Fig. 3
From: Pathophysiology and clinical consequences of arterial blood gases and pH after cardiac arrest
Effect of carbon dioxide on microglia, cardiomyocytes, and lung epithelial cells. Microglia: hypercapnia decreases extracellular pH and intracellular pH (Phi). Increased Phi increases firing rate of CO2/H2 chemosensitive neurons, by an oxidant-induced decrease in K+ conductance. Hypocapnia with cerebral vasoconstriction and ischemic insult shifts the anaerobic metabolism and activates local and systemic inflammatory response. Cardiomyocytes: hypercapnia and acidosis reduce the sensitivity of the adrenergic receptor and expression. Hypocapnia has effect on intracellular buffers (mostly hemoglobin within red blood cells) determining release of hydrogen. Hydrogen combines with bicarbonate to form carbonic acid, which then disassociates to form water and CO2, thus replenishing the depleted PaCO2. Lung epithelium: hypercapnia inhibits proliferation of alveolar epithelial cells due to mitochondrial dysfunction resulting from hypercapnia-induced miR-183 which downregulates the TCA cycle enzyme isocitrate dehydrogenase-2 (IDH). Hypercapnic acidosis impairs alveolar epithelial cell migration by the NF-kB dependent mechanism. Hypercapnia inhibits mRNA and protein expression of IL-6 and TNF and decreases phagocytosis in macrophages. Hypocapnia and hyperventilation can determine increase of mechanical power and activation of the inflammatory system. CO2, carbon dioxide; PaCO2, partial pressure of carbon dioxide; TCA, tricarboxylic acid cycle; NF-kB, nuclear factor kappa-light-chain-enhancer of activated B cells; IDH, enzyme isocitrate dehydrogenase-2; TNF, tumor necrosis factor; IL, interleukin; mRNA, ribonucleic acid