Acid-Base Approach: Stewart model
Running title: Approach to Acid-Base Disturbance
Authors: Cai-mei Zheng, Kuo-Cheng Lu, Chin-Feng Tseng
Institution:
Division of Nephrology, Department of Medicine, Cardinal-Tien Hospital,
School of Medicne, Fu-Jen Catholic University
Correspondence author: Chin-Feng Tseng, MD
Division of Nephrology, Department of Medicine, Cardinal-Tien Hospital,
School of Medicne, Fu-Jen Catholic University
Address: 362, Chung-Cheng Rd, Hsin-Tien City, Taipei County, Taiwan
Tel: 886-2-22193391 ext 65340
Fax: 02-22193153
Reprint request address: 362, Chung-Cheng Rd, Hsin-Tien City, Taipei
County, Taiwan
E-mail: echo910@yahoo.com
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Abstract
Acid-base disequilibrium and electrolyte disturbances are the common
and time consuming problems we face daily in clinical practice. Traditionally,
we use the concept proposed by Henderson and Hasselbalch to solve these
problems. The proper treatment of acid-base disturbances depend on the well
understanding of underlying mechanisms. The physical chemical approach
proposed by Peter Stewart becomes popular among intensivists and
anesthesiologists nowadays. This new approach can explore and address
some metabolic disturbances not well explained by the traditional approaches.
Key words: acid-base, Handerson-Hasselbach, Stewart, strong ion
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Introduction
Acid-base disturbances encountered daily in clinical grounds are often
predictors of disease severity and prognosis. They are also the commonly
missed events in daily care. Traditionally, [HCO3-] centered approach using
Henderson-Hassel Balch equation was widely accepted to calculate acid-base
disturbances. But, this approach based on data interpretation rather than the
mechanism of development 1. Peter Stewart (1981) 2-4 used physical chemical
properties of fluid to analyze the buffer system of body and place emphasis on
quantitative explanation of those disturbances. The great difference of this
approach from traditional one is that [H+] and [OH-] depends on independent
variables (SID, pCO2 and ATot)5. In this article, we’ll review the basic concept
of Stewart approach in acid-base disorders.
The traditional approach
According to Henderson-Hasselbalch equation 6,7,
pH = pKa× log[HCO3-/(0.03 ×(pCO2)]
Changes in plasma bicarbonate or pCO2 determine pH and lead to
metabolic or respiratory acid-base anomalies. Plasma bicarbonate and pCO2
are completely depending on each other according to the formula. So, it fails to
explain complex disturbances accurately. The weak acids, such as albumin,
and phosphates are also excluded in determining of plasma pH. The
Henderson-Hasselbalch equation provides an estimate of the magnitude of
metabolic disorders but cannot explain the mechanisms that lead to its
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development.
Stewart approach 5,7
The physical–chemical properties of biologic solutions are the backbone
of the Stewart approach in analyzing their buffering properties. These are:
1. Electro neutrality (the sum of all positively charged ions equal the sum of all
negatively charged ions)
2. Conservation of mass (the amount of a substance in a system remains
constant unless it is added to or generated, or removed or destroyed) and
3. Dissociation equilibriums
According to Stewart, all these 3 conditions must be satisfied in biologic
solutions with buffering capacities 8. These basic principles are usually
overlooked by the clinical acid–base analyzers during past times. By using the
Stewart model, the mechanisms of complex metabolic acid-base disorders
such as hyperchloremic metabolic acidosis, hypoalbuminemic acidosis and
renal tubular acidosis, etc. become well cited and applied in managements.
Stewart divided the variables into independent and dependent forms.
Dependent variables are determined internally by the system. Their values can
be altered by changes in the values of the independent variables. Independent
variables are determined by factors external to the system. The changes in
their values affect the values of the dependent variables. Plasma [H+] and
plasma pH are dependent variables and determined by the water dissociation,
which again depend on three independent variables.2-4 These independent
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variables are:
1. SID : the 'strong ion difference' in the solution
2.
pCO2: the partial pressure of CO2 in the solution
3.
[ATot] : the total concentration of weak acids in the solution.
