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Carbon Dioxide (CO2) Content

Regulation of the amount of carbon dioxide (CO2) in blood, or more precisely of the ratio of bicarbonate to dissolved carbon dioxide concentration, is essential for maintaining acid-base balance. CO2 is a major determinant of blood pH because of its conversion to carbonic acid. As CO2 concentration rises, so does hydrogen ion (H+) concentration. Respiration rate, which is controlled bypCO2 sensitive chemoreceptors in the brain stem and carotid artery, is increased ifpCO2 is rising and decreased ifpCO2 is declining. Increased respiratory rate results in increased rate of CO2 elimination and decreased respiratory rate promotes CO2 retention. A low CO2 level may be associated with metabolic acidosis or compensated respiratory alkalosis. High CO2 content may be associated with metabolic alkalosis or compensated respiratory acidosis.

All cells depend on aerobic metabolism for generation of energy, in the form of ATP. During this process, mitochondria consume oxygen and produce carbon dioxide. Carbon dioxide diffuses from mitochondria into the cell cytoplasm, across the cell membrane and into the capillary network. It is transported by the blood to the lungs for excretion in expired air.

A little of the CO2 remains physically dissolved in blood plasma and an even smaller proportion binds to NH2 (amino) terminal groups of plasma proteins, forming carbamino compounds. However, most diffuses down a concentration gradient into red cells, where a small fraction remains dissolved in the cytoplasm and some is loosely bound to amino terminal groups of reduced hemoglobin forming carbamino-Hb. Most of the carbon dioxide arriving in red cells is rapidly hydrated to carbonic acid by the enzyme carbonic anhydrase. At physiological pH almost all (? 96 %) of this carbonic acid dissociates to bicarbonate and hydrogen ions:

Carbon Dioxide Content

When red blood cells reach the pulmonary circulation, carbon dioxide diffuses from the blood to alveoli. This loss of carbon dioxide from blood favors reversal of the red cell reaction described above. Bicarbonate passes from plasma to red cell, buffering hydrogen ions released from hemoglobin, as it is oxygenated. Reversal of the carbonic anhydrase reaction, results in production of CO2 that diffuses from red cells to plasma and ultimately to alveoli. Mixed venous blood arriving at the lungs has a total CO2 content of 23.5 mEq/L whereas arterial blood leaving the lungs has a total CO2 content of 21.5 mEq/L.

In summary, most carbon dioxide is transported as bicarbonate plasma, but there are three other modes of CO2 transport:

  • 90 % is transported as bicarbonate in plasma (65 %) and red cells (25 %)
  • 5 % is transported physically dissolved in plasma and red cell cytoplasm
  • 5 % is transported loosely bound to hemoglobin and plasma proteins
  • < 0.1 % is transported as carbonic acid

Total carbon dioxide blood content is the sum of these four components.

Arterial blood gas analysis includes three parameters related to the carbon dioxide content of blood.

  • Partial pressure of carbon dioxide (pCO2)
  • Plasma bicarbonate concentration (HCO3-)
  • Plasma total concentration carbon dioxide (ctCO2)

Of the three, only bloodpCO2 is actually measured during blood gas analysis, the other two are calculated from pCO2 and pH. Total concentration of carbon dioxide can also be measured in plasma or serum by chemical methods and is included in all chemistry panels containing electrolytes.

Partial pressure of carbon dioxide (pCO2) is a measure of the pressure exerted by that small portion (? 5 %) of total carbon dioxide in blood that is dissolved in the aqueous phase of plasma and blood cell cytoplasm. The measurement is made using a CO2 specific pH electrode. In health, pCO2 of arterial blood is maintained within the range of 35-45 mm Hg; pCO2 of venous blood is a little higher, 41-51 mmHg.

Most of the carbon dioxide (90%) is transported in blood as plasma bicarbonate. This parameter is calculated. In health, arterial plasma bicarbonate is maintained between 21-28 mEq/L. Venous bicarbonate is slightly higher at 24-30 mEq/L.

Total carbon dioxide content is calculated during blood gas analysis as the sum of all forms of carbon dioxide. Dissolved CO2 contributes approximately 1.2 mEq/L to the total CO2 in the plasma of arterial blood, explaining why ctCO2 is usually this much higher than plasma bicarbonate. The ctCO2 reference range is 23-29 mEq/L in arterial blood. Critical values are <10 mEq/L and >40 mEq/L.

AlthoughctCO2 and bicarbonate provide essentially equivalent information, bicarbonate is invariably used in conjunction with pH andpCO2 to evaluate acid-base status.The clinical value of calculated ctCO2 generated during blood gas analysis is limited.

Unlike bicarbonate, which cannot be measured,ctCO2 can be measured chemically and this parameter is routinely included with electrolytes. Since electrolytes are ordered much more frequently than arterial blood gases, measuredctCO2 is often the first indication of a disturbance in acid-base balance. For all practical purposes, ctCO2 and bicarbonate are equivalent, but a difference of 2-3 mEq/L may be observed. The major difference is that electrolytes are usually measured on venous blood and blood gases on arterial blood so there is a 1-2 mEq/L due to the arterial-venous difference. There is an additional potential difference of 1.5 mEq/L due to the inclusion of dissolved CO2 and carbonic acid in measuredctCO2. However, this difference presupposes that no dissolved carbon dioxide is lost to the atmosphere prior to analysis, but this is often not case because electrolyte samples are not handled anaerobically. Since ambient air contains less CO2 than blood, there is a tendency for dissolved CO2 to be lost from the sample if tubes are left uncapped. If this occurs, measured CO2 can decrease at a rate of 6 mEq/h. By contrast calculated bicarbonate is not associated with the same risk of pre-analytic variation because blood gas analyses are sampled anaerobically with minimal delay.

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