A Corrected Equation Interrelating Physiological, base Excess and Physio-Chemical Metabolic Components of Arterial Blood Gas

London Journal of Medical Research
Volume | Issue | Compilation
Authored by Dr. T. Rajini Samuel , NA
Classification: NA
Keywords: Bicarbonate, base excess, strong ion difference, non-volatile weak acids
Language: English

Introduction: The physiological approach using Henderson hasselbach equation for Arterial Blood Gas(ABG) interpretation  is unable to quantify the metabolic component and does not explain the causative mechanism of metabolic acid-base disturbances. So, Base excess approach developed by Siggard Anderson  and the Physiochemical approach by Fencl-Stewart serve as an alternative approaches.

Aim:  The aim of the current study is to discuss in detail the interrelationship between the three approaches citing with examples for better understanding

Materials & Methods: An equation incorporating the parameters of Stewart’ theory in Henderson hasselbach equation inter-relates the physiological and physiochemical approach. In the Fencl-Stewart approach the contribution of individual effects of ions on the base excess interrelates the base excess parameter with the Stewart’s parameters.

Results: The equation relating the pH and strong ion difference has to be corrected for strong ion gap. The estimation of unmeasured ions in the Fencl-Stewart (Semi-quantitative) approach is grossly different if Corrected standard base excess  is used instead of calculated standard base excess.

Conclusion: The study concludes that although Stewart’s theory is very useful for providing mechanistic explanation for the metabolic acid-base disturbances, Physio-chemical approach cannot completely replace the physiological and Base Excess approach.

Clinical Significance: The understanding of the inter-relationship between bicarbonate, base excess, strong ion difference and non-volatile weak acids in the three different approaches is very essential to overcome the arduous task of confusing and challenging ABG cases.

 

               

A Corrected Equation Interrelating Physiological, Base Excess and Physico-Chemical Metabolic Components of Arterial Blood Gas

Dr. T. Rajini Samuel M.D

____________________________________________

ABSTRACT

Introduction: The physiological approach using Henderson Hasselbach equation for Arterial Blood Gas(ABG) interpretation  is unable to quantify the metabolic component and does not explain the causative mechanism of metabolic acid-base disturbances. So, Base Excess approach developed by Siggard Anderson  and the Physicochemical approach by Fencl-Stewart serve as an alternative approaches.

Aim: The aim of the current study is to discuss in detail the interrelationship between the three approaches citing with examples for better understanding

Materials & Methods: An equation incorporating the parameters of Stewart’ theory in Henderson Hasselbach equation inter-relates the physiological and physicochemical approach. In the Fencl-Stewart approach the contribution of individual effects of ions on the base excess interrelates the base excess parameter with the Stewart’s parameters.

Results: The equation relating the pH and strong ion difference has to be corrected for strong ion gap. The estimation of unmeasured ions in the Fencl-Stewart (Semi-quantitative) approach is grossly different if Corrected standard base excess  is used instead of calculated standard base excess.

Conclusion: The study concludes that although Stewart’s theory is very useful for providing mechanistic explanation for the metabolic acid-base disturbances, Physico-chemical approach cannot completely replace the physiological and Base Excess approach.

Clinical Significance: The understanding of the inter-relationship between bicarbonate, base excess, strong ion difference and non-volatile weak acids in the three different approaches is very essential to overcome the arduous task of confusing and challenging ABG cases.

Keywords:  bicarbonate, base excess, strong ion difference, non-volatile weak acids.

Author: Assistant Professor of Biochemistry, Shri Sathya Sai Medical College & Research Institute Sri Balaji Vidyapeeth Deemed to be University.

