Old and new approaches to the interpretation of acid-base metabolism, starting from historical data applied to diabetic acidosis.

The approach to acid-base chemistry in medicine includes several methods. Currently, the two most popular procedures are derived from Stewart's studies and from the bicarbonate/BE-based classical formulation. Another method, unfortunately little known, follows the Kildeberg theory applied to acid-base titration. By using the data produced by Dana Atchley in 1933, regarding electrolytes and blood gas analysis applied to diabetes, we compared the three aforementioned methods, in order to highlight their strengths and their weaknesses. The results obtained, by reprocessing the data of Atchley, have shown that Kildeberg's approach, unlike the other two methods, is consistent, rational and complete for describing the organ-physiological behavior of the hydrogen ion turnover in human organism. In contrast, the data obtained using the Stewart approach and the bicarbonate-based classical formulation are misleading and fail to specify which organs or systems are involved in causing or maintaining the diabetic acidosis. Stewart's approach, despite being considered 'quantitative', does not propose in any way the concept of 'an amount of acid' and becomes even more confusing, because it is not clear how to distinguish between 'strong' and 'weak' ions. As for Stewart's approach, the classical method makes no distinction between hydrogen ions managed by the intermediate metabolism and hydroxyl ions handled by the kidney, but, at least, it is based on the concept of titration (base-excess) and indirectly defines the concept of 'an amount of acid'. In conclusion, only Kildeberg's approach offers a complete understanding of the causes and remedies against any type of acid-base disturbance.

Electrochemical biosensor with ceria-polyaniline core shell nano-interface for the detection of carbonic acid in blood.

The normal physiological concentration of carbonic acid in human blood is in the range of 1.08-1.32 mM. However, if the concentration of carbonic acid rises above 3.45 mM, it may lead to respiratory acidosis. In this context, an electrochemical biosensor with CeO2-PANI (polyaniline) core-shell nano-interface was developed for sensing carbonic acid using carbonic anhydrase (CA). CA was immobilized on CeO2-PANI via chitosan on a glassy carbon electrode (GCE/CeO2-PANI/CA/chitosan). The X-ray diffraction (XRD) patterns confirmed the polycrystalline nature of CeO2 and CeO2-PANI nanoparticles. Field emission scanning electron microscopy (FE-SEM) studies showed the aggregation of spherical nanoparticles with size ranging from 37.6 to 47.8 nm and Field emission transmission electron microscopy (FE-TEM) study confirmed the presence of core-shell structure of CeO2-PANI. Immobilization of CA on CeO2-PANI was confirmed by Fourier transform infrared (FT-IR) spectra. Electrochemical studies were carried out with the help of GCE/CeO2-PANI/CA as a working electrode, Ag/AgCl saturated with 0.1 M KCl as a reference electrode and Pt wire as a counter electrode. This biosensor exhibited sensitivity of 696.49 µA cm(-2) mM(-1) with a linear range of 1.32-2.32 mM. It also showed a fast response time of less than 1s, lowest detection limit of 19.4 µM, Michaelis-Menten constant (KM) of 1.8191 mM and dry stability of 96% up to 18 days. The observed results revealed the potential of the modified working electrode with CeO2-PANI core-shell nano-interface for carbonic acid sensing. The developed biosensor can be applied for the real time clinical diagnosis of diseases such as obstructive pulmonary diseases (COPD).

Arterial blood gas analysis. 2: compensatory mechanisms.

This is the second of a two-part unit discussing arterial blood gas (ABG) analysis. Part 1 outlined background information on ABG reports and focused on a systematic approach to ABG analysis. This part examines the physiology of the various lines of defence in the body and explores the concept of compensation. A step-by-step guide to interpretation and examples of uncomplicated ABGs are available in the Portfolio Pages for this unit at nursingtimes.net, as well as further practice examples relevant to this part of the unit.

Surplus dietary tryptophan reduces plasma cortisol and noradrenaline concentrations and enhances recovery after social stress in pigs.

