The Pre-brief
Life starts and ends with a breath, thus making breathing synonymous with living. It is the fundamental process by which the respiratory system performs the two tasks for which it has been charged:
- To provide our cells with oxygen (O2) rich from the environment
- To remove carbon dioxide (CO2) from our cells and into the environment
These tasks are accomplished through mechanical effectors (lungs, large & small airways, chest wall, diaphragm) and central controllers (central nervous system, brain stem). Inability to effectively carry out either of its two tasks results in respiratory failure, an often-encountered clinical entity among hospitalized patients regardless of setting. Moreover, failure to effectively provide the cells with O2 and/or eliminate CO2 may yield pathophysiological changes that create an imbalance between work of breathing relative to the capacity of the respiratory muscles of an individual to achieve said work. This so-called “respiratory drive” and its varying degrees of intensity becomes a major factor in the progression of respiratory failure that ultimately leads to mechanical ventilation.
Defining the Respiratory Drive
Breathing is a centrally controlled process that, at baseline physiological states, is largely passive and occurs unnoticed. Respiratory drive is primarily derived by the intensity of signal output from respiratory centers located in the brain stem. These centers comprise a vast network of interconnected neurons that continuously interpret sensory input regarding physiochemical, emotional, and mechanical conditions, and generate neural output that determine the respiratory rate along with rhythm and pattern throughout each phase of the respiratory cycle.
Determinants of the Respiratory Drive
Arterial pH & Arterial Carbon Dioxide (pH & PaCO2)
The retrotrapezoid nucleus comprises a cluster of neurons located on the ventral surface of the medulla and play the most critical role in determining the respiratory drive. These central chemoreceptors detect changes in the pH of the cerebrospinal fluid (CSF) which is influenced by PaCO2. Because of its lipid soluble nature, CO2 freely diffuses across the blood-brain barrier affecting the pH of CSF through the generation of protons (H+). At baseline physiological states, there exists a tight balance between pH and PaCO2 that dramatically affects the respiratory drive if disturbed.
Arterial Oxygenation (PaO2)
The carotid bodies comprise a group of highly vascularized sensory organs located at the bifurcation of the common carotid artery. These peripheral chemoreceptors detect changes in arterial oxygenation, relaying this information via the ninth cranial nerve, to respiratory centers located in the pons and medulla. Sensory feedback from the carotid bodies is relatively constant over a wide range of PaO2, rising sharply below a PaO2 of 60 and is also potentiated by the presence of coexisting hypercapnia and acidosis.
Thoracic Neural Receptors
Neural receptors in the upper airways, lungs, chest wall, and pulmonary vasculature relay information regarding lung stretch, volume, and vascular congestion to the respiratory centers in the brain. Inspiratory time and tidal volume are influenced by pulmonary stretch receptors that relay inhibitory signals to the respiratory centers, ultimately terminating inspiration at adequate lung expansion; this is known as the Hering-Breuer reflex. J-receptors in the lung parenchyma and C-fibers in the small airways and pulmonary vasculature respond to interstitial edema and pulmonary vascular congestion, respectively.
Emotional Responses
The cerebral cortex, hypothalamus, and limbic structures play key roles in the interpretation of stimuli from the external environment. Emotions along with sensations such as fear, pain, anxiety, and discomfort are powerful stimuli that both directly and indirectly affect the respiratory drive through reflex mechanisms in the cortex and through behavioral responses, respectively.
The Debrief
- The primary purpose of the respiratory system is to effectively oxygenate the tissues and eliminate carbon dioxide.
- In the setting of disease, changes in the physiological environment can influence the intensity of signal output from the respiratory centers, dramatically affecting the respiratory drive.
- In the next article we will explore the impact of critical illness on the respiratory drive and its implications on clinical outcomes.
References
- Guyenet PG, Bayliss DA. Neural control of breathing and CO2 homeostasis. Neuron 2015;87:946-961.
- Kam K, Worrell JW, Janczewski WA, Cui Y, Feldman JL. Distinct inspiratory rhythm and pattern generating mechanisms in the preBötzinger complex. J Neurosci 2013;33:9235–9245.
- Blain GM, Smith CA, Henderson KS, Dempsey JA. Peripheral chemoreceptors determine the respiratory sensitivity of central chemoreceptors to CO(2). J Physiol. 2010 Jul 01;588(Pt 13):2455-71.
- Prabhakar NR, Peng YJ. Peripheral chemoreceptors in health and disease. J Appl Physiol (1985). 2004;96:359–66.
- Shi ZH, Jonkman A, De Vries H, et al. Expiratory muscle dysfunction in critically ill patients: towards improved understanding. Intensive Care Med. 2019;45:1061–71.
- Telias I, Brochard L, Goligher EC. Is my patient’s respiratory drive (too) high? Intensive Care Med 2018;44:1936–1939.
