The ludicrous nature of the answer is exactly the view that Peter Stewart opposed with regards the central the role of bicarbonate in any metabolic disorder. The traditional school, when asked what caused pH to drop to 7.2 in a patient with diarrhoea, would answer the loss of bicarbonate. Stewart emphatically answers his own rhetorical question "What is the role of bicarbonate in acid base balance?" with "NONE".
H + = 24 * PaCO2 * HCO3 (HENDERSON EQUATION)
The equation is a valid statement of the dissociation equilibrium for carbonic acid. However, it is of no help in deciding "what determines what" in the sense of physical causality. How is it then possible to get meaningful answers by plugging into the Henderson- Hasselbalch (HH) the bicarbonate value?
Siggaard - Andersen asked a similar such question in 1963, when answering how generations of physiologists could define acid and bases in diametrically opposite ways, and yet still come up with meaningful results. Simply stated, the paradox can be explained by the law of electroneutrality-an anion is always accompanied by a cation. Formally, there is disgreement in defintions, but not electrically. The answer to the question posed above is that bicarbonate is always accompanied by a cation, Na +. Thus any change in bicarbonate represents a simultaneous change is Na +.
The gold standard for acid base balance to date is the Henderson-Hasselbalch (HH) equation (directly measured H +). A multitude of buffers exist in the body, all of which to some extent share the same pool of H +ions (isohydric principle). Any change in acidity must involve redistribution of H + ions among all participating acid-base pairs. However, one need only know the component concentration from a single acid-base pair to monitor the acid-base behaviour of the entire system. In this sense, the HH equation in an inductive step, which generalises from one acid-base pair to the acid base changes in the body fluid.
Stewart was at pains to point out that mathematical dependence (of the HH equation on HCO 3 -) does not in any way imply physical dependence. Where Stewart makes his quantum leap is that his rationale is not based on inductive steps. His data are mathematically sound relationships between (H +) and the independent control variables (PaCO2, SID, and weak acids). His mathematical reasoning has subsequently been verified. To argue with his results is akin to disputing that 1+1 =2. Stewart's method is based on sound deductive principles. His primer on acid base balance is titled "A QUANTITATIVE APPROACH…..".
However, we have used the traditional approach for decades, and this is our current tested gold standard. Stewart's methods will have to be tested in the clinical scenario over the next few decades, even though it is more mathematically sound than prior methods. In, the same way, even Einstein's theory of relativity had to be tested by confirming that light bent during the solar eclipse. The challenge will be to maximise the information based on the Stewart technique at the patient's bedside. This may be made accessible in the future by ready availability of computers. Without these abilities, one is nevertheless still able to use his basic strong ion difference principle profitably at the bedside, in combination with the Gamblegram. The litmus test for Stewart will be to see if the calculated H + is reliable in predicting measured H + in different conditions (eg. through an entire range of SID).
Whereas Stewart's analysis has refocussed critical attention to the role of electrolytes in acid base balance, this concept is not new. It has previoulsy been recognised that there was a close connection between acid-base balance and electrolyte balance. Where Stewart is revolutionary is that he mathematically proves that strong electrolytes act as the control (independent variable) in determining the pH. Hitherto, a mere correlation (not causation) between electroltyes and acid-base balance had been recognised. This can be quite easily demonstrated using the Gamblegram: (Na +) = (Cl - ) + (HCO 3 -) + (Prot -) ; However, it is well recognised that (HCO 3 -) + (Prot -) constitute the major component of the buffer base (BB). Therefore BB ~ (Na +) - (Cl - ). The strong ion difference which Stewart alludes to is simplistically no other than (Na +) - (Cl - )
Thus BB and (Na +) - (Cl - ) are mirror images of each other. Because of the correlation between the change in pH and (HCO 3 -), clinicans were fooled into acscribing buffering power to (HCO 3 -). Whereas the Copenhagen school of Siggaard-Andersen emphasises the concept of buffer base, for Stewart this is another dependent variable, which is controlled by the SID ie. (Na +) - (Cl - ).
What about the other traditional buffers(weak acid): Haemoglobin, albumin, PO4??
Stewart's totally counterintuitive answer (which is chemically and mathematically valid) shocks one. A solution with weak acids "resists" changes in H + much less effectively than the same solution without any weak acid. Physiochemical analysis therefore contradicts the conventional belief of protein as a "buffer", which resists pH changes in a solution. A weak acid "buffer" is not therefore an H + or pH “regulator", but rather a H + or pH "setter".
This is where Ole Siggaard Andersen waxed furious in slating the SID; it is essentially exactly the same as the BB quantitatively. If one looks at the Henderson equation H + = 24 * PaCO2 * HCO3, and compares it to the independent variables of Stewart (PaCO2, SID (BB-mainly HCO 3 -), and weak acids) great overlap can be noticed. While the concepts may be quantitatively similar in terms of H +, they are miles apart qualitatively. An analogy which highlights the logical difference between the two approaches is that both reach the same answer, for example 20, but method A is 10 * 2; whereas method B is 5*4.
