Lung Function In Health And Disease: Basic Concepts of Respiratory Physiology and Pathophysiology

This chapter reviews major steps in the history of respiratory physiology, without laying claims to completeness. Throughout the centuries, the growth to present knowledge of pulmonary physiology and pathophysiology has not been a smooth steady climb, but rather a slow, often clumsy, walk punctuated by clever inventions, startling discoveries and amazing insights, but also by backward steps, misunderstandings, mistakes, controversies, rediscoveries, conflicts, prejudices and superstitions. In this brief review, we will travel in time from centuries before common-era to present, witnessing the progress of knowledge through periods such as the Greco-Roman era, the Middle Ages, the Renaissance, the 17^th, 18^th, 19^th and early 20^th centuries, the three golden decades of the 20th century (1940-1970) and beyond.

This chapter briefly reviews major elements of pulmonary anatomy and histology. In particular, it describes the anatomy of lungs, airways, respiratory muscles and nerves, and both vascular and lymphatic circulation. It reviews the histology of airways: nose, pharynx, larynx, trachea, bronchi, bronchioles, alveolar ducts, alveolar sacs and alveoli. The histology of the pleura and neuroreceptors is also briefly described.

This chapter focuses on the elastic properties of the respiratory system and on the mechanisms by which gases are flown in and out of the lungs during the breathing cycle. It begins by defining the lung volumes (capacities) and describing methods used for measuring them. Then, it describes the mechanisms of inspiration and expiration and the relationship between respiratory muscles and elastic characteristics of the respiratory system. The properties of respiratory mechanics are then divided into two sections: static and dynamic. Static mechanics deals with elastic characteristics of lungs, chest wall and the combined lungs + chest wall system, and with methods used for quantifying them. The relevance of surface tension and surfactant in modulating lung compliance and in maintaining the alveoli dry is discussed in detail. Dynamic mechanics discusses how gases flow through airways during the breathing cycle. Alveolar and intra-pleural pressures changes during normal breathing and while breathing through narrowed airways are described, as well as mechanism causing airway collapse in patients with loss of lung elasticity (emphysema), or suffering from extra-thoracic airway obstruction. The last two sections deal with the work of breathing and the most common pulmonary function tests.

This chapter focuses on the mechanisms of gas exchange between lungs and environment. In particular, it describes the changes in gas composition and physical property that take place as gases are flown in and out of the lungs. It explains the meaning of anatomical (conductive) dead space and describes methods for quantifying dead space, alveolar ventilation, oxygen consumption and carbon dioxide production. It introduces concepts of ideal versus average alveolar ventilation, alveolar dead space ventilation, right-to-left blood shunt (venous admixture), and body gas stores. It begins to explain how the complex relationship between alveolar ventilation and blood perfusion can be simplified into a “three compartment model” of the real lung. Finally, the relationship among alveolar ventilation, arterial PCO2 and metabolic rate is discussed and presented quantitatively.

The primary function of the respiratory system is to supply oxygen (O2) and eliminate carbon dioxide (CO2), a task that is accomplished in conjunction with the circulatory system, which transports these gases between the lungs and peripheral tissues. This chapter covers the principles and mechanisms involved in the transport of O2 and CO2 in the blood. In particular, it discusses the passive diffusion of gases across the alveolar blood-gas barrier and related factors, and the physical laws and gas properties; it provides a comparison of gas transfer profiles among O2, CO2, carbon monoxide, and nitrous oxide; it defines the lung diffusion capacity (transfer factor) and its measurement; it describes the function of hemoglobin in the transport of O2, the hemoglobin-oxygen dissociation curve, and the factors that regulate hemoglobin oxygen affinity; and finally, it describes the transport of CO2 in the blood, the role of carbonic anhydrase, and the Haldane effect.

This chapter deals with acid-base homeostasis with special emphasis on the role of the respiratory system. After explaining why maintaining a relatively constant proton activity is critical to optimal cellular function we define acid-base balance and describe the basic mechanisms responsible for acid-base homeostasis. After describing the unique role of the HCO₃^-/CO₂ buffer pair in acid-base regulation the four primary acid-base disturbances are defined. Finally an extensive outline is presented of the various approaches for the evaluation of acid-base disorders followed by examples and a few clinical cases.

This chapter focuses on the relationship between alveolar ventilation and blood perfusion in normal and diseased states. In particular, it explains the reasons for different ventilation-perfusion ratios among lung regions. It explains the functional consequences of pulmonary diseases that alter the ventilation-perfusion ratio, and demonstrates how ventilation-perfusion abnormalities can be quantified. It describes in more detail the “three compartment model” (equivalent of the real lung), the methods used to quantify the fraction of pulmonary blood that does not undergo gas exchange (right-to-left blood shunt or venous admixture) and those used for differentiating between the two major components of venous admixture: maldistribution shunt-like effect and conductive (anatomical) shunt. The various normal and abnormal conditions that result in venous admixture (right-to-left blood shunt) are schematically represented, and the method for quantifying the fraction of alveolar ventilation wasted in alveolar dead space is described. Finally, pros and cons of oxygen therapy and potential complications of prolonged lung exposure to high O2 fractions, leading to oxygen toxicity, are detailed.

The automatic rhythm of breathing is generated by specialized neurons of the medulla oblongata: the Dorsal Respiratory Group (DRG) and the Ventral Respiratory Group (VRG). The DRG represents the “inspiratory center” whereas the VRG is mostly expiratory; the caudal portion of VRG, together with the Bötzinger complex in its vicinity, constitutes the “expiratory center”. Normally, inspiration occurs actively via signals from the inspiratory neurons to the inspiratory muscles (mainly the diaphragm). Expiration occurs passively owing to the elastic recoil of the lungs. Expiratory neurons are activated only under certain conditions such as increased physical activity. The Pontine Respiratory Group (PRG, upper pons) represents the “pneumotaxic center”, which acts as an “off” switch controlling the point at which inspiration is terminated and therefore determining the depth and frequency of breathing. Ventilation is also subject to direct voluntary control by the cerebral cortex, as it occurs during such maneuvers as breath holding. The activity of the respiratory centers is constantly modified in response to feedback from a variety of sensors in the periphery as well as within the brain. Both the long term and the moment-to-moment regulation of alveolar ventilation are primarily the task of chemosensitive cells in the ventrolateral aspect of the medulla (central chemoreceptors) and in the carotid and aortic bodies (the peripheral chemoreceptors). These chemical sensors monitor the levels of CO₂, O₂, and H⁺ in arterial blood.

This chapter describes the physiological changes that occur when the organism is subjected to physical exercise, from resting state, at sea level and at high altitude. In particular, it focuses on compensatory mechanisms that regulate major respiratory functions, such as: gas exchange, ventilation-perfusion distribution, tissue oxygenation, pulmonary and systemic circulation, and acid-base balance. In addition, mechanisms involved in acclimatization to high altitude, acute and chronic mountain sickness, and adaptation to high altitude are briefly described.

This chapter briefly details the major functional consequences of pulmonary diseases. In particular, respiratory disorders are reviewed in terms of their etiopathology and effects on alveolar dead space, conductive shunt, maldistribution shunt-like effect, diffusion impairment, partial pressure of arterial blood gases, acid-base balance, tissue oxygenation, pulmonary circulation, mechanics (static and dynamic) and control of breathing.