## Co2 Dissociation Curve

Hemoglobin carbamate

CO2 Binding in Blood, CO2 in CSF

The total carbon dioxide concentration (= chemically bound "CO2" + dissolved CO2) of mixed venous blood is about 24-25 mmol/L; that of arterial blood is roughly 22-23 mmol/L. Nearly 90% of this is present as HCO3- (^ A, right panel, and table on p. 124). The partial pressure of CO2 (Pco2) is the chief factor that determines the CO2 content of blood. The CO2 dissociation curve illustrates how the total CO2 concentration depends on PCO2 (^ A).

The concentration of dissolved CO2, [CO2], in plasma is directly proportional to the Pco2 in plasma and can be calculated as follows: [CO2] = aco2 ■ Pco2 (mmol/L plasma or mL/L plasma), [5.6]

§ where aco2 is the (Bunsen) solubility coefficient '■{= for CO2. At 37 °C, ■¡^ aco2 = 0.225 mmol ■ L-1 ■ kPa-1, £ After converting the amount of CO2 into ^ volume CO2 (mL = mmol ■ 22.26), this yields 10 aco2 = 5 mL ■ L-1 ■ kPa-1.

The curve for dissolved CO2 is therefore linear (^ A, green line).

Since the buffering and carbamate formation capacities of hemoglobin are limited, the relation between bound "CO2" and PCO2 is curvilinear. The dissociation curve for total CO2 is calculated from the sum of dissolved and bound CO2 (^ A, red and violet lines).

CO2 binding with hemoglobin depends on the degree of oxygen saturation (So2) of hemoglobin. Blood completely saturated with O2 is not able to bind as much CO2 as O2-free blood at equal Pco2 levels (^ A, red and violet lines). When venous blood in the lungs is loaded with O2, the buffer capacity of hemoglobin and, consequently, the levels of chemical CO2 binding decrease due to the Hal-dane effect (^ p. 124). Venous blood is never completely void of O2, but is always O2-satu-rated to a certain degree, depending on the degree of O2 extraction (^ p. 130) of the organ in question. The SO2 of mixed venous blood is about 0.75. The CO2 dissociation curve for SO2 = 0.75 therefore lies between those for So2 = 0.00 and 1.00 (^ A, dotted line). In arterial blood, Pco2 ~ 5.33 kPa and So2 ~ 0.97 (^ A, point a). In mixed venous blood, PCO2 ~ 6.27 kPa and SO2

dissociation is determined by connecting these two points by a line called "physiologic CO2 dissociation curve."

The concentration ratio of HCO3- to dissolved CO2 in plasma and red blood cells differs (about 20:1 and 12:1, respectively). This reflects the difference in the pH of plasma (7.4) and erythrocytes (ca. 7.2) (^ p. 138ff.).

### CO2 in Cerebrospinal Fluid

Unlike HCO3- and H+, CO2 can cross the blood-cerebrospinal fluid (CSF) barrier with relative ease (^ B1 and p. 310). The PCO2 in CSF therefore adapts quickly to acute changes in the Pco2 in blood. CO2-related (respiratory) pH changes in the body can be buffered by non-bicarbonate buffers (NBBs) only (^ p. 144). Since the concentration of non-bicarbonate buffers in CSF is very low, an acute rise in Pco2 (respiratory acidosis; ^ p. 144) leads to a relatively sharp decrease in the pH of CSF (^ B1, pH ||). This decrease is registered by central chemosen-sors (or chemoreceptors) that adjust respiratory activity accordingly (^ p. 132). (In this book, sensory receptors are called sensors in order to distinguish them from hormone and transmitter receptors.)

The concentration of non-bicarbonate buffers in blood (hemoglobin, plasma proteins) is high. When the CO2 concentration increases, the liberated H+ ions are therefore effectively buffered in the blood. The actual HCO3- concentration in blood then rises relatively slowly, to ultimately become higher than in the CSF. As a result, HCO3- diffuses (relatively slowly) into the CSF (^ B2), resulting in a renewed increase in the pH of the CSF because the HCO3/CO2 ratio increases (^ p. 140). This, in turn, leads to a reduction in respiratory activity (via central chemosen-sors), a process enhanced by renal compensation, i.e., a pH increase through HCO3- retention (^ p. 144). By this mechanism, the body ultimately adapts to chronic elevation in PCOj— i.e., a chronically elevated PCO2 will no longer represent a respiratory drive (cf. p. 132).

|— A. CO2 dissociation curve

6 kPa 8