Various nomograms and curves of acid base could quite easily have substituted SID for BB. However, from a practical point, measurement of the BB was more accurate and easier than quantifying electrolytes in the past. The validity of the Stewart method in accurately predicting H + at small SID has recently been questioned. This may be because the standard deviation of the concentration of strong electrolytes ( measured via ion specific electrodes ) is fairly wide. Hence these “inaccuracies" magnify (widen or narrow) the true SID at low SID eg. SID < 25.
From the clinical bedside however, the words "absurd and anachronistic" of Siggaard-Andersen in describing the Stewart method, are extremely harsh. A thesis based on mathematical deduction is impossible to be absurd. The ability the Stewart technique provides in properly analysing crystalloid and colloid solutions suggests that the method is far from anachronistic. For example, no prior theory and understanding of electrolytes has enabled the intensivist to understand the rationale behind saline induced hyperchloremic acidosis and futhermore, to provide a platform for a more physiological crystalloid. To use another astrophysics analogy, the precession (not completing a closed ellipse) of Mercury could not be explained by classical physics, but Einstein's General Theory of Relativity gave a precise explanation for it
The great transatlantic debate (the use of in vivo vs. in vitro measurements) seems to be temporarily buried, and hopefully, like the Titanic, will remain permanently at the bottom of the ocean. It is a circuitous debate among the world's best physiologists/chemists /clinicians which will have no clear answer because of its qualitative nature. Hopefully, both schools (Boston-in vivo- HCO 3 - vs Copenhagen- in vitro-BB) will find a safer common ground in Stewart's method of analysis. In addition, his technique is valid for all types of body fluids. It is often said that the one true sign of a genius is that all the dunces were/ are against him. The clinicians, physiologists and chemists to whom Stewart addressed his primer will in the future discover the great debt which is owed to him.
The HH equation provides no extra information compared to the Henderson equation at its very best. At the very worst it is misleading. It is both insensitive and misleading in alerting the clinician to underlying problems. For example, it is important to realise that a fall in pH of 0.3 units from 7.4 to 7.1 represents a doubling of (H +) from 40 to 80 nmol/l, whereas a rise in pH from 7.4 to 7.7 represents a fall in (H +) by only 20 nmol/l, from 40 nmol/l to 20nmol/l. Thus it is difficult to appreciate the magnitude of the change in (H +) commensurate with a change in pH. A 0.1 unit decrease in the pH from 7.4 to 7.3 represents a 25% increase in H +. A similar percentage change in serum Na+ would raise its value from a normal of 140 meq/l to 175 meq/l. An analogy is that if one were involved in an earthquake which registers 2 on the Richter scale, and could predict another one which was potentially 4 on the scale, should one double ones efforts in preventing catastophe? This would be a fatal error as the Richter scale is essentially base 30. The second quake is actually 900 times more powerful than the first.
The pH is a double inverse relationship. Just an inverse relationship is confusing enough. pH = -log H += log (1/H +). Both log and (1/H +) are inverse relationships. We know that our normal pH is 7.4. Therefore 7.4 = -log H +. Stated differently, 10 -7.4 = H +(equivalents/litre). Stated differently, our body would need a theoretical volume of distribution of about 25 000 000 litres to accommodate 1 equivalent of H +.
SEVEN STEPS TO ACID BASE ANALYSIS
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| COMMON CLINICAL STATES AND ASSOCIATED ACID-BASE DISORDERS | |
| Clinical state | Acid-base disorder |
| pulmonary embolus | respiratory alkalosis |
| shock | metabolic acidosis |
| vomiting | metabolic alkalosis |
| severe diarrhoea | metabolic acidosis |
| cirrhosis | respiratory alkalosis |
| renal failure | metabolic acidosis |
| sepsis | respiratory alkalosis, metabolic acidosis |
| pregnancy | respiratory alkalosis |
| diuretic use | metabolic alkalosis |
| Chronic Obstructive Pulmonary Disease | respiratory acidosis |
ORDER SIMULTANEOUS ABG AND CHEMISTRY PROFILE
The HCO3 and total CO2 should correspond. If they do not correspond, the specimens most likely were taken at different times and are not valid.
ASSESS ACCURACY OF DATA
There could have been an error in calculation (unlikely as this is done via the ABG analyser), error in transcribing the results, or using data results which were done from more than one blood gas result (ie. inadvertently interpret data of ABG's done at different times). Most modern blood gas analysers in the ICU/operating room measure PaCO2 and pH directly and calculate the HCO 3 -.
Eg. pH 7.167; CO2 134 mmHg, HCO 3 - 48 mmol/l.
First verify H + according to the Hendersen equation: H + = 24 * PaCO2 * HCO3 : H += 24 * 134.4/48.4 =66 nmol/l
Secondly, estimate H + from the pH: An easy method though not completely accurate is H + = 80 - decimal fraction of pH: Therefore H + = 80 - 16= 64nmol/l. (NB:pH was 7.16) There is good correlation between the measured H + and the calculated H +. Therefore the data are valid.
