Carbon monoxide

In respiratory testing, the diffusing capacity for carbon monoxide (DLCO) is a measure of the ability of gas to transfer from the alveoli across the alveolar epithelium and the capillary endothelium to the red blood cells. The DLCO depends not only on the area and thickness of the blood-gas barrier but additionally on the volume of blood in the pulmonary capillaries. The distribution of alveolar volume and ventilation also has an impact on the measurement.

DLCO is measured by sampling end-expiratory gas for carbon monoxide (CO) after patients inspire a small and safe amount of exogenous CO, hold their breath, and exhale. Measured DLCO is adjusted for alveolar volume (which is estimated from dilution of helium) and the patient’s hematocrit level. DLCO is reported as mL/min/mm Hg and as a percentage of a predicted value.

Carbon monoxide exerts effects on cell metabolism through both hypoxic and non-hypoxic modes of action. Both mechanisms of action are thought to be the result of the ability of carbon monoxide to bind strongly to heme and alter the function and/or metabolism of heme proteins. The binding affinity of carbon monoxide for hemoglobin is more than 200 times greater than that of oxygen for hemoglobin. The formation of carboxyhemoglobin (COHb) decreases the O2 carrying capacity of blood and disrupts the release of O2 from Hb for its use in tissues. Through similar mechanisms, carbon monoxide diminishes the O2 storage in muscle cells by binding to and displacing O2 from, myoglobin. Though all human tissues are vulnerable to carbon monoxide-induced hypoxic injury, those with the highest O2 demand are especially vulnerable, including the brain and heart.

Most of the non-hypoxic mechanisms of action of carbon monoxide have been thought to be due to binding of carbon monoxide to heme in proteins other than Hb. The most notable targets of carbon monoxide include components of many important physiological regulatory systems, including brain and muscle oxygen storage and use(myoglobin, neuroglobin); nitric oxide cell signaling (e.g., nitric oxide synthase, guanylyl cyclase); prostaglandin cell signaling (cyclooxygenase, prostaglandin H synthase); energy metabolism and mitochondrial respiration (cytochrome c oxidase, cytochrome c, NADPH oxidase); steroid and drug metabolism (cytochrome P450); cellular redox balance and reactive oxygen species (ROS; catalase, peroxidases); and numerous transcription factors (e.g., neuronal PAS domain protein, NPAS2, implicated in regulation of circadian rhythm).

In meat processing, carbon monoxide reacts with myoglobin, to form carboxymyoglobin, imparting a red appearance to the meat.