Introduction

Carbon dioxide is formed intracellularly in the human body as a byproduct of metabolism. It is transported in the bloodstream to the lungs, where it is ultimately removed from the body through exhalation. CO₂ plays various roles in the human body, including regulating blood pH, respiratory drive, and hemoglobin's affinity for oxygen (O₂). Fluctuations in CO₂ levels are highly regulated and can cause disturbances in the human body if normal levels are not maintained.

Issues of Concern

CO2 retention is known as hypercapnia or hypercarbia. Hypercapnia is often caused by hypoventilation or failure to remove excess CO₂ and may be diagnosed by arterial or venous blood gas. Elevations of CO₂ in the bloodstream can lead to respiratory acidosis. Normal respiratory drive, and thus CO₂ exhalation, is primarily maintained by the chemoreceptor reflex. The chemoreceptor reflex is important in allowing the body to respond to changes in pO₂, pCO₂, and pH. Chemoreceptors can be categorized as peripheral or central. Peripheral chemoreceptors are located in the carotid and aortic bodies. The carotid body is the principal sensor of increased pCO₂, decreased pO₂, and decreased pH. The glomus cells of the carotid body relay changes in peripheral arterial pH to the central nervous system via the glossopharyngeal nerve.[1]

Central chemoreceptors are located near the ventrolateral surfaces of the medulla. While peripheral chemoreceptors are primarily sensitive to changes in O₂ and CO₂, central chemoreceptors are responsive to changes in pCO₂ and pH. Central chemoreceptors can detect changes in PCO₂ rapidly. The blood-brain barrier is permeable to CO₂, thus allowing chemosensitive cells within the medulla to respond to elevated CO₂ and the subsequently lowered pH. The decrease in pH of the cerebrospinal fluid ultimately increases minute ventilation, defined by the product of respiratory rate and tidal volume. Interestingly, central chemoreceptors have shown a greater response to hypercapnic acidosis than isocapnic acidosis, in part likely due to the impermeability of the blood-brain barrier to H+ ions.[2] As a result, the sympathetic outflow to the vasculature is increased, and efforts are made to increase the respiratory rate.[3][4][5]

Cellular Level

Cellular respiration converts ingested nutrients, such as glucose (C₆H₁₂O₆) and oxygen, to energy, adenosine triphosphate (ATP). CO₂ is produced as a byproduct of this reaction.

• C₆H₁₂O₆ + 6O₂ --> 6CO₂ + 6H₂O

The O₂ needed for cellular respiration is obtained via inhalation. The CO₂ that is generated is removed from the body via exhalation.

Organ Systems Involved

Together, the respiratory and circulatory systems play a remarkable role in the regulation of CO₂. While the respiratory system is responsible for gas exchange, the circulatory system is responsible for transporting blood and its components to and from the tissues. Gas exchange occurs in the lungs and tissues. During inspiration, air travels into the alveoli, the lungs' primary site of gas exchange. At the alveolar-capillary interface, O₂ freely diffuses into the blood, and CO₂ diffuses from the blood into the alveolar spaces. In contrast, gas exchange in the tissues results in the diffusion of CO₂ produced by respiration from the tissues into the blood. At the same time, O₂ is offloaded from hemoglobin in red blood cells to replenish tissue oxygen stores.[6][7] In the long term, respiratory acidosis is compensated by bicarbonate retention in the kidneys, which increases pH towards normal values.

Function

CO₂ is a regulator of blood pH. In the blood, CO₂ is carried in several different forms. Approximately 80% to 90% is dissolved in water, 5% to 10% is dissolved in the plasma, and 5% to 10% is bound to hemoglobin.

Related Testing

An arterial blood gas (ABG) is needed to evaluate patients with suspected hypercapnia. Hypercapnia is defined as a PaCO₂ greater than 42 mm Hg. If the PaCO₂ is greater than 45 mm Hg and the PaO₂ is less than 60 mm Hg, a patient is said to be in hypercapnic respiratory failure.

Pathophysiology

In the bloodstream, dissolved CO₂ is neutralized by the bicarbonate-carbon dioxide buffer system, forming a weak carbonic acid (H2CO3). H2CO3 can dissociate into a hydrogen ion and a bicarbonate ion. This buffer system allows the body to maintain physiologic pH.[8][9][10][11]

• CO₂ + H₂O --> H₂CO₃ --> H+ + HCO₃-

When CO₂ levels are high, there is a right shift in the reaction mentioned above. As a result, the concentration of H+ ions in the bloodstream rises, lowering the pH and introducing a state of acidosis. In contrast, when CO₂ levels are low, there is a left shift in the reaction, resulting in an alkalotic state.

Carbonic anhydrase catalyzes the conversion of CO₂ and water to H+ and bicarbonate.

• CO₂ + H₂O --> H+ + HCO₃-

Carbonic anhydrase helps to maintain the acid-base balance in the bloodstream and is present in high concentrations in erythrocytes. As levels of CO₂ in the blood begin to rise, the body can respond through hyperventilation or hypoventilation, respectively.

The CO₂ that is bound to hemoglobin forms a carbamino compound. In circumstances where the CO₂ and H+ concentrations are high, the affinity of hemoglobin for O₂ is decreased. When CO₂ concentrations are low, the affinity of hemoglobin for O₂ is increased. This is known as the Bohr effect. Conversely, if O₂ concentrations are high, there is increased unloading of CO₂ from the tissues. This is known as the Haldane effect.

Clinical Significance

A thorough history should be taken to understand any factors that may have precipitated signs and symptoms of hypercapnia. Patients with hypercapnia can present with tachycardia, dyspnea, flushed skin, confusion, headaches, and dizziness. If the hypercapnia develops gradually over time, symptoms may be mild or not present. Other cases of hypercapnia may be more severe and lead to respiratory failure. In these cases, symptoms such as seizures, papilledema, depression, and muscle twitches can be seen. If a patient with COPD presents with signs and symptoms of hypercapnia, immediate medical attention should be attained before CO2 reaches life-threatening levels.[12][13]

Hypercapnia should be managed by addressing its underlying cause. A noninvasive positive pressure ventilator may provide support to patients with inadequate respiratory drive. If a noninvasive ventilator is not efficient, intubation may be indicated. Bronchodilators may also be used in patients suffering from obstructive airway disease. Recent studies have also shown that the esophageal balloon is effective in managing hypercapnia in patients with acute respiratory distress syndrome.