книги студ / color atlas of physiology 5th ed[1]. (a. despopoulos et al, thieme 2003)

Bicarbonate/Carbon Dioxide Buffer

The pH of any buffer system is determined by the concentration ratio of the buffer pairs and the pKa of the system (!p. 378). The pH of a bicarbonate solution is the concentration ratio of bicarbonate and dissolved carbon dioxide ([HCO3–]/[CO2]), as defined in the Henderson– Hasselbalch equation (!A1). Given [HCO3–] = 24 mmol/L and [CO2] = 1.2 mmol/l, [HCO3–]/ [CO2] = 24/1.2 = 20. Given log20 = 1.3 and pKa = 6.1, a pH of 7.4 is derived when these values are set into the equation (!A2). If [HCO 3–] drops to 10 and [CO2] decreases to 0.5 mmol/L, the ratio of the two variables will not change, and the pH will remain constant.

When added to a buffered solution, H+ ions combine with the buffer base (HCO3– in this case), resulting in the formation of buffer acid (HCO3– + H+ !CO2 + H2O). In a closed system from which CO2 cannot escape (!A3), the amount of buffer acid formed (CO2) equals the amount of buffer base consumed (HCO3–). The inverse holds true for the addition of hydroxide ions (OH– + CO2 !HCO3–). After addition of 2 mmol/L of H+, the aforementioned baseline ratio [HCO3–]/[CO2] of 24/1.2 (!A2) changes to 22/3.2, making the pH fall to 6.93 (!A3). Thus, the buffer capacity of the HCO3–/ CO2 buffer at pH 7.4 is very low in a closed system, for which the pKa of 6.1 is too far from the target pH of 7.4 (!pp. 138, 378ff).

If, however, the additionally produced CO2 is eliminated from the system (open system; !A4), only the [HCO3–] will change when the same amount of H+ is added (2 mmol/L). The corresponding decrease in the [HCO3–]/[CO2] ratio (22/1.2) and pH (7.36) is much less than in a closed system. In the body, bicarbonate buffering occurs in an open system in which the partial pressure (PCO2) and hence the concentration of carbon dioxide in plasma ([CO2] = α · PCO2; !p. 126) are regulated by respiration (!B). The lungs normally eliminate as much CO2 as produced by metabolism (15 000– 20 000 mmol/day), while the alveolar PCO2 remains constant (!p. 120ff.). Since the plasma PCO2 adapts to the alveolar PCO2 during each respiratory cycle, the arterial PCO2 (PaCO2) also remains constant. An increased supply of H+ in the periphery leads to an increase in the PCO2 of

venous blood (H+ + HCO3– !CO2 + H2O) (!B1). The lungs eliminate the additional CO2 so quickly that the arterial PCO2 remains practically unchanged despite the addition of H+ (open system!).

The following example demonstrates the quantitatively small impact of increased pulmonary CO2 elimination. A two-fold increase in the amount of H+ ions produced within the body on a given day (normally 60 mmol/day) will result in the added production of 60 mmol more of CO2 per day (disregarding non-bicarbonate buffers). This corresponds to only about 0.3% of the normal daily CO2 elimination rate.

An increased supply of OH– ions in the periphery has basically similar effects. Since OH– + CO2 !HCO3–, [HCO3–] increases and the venous PCO2 becomes smaller than normal. Because the rate of CO2 elimination is also reduced, the arterial PCO2 also does not change in the illustrated example (!B2).

At a pH of 7.4, the open HCO3–/CO2 buffer system makes up about two-thirds of the buffer capacity of the blood when the PCO2 remains constant at 5.33 kPa (!p. 138). Mainly intracellular non-bicarbonate buffers provide the remaining buffer capacity.

Since non-bicarbonate buffers (NBBs) function in closed systems, their total concentration ([NBB base] + [NBB acid]) remains constant, even after buffering. The total concentration changes in response to changes in the hemoglobin concentration, however, since hemoglobin is the main constituent of NBBs (!pp. 138, 146). NBBs supplement the HCO3–/ CO2 buffer in non-respiratory (metabolic) acid–base disturbances (!p. 142), but are the only effective buffers in respiratory acid–base disturbances (!p. 144).