Social stress occurs in intensive pig farming due to aggressive behavior. This stress may be reduced at elevated dietary levels of tryptophan (TRP). In this study, we compared the effects of high (13.2%) vs. normal (3.4%) dietary TRP to large neutral amino acid (LNAA) ratios on behavior and stress hormones in catheterized pigs ( approximately 50 kg BW), which were exposed to social stress by placing them twice into the territory of a dominant pig ( approximately 60 kg) for 15 min. Pre-stress plasma TRP concentrations were 156+/-15 vs. 53+/-6 micromol/l (p<0.01) in pigs on the high vs. normal TRP diets, respectively. Pre-stress plasma cortisol and noradrenaline concentrations were twofold (p<0.01) and 1.4-fold (p<0.05) lower but plasma adrenaline concentration was similar in pigs on the high vs. normal TRP diets, respectively. During the social confrontations, pigs on the high vs. normal TRP diets show a tendency towards reduced active avoidance behavior (3.2+/-1.1 vs. 6.7+/-1.2 min, p<0.1) but their physical activity (8.5+/-0.6 vs. 10.2+/-0.8 min) and aggressive attitude towards the dominant pig (11+/-3 vs. 7+/-2 times biting) were similar. Immediate (+5 min) post-stress plasma cortisol, noradrenaline and adrenaline responses were similar among dietary groups. After the social confrontations, the post-stress plasma cortisol, noradrenaline and adrenaline concentrations and/or curves (from +5 min to 2 h) were lower/steeper (p<0.05) in pigs on the high vs. normal TRP diets. In summary, surplus TRP in diets for pigs (1) does not significantly affect behavior when exposed to social stress, (2) reduces basal plasma cortisol and noradrenaline concentrations, (3) does not affect the immediate hormonal response to stress, and (4) reduces the long-term hormonal response to stress. In general, pigs receiving high dietary TRP were found to be less affected by stress.

[Influence of physical effort on concentration of lactic acid and acid-base equilibrium in patients with mild and moderate bronchial asthma]. / Wplyw wysilku fizycznego na stezenie kwasu mlekowego i równowage kwasowo-zasadowa u chorych na astme oskrzelowa lekka i umiarkowana.

PURPOSE: Estimate influences of standard physical exercise on lactic acid concentration and acid-base equilibrium in patients with mild and moderate bronchial asthma compared with healthy trained persons and do not ones. MATERIAL AND METHODS: In 47 asthmatic patients and 20 healthy persons: 1) bronchial reactivity was investigated; 2) at rest and 1, 5 and 10 min after 8 min exercise (PWC85%max, bicycle ergometer): FEV1, lactic acid concentration (LAC), pH, pO2, pCO2 and HCO3 (in capillary blood) were investigated. Among asthmatic patients: 1) 21 experienced exercise-induced asthma (EIA), 2) 20 reacted to histamine in concentration of 0.125 mg/ml/3', 3) 6 reacted to histamine in concentration of 0.25 mg/ml/3'. In healthy persons, without EIA and reaction to histamine, were: 12 who did not train, and 8 athletes. RESULTS: After exercise LAC increased in all groups (p<0.05); the increase was significantly higher in patients and persons who did not train, then athletes, and did not normalised, in opposite to athletes, however in persons who did not train was significantly lower then in asthmatics. pH and pCO2 did not change significantly in all examined persons, but HCO3 decreased significantly in patients with bronchial hyperactivity and in persons who did not train. Significant increase of pO2 appeared only in healthy persons. CONCLUSION: Physical effort caused significant greater metabolic changes in asthmatic patients then in healthy persons, especially athletes

Decreased colostral immunoglobulin absorption in calves with postnatal respiratory acidosis.

The effect of postnatal acid-base status on the absorption of colostral immunoglobulins by calves was examined in 2 field studies. In study 1, blood pH at 2 and 4 hours after birth was related to serum IgG1 concentration 12 hours after colostrum feeding (P less than 0.05). Decreased IgG1 absorption from colostrum was associated with respiratory, rather than metabolic, acidosis, because blood PCO2 at 2 and 4 hours after birth was negatively related to IgG1 absorption (P less than 0.05), whereas serum bicarbonate concentration was not significantly related to IgG1 absorption. Acidosis was frequently observed in the 30 calves of study 1. At birth, all calves had venous PCO2 value greater than or equal to 60 mm of Hg, 20 of the calves had blood pH less than 7.20, and 8 of the calves had blood bicarbonate concentration less than 24 mEq/L. Blood pH values were considerably improved by 4 hours after birth; only 7 calves had blood pH values less than 7.20. Calves lacking risk factors for acidosis were examined in study 2, and blood pH values at 4 hours after birth ranged from 7.25 to 7.39. Blood pH was unrelated to IgG1 absorption in the calves of study 2. However, blood PCO2 was again found to be negatively related to colostral IgG1 absorption (P less than 0.005). Results indicate that postnatal respiratory acidosis in calves can adversely affect colostral immunoglobulin absorption, despite adequate colostrum intake early in the absorptive period.

Relationship between the apparent dissociation constant of blood carbonic acid and severity of illness.