  1. INTRODUCTION

The most commonly used approach is physiological approach based on bicarbonate -carbon dioxide buffer system but it is unable to quantify the metabolic component and offers no mechanistic explanation for the metabolic acid-base disorders.[1,2] The bicarbonate value is a calculated parameter derived by modified Henderson equation so alteration in dissociation constant and solubility co-efficient may result in significant error under certain circumstances. [3,4] Base excess approach can quantify the metabolic component but also unable to give mechanistic explanation for the cause.[2]

Physicochemical approach is used to give better information about the causative mechanism of metabolic acid-base disturbances.[1,2] This is based on Stewart’s theory later modified by Fencl and others. Initially the Stewart’s theory did not get attraction because of its complexity and difficulty in practical applications. But recently after simplification and modification by other researchers, it has gained popularity especially in the intensive care units. [1,2] An equation incorporating the parameters of Stewart’ theory  in Henderson Hasselbach equation interrelates the Physiological  and Physicochemical approach.[5]

pH = 6.1 + log { SID - [Atot] } / 0.03*pCO2

Fencl-Stewart approach inter-relates the base excess parameter with the Stewart’s theory parameters namely strong ion difference and total concentration of non-volatile weak acids.[1,2,6 &7] Numerous publications have been done recently using the physicochemical approach for ABG interpretation explaining its merits and drawbacks.

The current study clearly discusses the theoretical description of the inter-relationship between the three different approaches citing with examples. This study corrects the equation relating the pH and strong ion difference for strong ion gap. The estimation of effects of unmeasured ions is grossly different if corrected standard base excess (correction done for albumin and phosphate) is used for calculation instead of calculated standard base excess. The aim of the study is to discuss in detail the inter-relationship between bicarbonate, base excess, strong ion difference and concentration of non-volatile weak acid and its  application.

  1. MATERIALS AND METHODS

The relation between  bicarbonate buffer, non-bicarbonate buffers and base excess is discussed below.[8]

Buffer Base (BB):

Buffer base includes the sum of the concentration of bicarbonate and dissociated non-volatile weak acids. The non-volatile weak acid denotes the non-bicarbonate buffers namely albumin and phosphate.

BB= HCO3 + NBBnon-B  + βnon-B  X(ΔpH)

NBBnon-B  : concentration of  non-bicarbonate buffers at pH 7.4 and pCO2 40 mm of Hg.

βnon-B: buffer value or buffer capacity of non-bicarbonate buffers.

The ability of the buffer solution to resist pH changes can be measured using buffer capacity β, also known as buffer value.[9]

β = changes in buffer concentration/ changes in pH

Changes in buffer concentration = β X changes in pH

                                 = β X ΔpH

βnon-Bx(ΔpH): changes in buffer concentration

The sum of the terms NBBnon-B  + βnon-Bx(ΔpH) denote the concentration of non-bicarbonate buffers( dissociated non-volatile weak acids)

Total Normal Buffer Base:

BBpHn = [HCO3]N  +  NBBnon-B 

[HCO3]N  -denote the normal concentration of bicarbonate that can be derived using Modified Henderson Equation.

Base Excess(BE):

Base excess(BE) is the difference between concentration of buffer base(BB) and the normal concentration of buffer base at pH 7.4 and pCO2 40 mm of Hg (BBpHn). [8]

BE = BB – BBpHn

BE = BB – BBpHn

= HCO3 + NBBnon-B  + βnon-BX(ΔpH) - [HCO3]N  -  NBBnon-B 

 = HCO3  - [HCO3]N  + βnon-BX(ΔpH)

If [HCO3]N  is 24.4 then the formula is

BE = HCO3  - 24.4  + β*(ΔpH)

Where β (buffer value) = 1.2*Albumin g/dl + 0.097*Phosphate mg/dl. [9]

Standard Base Excess (Corrected) = HCO3 – 24.4 + β(ΔpH)

The above equation requires bicarbonate, albumin and phosphate values to calculate standard base excess.

Calculation of standard base excess or extracellular base excess (cBase(ecf)):

The calculations of cBase(ecf) are very standardized.[10] The most used algorithm is:

cBase(ecf) = cHCO3 - 24.8 + 16.2 × (pH - 7.40)

The above equation is based on the assumption that the total concentration of weak acids (ATOT) is normal. In critically ill patients the total concentration of weak acids is mostly abnormal. So, this is a major drawback of this equation. [6]

Relation between Stewart’s theory parameters and bicarbonate:

The relation between Stewart’s theory parameters and bicarbonate is discussed below.

Strong ion difference:

The difference between sum of the strong cations and strong anions is called apparent strong ion difference (SIDa).

SIDa= [sum of the strong cations] – [sum of the strong anions]

Buffer base ( [HCO3- ] + [A-] ) is numerically the same as effective strong ion difference[SIDe].

