Description

• Carbon dioxide (CO₂) is a by-product of cellular metabolic pathways. Rapid diffusion of CO₂ from cells into capillaries occurs despite a partial pressure of only 1–6 mm Hg, compared with ~64 mm Hg for oxygen.
• CO₂ is transported through the blood to alveoli for excretion in three different forms:
  • Dissolved in blood
  • Carbamino compounds
  • Bicarbonate ion

Physiology Principles

• At a cardiac output of 5 L/min, each 100 mL of blood passing through the lungs unloads 4–5 mL of CO₂. The amount circulating is a function of both CO₂ elimination and production.
• Transport to the lungs occurs in three different forms; the sum comprises the total CO₂ content of blood. The three forms are as follows:
  • Physically dissolved in plasma solution (7%). CO₂ is 20 times more soluble than oxygen and results in the rapid transfer between tissues, blood, and the alveoli. Dissolved CO₂ increases linearly with increases in PaCO₂.
  • Carbamino compounds (13%). CO₂ can enter the erythrocyte and reversibly bind with nonionized terminal amino groups of blood-borne proteins. The resulting compound is called carbaminohemoglobin.
    • The Haldane effect facilitates the passage of CO₂ in the blood and excretion by the alveoli. In tissue, deoxyhemoglobin's increased affinity to CO₂ (3.5 times greater) results in effective uptake. In the pulmonary capillaries, oxyhemoglobin's reduced affinity to CO₂ results in "off-loading" and excretion. This liberates CO₂ that then diffuses from pulmonary capillary blood into alveoli.
  • Bicarbonate (80%)
    • CO₂ enters the erythrocyte where it reacts with water to form carbonic acid. This reaction is almost immediate in the presence of the enzyme carbonic anhydrase: H₂O + CO₂ H₂CO₃ H⁺ + HCO₃^- (Note: this enzyme is absent in plasma). Most of the hydrogen ions combine with hemoglobin, a powerful buffer.
    • Buffering capacity. Bicarbonate is considered the most important buffer in extracellular fluid. It provides immediate and effective chemical buffering against metabolic acid–base disturbances. If a strong acid is added to the extracellular fluid, bicarbonate reacts with the H⁺ to produce CO₂.
    • Chloride effect: Occurs in the venous side of capillaries. Bicarbonate ions diffuse from erythrocytes into plasma, accompanied by the opposite movement of chloride ions into the cells to maintain electrochemical neutrality (chloride shift). The increase in osmotically active ions (chloride and bicarbonate) in venous erythrocytes encourages the entry of water, thus increasing their volume. This explains why the venous hematocrit is ~3% higher than the arterial hematocrit.
• The kidneys indirectly affect CO₂ homeostasis through its ability to control the amount of HCO₃^- reabsorbed from filtrated tubular fluid, form new HCO₃^-, and eliminate H⁺ in the form of titratable acids and ammonium ions.
  • HCO₃^- is filtered at the glomerulus.
    • Approximately 85% is reabsorbed at the proximal tubules. After diffusing into the renal tubular cell, CO₂ combines with water to form carbonic acid (in the presence of carbonic anhydrase). Carbonic acid rapidly dissociates into H⁺ and HCO₃^-; the bicarbonate ion enters the bloodstream while H⁺ is secreted into the renal tubule.
    • HCO₃^- that is not reabsorbed may bind with H+ within the lumen to form carbonic acid. Carbonic anhydrase on the luminal brush border catalyzes the dissociation of H₂CO₃ into CO₂ and H₂O. This CO₂ replaces the CO₂ that was utilized in the renal tubular cell.
• Correction of the imbalance between production and elimination of CO₂ takes about 30 minutes. Central chemoreceptors respond rapidly to a change in hydrogen ion concentration (which is affected by the arterial CO₂ content), while peripheral chemoreceptors respond to the arterial content of oxygen.

