4. DESCRIPTION OF pH OR "ACID-BASE STATUS" IN THE BLOOD

4. DESCRIPTION OF pH OR


"ACID-BASE STATUS" IN THE BLOOD


Controversy and confusion surrounds  this subject as there are many ways of expressing and presenting pH disturbance of the blood. Much of the literature deals with conflicting claims of superiority of one method over another.

It seems to me that one can deduce from any of the current methods of measurement on blood, the direction and to a lesser but acceptable extent, the magnitude of changes in the whole organism.


In practical clinical situations we want to know the direction of change, the size of the change and how it alters with time, physiological events and treatment. In such circumstances only large abnormalities are important.
At present the most popular system of description is that proposed by Astrup et al (1960) which uses pH, PCO2, base excess and/or standard bicarbonate. For reasons of logic this system is not described first. It must be emphasized that all the systems are compatible, so that results from one system can be converted to another by mathematical manipulation. In particular if base excess is positive both standard bicarbonate, non-respiratory pH, serum bicarbonate and total carbon dioxide will be greater than normal and vice-versa.
4.1 DIRECT ANALYSIS
It is logical to analyse blood for abnormal quantities of acids or bases which can cause changes in pH, e.g. lactic acid level in lactic acidosis or to quantitate part of the acid or base, e.g. Cl^- level in pyloric obstruction. Some of these investigations are not routinely available, e.g. keto acids, and in most clinical situations are unecessary as the chemical cause can be deduced from other clinical evidence.
Most clinical disturbances can be understood by deciding if the blood pH has changed and whether or not CO2 or other acid or base changes are the primary cause.
When there is more than one possible chemical cause for a change in pH and management of the possible chemical causes differ, it will be essential to chemically differentiate the possibilities, e.g. some cases of diabetic acidosis where either lactic or keto-acids may be involved.
4.2 ACTUAL pH, P CO2, NON-RESPIRATORY pH
4.2.1 Actual pH and PaCO2.
The simplest way of describing pH status abnormalities is in terms of actual pH and PaCO2 . If the actual pH is low, the primary disturbance is probably one that would lower the pH (i.e. an acidosis). If as well, the PCO2 is high, it is a primary respiratory acidosis; if low it must be a primary non-respiratory acidosis.

Table 4.2.1. shows the possible combinations of actual pH and PaCO2.