The Henderson-Hasselbalch equation is commonly used to calculate plasma bicarbonate and CO2 content (tCO2) from blood gas measurements and an assumed constant value of the apparent dissociation constant of blood carbonic acid (pK'). Several studies have reported pK' to be variable in critically ill patients. We prospectively compared the pK' of patients in an intensive care unit to their severity of illness. Blood specimens were analyzed for pH, Pco2, and tCO2, and the results were used to calculate pK'. The tCO2 was also calculated from this equation by means of the measured pH and Pco2 and from an assumed constant pK'. Severity of illness was evaluated with the acute physiology score and the Therapeutic Intervention Scoring System. A total of 2004 specimens were analyzed; they had a mean pK' of 6.126. A strong correlation was shown between calculated and measured tCO2; however, there was essentially no correlation between disease severity and pK'. We conclude that bicarbonate and tCO2 can be accurately calculated in critically ill patients.

Na+-H+ exchange and pH regulation in red blood cells: role of uncatalyzed H2CO3 dehydration.

Erythrocytes of rainbow trout respond to adrenergic stimulation by activation of a Na+-H+ exchange. When red blood cells are suspended in their own plasma and equilibrated with a convenient gas mixture in a tonometer, the extrusion of H+ induces a fast, very strong acidification of the blood (by 0.5-0.7 pH units), explained as follows. Excretion of H+ into a medium containing HCO3- causes the formation of H2CO3. The uncatalyzed dehydration of H2CO3 is slow so that H+ accumulates above the level that would prevail at equilibrium, promoting a strong acid disequilibrium pH. Then the blood pH progressively returns to a value close to its initial value because of the slow uncatalyzed dehydration of H2CO3 and washout of the CO2 so produced. The period of acid disequilibrium pH, however, is lengthened because part of the CO2 generated by the spontaneous dehydration is not washed out by tonometry but diffuses into the red cells where it is rapidly converted into HCO3- and H+ by carbonic anhydrase and then excreted by Na+-H+ and Cl-HCO3- exchangers. This recycling process "refuels" the ionic reaction, increasing the time needed to reach equilibrium. The anion exchanger does not sense this strong acid disequilibrium pH, since the external HCO3- concentration is practically unchanged at that time. During the extracellular pH (pHe) recovery period, simultaneously extracellular HCO3- content decreases and intracellular Cl- content increases. Thus intracellular pH and pHe appear to be uncoupled. This overall interpretation is confirmed by experiments using carbonic anhydrase and drugs such as propranolol and amiloride.(ABSTRACT TRUNCATED AT 250 WORDS)

Constancy of blood carbonic acid pK' in patients during cardiopulmonary resuscitation.

Previous studies have suggested that the apparent dissociation constant of blood carbonic acid (pK') may actually vary in acutely ill patients. We prospectively compared the pK' of healthy control subjects to that of patients undergoing cardiopulmonary resuscitation (CPR). Arterial blood obtained from 20 patients undergoing CPR and from 30 healthy volunteers was analyzed for Na+, pH, PCO2, and total CO2 content (tCO2). pK' was calculated from this data, using the Henderson-Hasselbalch equation. Total CO2 was then calculated in the CPR patients, using this equation and the control pK'. Mean pK' was 6.109 +/- 0.004 (SEM) for the control group and 6.123 +/- 0.007 for the CPR group (p = NS). In the CPR group, calculated tCO2 was not significantly different from measured from tCO2, and the correlation between calculated and measured tCO2 was 0.99. In patients undergoing CPR, pK' does not differ significantly from normal, and tCO2 can be accurately estimated with the Henderson-Hasselbalch equation.

The apparent pK of carbonic acid in rainbow trout blood plasma between 5 and 15 degrees C.

Values for carbon dioxide solubility (alpha CO2) and the apparent first dissociation constant (pKapp) of carbonic acid in rainbow trout plasma were measured at 5, 10 and 15 degrees C so as to eliminate the uncertainties with continued use of mammalian values extrapolated from the much higher temperatures of their determination. Estimates of pKapp were based on the in vivo measurement criteria most commonly used (i.e. whole blood pH, PCO2 and the CCO2 of true plasma separated from red cells at room temperature). Apparent pK varied inversely with pH, the dpKapp/dpH slopes at 10 and 15 degrees C (-0.075 and -0.080, respectively) being significantly elevated with respect to that at 5 degrees C (-0.004). At constant pH, dpKapp/dTemp varied between -0.0160 (pH 7.4) and -0.0208 (pH 8.0), both of which are higher than theoretically and experimentally based literature data on separated plasma. When we repeated our pKapp determinations (using identical methods) on rainbow trout separated plasma, we obtained dpKapp/dT slopes ranging from -0.009 to 0.0110, similar to all previous determinations. In attempts to account for the discrepancies between our whole blood and plasma based pKapp estimates, we found that the pH of whole blood was always lower than that of its isothermally separated true plasma (0.015 units lower at 15 degrees C) and that this difference became magnified at lower temperatures (0.033 units lower at 5 degrees C). Also, if cool blood was allowed to warm towards room temperature before and/or during anaerobic centrifugation for true plasma, CO2 was found to leave the red cells and result in a higher plasma total CO2 content relative to the amount contained in the original blood plasma (0.40 mM for a 15 degree C dT of separation). We conclude that use of pKapp values obtained from gasometric determinations on separated plasma is not appropriate for PCO2 or [HCO3-] calculation by the Henderson-Hasselbalch equation when the practice is to measure the whole blood pH and the total CO2 content of true plasma separated at temperatures other than that of the original blood plasma.