The use of the Henderson equation thus avoids the need to deal with logarithms.
IDENTIFY THE PRIMARY DISTURBANCE
a) pH <7.36 :ACIDAEMIA
b) pH >7.44: ALKALAEMIA
CALCULATE THE EXPECTED COMPENSATION: USE ONE OF THE 6 "REGRESSION EQUATIONS"- THESE ARE JUST SCARY WORDS FOR FORMULAE WHICH WERE DERIVED FROM DIFFERENT POPULATIONS (WHICH PHYSIOLOGICALLY DON'T NECESSARILY MIMIC SICK PATIENTS, ESPECIALLY PATIENTS IN THE ICU).
The 6 regression equations for expected compensation are at best, mere hypotheses of the true state of compensation. It is known that there are problems with the populations from which the regression equations were drawn. In other words, they are our current best guesses expected compensation.
| Regression equations for pH compensation | ||
| TYPE OF DISORDER | DEGREE OF COMPENSATION | DURATION |
| Metabolic acidosis | D PaCO2=(D HCO 3 - * 1.2) +2 or |
12-24 hours |
| Metabolic alkalosis | D PaCO2=(D HCO 3 - * 0.7) + 5 | 12-24 hours |
| Acute respiratory acidosis | D HCO 3 -=(D PaCO2 * 0.07) +1.5 | Minutes |
| Chronic respiratory acidosis | D HCO 3 -=(D PaCO2 * 0.4) +3 (max D 45mmol/l) |
3-5 days |
| Acute respiratory alkalosis | D HCO 3 -=(D PaCO2 * 0.2) +2.5 | Minutes |
| Chronic respiratory alkalosis | D HCO 3 -=(D PaCO2 * 0.5) +2.5 | 2-3 days |
CALCULATE THE "GAPS"
| RAJAH'S 3 GAP RULES: |
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ANION GAP = (Na+K-CL- HCO3)- DO include K in the formula. This has been shown to provide a more accurate result.
Quite simply, the major component of the anion gap is albumin, which in health (40g/l) contributes a charge of about 10meq/l. As a very rough rule, for those scared of formulae, the average ICU patient has a albumin of about 20g/l. Thus the anion gap is decreased by 5 meq/l. Therefore, if a critically ill patient has a anion gap of for example 12 meq/l, ONE CAN ADD 5 MEQ/L TO THAT NUMBER ( calculated anion gap). 17 meq/l is his unmasked anion gap-ie if my patient had a normal albumin of 40g/l. Hence the first rule of the gaps, TAKE FIVE. Therefore, this patients still has ongoing pathology for whatever reason accounting for the anion gap of 17 meq/l. If one did not correct, one would inadvertently miss ongoing pathology (lactic acidosis, keto-acidosis, uraemia, drugs etc), in the face of a normal anion gap of 12 meq/l in this example.
Certain clinicians are of the opinion that the correction need not be made. The line of argument is that a few meq/l difference does not make any difference. However, in the ICU, burns unit etc. the degree of hypoalbuminaemia IS severe and hence the number of meq/l the anion gap changes by IS significant. Furthermore, if one looks at a simple example of ethylene glycol poisoning, a small increase in the anion gap in the face of a osmolar gap >10 indicates that dialysis is not far away!
The strong ion gap provides one with no more additional information than the corrected anion gap (correcting for hypoalbuminaemia). However, it provides another conceptual method of measuring "other strong anions" and is in keeping with Stewart's strong ion difference. If there is a difference in the actual SID (SID a , calculated by subtracting chloride from sodium + potassium ion concentration), and expected SID (SID e ) then this must be made up by OTHER "NON PHYSIOLOGICAL" STRONG ANIONS-eg. Drugs, ketones, organic acids, lactic acid.
This process is simplified by drawing the Gamblegram. Hence the second rule of the gaps, ALWAYS GAMBLE. DRAW THE GAMBLEGRAM! (DRAW, do NOT write out the Gamblegram FOR EVERY PATIENT)
Dr J.L. Gamble was a pediatrician who introduced the world to the Gablegram. To properly understand this simple diagram sets one on the path to nirvana for acid base balance.
IN THE MOST SIMPLIFIED FORM USE THE FOLLOWING EQUATION FOR THE BICARBONATE GAP: (Na+) - (Cl- ) - 39.
If it is < -6 this implies an associated hyperchloremic metabolic acidosis. If it is > +6 , this implies an associated metabolic alkalosis. (The bicarbonate gap is also called the delta gap)
ACID BASE MAPS - TAKING THE MAZE OUT OF THE MAP
CAVEATS PERTAINING TO THE MAP
Take note of the following:
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| Date of First Publication: 2001-05-12 | Date of Last Update: 2006/10/24 | Web page author: Click here |