Strong ions refer to ions which are always fully dissociated in solutions,
and tend to exist only in the charged form. For example, adding sodium
chloride to water produces a solution containing Na+ and Cl-. No NaCl is
present in that solution as such since all the Na+ and Cl- ions are fully
dissociated. The total amount of the strong ion is not changed when the
solution is converted back to the parent compound and the dissociation
equilibrium of the reaction constant, i.e., the concentration of any individual
strong ion in the solution is fixed. Strong ions are mostly inorganic (e.g. Na+,
Cl- , K+); some are organic, such as lactate. Any substance with a dissociation
constant greater then 10-4 Eq/l is considered a strong ion.
Strong Ion Difference (SID)
According to the electrical neutrality,
SID = (the sum of all the strong cation concentrations in the solution)
minus (the sum of all the strong anion concentrations in the solution).
If the solution contains Na+, K+ and Cl- as the only strong ions present,
then: SID = [Na+] + [K+] - [Cl-]
In human plasma, SID is derived by:
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SID = { [Na+] + [K+] + [Ca++] + [Mg++] } - { [Cl-] + [other strong anions-] }
If only healthy patients are considered, the ‘apparent SID’ (SIDa) can be
calculated as:
SIDa = { [Na+] + [K+] + [Ca++] + [Mg++] } - { [Cl-]+ [lactate-] }
SIDa has a normal value of 40 to 42 mEq/l. To maintain electrical
neutrality, SID must be zero (e.g. a solution with only strong ions). Since
normal human plasma SID is not zero, this strong ion difference must be
balanced by an equal amount of unmeasured ions 9. The solution must contain
charged ions other than the strong ones, i.e., weak ions, which are mostly
weak acids. Thus, SID refers to the total weak ions present in a solution which
are in the same amount but having the opposite charge as the strong ions to
be balanced. SID independently influences water dissociation via electrical
neutrality and mass conservation [i.e. if all other factors such as pCO2, albumin
and phosphate are kept constant]. An increase in SID leads relative increase
cations and decreases hydrogen ion release from water 10 (and increase
hydroxyl ion liberation) and cause alkalosis. Accordingly, a decrease in SID
may increases hydrogen ion release from water and causes acidosis. Thus,
[H+] and [OH-] becomes dependent variables in this approach.
The strong ions used in the SID formula are controlled by reactions
outside the system (i.e. independent variable). Inorganic strong ions (e.g. Na+,
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Cl-) are mostly absorbed from the gut; they are neither produced nor
consumed. The kidney is the most important organ regulating the
concentration of these strong ions, which is achieved mostly by varying their
rates of renal excretion. 5 Organic strong ions (e.g. lactate, Keto-anions) are
produced by various mechanisms of metabolism and may be catabolized in
the tissues or excreted in the urine. However, their concentrations in most
body fluids are not dependent on the reactions within the solution but are
regulated by mechanisms external to the system.
Since the extra-cellular [Na+] is tightly controlled for blood osmolarity, the
ECF pH can really be changed by alterations in strong anion, [Cl-] relative to
constant strong cation, [Na+] . This Stewart approach offers a better
explanation in hyperchloremic acidosis due to NaCl or HCl infusion. Normal
plasma SID is +40 and normal saline SID is zero { [Na+] –[Cl-] = 0 }. Addition of
normal saline to plasma results in reduced SID. H+ is released from water and
acidosis ensues.
Isotonic NaCl (0.9% saline) contains equal quantities of [Na+] and [Cl-],
but its infusion will result in unequal changes in the respective plasma
concentrations of these electrolytes. Since actual plasma water [Na+] is really
154 mEq/L when adjusted for the normal value of plasma water content,
plasma [Na+] will really only increase from 140mEq/L (normal plasma value) to
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143mEq/L (plasma [Na+]: 154 x 0.93 =143 mEq/L). Plasma [Cl-], however, will
increase from the normal plasma level of 103mEq/L to 143mEq/L by the same
calculation (plasma [Cl-]: 154 x 0.93 =143 mEq/L). The relatively higher
increase in negative strong ion [Cl-] compared to that in positive strong anion
will decrease the SID and a fall in pH would be observed. The hyperchloremia
is the cause of metabolic acidosis here .The higher the [Cl-] infused, the more
acidic the plasma results. Hence, the rate and dose of NaCl (0.9% saline)
infusion 11 is the main determinant of acidosis. Metabolic acidosis may be
worsened when this hyperchloremic acidosis is undiagnosed or misinterpreted
as dehydration and infuse more hyperchloremic fluids. Accordingly, infusions
of sodium bicarbonate or sodium lactate can result in metabolic alkalosis since
sodium remains in plasma, and weak ions, lactate or bicarbonate are
metabolized. The retained plasma sodium, a strong cation, increases plasma
SID and causes metabolic alkalosis.