[A-] or [Atot] - denotes the total concentration of dissociated non-volatile weak acids namely albumin (Alb) and phosphate (Pi). [5]

The electric charge on albumin (mmol/L) is calculated on the basis of the below equation:

[Alb] = [Alb] × (0.123*pH – 0.631)

The electric charge on inorganic phosphate (mmol/L) is calculated by the below equation: [5]

[Pi ] = [Pi] × (0.309*pH – 0.469)

SIDe = [HCO3 ] + [Alb] +  [Pi ]

Strong ion Gap (SIG):

                          SIG  = SIDa – SIDe

            { SIDe = HCO3-   + A-tot }

Strong ion gap = SIDa - HCO3-  -  A- tot  

HCO3  =   SIDe  - A-tot

HCO3  =  SIDa   - A-tot  - SIG 

If SIG is zero then SIDe and SIDa are interchangeable.

An equation relating the pH and Stewart’s theory parameters (strong ion difference and total concentration of dissociated non-volatile weak acids) is given in the previous study.[5]

 pH = 6.1 + log { SID - [Atot] } / 0.03*pCO2

In this study both the apparent and effective strong ion difference is equated but in abnormal conditions they are not equal and the difference between them denote the Strong ion Gap (SIG). So the current study corrects this equation for the strong ion gap.

The relation between pH and effective strong ion difference is as follows.

pH = 6.1 + log { SIDe - [Atot] } / 0.03*pCO2

The relation between pH and apparent strong ion difference is as follows.

pH = 6.1 + log { SIDa - [Atot] – SIG  } / 0.03*pCO2

Anion Gap:

The calculation of anion gap is discussed below.

Sum of the cations = sum of the anions ( law of electrical neutrality)

Measured cations + unmeasured cations = measured anions+ unmeasured anions

Re-arranging the equation,

Measured cations – measured anions = unmeasured anions- unmeasured cations

Anion gap  = measured cations- measured anions

            = unmeasured anions – unmeasured cations

As the unmeasured anions increases, the anion gap increases.[2]

Anion gap = [Sum of the cations] – [sum of the anions]

                   = [Na+ + k+ } – {Cl-  + HCO3-}

Strong ion gap = SIDa - HCO3-  -  A- tot  

If SIDa =   [Na+ + k+ } – {Cl- }

Usually sodium, potassium and chloride are considered for calculation because calcium, magnesium and lactate are not routinely measured.

SIG = [Na+ + k+ } – {Cl- } - HCO3-  -  A- tot  

SIG = AG -  A- tot    or  AG = SIG + A- tot  

This relation is true only if sodium, potassium and chloride are considered for calculation.

Strong ion gap denotes the difference between unmeasured anions and cations. [12,13]  It’s value is positive for increased unmeasured anions and negative for increased unmeasured cations. Anion gap has to corrected for albumin which is given below. [6,9]

Albumin corrected anion gap= anion gap + 0.25 *(44 –observed albumin g/L)

Individual ion effects on Base Excess:

Strong Ion Difference effect on Base Excess:

Sodium and chloride are the major strong ions that significantly contribute to the strong ion difference. Fencl divided the effect of strong ion difference on base excess into sodium and chloride effects. [1]

Water Effect or sodium effect:

The dilution or concentration effects of changes by water can be identified by the deviations of plasma sodium level from a given  standard value. The ratio between the normal SID and normal sodium concentration is approximately 0.3. This is then multiplied by the difference between the measured [Na+] and the standard value. [1,2].

Water effect = 0.3× ( [Na+]−140) mEq/L or mmol/L

Chloride Effect:

The dilution effect of water on chloride has to be corrected, by multiplying chloride by standard sodium and dividing by measured sodium.[1,2]

 Corrected chloride =  [Cl] × (140 / [Na+]) mEq/L

The corrected [Cl-] is subtracted from the standard value (102 mmol/L)

Chloride effect = 102– ([Cl] × (140 / [Na+])

The sum of the sodium and chloride effects will give the Fencl–Stewart estimate of the strong ion difference effect on base excess. [1,2 & 6] The calculation of the strong ion difference effect on base excess was simplified. The constant 38 denotes the difference between the median value for sodium(140 mmol/L) and chloride (102 mmol/L). 