	4.2.2 Actual pH, PaCO2, Non-Respiratory pH. Use the Siggaard-Andersen nomogram when reading this section. This is supplied by Radiometer, A/S, Emdrupvej 72, Dk2400, Copenhagen, Denmark. This is the preferred method of quantitating pH or acid-base status. pH in the blood may be altered by changes in the quantities of carbonic acid and/or acids other than carbonic or bases. Actual pH (pH of anaerobically collected blood), and [H2CO2] (i.e. PaCO2) are standard clinical laboratory estimations. The changes in pH due to non-respiratory acids or bases are estimated by measuring the pH of the blood in vitro having corrected the PCO2 to 40mmHg. This parameter is called the non-respiratory pH (Siggaard-Andersen, 1962). It was recognised by Jorgensen and Astrup (1957) who used it to calculate standard HCO3-. Nunn (1962) called it reduced pH and recognised that it was a valid indication of non-respiratory acid-base status but he did not emphasize the idea. Pierce (1966) called it eucapnic pH, and advocates the system of expression used in this book. Hasselbalch (1918) also proposed the same thing (Siggaard-Andersen 1967). The actual pH, the PaCO2 (or [H2CO2] ) and non-respiratory pH are derived by measuring the blood pH and constructing the pH/PCO2 titration curve. This curve is approximately a straight line on pH/ log PCO2 coordinates. It is called a "buffer" line although "pH/log PCO2" line is a better description. The PaCO2 is read off at the point where the pH/log PCO2 line crosses the actual pH value: Figure 1 for Section 4.2.2. - Siggaard-Andersen Nomogram. This is a PCO2-pH plot. I and II represent PCO2 - pH plots for two samples with pH 7.08 and PCO2 70mmHg. I is plasma. II is whole blood. III represents a similar plot for a fluid containing plasma but a haemoglobin concentration of 5g/100mls. The PCO2-pH plot can be constructed by plotting several pH's while altering PCO2. As the graph is approximately a straight line on log PCO2-pH coordinates, two points are usually sufficient. Alternatively, if one point on the plot is defined by measuring pH and PCO2 of anaerobically collected blood the line can be defined by determining its slope. When the slope is correct the reading on the Base excess curve will be equal to the reading on the Buffer base curve minus the number on the Buffer base curve opposite the Haemoglobin level in the blood sample, i.e. the Base excess read from the two curves will have to be the same. Figure copied from O.Siggaard-Andersen. Therapeutic Aspects of Acid-Base Balance from Modern Trends in Anaesthesia, 3rd Ed. F.T. Evans & T.C. Gray. Pub. Butterworths, 1967, p.102. The non-respiratory pH is read off at the point where the line crosses the isobar PCO2 = 40mmHg - see Figures 2 and 3 below: Figure 2 - Section 4.2.2. Non-respiratory pH. A Siggaard-Andersen Nomogram on which a pH/PCO2 line has been plotted and the actual pH marked. Non-respiratory pH is where the pH/PCO2 line crosses the PCO2=40mmHg line. In this case it is 7.1. Figure 3 - Section 4.2.2. Non-respiratory pH plotted as in Fig. 2. In this case non-respiratory pH is 7.23 (approx). 7.4 minus non-respiratory pH equals the fall in pH due to acids other than carbonic or to bases (change in pH due to non-respiratory acids or bases). Non-respiratory pH minus actual pH equals the fall in pH due to carbonic acid (change in pH due to respiratory (carbonic) acid). Negative results equal rises. (see figures 4 and 5 below) Figure 4 - Section 4.2.2. Separation of pH changes due to CO2 from those due to other acids or bases. This plot is the same as in Figure 2. pH change due to CO2 is +0.14 units. pH change to other acids and bases is -0.3 units. Figure 5 - Section 4.2.2. Separation of pH changes due to CO2 from those due to other acids or bases. This plot is the same as in Figure 3. pH change due to CO2 is -1.3 units. pH change due to other acids or bases is -1.7 units. SUMMARY A. Actual pH of the blood may be affected by changes in: 1. Carbonic acid, and/or, 2. in acids other than carbonic, or in bases. B. If the PCO2 is corrected to normal (40mmHg), the resulting pH deviation from 7.4 (7.4 minus non-respiratory pH) is due to acids other than carbonic acid or to bases. C. Any other deviation in pH (non-respiratory pH minus actual pH) is due to carbonic acid changes. D. The primary disturbance usually porduces the greater change in pH. TABLE 4.2.2, showing possible combinations of actual pH, PaCO2 and non-respiratory pH.To show compatibility between this system and the base excess/standard bicarbonate system (Section 4.3), these parameters are also noted. Table 4.2.2

	Actual pH PaCO2 Non-resp. pH Base excess Status N N N 0 Normal ↑ ↓ N 0 Acute resp.alkalosis(a) ↑ ↓ ↓ Negative Chronic resp.alkalosis with renal compensation ↑ ↓ ↓ Negative Chronic resp.alkalosis ↑ ↑ ↑ Positive Non-resp. alkalosis with respiratory compensation ↓ ↑ N 0 Acute resp. acidosis(a) without compensation ↓ ↑ ↑ Positive Chronic CO2 retention with compensation(b) ↓ ↓ ↓ Negative Non-resp. (metabolic) acidosis with compensation ↓ N ↓ Negative Non-resp acidosis without respiratory compensation N ↓ ↓ Negative Complete compensation or N ↑ ↑ Positive Mixed disturbance ↓ ↑ ↓ Negative Mixed respiratory & non-respiratory acidosis ↑ ↓ ↑ Positive Mixed respiratory & non-respiratory alkalosis

(a) Brackett et al (1965) have shown that the in vivo pH-PCO2 curve differs slightly from the in vitro curve. In vitro PCO2 = 80mmHg gives a pH of 7.21 whereas in vivo the pH is about 7.16. This corresponds to a non-respiratory pH of 7.36, a base excess of -3meq/l and standard HCO3- of 22 meq/l. The difference between the two curves is trivial clinically. Although the slight apparent in vivo non-respiratory acidosis is not a true non-respiratory disturbance, some change between body compartments must occur for it to happen. (See Appendix 4.2). (b) Schwartz et al (1965) have tried to define what is the "normal" actual HCO3-level in chronic hypercapnia. They conclude that if the HCO3- (and therefore actual and non-respiratory pH) level deviates from an experimentally defined range some other complicating disturbance apart from "normal" compensation has occurred, e.g. a non-respiratory acidosis or alkalosis independent of the "normal" renal response to CO2 retention. The experimental work was done in dogs but even if we assume that it applies to man (Brackett et al 1969), the clinical situation of CO2 retention is rarely "pure" and rarely is the degree of CO2 retention constant. That is the initial assumptions of these studies is wrong. (See Appendix 3.1). 4.3 OTHER METHODS OF ASSESSING NON-RESPIRATORY pH CHANGES (There are at least 6 indirect methods of assessing non-respiratory pH change. See Appendix A4.3. Base excess and Standard HCO3- are still in current use, and will be defined here. They can be read off the Siggaard-Andersen nomogram. (Fig. 1 for Section 4.3)) 4.3.1 STANDARD HCO3. This is obtained by solving the Henderson-Hasselbalch equation for [HCO2] when the pH is known and PCO2=40mmHg. 24.5meq/l = normal; >24.5meq/l = a high non-respiratory pH, <24 .5meq="" font="" l="a" low="" nbsp="" non-respiratory="" ph.="">

