Carbon dioxide (CO2) is a colorless gas that comprises approximately 0.04% of Earth’s atmosphere. In the human body, carbon dioxide is formed from the metabolism of carbohydrates, fats, and amino acids, in a process known as cellular respiration. While cellular respiration is notable for being a source of ATP, it also generates the waste product, CO2. The body gets rid of excess CO2 by breathing it out. However, CO2 in its normal range from 38 to 42 mm Hg plays various roles in the human body. It regulates the pH of blood, stimulates breathing, and influences the affinity hemoglobin has for oxygen (O2). Fluctuations in CO2 levels are highly regulated and can cause disturbances in the human body if normal levels are not maintained.
CO2 retention is known as hypercapnia. Hypercapnia is usually due to hypoventilation or increased dead space in which the alveoli are ventilated but not perfused. In a state of hypercapnia or hypoventilation, there is an accumulation of CO2. The increased CO2 causes a drop in pH, leading to a state of respiratory acidosis. 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 positioned in the carotid and aortic bodies. Central chemoreceptors are located near the ventrolateral surfaces of the medulla. While peripheral chemoreceptors are sensitive to changes in mostly O2 and CO2 and pH to a lesser degree, central chemoreceptors are sensitive to changes in pCO2 and pH. The glomus cells in the carotid and aortic bodies detect states of hypoxia, hypercapnia, and acidosis. On the other hand, central chemoreceptors do not detect states of hypoxia. They detect a change in PCO2 very rapidly because CO2 diffuses through the blood-brain barrier (BBB) and into the CSF easily. On the other hand, central chemoreceptors take longer to detect a change in arterial pH because H+ does not cross the BBB. When a state of hypercapnia is introduced, central chemoreceptor activity is increased. As a result, the sympathetic outflow to the vasculature is increased, and efforts are made to increase the respiratory rate.
Cellular respiration is the process of converting ingested nutrients by combining it with O2 in tissues to produce energy in the form of ATP. The following chemical reaction represents it.
C6H12O6 + O2 -> 6CO2 + 6H2O
The O2 needed for cellular respiration is obtained during inhalation. The CO2 that is generated is removed from the body during exhalation.
The respiratory and circulatory systems, in conjunction, 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 the tissues. During inspiration, air travels ultimately from the atmosphere into the alveoli where it begins the process of gas exchange. At the alveolar-capillary interface, O2 is released into blood and CO2 is taken up by the alveoli. In contrast, gas exchange in the tissues releases the CO2 into the blood and picks up O2 from the blood so that O2 can be delivered to the tissues. The gases are exchanged via simple diffusion from an area of higher pressure to lower pressure.
CO2 is a regulator of blood pH. In the blood, CO2 is carried in several different ways. Approximately 80% to 90% of it dissolves in water, 5% to 10% dissolves in the plasma, and 5% to 10% is bound to hemoglobin.
An arterial blood gas (ABG) is needed to evaluate patients with suspected hypercapnia. Hypercapnia is defined as the PaCO2 being 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 in hypercapnic respiratory failure.
When CO2 dissolves in water, it forms a weak acid known as carbonic acid, H2CO3. H2CO3 can dissociate into a hydrogen ion and bicarbonate ion. The following chemical reaction represents this process.
CO2 + H2O -> H2CO3 -> H+ + HCO3-
A solution is acidic when H+ ions are lost in solution. When CO2 levels are high, there is a right shift in the reaction mentioned above. As a consequence, the pH decreases, introducing a state of acidosis. In contrary, when CO2 levels are low, there is a left shift in the reaction. In that case, the pH increases because of a decrease in the concentration of H+ ions, introducing a state of alkalosis. CO2 also allows for the formation of a buffer system that maintains blood pH in a normal range. H2CO3 neutralizes the base that is responsible for increasing blood pH, whereas HCO3- neutralizes the acid that is responsible for decreasing blood pH.