The traditional approach accepted that hyperchloremic acidosis should be
treated by administering bicarbonate donor, sodium bicarbonate, but it failed to
explain the underlying mechanism.
Weak ions in plasma considered in acid-base balance are
1.
pCO2 (volatile)
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2. Weak acids (nonvolatile): HA <=> H+ + AThe pCO2 is accepted as independent variable in both traditional and
Stewart’s approach since its value in arterial blood and in all body fluids is
determined and controlled by factors external to the chemical system in the
body fluids. It is under sensitive and powerful feedback control via the
peripheral and central chemo-receptors, and is excreted from the lungs.
Weak acids are derived when partially dissociated substances are
dissolved in water. The dissociation reaction is:
[H+] x [A-] = Ka x [HA]
Where Ka is the dissociation constant for the weak acid.
In contrast to strong ions, the plasma contains both the weak acid (weak
ions) and its products of dissociation due to incomplete dissociation.
[ATot] = [HA] + [A-]
(law of conservation of mass)
1. [ATot]: the total amount of non-volatile weak acids present in the system.
2.
[HA]: all the weak acids in the system
3.
[A-]: the dissociated form of weak acids
The major non-volatile weak acids present in plasma are:
1. Proteins ( [PrTot] = [Pr-] + [HPr])
2.
Phosphates ( [PiTot] = [PO4-3] + [HPO4-2] + [H2PO4-] + [H3PO4])
In plasma proteins, the albumin level has a major impact on the acid-base
system. The plasma phosphate level is normally fairly constant and is
controlled as part of the calcium regulating system. At normal phosphate
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levels, the plasma phosphates contribute only about 5% of ATot. However, in
hyperphosphatemic patients, phosphate levels contribute most of the weak
acid in plasma.
In a healthy person, ATot ～ [Albumin]
Albumin gives an anionic effect in plasma. In other words,
hyperalbuminemia may lead to increase total weak acid concentration and
metabolic acidosis (eg. acidosis of chlorea) 12. But, in practice,
hypoalbuminemic status is more commonly encountered especially in critically
ill patients. Metabolic alkalosis is found in patients with hypoalbuminemia.
Thus, plasma albumin level must be considered in interpretation of acid-base
disturbances especially in critically ill patients13-16. But, it does not mean to
correct albumin level for acid-base disturbances.
Some critics criticize Stewart’s approach of acid-base balance since there
was many variables to be considered and due to it’s complexity. There is no
statistical evidence to support his contention that SID could mechanically
influence [H+] to maintain electro-neutrality. Furthermore, the Stewart formula
does not provide any prognostic advantage.
Despite these limitations, Stewart’s approach is widely applied in medical
centers in Europe, especially in emergency departments, intensive care
centers,17,18 trauma units and anesthetic centers since it can identify most of
the complex acid-base disturbances encountered in patients with major
injuries and critical illnesses.
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Conclusion:
According to the traditional approach, changes in [H+] were primary cause
of acidosis. Stewart’s approach considered SID, pCO2 and ATot as
independent variables which determine the dissociation of water, which again
influence [H+] in plasma. Physiologically, the change in SID level occurs more
rapid than change in plasma protein level. Thus, the change in SID level
becomes important determinant in metabolic acid-base disturbances. Both
approaches apply pCO2 as primary cause of respiratory acid-base
disturbances. Stewart includes the weak acids in patho-physiological analysis
of complex metabolic acid-base derangements, which is observed most
frequently in critically ill patients. Unmeasured anions and weak acids are
generally not considered in traditional work-up. But, none of these variants can
be used as prognostic indicator in acid-base disturbances until now.
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References
1. Narins R, Emmett M: Simple and mixed acid-base disorders: A practical
approach. Medicine (Baltimore) 1980; 59: 161-87.
2. Stewart PA: Independent and dependent variables of acid-base control.
Respir Physiol 1978; 33: 9-26.