sodium–chloride effect  = [Na+] – [Cl] – 38 mEq/L

Albumin Effect:

 The effect of albumin on the base excess is due to the anionic effect of albumin. A pH‐dependent formula to calculate the anionic effect of albumin (electric charge on albumin) was developed by Figge and their colleagues. The electric charge on albumin or anionic effect is calculated on the basis of  the given equation:[5]

albumin anionic effect  = [Alb g/L] × (0.123pH – 0.631) mEq/L

Changes in the concentration of albumin will cause changes in the anionic effect of albumin. Changes in the anionic effect of albumin will change the base excess.[11,13] As the albumin concentration is decreased the blood becomes more alkaline.

albumin effect mEq/L  = [42 – albumin g/L] x  (0.123×pH–0.631) 

The standard here for albumin is 42 g/L (or 4.2 g/dL).

The equation is simplified to the below equation. [2,6]

albumin effect mEq/L  = 0.25 × [42–albumin  g/L]

or  = [42 – albumin  g/L] / 4

Phosphate Effect:

The electric charge on inorganic phosphate or the anionic effect is calculated  according to the below equation: [5]

[Pi ] = [Pi] × (0.309 × pH – 0.469)

Phosphate effect = (1.15- Pi) X (0.309*pH -0.469) mmol/L.

The standard here used is 1.15 mmol/L. [11,13]

1mmol/L (of phosphate)   = 3.1 mg/dl

Lactate  Effect:

Lactate effect =  -1 X lactate mmol/L

Unmeasured ions effect on Base excess:

Fencl-Stewart approach (Semi-quantitative approach) calculates the effects of the individual ions on the base excess- namely free water effects (marked by sodium concentration), changes in the concentration of chloride, albumin, phosphate and Lactate. The semi-quantitative estimation of unmeasured ions  is the difference between base excess and the total sum of effects of individual ions on the base excess.[1,2,6 & 13]

  1. RESULTS

In this current study, 4 cases were considered whose values were taken from previously published research articles.[5,13]  The apparent strong ion difference (SIDa), total concentration of dissociated non-volatile weak acids(A-tot) , effective strong ion difference (SIDe) ,Standard base excess, buffer value, corrected standard base excess, anion gap, albumin corrected anion gap and strong ion gap  values were calculated for all the 4 cited examples. The individual effect of ions on the base excess by the Fencl-Stewart approach were  calculated. The water effect, chloride effect, albumin effect and phosphate effect were calculated for all the 4 cases. The strong ion difference effect and albumin effect by simple formula was also calculated for all the cases.

The results are tabulated and shown in the tables 1 & 2. The cases 1 and 2 were shown in the table 1 and the cases 3 and 4 were shown in the table 2. When ΔpH is greater, difference between SBE & SBE(c) values are greater. So, the estimation of unmeasured ions will be grossly different if the individual effects of ions on base excess are subtracted from corrected  standard base excess instead of calculated standard base excess usually available in the blood gas report.

If the total concentration of dissociated weak acids is normal, the calculated anion gap will be correct. Under abnormal conditions in which the total concentration of dissociated weak acids is abnormal, either strong ion gap should be used or  the calculated anion gap  should be corrected.

Table 1:  Comparison of Metabolic components of Physiological, Base excess & Physico-chemical Approach of cases 1 & 2

Cases

Parameters

Strong Ion Difference

Standard Base Excess

Unmeasured Ions

Case 1:

pH: 7.33; pCO2: 30; HCO3: 15;

Na+: 117; K+: 3.9; Cl-: 92;    

Alb: 6 g/L;  

Phos: 0.6 mmol/L or 1.86 mg/dl

SIDa:    28.9

SIDe:    17.7  

A- tot:     2.7

SBE:                     - 10.9

β value: 0.9

SBE(c):                - 9.46

AG:        13.9

Albumin corrected AG:   23.4

SIG:        11.2

Individual ion effects on base excess:

 Water effect + Cl- effect+  Alb effect +  Phos effect = - 6.9 – 8.08 + 9.74 + 0.99 =     - 4.25

By simple formula: SID(Na-Cl difference ) effect + albumin effect =  - 13 + 9 =          - 4