An important enzyme that catalyzes the conversion of
CO2 + H2O -> H+ + HCO3-
is carbonic anhydrase. Carbonic anhydrase also helps maintain the acid-base balance in the blood and is present in high concentrations in erythrocytes. In response to increased or decreased levels of CO2 in the blood, the body can respond by hyperventilating or hypoventilating, respectively.
The CO2 that is bound to hemoglobin forms a carbamino compound. In circumstances where the CO2 and H+ concentrations are high, there is decreased the affinity of hemoglobin to carry O2. If CO2 concentrations are low, there is increased the affinity of hemoglobin to carry O2. This is known as the Bohr effect. On the other hand, if O2 concentrations are high, there is an increased capacity to unload CO2 from the tissues. This is known as the Haldane effect.
A thorough history should be taken to gain an understanding of 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 may not be present at all. 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.
Hypercapnia should be managed by addressing its underlying cause. A noninvasive positive pressure ventilator may provide support to patients who are having trouble breathing normally. If a noninvasive ventilator is not efficient, intubation may be indicated. Bronchodilators may also be used in patients suffering from an obstructive airway disease.
In recent studies, the use of the esophageal balloon in managing hypercapnia in a patient with acute respiratory distress syndrome was also shown to be effective.
|||Vasileiadis I,Alevrakis E,Ampelioti S,Vagionas D,Rovina N,Koutsoukou A, Acid-Base Disturbances in Patients with Asthma: A Literature Review and Comments on Their Pathophysiology. Journal of clinical medicine. 2019 Apr 25; [PubMed PMID: 31027265]|
|||Baillieul S,Revol B,Jullian-Desayes I,Joyeux-Faure M,Tamisier R,Pépin JL, Diagnosis and management of central sleep apnea syndrome. Expert review of respiratory medicine. 2019 Apr 24; [PubMed PMID: 31014146]|
|||Bigatello L,Pesenti A, Respiratory Physiology for the Anesthesiologist. Anesthesiology. 2019 Apr 12; [PubMed PMID: 30998510]|
|||de Carvalho M,Swash M,Pinto S, Diaphragmatic Neurophysiology and Respiratory Markers in ALS. Frontiers in neurology. 2019; [PubMed PMID: 30846968]|
|||Eikermann M,Santer P,Ramachandran SK,Pandit J, Recent advances in understanding and managing postoperative respiratory problems. F1000Research. 2019; [PubMed PMID: 30828433]|
|||Athayde RAB,Oliveira Filho JRB,Lorenzi Filho G,Genta PR, Obesity hypoventilation syndrome: a current review. Jornal brasileiro de pneumologia : publicacao oficial da Sociedade Brasileira de Pneumologia e Tisilogia. 2018 Nov-Dec; [PubMed PMID: 30726328]|
|||Comellini V,Pacilli AMG,Nava S, Benefits of non-invasive ventilation in acute hypercapnic respiratory failure. Respirology (Carlton, Vic.). 2019 Apr; [PubMed PMID: 30636373]|
|||Frat JP,Coudroy R,Thille AW, Non-invasive ventilation or high-flow oxygen therapy: When to choose one over the other? Respirology (Carlton, Vic.). 2018 Nov 8; [PubMed PMID: 30406954]|
|||Thille AW,Frat JP, Noninvasive ventilation as acute therapy. Current opinion in critical care. 2018 Dec; [PubMed PMID: 30299309]|
|||Berbenetz N,Wang Y,Brown J,Godfrey C,Ahmad M,Vital FM,Lambiase P,Banerjee A,Bakhai A,Chong M, Non-invasive positive pressure ventilation (CPAP or bilevel NPPV) for cardiogenic pulmonary oedema. The Cochrane database of systematic reviews. 2019 Apr 5; [PubMed PMID: 30950507]|
|||Diaz Milian R,Foley E,Bauer M,Martinez-Velez A,Castresana MR, Expiratory Central Airway Collapse in Adults: Anesthetic Implications (Part 1). Journal of cardiothoracic and vascular anesthesia. 2018 Aug 31; [PubMed PMID: 30279064]|