The Bernard-Cannon concept
The term “milieu interieur” was coined by Claud Bernard in 1865 to mean the composition of body fluids constituting the body internal environment. The term “homeostasis” was coined by WB Cannon in 1929 to mean constancy of the internal environment after its distortion by external stresses. (1) The Bernard-Cannon concept can be achieved through a variety of biochemical, endocrinal and metabolic regulatory mechanisms.  Many of these mechanisms operate on the principle of negative feedback.  Deviations from a given normal set point are detected by a sensor, and signals from the sensor trigger compensatory changes that continue until the set point is reached.
Regulation of fluid, electrolyte and acid-base balance is concerned with total body water , and concentrations of substances distributed between different fluid compartments.
Maintaining homeostasis or constancy of the internal environment is a function of many organ systems.  It follows that malfunction of any of them can disturb fluid, electrolyte, and acid-base balance.  However, those systems do not play independent roles but rather they play a collective effect, or an inter-related effect.
Advantages of homeostasis mechanisms include increased chance of survival, allowing free and independent life, under different stressful circumstances with proper functioning of the brain and higher faculties for decision-making during human life.

Homeostasis Mechanisms
The buffering properties of body fluids, and the renal and respiratory adjustments to the presence of excess acid or alkali are important acid-base homeostasis mechanisms.
I. The Henderson-Hasselbalch model  
Acid-base balance is generally explained in terms of carbonic acid/ bicarbonate system, as the most important buffer system.  This system describes the relationship between the respiratory and metabolic components of acid-base balance; the partial pressure of carbon dioxide (PaCO2), and bicarbonate, respectively.  This relationship is defined by the Henderson-Hasselbalch equation.  It incorporates a carbon dioxide solubility coefficient of 0.0307, and an apparent overall dissociation constant for carbonic acid of 6.105.  The reliability of these constants has been questioned, specially when applied to plasma of critically ill patients(2).  
As bicarbonate is not an independent variable, it varies with changing PaCO2.  Thus, the changes of HCO3- per se cannot be used as an indicator of the metabolic contribution of any disorder unless this is taken into account.  This means that empirically derived correction formulae have to be used to adjust the bicarbonate for both acute and chronic changes in PaCO2.
A number of methods of assessing the metabolic component have been devised including “the buffer base”, “the standard bicarbonate: SHCO3-”, “the base excess: BE”, and “the Siggard-Andersen nomogram”.
The term “buffer base” calculates the sum of all the plasma buffer anions i.e. HCO3-  plus the non volatile weak acid buffers. The later results from the metabolism of methionine and cystine in dietary proteins and the incomplete metabolism of carbohydrates and fats.
The term “standard bicarbonate ,SHCO3” is defined as “the plasma HCO3- in blood, fully saturated with oxygen, and equilibrated with PaCO2 of 40 mmHg at 38°C”.  It is used as a reference value to assess the metabolic change in HCO3-. (3)
“The base excess ,BE” is a more accurate measure of metabolic disturbances. Actual BE is “the concentration of strong acid or base required to return the PH of invitro whole  blood sample, while maintaining PaCO2 at 40mmHg by equilibration at 37°C” (3).  The standard base excess (SBE) uses the blood diluted threefold with its own plasma giving an effective haemoglobin concentration of about 5g/dl (4).  With a negative SBE (base deficit), PH is lower than normal, and an alkali must be added, while with a positive SBE (base exess), PH is higher than normal, and an acid must be added to titrate the PH back to normal. However, two equal opposite effects can exist producing a normal BE.  Also, two metabolic acid-base abnormalities can exist while BE is normal. For example, hyperchloremic acidosis may develop by renal absorption of Cl-, with compensation by the alkalinizing effect of low albumin concentration, often developing in critically ill patients.  Hypoalbuminemia has been shown to be a common cause of metabolic alkalosis in the critically ill(4,5).
An original acid-base nomogram was developed by Siggaard-Andersen in the 1960s.  It shows reference areas for the different classes of acid-base disturbances, with PH on the abscissa and PaCO2 on a logarithmic ordinate (6).  It illustrates metabolic and respiratory patient conditions, and differentiates between acute and chronic cases. An important value on the monogram is the standard base excess (SBE), which allows estimation of base excess or deficit of the ECF.  
Siggaard-Andersen published the Van Slyke equation, which was derived from known physico-chemical relationships, and enabled calculation of the BE from the variables PH, HCO3- and Hb (7). This equation has been validated by others as showing good agreement with nomogram results when applied in vitro over a wide spectrum of PaCO2 values (8). This equation is now widely used in blood gas analyzers.
Although the Siggaard-Andersen monogram may be used to establish whether an acid-base abnormality is present or not, it does not identify its underlying cause (6).  It only allows the conclusion that the PH and PaCO2 values fall within an area of specific acid-base abnormality.  It does not show how the diagnostic point has arrived at this particular area.  What is currently needed clinically for acid-base estimation, is an arterial blood sample collected in a heparinized blood-gas syringe, and immediately analyzed in the blood-gas analyzer, measured at 37°C. 
Classification of acid-base disorders:
There are four primary acid-base disturbances. Respiratory acidosis or alkalosis refers to an increase or decrease in PaCO2 respectively, while metabolic acidosis or alkalosis refers to a decrease or increase in extracellular base excess in the form of plasma HCO3- respectively.  Academia or alkalemia refers to a decrease or increase in serum PH (<7.42 and > 7.38 ) ,respectively.  
For each primary acid-base disturbance, there is a secondary physiologic compensation, the quality and quantity of which can be predicted (9). Qualitatively the compensatory variable moves in the same direction as the primary disturbance. 
A primary decrease in serum HCO3- (metabolic acidosis) stimulates hyperventilation and a secondary decrease in PaCO2 (compensatory respiratory alkalosis). Compensation tends to return the PH towards normal. To quantitate this physiologic compensation, expected PaCO2 corresponding to the serum HCO3- value equals (1.5 x HCO3-  + 8 ±2).  If the patient PaCO2 value is greater than that predicted, it means less adequate or partial compensation. If the patient PaCO2 value is less than that predicted it refers to over-compensation by a primary respiratory alkalosis, a condition of type II mixed disorder.
A primary increase in serum HCO3- (metabolic alkalosis) causes hypoventilation and a physiologic increase in PaCO2 (compensatory respiratory acidosis).  To quantatiate this physiologic compensation, a formula is used with expected PaCO2 value which equals (HCO3- x 0.7 + 20 ± 1.5) to deduce a partial compensation or a primary respiratory acidosis denoting a mixed type II disorder.
The causes of metabolic alkalosis are usually classified by their response or resistance to chloride (or saline) administration. Not surprisingly, those who are saline responsive are volume depleted patients with low urinary chloride of < 20 mEq/L.  This is due to vomiting, gastric suction, diuretics or post-hypercapnia. So, they improve with extracellular volume repletion. Patients with metabolic alkalosis are resistant to chloride (or saline) administration, and have high urinary chloride of > 20 mEq/L.  Patients with excess mineralocorticoids as in Cushing’s syndrome with hyperaldosteronism are volume expanded and improve with diuretic therapy. Hypokalemia contributes to chloride (or saline) responsive or resistant conditions, and carries significant therapeutic implications.
The compensation of primary respiratory acidosis or alkalosis involves renal reabsorption or excretion of HCO3- , respectively, a process that is not immediate. So, the acute (24 hours) response is less than that achieved in more chronic conditions. Complete HCO3- compensation by the kidney takes five days approximately. In respiratory acidosis, each 10mmHg increase in PaCO2 is compensated by an increase of 1 and 3 mmoL in serum HCO3- level for the acute and chronic respiratory disorder, respectively. In respiratory alkalosis, each 10 mmHg decrease in PaCO2 is compensated by corresponding HCO3- decreases of 2 and 5 mmol, respectively. Again, any deviation of the compensatory reaction from that predicted, indicates partial compensation or the presence of another primary acid-base disturbance referring to a mixed type II disorder.
The co-existence of two or more primary acid-base disturbances is termed mixed disorder. Clues to mixed disorders include a change in PaCO2  and serum HCO3- in opposite directions (type I) or over compensation by PaCO2 or HCO3- in the same direction (type II).  It is not unusual to find multiple causes of acid-base disturbances in the same critically-ill patient.
The Henderson-Hasselbalch approach works well whenever total proteins, albumin, and phosphate concentrations in the serum are approximately normal. However, when they are markedly abnormal, this approach frequently provides erroneous conclusions regarding the cause of acid-base disturbance. In this way, this approach is more descriptive than mechanistic. So, new tools are needed to identify the etiology of simple or complex acid-base abnormalities.