Case 2:

pH: 7.55; pCO2: 29 mm of Hg;

 HCO3: 25.5;

Na+: 159 ; K+: 3.6 ; Cl- : 121 ;

 Alb: 9 g/L

Phos: 0.5 mmol/L or 1.55 mg/dl

SIDa:      41.6

SIDe:      29.11

A- tot:      3.61

SBE:  

   3.13

β value: 1.23

SBE(c):

 1.28

AG:        16.1

Albumin corrected AG: 24.85

SIG:       12.49

Individual ion effects on base excess:

 Water effect + Cl-  effect+  Alb effect +  Phos effect  = 5.7 – 4.54 + 9.82+ 1.21 =        12.19

By simple formula: SID(Na-Cl difference ) effect + albumin effect = 0 + 8.25 =            8.25 

Table 2: Comparison of Metabolic components of Physiological, Base excess &Physico-chemical Approach of cases 3 & 4

Cases

Parameters

Strong ion difference

Standard base excess

Unmeasured ions

Case 3:

pH: 7.05; pCO2: 15 mm of Hg;

HCO3: 4.0;

Na+ :129 ; K+: 5.0 ; Cl-: 96 ;    

Alb: 20 g/L

 Phos: 3.41 mg/dl or 1.1 mmol/L

SIDa:      38

SIDe:     10.6

A- tot:     6.6

SBE:  

 - 26.47

β value: 2.73  

SBE(c):  

  - 21.35

AG:           34

Albumin corrected AG: 40

SIG:        27.4

Individual ion effects on base excess:

 Water effect + Cl- effect+  Alb effect +  Phos effect = -3.3 - 2.19 + 5.19 + 0.085 = - 0.215

By simple formula:  SID(Na-Cl difference ) effect + albumin effect =  - 5 +5.5 =    0.5 

Case 4:

pH: 7.41; pCO2: 58 mm of Hg;

HCO3: 35;

Na+ : 138 ; K+: 3.2 ; Cl-: 101 ;

Alb: 15 g/L

 Phos: 1.55 mg/dl or 0.5 mmol/L  ;

SIDa:     40.2

SIDe:     40.1

A- tot:       5.1

SBE:  

 10.36

β value: 1.95

SBE(c):

10.61

AG:         5.2

Albumin corrected AG:

12.45

SIG:         0.1

Individual ion effects on base excess:

 Water effect + Cl- effect+  Alb effect +  Phos effect = - 0.6 - 0.46 + 7.57 + 1.18 = 7.69

By simple formula: SID(Na-Cl difference ) effect + albumin effect =  - 1 + 6.75 = 5.65 

  1. DISCUSSION

The most commonly used approach for  Arterial Blood Gas (ABG) interpretation is physiological approach based on the bicarbonate-carbon dioxide buffer system.[1,2 & 12]  Whenever there is a change in hydrogen ion concentration in the extracellular fluid, the balance of all the buffer systems changes at the same time. This phenomenon is called the iso-hydric principle. Henderson-Hasselbach equation concentrating on the bicarbonate-pCO2 buffer is based on this principle.[13] This approach is very simple and easier but  it is unable to quantify the metabolic component (non-respiratory) component and does not explain the causative mechanism of metabolic acid-base disturbances.[2]

Base excess approach was developed to quantify the metabolic component but it was criticized because it represents the whole blood and did not accurately represent the whole body behaviour. Standard base excess or extracellular base excess was developed to represent the in-vivo base excess which  is the base excess at haemoglobin concentration of 5g/dl.[1,2,13] Oxy-haemoglobin is a stronger acid than de-oxy-haemoglobin. Oxygenation of haemoglobin causes an increase in net titratable hydrogen ion due to the Haldane effect. So, the variation of oxygen saturation of haemoglobin (sO2) influence the base excess result. [10].

 

The formula for calculating this is:

cBase(B,actual)  = cBase(B,oxygenated)  +  0.2 × ctHb × (1 - sO2)

As the sO2 increases, the term 0.2 × ctHb × (1 - sO2) decreases so the base excess is changed in the acidic direction because it is slightly decreased  or as the sO2 decreases the term        0.2 × ctHb × (1 - sO2) increases, so the base excess is changed in alkaline direction because it is slightly increased.

