5 Respiratory System Physiology

How the respiratory system works

The respiratory system brings $\mathrm{O_2}$ into the body and removes $\mathrm{CO_2}$, a waste product of cellular metabolism. Its function depends on linked processes: pulmonary ventilation moves air to and from the lungs, gas exchange moves gases between air and blood and between blood and tissues, and blood transports the gases. Respiratory control adjusts ventilation to help maintain appropriate blood-gas levels and pH.

Ventilation and breathing mechanics

Pulmonary ventilation moves air because of pressure differences: air flows from higher pressure toward lower pressure. During quiet inhalation, the diaphragm contracts and flattens, while the external intercostal muscles help expand the chest. Thoracic and lung volume increase, lowering pressure in the alveoli below atmospheric pressure and drawing air inward.

During quiet exhalation, these muscles relax. Elastic recoil reduces lung volume and raises alveolar pressure, pushing air outward. Inhalation is normally active, while quiet exhalation is mostly passive.

Not all inhaled air reaches gas-exchanging surfaces. Anatomical dead space is air remaining in the conducting airways; alveolar dead space is additional air that reaches alveoli receiving little or no blood flow. Tidal volume is the air moved in an ordinary breath, and breathing rate is the number of breaths per minute.

Minute ventilation is the total volume of air moved per minute:

Alveolar ventilation estimates the fresh air reaching functioning alveoli each minute:

For a tidal volume of $500\,\mathrm{mL}$, dead space of $150\,\mathrm{mL}$, and a breathing rate of $12$ breaths per minute, minute ventilation is $6{,}000\,\mathrm{mL/min}$, while alveolar ventilation is $4{,}200\,\mathrm{mL/min}$. This illustrates why breathing depth matters: at the same minute ventilation, slower, deeper breaths generally devote a larger fraction of each breath to alveolar ventilation than rapid, shallow breaths.

Gas exchange and blood flow

Gas exchange occurs by diffusion: each gas moves down its own partial-pressure gradient. A gas’s partial pressure reflects its contribution to the total pressure of a gas mixture. Oxygen and carbon dioxide cross the thin respiratory membrane between alveoli and pulmonary capillaries. The membrane’s large surface area and short diffusion distance support efficient exchange.

In the lungs, alveolar oxygen partial pressure is typically higher than that of incoming pulmonary-capillary blood, so oxygen diffuses into blood. Blood arriving at the lungs has a higher carbon dioxide partial pressure than alveolar air, so carbon dioxide diffuses into the alveoli and is exhaled. At the tissues, the gradients are reversed: cells use oxygen and produce carbon dioxide, so oxygen moves from blood into tissues and carbon dioxide moves into blood. Exchange between alveoli and blood is external respiration; exchange between blood and tissues is internal respiration.

Effective lung gas exchange also requires suitable matching of ventilation, or air reaching alveoli, with perfusion, or blood flowing through surrounding capillaries. If an alveolus is poorly ventilated, local pulmonary arterioles constrict, tending to redirect blood toward better-ventilated regions. This response can improve matching, though disease or other disturbances may still impair overall gas exchange.

Oxygen transport

Only a small fraction of blood oxygen is dissolved in plasma. Most is carried by hemoglobin, a protein in red blood cells. Each hemoglobin molecule can bind up to four oxygen molecules. Oxygen binding is reversible: hemoglobin loads oxygen where oxygen partial pressure is high, especially in pulmonary capillaries, and releases it where oxygen partial pressure is lower, especially in tissues.

The oxygen–hemoglobin dissociation curve describes how hemoglobin saturation changes with oxygen partial pressure. Its S-shape reflects cooperative binding: binding one oxygen molecule makes subsequent binding easier. The curve’s plateau at high oxygen partial pressures helps hemoglobin remain highly saturated in the lungs, while its steeper portion at lower pressures supports oxygen unloading in tissues.

Increased carbon dioxide, increased acidity (lower pH), higher temperature, and increased 2,3-bisphosphoglycerate shift the curve to the right. This reduces hemoglobin’s oxygen affinity and favors oxygen release. In metabolically active tissues, the shift helps deliver more oxygen where it is needed. The effect of carbon dioxide and pH on hemoglobin’s oxygen binding is the Bohr effect.

Carbon dioxide transport

Carbon dioxide travels in blood in three main forms:

• Bicarbonate ions: The largest share is converted inside red blood cells. Carbonic anhydrase speeds the reversible reaction:

  $$\ \mathrm{CO_2 + H_2O \rightleftharpoons H_2CO_3 \rightleftharpoons H^+ + HCO_3^-}$$

  Bicarbonate then moves into plasma in exchange for chloride ions, a process called the chloride shift.

• Carbaminohemoglobin: Some carbon dioxide binds to parts of hemoglobin’s protein chains.

• Dissolved carbon dioxide: A smaller fraction is carried dissolved in plasma.

In the lungs, these reactions reverse: bicarbonate returns to red blood cells, is converted back to carbon dioxide, and diffuses into alveoli for exhalation. Oxygenation of hemoglobin also promotes carbon dioxide release; this interaction is the Haldane effect. Together with the Bohr effect, it helps coordinate oxygen delivery and carbon dioxide removal.

Control of breathing

Brainstem respiratory networks generate and adjust the basic breathing pattern, sending motor signals to the diaphragm and other respiratory muscles. The medulla helps establish the rhythm, while pontine input modifies the pattern and transitions between inhalation and exhalation. Breathing can be consciously altered for a time, but automatic control continues to respond to the body’s needs.

Chemoreceptors monitor changes that influence ventilation. Central chemoreceptors respond primarily to changes in acidity of the fluid surrounding the brain. Carbon dioxide crosses into this fluid and generates hydrogen ions, so rising arterial carbon dioxide usually increases respiratory drive. Peripheral chemoreceptors, located in the carotid and aortic bodies, respond to changes in arterial oxygen, carbon dioxide, and pH. Falling arterial oxygen becomes a particularly strong stimulus when oxygen partial pressure drops substantially.

When carbon dioxide rises or pH falls, ventilation generally increases, helping exhale more carbon dioxide and bring pH toward its usual range. When carbon dioxide falls, respiratory drive tends to decrease. During exercise, increased metabolism, signals from moving muscles and joints, and other inputs contribute to increased ventilation. Emotions, temperature, and voluntary control can also modify breathing.