In… out… It seems so simple, but there is much more to respiration than air entering our lungs and appearing in our cells. A lot happens during these five seconds – you only have to think back on the litany of pulmonary volumes, capacities and graphs from your first year. Whether 

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Pulmonary ventilation

During inspiration, air is actively drawn into the lungs by the diaphragm and external and internal intercostal muscles. Accessory muscles such as the sternocleidomastoid and the anterior serrati come into play during labored breathing. In contrast, normal expiration is a passive process whereby the lungs are compressed by the elastic recoil of the lungs, rib cage and diaphragm. We can also force expiration with the use of abdominal and internal intercostal muscles.

Lining the chest cavity and wrapping the outside of your lungs, there is a membrane called the pleura. Between the two pleural layers is a small space normally filled with fluid. This fluid helps the pleura glide across each other smoothly during ventilation. The amount of pleural fluid, which is controlled through lymphatic drainage, also determines the pressure in the pleural space. This intrapleural pressure is formed by the opposing forces. The elasticity of the lungs and surface tension of alveolar fluid pull the lungs inward, whereas the elasticity of the chest wall pulls the lungs outward. Ultimately, the latter is slightly greater, creating a negative intrapleural pressure of -5 to -8 cmH2O. 

Lung compliance describes expandability, which is a function of alveolar surface tension and elastin and collagen fibers. Respiratory resistance describes the frictional forces in the airway and the elastic recoil of the thorax. These concepts can be represented in a compliance diagram, where inspiration and expiration produce the bottom and top curve, respectively. The total work of breathing is the area between the two curves, and compliance is the area of a triangle with the y-axis and midline of the loop as its sides.

The normal range of respiratory rate for adults is 12-16 breaths per minute, although this number is much higher in children. In a healthy, young adult, the volume of air in each breath is around 500mL (tidal volume, V_T). The volume of air that can be inspired or expired with full force is called the inspiratory or expiratory reserve volume (IRV or ERV), respectively. Residual volume (RV) is the air that cannot be expired, which gradually increases with age. Combinations of these volumes will give us four pulmonary capacities:

• Inspiratory capacity: total volume that can be inspired (V_T + IRV)
• Functional reserve capacity (FRV): volume left after normal expiration (RV + ERV)
• Vital capacity (FVC): volume expired after a full inspiration (V_T + IRV + ERV)
• Total lung capacity: maximum volume of the lungs

There are numerous respiratory function tests that estimate pulmonary volumes and capacities. Spirometry is the most common and measures expiratory volume (FEV1) and vital capacity (FVC) in a forced breath. Their ratio, FEV1/FVC, is normally around 75% and can be used to distinguish obstructive and restrictive lung disease. In obstructive lung disease, the airways are narrowed, making it difficult to exhale quickly (e.g. asthma, COPD, cystic fibrosis); thus, the FEV1/FVC ratio will decrease. In restrictive lung disease, the volume of the lungs is decreased (e.g. scoliosis, kyphosis, interstitial lung disease); both FEV1 and FVC will reduce and their ratio will remain at 75%.

Alveolar diffusion

Air passes from the upper (nasal cavity, pharynx, larynx) to the lower respiratory tract (trachea, bronchi, bronchioles, alveoli). The water vapor and CO₂ in the airways mix with the atmospheric air to dilute the O₂ partial pressure to 104 mmHg, and increase the CO₂ partial pressure to 40 mmHg. The air must then diffuse through a layer of surfactant, alveoli and endothelium to finally end up in the blood. Several factors influence the diffusion rate of gases across the respiratory membrane, such as the membrane’s thickness and surface area. The upper lung is relatively poorly vascularized, creating a dead space where the alveolar air is not being made use of fully. In contrast, the lower lung can only expand to a limited extent, creating a physiological shunt where there is an “excess” of blood in comparison to a lack of ventilation.

Gas transport

The oxygenated blood from the lungs and deoxygenated blood from the coronary and bronchial veins mix in the left atrium, decreasing the partial pressure of O₂ to 95 mmHg. This will drop further to 40 mmHg in peripheral capillaries and veins as O₂ is released to tissues. Most (97%) of the oxygen in blood is bound to hemoglobin, and 3% is in a dissolved form. The level of hemoglobin saturation primarily determines how much oxygen can be present in blood. With a saturation of 97% in arteries, the O₂ partial pressure is 95 mmHg. However, the partial pressure starts dropping drastically as saturation falls below 90%, requiring action to prevent hypoxia.

The O₂-hemoglobin dissociation curve describes this relationship between hemoglobin saturation and O₂ partial pressure. However, certain conditions will cause this curve to shift. A low blood pH, high CO₂ concentration and high temperature will cause hemoglobin to release O₂ more easily, rotating the curve to the right (a.k.a. the Bohr effect). The opposite of these conditions will conversely rotate the curve to the left. The remarkable ability of hemoglobin to adapt its O₂ affinity in different conditions allows it to maintain an almost constant O₂ level in tissues.

Guyton and Hall, figure 41-8

The process of CO₂ transport begins at the other end: the tissues. CO₂ partial pressure is 46 mmHg in cells and then drops to 40 mmHg in the alveoli. Most of the CO₂ is transported in the form of a bicarbonate ion, but some of it is dissolved or bound to hemoglobin. Similar to how a rise in CO₂ concentration displaced O₂ from hemoglobin, the binding of O₂ to hemoglobin displaces CO₂ from the blood and into the alveoli (the Haldane effect).

Regulation of respiration

Ventilation is regulated by the respiratory center in the medulla oblongata, which has 3 parts. The dorsal respiratory group generates the basic rhythm of breathing, where exhalation takes longer than inhalation. The ventral respiratory group comes into action during strenuous breathing by causing forceful inspiration and expiration. And the pneumotaxic center limits the duration of inspiration, thereby increasing the rate of breathing.

The respiratory center cannot function on its own, however, as it needs to respond to specific levels of CO₂ and O₂. Central chemoreceptors detect the level of CO2 and H⁺ and increase ventilation. This stimulatory effect is most important during the first two days, after which the effect diminishes. Peripheral chemoreceptors in the carotid and aortic bodies are exposed to arterial blood and are stimulated by low O₂ partial pressure. The effect is particularly strong when O2 falls below 60-80 mmHg. These receptors can also be stimulated by a raised CO₂ or H⁺ concentration, which produces a quick but weak increase in ventilation; this effect is thought to be especially important at the onset of exercise.