Stewart by applying basic physicochemical laws, such as the law of mass action, law of conservation of mass and the law of electrical neutrality gave detailed explanation for the acid-base systems of the body. [2, 12 &13] In Stewart’s approach hydrogen ions and bicarbonate ions are dependent variables. The cause for respiratory acid-base disorders are due to changes in the independent variable pCO2 which is similar to the physiological or traditional (Base Excess) approach. But Metabolic acid-base disorders are due to the changes in the independent variables namely strong ion difference and total concentration of non-volatile weak acids and not bicarbonate.[1,2,6 &13]

Strong ions completely dissociate in solution so it is always present in a fully dissociated state. But Weak acids partially dissociate in solution so, both the un-dissociated form (HA) and the dissociated form (anionic component A-) are present in the solution. The difference between the sum of strong cations and anions is called the apparent strong ion difference (SIDa), the normal value is around   40 mEq/L. This is balanced by the buffer base (also called as effective strong ion difference) to preserve electrical neutrality.[2,13]

The concept of water dissociation is very essential to understand the role of strong ion difference in causing acid-base disturbances. The normal pH of the extracellular fluid is around 7.4, so the [OH-] is almost always greater than [H+]. The water itself presents a huge source of [H+]  and the [H+] of pure water at standard temperature and pressure is actually more than double that of most bodily solutions.[1,6 & 12]

Water dissociation (auto-ionization) occurs endo-thermically due to electric field fluctuations between neighbouring molecules.[6,12]

Dissociation of water:

H2O  ↔ H+  +  OH-

By applying the law of mass action,

{[H+]  x  [OH-]} / [H2O] = K

K: Equilibrium constant

{[H+] x  [OH-]} =  [H2O] X K

Water is formed by strong covalent bonding between H and O and dissociates only very slightly. So, the concentration of water is altered very minutely by dissociation. Multiplying the equilibrium constant with [H2O] denotes the ionic product of water (k’w)which is a constant.[6,12]

{[H+] x  [OH-]} =  K’w

At 25⁰ c pure water has a k’w of 1.008 X 10-14  mol2 L-2 . At 37⁰ c in the body fluids, the value of k’w is 4.4 X 10-14  mol2 L-2. [12] The ionic product of water is the product between the concentration of hydrogen and hydroxyl ions which is a constant at a given temperature. In the body fluids, the hydrogen ions does not exist as naked protons but in the form of oxonium or hydroxonium ions (H3O+). [6,12] The oxonium ion concentration (commonly called 'hydrogen ion concentration') is related to  the pH, where pH = - Log10([H3O+])

2 H2O ↔  H3O+  + OH- 

K’w = [H3O+] X [OH-]

So when the hydrogen ion([H+]) concentration increases, the hydroxyl ion ([OH-])  concentration decreases, similarly when [H+]  decreases the [OH-] increases because their product ( ionic product of water) is a constant.[6,12]The dissociation of water molecules is very little so, the concentration of hydrogen ions in the body fluids are in nanomoles/L. [1]

The strong ion difference has a powerful electrochemical effect on water dissociation and hence on hydrogen ion concentration. The water can behave both as an acid and a base. As the strong ion difference becomes less positive or the concentration of chloride ion is increased (more negative), water dissociates more to form hydrogen ions (positive charge) to maintain electrical neutrality. In this situation, the water behaves like an acid.  As the hydrogen ion concentration is increased, hydroxyl ion concentration is decreased to maintain constant ionic product of water. So whenever SID is decreased it results in acidosis.

As the strong ion difference becomes more positive or the concentration of chloride ion is decreased (less negative), water dissociates more to form hydroxyl ions (negative charge) to maintain electrical neutrality. So, in this condition the water behaves like a base. As the hydroxyl ion concentration is increased, hydrogen ion concentration is decreased to maintain constant ionic product of water. So, whenever SID is increased it results in alkalosis. The relation between bicarbonate and hydrogen ion concentration is given by the modified Henderson equation HCO3 = [24 x pCO2 ] / H+. As the hydrogen ion concentration is increased, the bicarbonate value is decreased and vice versa. So, according to Stewart’s theory, changes in bicarbonate ion concentration is a marker of metabolic acid-base disturbances and not its causative mechanism.