Actual pH

PaCO2

Primary pH Status

N

N

Normal

↑

↓

Respiratory alkalosis

↑

↑

Non-respiratory alkalosis

↓

↑

Respiratory acidosis

↓ ↓ Non-respiratory acidosis

	Actual pH PaCO2 Primary pH Status N N Normal ↑ ↑ Non-respiratory alkalosis ↑ ↓ Respiratory alkalosis ↓ ↑ Respiratory acidosis ↓ ↓ Non-respiratory acidosis

	4.2.2 Actual pH, PaCO2, Non-Respiratory pH. Use the Siggaard-Andersen nomogram when reading this section. This is supplied by Radiometer, A/S, Emdrupvej 72, Dk2400, Copenhagen, Denmark. This is the preferred method of quantitating pH or acid-base status. pH in the blood may be altered by changes in the quantities of carbonic acid and/or acids other than carbonic or bases. Actual pH (pH of anaerobically collected blood), and [H2CO2] (i.e. PaCO2) are standard clinical laboratory estimations. The changes in pH due to non-respiratory acids or bases are estimated by measuring the pH of the blood in vitro having corrected the PCO2 to 40mmHg. This parameter is called the non-respiratory pH (Siggaard-Andersen, 1962). It was recognised by Jorgensen and Astrup (1957) who used it to calculate standard HCO3-. Nunn (1962) called it reduced pH and recognised that it was a valid indication of non-respiratory acid-base status but he did not emphasize the idea. Pierce (1966) called it eucapnic pH, and advocates the system of expression used in this book. Hasselbalch (1918) also proposed the same thing (Siggaard-Andersen 1967). The actual pH, the PaCO2 (or [H2CO2] ) and non-respiratory pH are derived by measuring the blood pH and constructing the pH/PCO2 titration curve. This curve is approximately a straight line on pH/ log PCO2 coordinates. It is called a "buffer" line although "pH/log PCO2" line is a better description. The PaCO2 is read off at the point where the pH/log PCO2 line crosses the actual pH value: Figure 1 for Section 4.2.2. - Siggaard-Andersen Nomogram. This is a PCO2-pH plot. I and II represent PCO2 - pH plots for two samples with pH 7.08 and PCO2 70mmHg. I is plasma. II is whole blood. III represents a similar plot for a fluid containing plasma but a haemoglobin concentration of 5g/100mls. The PCO2-pH plot can be constructed by plotting several pH's while altering PCO2. As the graph is approximately a straight line on log PCO2-pH coordinates, two points are usually sufficient. Alternatively, if one point on the plot is defined by measuring pH and PCO2 of anaerobically collected blood the line can be defined by determining its slope. When the slope is correct the reading on the Base excess curve will be equal to the reading on the Buffer base curve minus the number on the Buffer base curve opposite the Haemoglobin level in the blood sample, i.e. the Base excess read from the two curves will have to be the same. Figure copied from O.Siggaard-Andersen. Therapeutic Aspects of Acid-Base Balance from Modern Trends in Anaesthesia, 3rd Ed. F.T. Evans & T.C. Gray. Pub. Butterworths, 1967, p.102. The non-respiratory pH is read off at the point where the line crosses the isobar PCO2 = 40mmHg - see Figures 2 and 3 below: Figure 2 - Section 4.2.2. Non-respiratory pH. A Siggaard-Andersen Nomogram on which a pH/PCO2 line has been plotted and the actual pH marked. Non-respiratory pH is where the pH/PCO2 line crosses the PCO2=40mmHg line. In this case it is 7.1. Figure 3 - Section 4.2.2. Non-respiratory pH plotted as in Fig. 2. In this case non-respiratory pH is 7.23 (approx). 7.4 minus non-respiratory pH equals the fall in pH due to acids other than carbonic or to bases (change in pH due to non-respiratory acids or bases). Non-respiratory pH minus actual pH equals the fall in pH due to carbonic acid (change in pH due to respiratory (carbonic) acid). Negative results equal rises. (see figures 4 and 5 below) Figure 4 - Section 4.2.2. Separation of pH changes due to CO2 from those due to other acids or bases. This plot is the same as in Figure 2. pH change due to CO2 is +0.14 units. pH change to other acids and bases is -0.3 units. Figure 5 - Section 4.2.2. Separation of pH changes due to CO2 from those due to other acids or bases. This plot is the same as in Figure 3. pH change due to CO2 is -1.3 units. pH change due to other acids or bases is -1.7 units. SUMMARY A. Actual pH of the blood may be affected by changes in: 1. Carbonic acid, and/or, 2. in acids other than carbonic, or in bases. B. If the PCO2 is corrected to normal (40mmHg), the resulting pH deviation from 7.4 (7.4 minus non-respiratory pH) is due to acids other than carbonic acid or to bases. C. Any other deviation in pH (non-respiratory pH minus actual pH) is due to carbonic acid changes. D. The primary disturbance usually porduces the greater change in pH. TABLE 4.2.2, showing possible combinations of actual pH, PaCO2 and non-respiratory pH.To show compatibility between this system and the base excess/standard bicarbonate system (Section 4.3), these parameters are also noted. Table 4.2.2

