integrated system affects all other components and elicits corresponding structural and functional adaptation aimed at matching the capacities across the entire system and restoring equilibrium under normal and pathological conditions.

Substantial advances have been made recently into the discovery of fundamental mechanisms underlying the neural control of breathing and even some inroads into translating these findings to treating breathing disorders. Here, we review several of these advances, starting with an appreciation of the importance of V̇_A:V̇CO₂:PaCO₂ relationships, then summarizing our current understanding of the mechanisms and neural pathways for central rhythm generation, chemoreception, exercise hyperpnea, plasticity, and sleep-state effects on ventilatory control. We apply these fundamental principles to consider the pathophysiology of ventilatory control attending hypersensitized chemoreception in select cardiorespiratory diseases, the pathogenesis of sleep-disordered breathing, and the exertional hyperventilation and dyspnea associated with aging and chronic diseases. These examples underscore the critical importance that many ventilatory control issues play in disease pathogenesis, diagnosis, and treatment.

A fundamental task of the respiratory system is to operate as a mechanical gas pump ensuring that fresh air gets in close contact with the blood circulating through the lung capillaries to achieve O₂ and CO₂ exchange. To ventilate the lungs, the respiratory muscles provide the pressure required to overcome the viscoelastic mechanical load of the respiratory system. From a mechanical viewpoint, the most relevant respiratory system properties are the resistance of the airways (R _aw), and the compliance of the lung tissue (C _L) and chest wall (C _CW). Both airflow and lung volume changes in spontaneous breathing and mechanical ventilation are determined by applying the fundamental mechanical laws to the relationships between the pressures inside the respiratory system (at the airway opening, alveolar, pleural, and muscular) and R _aw, C _L, and C _CW. These relationships also are the basis of the different methods available to measure respiratory mechanics during spontaneous and artificial ventilation. Whereas a simple mechanical model (R _aw, C _L, and C _CW) describes the basic understanding of ventilation mechanics, more complex concepts (nonlinearity, inhomogeneous ventilation, or viscoelasticity) should be employed to better describe and measure ventilation mechanics in patients.

Aerobic, or endurance, exercise is an energy requiring process supported primarily by energy from oxidative adenosine triphosphate synthesis. The consumption of oxygen and production of carbon dioxide in muscle cells are dynamically linked to oxygen uptake (V̇O₂) and carbon dioxide output (V̇CO₂) at the lung by integrated functions of cardiovascular, pulmonary, hematologic, and neurohumoral systems. Maximum oxygen uptake (V̇O_2max) is the standard expression of aerobic capacity and a predictor of outcomes in diverse populations. While commonly limited in young fit individuals by the capacity to deliver oxygen to exercising muscle, (V̇O_2max) may become limited by impairment within any of the multiple systems supporting cellular or atmospheric gas exchange. In the range of available power outputs, endurance exercise can be partitioned into different intensity domains representing distinct metabolic profiles and tolerances for sustained activity. Estimates of both V̇O_2max and the lactate threshold, which marks the upper limit of moderate-intensity exercise, can be determined from measures of gas exchange from respired breath during whole-body exercise. Cardiopulmonary exercise testing (CPET) includes measurement of V̇O₂ and V̇CO₂ along with heart rate and other variables reflecting cardiac and pulmonary responses to exercise. Clinical CPET is conducted for persons with known medical conditions to quantify impairment, contribute to prognostic assessments, and help discriminate among proximal causes of symptoms or limitations for an individual. CPET is also conducted in persons without known disease as part of the diagnostic evaluation of unexplained symptoms. Although CPET quantifies a limited sample of the complex functions and interactions underlying exercise performance, both its specific and global findings are uniquely valuable. Some specific findings can aid in individualized diagnosis and treatment decisions. At the same time, CPET provides a holistic summary of an individual's exercise function, including effects not only of the primary diagnosis, but also of secondary and coexisting conditions.

The well-known ways in which O₂ and CO₂ (and other gases) are carried in the blood were presented in the preceding chapter. However, what the many available texts about O₂ and CO₂ transport do not emphasize is why knowing how gases are carried in blood matters, and this second, companion, article specifically addresses that critical aspect of gas exchange physiology. During gas exchange, both at the lungs and in the peripheral tissues, it is the shapes and the slopes of the O₂ and CO₂ binding curves that explain almost all of the behaviors of each gas and the quantitative differences observed between them. This conclusion is derived from first principle considerations of the gas exchange processes. Dissociation curve shape and slope differences explain most of the differences between O₂ and CO₂ in both diffusive exchange in the lungs and tissues and convective exchange/transport in, and between, the lungs and tissues. In fact, each of the chapters in this volume describes physiological behavior that depends more or less directly on the dissociation curves of O₂ and CO₂.

While static mechanical forces govern resting lung volumes, dynamic forces determine tidal breathing, airflow, and changes in airflow and lung volume during normal and abnormal breathing. This section will examine the mechanisms, measurement methodology, and interpretation of the dynamic changes in airflow and lung volume that occur in health and disease. We will first examine how the total work of breathing can be described by the parameters of the equation of motion, which determine the pressure required to move air into and out of the lung. This will include a detailed description of airflow characteristics and airway resistance. Next, we will review the changes in pressure and flow that determine maximal forced inspiration and expiration, which result in the maximal flow-volume loop and the clinically important forced expired volume in 1 second. We will also assess the mechanisms and interpretation of bronchodilator responsiveness, dynamic hyperinflation, and airways hyperresponsiveness.