Weak acids cause a slight increase in the hydrogen ion concentration of the plasma. Therefore, a decrease in weak acids will cause alkalosis, and an increase produces acidosis.

At physiological pH, the weak acids reversibly combine with protons to form their conjugate base. [12]

HA  ↔   H+  +  A-

Whenever the hydrogen ion concentration increases( acidosis) in the blood, the equilibrium shifts to the left which results in decreased dissociation, the weak acids combining  with protons to form the neutral conjugate base. 

Similarly, when the hydrogen ion concentration decreases(alkalosis) in the blood, the equilibrium shifts to the right resulting in more dissociation to form hydrogen ions and the dissociated weak acids.[12]

Atot:  denotes the total concentration of weak acids including both the dissociated (anionic component  A-) and un-dissociated form (HA).

A-  or A-tot : denotes the total concentration of dissociated weak acids (anionic component only denoting  the sum of the electric charge carried by them  mainly albumin and phosphate).

The total concentration of non-volatile weak acids (Atot)  is a constant ( by law of conservation of mass)  and an independent variable causing metabolic acid-base disorders  but A-tot (anionic component) is a dependent variable because it varies with pH and Atot.[5]

An increase in SID results in alkalosis which causes increase in concentration of dissociated non-volatile acids. Similarly a decrease in SID results in acidosis which causes decrease in concentration of dissociated non-volatile acids.

An increase in pCO2 reacts with water molecules to form carbonic acid which dissociates to form [H+] and bicarbonate. So, increase in pCO2 reduces the dissociation of non-volatile weak acids. The changes in the strong ion difference (difference between strong cations and strong anions ) results in electrical force that affects the weak volatile acid pCO2/carbonic acid. As the SID increases, the bicarbonate also increases, and as the SID decreases, the bicarbonate also decreases.[12]

The relation between pH and apparent strong ion difference using Henderson-Hasselbalch equation interrelates the physiological and physio-chemical (Stewart’s theory) approach in ABG interpretation. [4,5]

The relation between pH and effective strong ion difference is as follows.

pH = 6.1 + log { SIDe - [Atot] } / 0.03*pCO2

              where HCO3 = SIDe - [Atot]  

The relation between pH and apparent strong ion difference is as follows.

pH = 6.1 + log { SIDa - [Atot] – SIG  } / 0.03*pCO2

             where HCO3 = SIDa - [Atot] – SIG 

Dehydration and over-hydration changes the strong ion difference by concentrating or diluting it respectively. Sodium and chloride are the principal contributors to the strong ion difference. The sum of the sodium and chloride effects will give the   Fencl–Stewart estimate of the strong ion difference effect on base excess and any change in the strong ion difference effect which change the base excess directly.[1,2,7,13] The changes in the strong ion difference will directly denote the changes in base excess only when non-volatile buffers are held constant. But in critically ill patients especially in multi-organ failure, non-volatile weak acid concentration is not always normal, so the changes in strong ion difference may not directly denote the changes in base excess.[9]

The unmeasured ions effect on base excess is estimated by subtracting  the strong ion difference effect (sodium-chloride effect which includes both water and chloride effects) and the weak non-volatile acid effect  (mainly albumin)  from the standard base excess value. The current study compares the interrelationship of the 3 approaches citing 4 cases as examples, the values were taken from previously published articles.[5,13]

In the case 1, bicarbonate value is low indicating severe metabolic acidosis due to the decreased  strong ion difference effect and  elevated  unmeasured ions. In the case 2, bicarbonate value is normal. Strong ion difference has no significant changes and the concentration of dissociated weak acid (A-tot) is very low. In this case, bicarbonate value is normal because the increased presence of unmeasured ions is not clearly noticed due to  the alkalizing effect of decreased (A-tot). So, the physiological or traditional method cannot identify the metabolic disturbances but Strong ion gap or the albumin corrected anion gap will identify it. Similarly strong ion difference effect has no significant changes but individually water and chloride effects contribute to the base excess but their net effect is very minimal because both their effects are opposite and so cancelled  out each other.