	Actual pH PaCO2 Non-resp. pH Base excess Status N N N 0 Normal ↑ ↓ N 0 Acute resp.alkalosis(a) ↑ ↓ ↓ Negative Chronic resp.alkalosis with renal compensation ↑ ↓ ↓ Negative Chronic resp.alkalosis ↑ ↑ ↑ Positive Non-resp. alkalosis with respiratory compensation ↓ ↑ N 0 Acute resp. acidosis(a) without compensation ↓ ↑ ↑ Positive Chronic CO2 retention with compensation(b) ↓ ↓ ↓ Negative Non-resp. (metabolic) acidosis with compensation ↓ N ↓ Negative Non-resp acidosis without respiratory compensation N ↓ ↓ Negative Complete compensation or N ↑ ↑ Positive Mixed disturbance ↓ ↑ ↓ Negative Mixed respiratory & non-respiratory acidosis ↑ ↓ ↑ Positive Mixed respiratory & non-respiratory alkalosis

(a) Brackett et al (1965) have shown that the in vivo pH-PCO2 curve differs slightly from the in vitro curve. In vitro PCO2 = 80mmHg gives a pH of 7.21 whereas in vivo the pH is about 7.16. This corresponds to a non-respiratory pH of 7.36, a base excess of -3meq/l and standard HCO3- of 22 meq/l. The difference between the two curves is trivial clinically. Although the slight apparent in vivo non-respiratory acidosis is not a true non-respiratory disturbance, some change between body compartments must occur for it to happen. (See Appendix 4.2). (b) Schwartz et al (1965) have tried to define what is the "normal" actual HCO3-level in chronic hypercapnia. They conclude that if the HCO3- (and therefore actual and non-respiratory pH) level deviates from an experimentally defined range some other complicating disturbance apart from "normal" compensation has occurred, e.g. a non-respiratory acidosis or alkalosis independent of the "normal" renal response to CO2 retention. The experimental work was done in dogs but even if we assume that it applies to man (Brackett et al 1969), the clinical situation of CO2 retention is rarely "pure" and rarely is the degree of CO2 retention constant. That is the initial assumptions of these studies is wrong. (See Appendix 3.1). 4.3 OTHER METHODS OF ASSESSING NON-RESPIRATORY pH CHANGES (There are at least 6 indirect methods of assessing non-respiratory pH change. See Appendix A4.3. Base excess and Standard HCO3- are still in current use, and will be defined here. They can be read off the Siggaard-Andersen nomogram. (Fig. 1 for Section 4.3)) 4.3.1 STANDARD HCO3. This is obtained by solving the Henderson-Hasselbalch equation for [HCO2] when the pH is known and PCO2=40mmHg. 24.5meq/l = normal; >24.5meq/l = a high non-respiratory pH, <24 .5meq="" font="" l="a" low="" nbsp="" non-respiratory="" ph.="">