Pediatric Considerations

Pregnancy Considerations

Anatomy

• PaCO₂ in alveoli
• PaCO₂ in tissue

Physiology/Pathophysiology

• Imbalances in CO₂ homeostasis can result in respiratory acidosis (pH <7.4) or alkalosis (pH >7.4). Deviations can have adverse consequences and be deleterious.
• Respiratory acidosis occurs when there is alveolar hypoventilation or increased metabolism, leading to the accumulation of CO₂ and carbonic acid formation.
• Respiratory alkalosis occurs when the PaCO₂ is decreased: The most likely perioperative cause is iatrogenic hyperventilation, which can be corrected by ventilator setting adjustments. Alkalosis is a normal occurrence with pregnancy; there is a 50% increase in alveolar ventilation.

Pediatric Considerations

Perioperative Relevance

• CO₂ levels can be manipulated under anesthesia, especially with controlled ventilation.
• Central chemoreceptors, located in the medulla, are very sensitive to changes in CSF hydrogen ion concentration. The blood–brain barrier is permeable to dissolved CO₂ but not to bicarbonate; therefore acute changes in arterial CO₂ content are reflected in the CSF. Increases in CO₂ elevate the CSF hydrogen ion concentration and activate the chemoreceptors.
  • This change has an intense initial effect and occurs within seconds; in interstitial fluid, it takes at least 1 minute. This stimulates the respiratory medullary centers to increase alveolar ventilation. Of note, central chemoreceptor activity is depressed by hypoxia.
  • After several hours, adaptation occurs and the CSF pH normalizes by active transport of bicarbonate ions.
  • The relationship between arterial CO₂ and minute ventilation is nearly linear.
  • Peripheral chemoreceptors are located outside the central nervous system; they include the carotid and aortic bodies. The carotid body transmits signals via the glossopharyngeal nerve to the respiratory center in the medulla. Carotid bodies affect ventilation primarily. Removal or denervation, as with carotid endarterectomies, can result in loss of the ventilatory response to arterial hypoxemia and about a 30% decrease in the ventilatory response to CO₂. The aortic body transmits signals via the vagus nerve and is primarily responsible for cardiovascular responses.
• Apneic threshold is the highest PaCO₂ at which ventilation is zero. Spontaneous respirations are absent under anesthesia when PaCO₂ falls below this value. This is not typically seen in the awake state due to cortical influences that prevent apnea. Opioids and anesthetic medications significantly depress ventilation by elevating the apneic threshold and hypoxic drive
• Apneic oxygenation. When apnea occurs, the alveolar CO₂ increases 5–10 mm Hg during the first minute and 3 mm Hg/minute thereafter. The first minute increase is due to equilibration of the alveolar gas with pulmonary capillary blood. After that first minute, metabolic production is responsible for the steady rise. In practice, the end tidal CO₂ monitor is utilized to assess and approximate alveolar CO₂.
• Body temperature can directly affect the measurements of the partial pressures of a gas. During hypothermia, both PaCO₂ and PaO₂ decrease because gas solubility is inversely proportional to temperature (cold temperatures lead to a decrease in the partial pressure of a gas in the solution). pH, on the other hand, increases because the bicarbonate ion remains unchanged. However, transport of CO₂ is not affected by body temperature.
• Hypermetabolism should be considered in a persistently hyperthermic patient in the intraoperative and immediate postoperative period. Hypermetabolic states increase CO₂ production and increase sympathetic activation. If not corrected, metabolic acidosis, electrolyte imbalance, and muscle breakdown occur. The differential diagnosis should include malignant hyperthermia, neuroleptic syndrome, thyroid storm, pheochromocytoma, and serotonin syndrome. The end-tidal CO₂ can double or triple in value. It is one of the earliest and most sensitive indicators of malignant hyperthermia.
• Administration of acetazolamide, a carbonic anhydrase inhibitor, can impair CO₂ transport between tissues and alveoli.

Equations

H₂O + CO₂ H₂CO₃ H⁺ + HCO₃^-

• Carotid Body
• Malignant Hyperthermia
• Buffering Systems

Melissa Flanigan , DO