Physiology, Carbon Dioxide Retention


Introduction

In the human body, carbon dioxide is formed intracellularly as a byproduct of metabolism. CO2 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 regulation of blood pH, respiratory drive, and affinity of hemoglobin 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 an 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 overall 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 O2 and CO2, central chemoreceptors are responsive to changes in pCO2 and pH. Central chemoreceptors are able to rapidly detect changes in PCO2. The blood-brain barrier is permeable to CO2, thus allowing chemosensitive cells within the medulla to respond to elevations in blood 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 rather 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

Cellular respiration converts ingested nutrients in the form of glucose (C6H12O6) and oxygen to energy in the form of 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 primary site of gas exchange in the lungs. At the alveolar-capillary interface, O2 freely diffuses into blood and CO2 diffuses from the blood into the alveolar spaces. In contrast, gas exchange at the tissues results in diffusion of CO2 produced by respiration from the tissues into the blood, while 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 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 said to be in hypercapnic respiratory failure.

Pathophysiology

In the bloodstream, dissolved CO2 is neutralized by the bicarbonate-carbon dioxide buffer system where it forms a weak acid, carbonic acid (H2CO3). H2CO3 can dissociate into a hydrogen ion and 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 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.[12][13]

Hypercapnia should be managed by addressing its underlying cause. A noninvasive positive pressure ventilator may provide support to patients who have inadequate respiratory drive. 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.


Article Details

Article Author

Shivani Patel

Article Author

Julia Miao

Article Author

Ekrem Yetiskul

Article Author

Anya Anokhin

Article Editor:

Sapan Majmundar

Updated:

1/4/2021 8:50:12 PM

References

[1]

Wong-Riley MT,Liu Q,Gao XP, Peripheral-central chemoreceptor interaction and the significance of a critical period in the development of respiratory control. Respiratory physiology & neurobiology. 2013 Jan 1     [PubMed PMID: 22684042]

[2]

Putnam RW,Filosa JA,Ritucci NA, Cellular mechanisms involved in CO(2) and acid signaling in chemosensitive neurons. American journal of physiology. Cell physiology. 2004 Dec     [PubMed PMID: 15525685]

[3]

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]

[4]

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]

[5]

Bigatello L,Pesenti A, Respiratory Physiology for the Anesthesiologist. Anesthesiology. 2019 Apr 12;     [PubMed PMID: 30998510]

[6]

de Carvalho M,Swash M,Pinto S, Diaphragmatic Neurophysiology and Respiratory Markers in ALS. Frontiers in neurology. 2019;     [PubMed PMID: 30846968]

[7]

Eikermann M,Santer P,Ramachandran SK,Pandit J, Recent advances in understanding and managing postoperative respiratory problems. F1000Research. 2019;     [PubMed PMID: 30828433]

[8]

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]

[9]

Comellini V,Pacilli AMG,Nava S, Benefits of non-invasive ventilation in acute hypercapnic respiratory failure. Respirology (Carlton, Vic.). 2019 Apr;     [PubMed PMID: 30636373]

[10]

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]

[11]

Thille AW,Frat JP, Noninvasive ventilation as acute therapy. Current opinion in critical care. 2018 Dec;     [PubMed PMID: 30299309]

[12]

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]

[13]

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]