Assessment of Acid–Base Status

The Henderson–Hasselbalch equation for the

Since [CO2] = α · PCO2 (!p. 126), Equation 6.5 contains two constants (pKa and α) and three variables (pH, [HCO3–], and PCO2). At 37 "C in plasma, pKa = 6.1 and α = 0.225 mmol · L–1 · kPa–1 (cf. p. 126). When one of the variables remains constant (e.g., [HCO3–]), the other two (e.g., PCO2 and pH) are interdependent. In a graphic representation, this dependency is reflected as a straight line when the logarithm of PCO2 is plotted against the pH (!A–C and p. 382).

When the PCO2 varies in a bicarbonate solution

(without other buffers), the pH changes but [HCO3–] remains constant ( !A, solid line). One can also plot the lines for different HCO3– concentrations, all of which are parallel (!A, B, dotted orange lines). Figures A through C use a scale that ensures that the bicarbonate lines intersect the coordinates at 45" angles. The Siggaard–Andersen nomogram (!C) does not use the lines, but only the points of intersection of the [HCO3–] lines with the normal PCO2 of 5.33 kPa (40 mmHg).

The blood contains not only the HCO3–/CO2 buffer but also non-bicarbonate buffers, NBB

(!p. 138). Thus, a change in the PCO2 does not alter the pH as much as in a solution containing the HCO3–/CO2 buffer alone (!p. 144). In the PCO2/pH nomogram, the slope is therefore steeper than 45" (!B, green and red lines). Hence, the actual bicarbonate concentration, [HCO3–]Act, in blood changes and shifts in the same direction as the PCO2 if the pH varies (!p. 144). Therefore, both the [HCO3–]Act and the standard bicarbonate concentration,

[HCO3–]St, can be determined in clinical blood tests. By definition, [HCO3–]St represents the [HCO3–] at a normal PCO2 of 5.33 kPa (40 mmHg). [HCO3–]St therefore permits an assessment of [HCO3–] independent of PCO2 changes.

and [HCO3–]Act are determined using measured PCO2 and pH values obtained with a blood gas analyzer. When plotted on the

Siggaard–Andersen nomogram, [HCO3–]St is read from the line as indicated by the points of intersect of the [HCO3–] line (!B, orange lines) and the PCO2/pH line (B and C, green and red

lines) at normal PCO2 = 5.33 (!B and C, points D

and d). [HCO3–]Act is read from the [HCO3–] line intersected by the PCO2/pH line at the level of

the actually measured PCO2. Since the normal and measured PCO2 values agree in normals,

their [HCO3–]Act is usually equal to [HCO3–]St. If PCO2 deviates from normal (!B, C, point c),

[HCO3–]Act is read at point e on the HCO3– line (!B, C, interrupted 45" line) on which the ac-

tually measured PCO2 lies (!B, C, point c). and pH measurement. When

using the equilibration method (Astrup method), three pH measurements are taken:

(1) in the unchanged blood sample; (2) after equilibration with a high PCO2 (e.g., 10 kPa [75 mmHg]; !C, points A and a), and (3) after equilibration with a low PCO2 (e.g., 2.7 kPa [20 mmHg]; !C, points B and b). The PCO2 of the original blood sample can then be read from lines A–B and a–b using the pH value obtained in measurement 1. In normals (!C, upper case letters, green), [HCO3–]Act =

[HCO3–]St = 24 mmol/L (!C, points E and D). Example 2 (!C, lower case letters, red) shows

an acid–base disturbance: The pH is too low (7.2) and [HCO3–]St (!C, point d) has dropped to 13 mmol/L (metabolic acidosis). This has been partially compensated (!p. 142) by a reduction in PCO2 to 4 kPa, which led to a consequent reduction in [HCO3–]Act to 11 mmol/L (!C, point e).

Total buffer bases (BB) and base excess (BE) (!p. 142) can also be read from the Siggaard– Andersen nomogram (!C). The base excess (points F and f on the curve) is the difference between the measured buffer base value (points G or g) and the normal buffer base value (point G). Point G is dependent on the hemoglobin concentration of the blood (!C; [Hb]/BB comparison). Like [HCO3–]St, deviation of BB from the norm (0 # 2.5 mEq/L) is diagnostic of primary non-respiratory acid–base disturbances.

The PCO2/pH line of the blood sample in plate C can also be determined if (1) the PCO2 (without equilibration), (2) the pH, and (3) the hemoglobin concentration are known. One point (!C, point c) on the unknown line can be drawn using (1) and (2). The line must be drawn through the point in such a way that

BB (point g) – BBnormal (dependent on Hb value) = BE (point f).

A. PCO2 /pH nomogram (without NBB)

B. PCO2 /pH nomogram (with NBB)