Another important ventilatory response occurs to alterations in acid-base status. When oxygen delivery can no longer meet tissue metabolic needs, anaerobic metabolism ensues and causes excess metabolic acid production (i.e., metabolic acidosis). Ventilation increases as pH is lowered, and elimination of additional CO2 aids in returning the blood pH toward normal. The peripheral chemoreceptors appear to be primarily responsible for sensing acute metabolic acidosis and stimulating the increase in ventilation, but the degree to which the central chemoreceptors modify or contribute to this response is not entirely settled.

Respiratory muscles

The purpose of signals emanating from the respiratory generator is to initiate inspiratory muscle activity. Although the primary inspiratory muscle is the diaphragm, other muscle groups contribute to optimal movement of the chest wall under a variety of conditions and needs. Notable among these other inspiratory muscle groups are the scalene and parasternal intercostal muscles, which display inspiratory activity even during normal quiet breathing. The so-called accessory muscles of inspiration (e.g., sternocleidomastoid and trapezius muscles) are not normally used during quiet inspiration but can be recruited when necessary, either when diaphragm function is impaired or when ventilation is significantly increased. Another set of intercostal muscles, the external intercostal muscles, are also inspiratory muscles, but their overall importance during inspiration is less clear. Finally, additional muscles coordinate upper airway activity during inspiration. Proper functioning of these muscles maintains patency of the upper airway, whereas dysfunction may be important in the pathogenesis of certain clinical disorders associated with upper airway obstruction, such as obstructive sleep apnea (see Chapter 18).

The diaphragm is the major muscle of inspiration. The less important inspiratory and accessory muscle activity is increased during exercise and disease states.

During inspiration, the diaphragm contracts and its muscle fibers shorten. To understand the effect of this contraction, consider the configuration of the diaphragm within the chest. At its lateral aspect, the diaphragm is adjacent to the inner part of the lower rib cage. This portion of the chest wall and the diaphragm is known as the zone of apposition (Fig. 17.5). In this region, the muscle fibers of the diaphragm are oriented vertically. When the diaphragm contracts, shortening of these vertically oriented fibers diminishes the zone of apposition and causes the more medial dome of the diaphragm to descend. At the same time, by pushing abdominal contents downward, diaphragmatic contraction increases both intraabdominal pressure and the lateral pressure on the lower rib cage transmitted through the apposed diaphragm. The effect of diaphragmatic contraction is thus to lift the lower ribs and expand the lower chest wall at the same time the abdominal wall moves outward. The external intercostal muscles, located between the ribs, also contract during inspiration, contributing as well to the lower rib cage being lifted and rotated outward.

ventilation, or certain disease states, the accessory muscles are additionally recruited to assist the primary inspiratory muscles.

An important determinant of the efficacy of diaphragmatic contraction is the initial shape and length of the diaphragm. For any muscle, the strength of contraction is decreased when its initial length is shorter. The diaphragm is no exception. Therefore, at high lung volumes, the diaphragm is lower and foreshortened before its active contraction, so the strength of contraction is diminished. At the same time, the lower, flatter diaphragm means that the zone of apposition is decreased, with less downward movement of the diaphragm and outward movement of the lower chest wall associated with inspiration. At the extreme, the diaphragm is flattened and horizontally (axially) oriented, there is no zone of apposition, and contraction draws in the lower rib cage but provides no useful inspiratory function. The importance of these factors will become apparent in the discussion of diaphragmatic function in obstructive lung disease, in which resting lung volume may be abnormally high and, even before contraction, the diaphragm is in a flatter, more horizontal and less efficient position.

The effectiveness of diaphragmatic contraction is decreased at high resting lung volumes when the diaphragm is flatter and shorter.

In contrast to inspiration, expiration is a relatively passive process in which the lung and chest wall return to their resting positions. However, when breathing is deep and forceful, when airway resistance is increased during expiration, or when a person coughs, the action of expiratory muscles may be important in aiding expiratory airflow. In particular, abdominal muscles (transverse abdominis, internal and external obliques) and internal intercostals are important in this role.

In summary, normal operation of the respiratory apparatus depends on signals generated by the respiratory center which are translated into an efficient pattern of respiratory muscle contraction. Although feedback and control systems ensure optimal functioning of this process, this finely coordinated mechanism may fail in numerous ways. Chapters 18 and 19 examine clinically important dysfunction occurring at various levels of this complex system.

Suggested readings

Respiratory control

Chowdhuri S. & Badr M.S. Control of ventilation in health and disease Chest 2017;151: 917-929.

Di Lascio S, Benfante R, Cardani S. & Fornasari D. Research advances on therapeutic approaches to congenital central hypoventilation syndrome (CCHS) Frontiers in Neuroscience 2021;14: 615666.

Garcia A.J,III, Zanella S, Koch H, Doi A. & Ramirez J.M. Chapter 3—Networks within networks: The neuronal control of breathing Progress in Brain Research 2011;188: 31-50.

Hedemark L.L. & Kronenberg R.S. Chemical regulation of respiration. Normal variations and abnormal responses Chest 1982;82: 488-494.

Ikeda K, Kawakami K, Onimaru H, Okada Y, Yokota S, Koshiya N., et al. The respiratory control mechanisms in the brainstem and spinal cord: Integrative views of the neuroanatomy and neurophysiology Journal of Physiological Sciences 2017;67: 45-62.

Muñoz-Ortiz J, Muñoz-Ortiz E, López-Meraz M.L, Beltran-Parrazal L. & Morgado-Valle C.

Pre-Bötzinger complex: Generation and modulation of respiratory rhythm Neurologia