3. Stewart PA: How to understand acid base balance, in A Quantitative
Acid-Base Primer for Biology and Medicine, edited by Stewart PA, New York,
Elsevier, 1981.
4. Stewart PA: Modern quantitative acid-base chemistry. Can J Physiol
Pharmacol 1983; 61: 1444–1461.
5. Corey HE: Stewart and beyond: new models of acid-base balance. Kidney
Int. 2003; 64: 777-87.
6. Hasselbalch KA. Die berechnung der wasserstoffzahl des blutes auf der
freien und gebundenen kohlensaure desselben, und die sauerstoffbindung
des blutes als funktion der wasserstoffzahl. Biochem Z 1916; 78: 112–44.
7. Kellum JA: Diagnosis and Treatment of Acid Base Disorders, Textbook of
Critical Care Medicine, 4th Edition. Edited by Shoemaker. Saunders, 2000,
pp 839-53.
8. Fencl V, Leith DE: Stewart's quantitative acid-base chemistry: applications
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in biology and medicine. Respir Physiol 1993; 91: 1-16.
9. Figge J,Mydosh T,Fencl V: Serum proteins and acid-base equilibria: a
follow-up. J Lab Clin Med 1992, 120: 713-719.
10. Rini M, Magnes BZ, Pines E, Nibbering ETJ: Real-Time Observation of
Bimodal Proton Transfer in Acid-Base Pairs in Water. Science 2003; 301:
349-52.
11. Wilkes NJ, Woolf R, Mutch M, et al. The effects of balanced versus saline
based intravenous solutions on acid base and electrolyte status and gastric
mucosal perfusion in elderly surgical patients. Anesth Analg 2001; 93: 811-6.
12. Wang F, Butler T, Rabbani GH, Jones PK: The acidosis of cholera.
Contributions of hyperproteinemia, lactic acidemia, and
hyperphosphatemia to an increased serum anion gap. N.Engl.J.Med. 1986;
315: 1591-5.
13. Story DA, Poustie S, Bellomo R: Quantitative physical chemistry analysis
of acidbase disorders in critically ill patients. Anaesthesia 2001; 56: 530-3.
14. Balasubramanyan N, Havens PL, Hoffman GM. Unmeasured anions
identified by the Fencl, Stewart method predict mortality better than base
excess, anion gap, and lactate in patients in the pediatric intensive care unit.
Critical Care Medicine 1999; 27: 1577–81.
15. Fencl V, Jabor A, Kazda A, Figge J. Diagnosis of metabolic acid-base
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disturbances in critically ill patients. American Journal of Respiratory and
Critical Care Medicine 2000; 162: 2246–51.
16. Gilfix BM, Bique M, Magder S. A physical chemical approach to the
analysis of acid-base balance in the clinical setting. Journal of Critical Care
1993; 8: 187–97.
17. Dubin A, Menises MM, Masevicius FD, Moseinco MC, Kutscherauer DO,
Ventrice E, Laffaire E, Estenssoro E. Comparison of three different methods
of evaluation of metabolic acid-base disorders. Crit Care Med 2007; 35:
1254-1270.
18. Boniatti MM, Cardoso PR, Castilho RK, Vieira SR. Intensive Care Med.
2009 Apr 15. [Epub ahead of print]
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中文摘要
題目：以史都華模式剖析臨床酸鹼問題
鄭彩梅 盧國城 曾金鳳
酸鹼平衡失調及電解質異常是我們在臨床實踐上常見的問題。
傳統上，我們使用 Henderson-Hasselbach 公式去運算並處理這些問
題。當然恰當的酸鹼平衡失調診治，必需要對潛在之酸鹼平衡機制有
充分了解。Peter Stewart 提議從物理化學方向著手處理此一常見問
題。現今歐洲國家較普遍運用於加護中心及麻醉醫療方面。此一新的
方法，可更進一步探索及說明某些傳統方法無法完整解釋的酸鹼平衡
失調現象。
關鍵詞：酸鹼, 漢得昇-黑索背, 史都華, 強離子
耕莘醫院 腎臟科
抽印本索取：曾金鳳 醫師
地址：台北縣 新店市 中正路 362 號
電話：02-22193391 ext 65340
傳真：02-22193153
E-mail: echo910@yahoo.com
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