In the case 3, bicarbonate value is very low indicating severe metabolic acidosis due to the decreased  strong ion difference effect and highly elevated  unmeasured ions. In the case 4, bicarbonate value is high indicating metabolic alkalosis. Here the strong ion difference effect and the strong ion gap is normal but A-tot parameter is highly decreased. In this case, the stewart’s parameter and the fencl-stewart approach parameters lead to confusion  if bicarbonate value is not properly correlated. Here, the potassium value is below normal, so potassium ions are conserved and the hydrogen ions are excreted in response to hypokalemia resulting in alkalosis. Greater changes in concentration of potassium ions leading to changes in strong ion difference effect is not quiet possible.

In the previous studies it is not clearly mentioned whether to use the standard base excess or the corrected standard base excess (correction done for albumin and phosphate).When ΔpH is greater, difference between SBE & SBE(c) values are greater. So, the estimation of unmeasured ions will be grossly different when corrected standard base excess (SBE(c)) is used instead of calculated standard base excess. It seems logical to correlate the strong ion difference effect and non-volatile weak acid effects on the base excess with the corrected standard base excess. 

SBE(c) = SID Effect + non-volatile weak acid effect + unmeasured ions effect

The above equation interrelates the traditional (base excess) and physio-chemical (Fencl -Stewart) approach for ABG interpretation. The simplified parameters for strong ion difference effect ( Na+ – Cl- - 38) and the albumin effect (42 – Alb g/L) / 4 may serve as a useful  screening tool for the    assessment of acid-base status.

V.    CONCLUSION

Arterial blood gas analysis and interpretation is sometimes very difficult especially in identifying the causative mechanism of the metabolic acid-base disorder. The physicochemical approach gives mechanistic explanation for the causes of metabolic acid-base disturbances but it cannot completely replace the physiological or traditional approach. Therefore understanding the relationship between bicarbonate, base excess, strong ion difference and non-volatile weak acids in the three different approaches is very essential to overcome this arduous task.

Acknowledgement: None + Conflict Of Interest: Nil

REFERENCES

  1. Magder S, Emami A. Practical approach to physical-chemical acid-base management. Stewart at the bedside. Ann Am Thorac Soc. 2015;12:111–117
  2. Adel Badr, Peter Nightingale Alternative approach to acid–base abnormalities in critically ill patients Continuing Education in Anaesthesia, Critical Care & Pain  2007;7(4)107-111.
  3. Nadzimah Mohd Nasir , Pavai Sthaneshwar , Putri Junaidah Megat Yunus  And Sook-Fan Yap Comparing measured total carbon dioxide and calculated bicarbonate Malaysian J Pathol 2010; 32(1) : 21 – 26
  4. L. I. G. Worthley Strong Ion Difference: A New Paradigm or New Clothes for the Acid-Base Emperor Critical Care and Resuscitation 1999; 1: 211-214
  5. Otto Schücka, Karel Matoušovicb relation between pH and the strong ion difference (SID) in body fluids Biomed. Papers 149(1), 69–73 (2005).
  6. Patrick J. Neligan , Clifford S. deutschman, chapter 60, Perioperative Acid-Base Balance part IV anaesthesia management 1811-1829
  7. Story D, Morimatsu H, Bellomo R: Strong -ions, weak-acids, and base-excess: a simplified Fencl-Stewart approach to clinical acid-base disorders. Br J Anaesth 2004,  92: 54-60
  8. MUDS Matoušek Reunified description of acid-base physiology and chemistry of blood  Pages 76- 80 available online: patfbiokyb.lf1.cuni.cz/wiki/_media/projekty/dizertace_matousek.pdf
  9.  Howard E Corey Bench-to-bedside review: Fundamental principles of acid-base physiology Crit Care. 2005; 9(2): 184–192.
  10. J. Kofstad: All about base excess – to BE or not to BE Article downloaded from acute caretesting.org Pages 1-5
  11.  POW ICU © 7/02, MB, JL Guide to Acid/Base Analysis Pages  1-18.
  12. Gunjan Chawla, Gordon Drummond Water, strong ions, and weak ions Continuing Education in Anaesthesia, Critical Care & Pain  2008; 8(3):  108-112
  13. Horacio J. Adrogue ,F. John Gennari, John H. Galla and Nicolaos E. Madias Assessing acid–base disorders Kidney International (2009) 76, 1239–1247



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