Radial presentation of results of blood acid-base analyses.

Both students and clinical users find interpretation of blood acid-base numerical values to be difficult. A radial plot provides patterns which are easy to understand, and which can be applied to many groups of laboratory results.

Carbonic acid dissociation constant (pK1) in critically ill newborns.

In the Henderson-Hasselbalch equation, the apparent first dissociation constant for carbonic acid in plasma, pK1, is 6.10 +/- 0.01 (+/- SD) in healthy adults. In contrast, values for pK1 in sick adults and in sick infants and children have been reported to vary widely. Because of the far reaching implications of these findings, we repeated the measurements in 19 newborns in a neonatal intensive care unit. Two measurements were made in each infant, one while the infant was acutely ill and another after recovery. We found that neither the mean value nor the range of pK1 values was affected by the infants' clinical status. The values during the acute phase of the hospitalization (range, 6.01-6.12; mean +/- SD, 6.08 +/- 0.03) did not differ from those after recovery (6.02-6.17; 6.08 +/- 0.04). A second study was performed in order to see if the wide range of pK1 values seen in other studies might be the result of an unstable state accompanying acute changes in acid-base status similar to those that might be encountered in clinical situations. However, data in seven lambs showed no significant difference when pK1 before an acute alteration in acid-base status (6.10 +/- 0.04) was compared with that 10 min after (6.09 +/- 0.03). In newborn intensive care units, nomograms are used to calculate total CO2 from pH and PCO2 assuming a pK1 = 6.10. Our data support this practice.

Variability in pK'1 of human plasma.

(1) Results were presented of an investigation of the relationship between ionic strength and PK'1 (negative logarithmic form of the apparent overall first dissociation constant of carbonic acid in plasma) in separated human plasma at constant PCO2. (2) Ionic strength was varied by adding dry NaCl to diluted aliquots of plasma from six healthy people and dry NaCl plus dry NaHCO3 to diluted aliquots of plasma from six other healthy people. pK'1 was determined from simultaneous measurements of pH and PCO2, and measurements of TCO2. Values for solubility factor for CO2 (s) were corrected for differences in plasma water and in Na concentration. All plasmas were equilibrated at 37 degrees C in a tonometer with a constant gas mixture (5% CO2, 12% O2, 83% N2). Precision of pK'1 determinations averaged 0.003. pK'1 was also determined on fresh undiluted healthy plasma, similarly tonometered. (3) We report (a) considerable variability in pK'1 of fresh undiluted healthy plasma (from 6.0197 to 6.1217); and also in extrapolated values for pK'1 at a notional zero ionic strength (6.179 to 6.325); (b) that variation in plasma ionic strength alters pK'1; (c) that change in plasma bicarbonate [HCO3]p can also change pK'1; (d) that change in pK'1, changes measured pH. (4) Implications are discussed.

Ventilation and acid-base balance during graded activity in lizards.

Arterial PCO2, hydrogen ion ([H+]a), and lactate ([L]a) concentrations, rates of metabolic CO2 production (VCO2) and O2 consumption (VO2), and effective alveolar ventilation (Veff) were determined in the lizards Varanus exanthematicus and Iguana iguana at rest and during steady-state treadmill exercise at 35 degrees C. In Varanus, VCO2 increased ninefold and VO2 sixfold without detectable rise in [L]a at running speeds below 1.0 to 1.5 km x h-1. In this range, Veff increased 12-fold resulting in decreased levels of PaCO2 and [H+]a. At higher speeds [L]a rose. Increments of 5 mM [L]a were accompanied by hyperventilation, reducing PaCO2 and thus maintaining [H+]a near its resting level. When [L]a increased further, [H+]a increased. Sustainable running speeds (0.3-0.5 km x h-1 and below) were often associated with increased VO2, VCO2, and [L]a in Iguana. Sixfold increases in VCO2 and 9-mM increments in [L]a were accompanied by sufficient increase in Veff (9-fold) to maintain [H+]a at or below its control level. When [L]a increased further, [H+]a increased. These results indicate that both lizard species maintain blood acid-base homeostasis rather effectively via ventilatory adjustments at moderate exercise intensities.