II. The Anion Gap
An electrolyte abnormality is often the first laboratory sign of an acid-base disorder.  The principle of electroneutrality in body fluids necessitates that the number of positive charges contributed by cations equals the number of negative charges contributed by anions:
(Na+) + (K+) + (Ca++) + (Mg++) = (HCO3-) + (Cl-)+(HPO4)+(SO4)+ (proteins) + (organic acids).
For simplification, K+, Ca++, and Mg++ are considered unmeasured cations (UC), while HPO-4, SO-4, proteins, and organic acids are considered unmeasured anions (UA).
Na+ + UC = HCO3- + Cl- + UA
The UC and UA are those not routinely measured, or those of clinical insignificance for calculation of the anion gap (AG).
The AG can be calculated through one of two formulas.
AG = UA – UC
AG = Na+ - (HCO3- +Cl-)
The term AG is actually a misnomer, because it may be even negative or reversed when cations exceed anions as occurs in COPD or hepatic encephalopathy.  It is also a misnomer because in reality there is no true AG; because in any body fluid, the sum of cations must equal the sum of anions. 
The normal AG value is about 12 mEq/L (10) (table 1).  However, it has undergone a downward shift to 3-11 mEq/L, being more reflective of the current methods of measuring HCO3- and Cl-.  (11)

Table (1) : Components of the normal anion gap (10)

An increased AG may be due to an increase in the concentration of UA, a decrease in the concentration of UC, or both (12).
The AG may be high when organic acids such  lactate or ketone bodies (generated by incomplete combustion of carbohydrates or fatty acids, respectively) accumulate in the blood, when concentrations of phosphates and sulfates (derived from tissue metabolism) increase, when concentration of plasma proteins increase, and when K+, Ca++ or Mg++ concentrations decrease.
The AG concept is used to differentiate normal from high AG metabolic acidosis.
Normal AG metabolic acidosis is due to loss of HCO3-, either from the gastrointestinal tract or from the renal system, with a compensatory increase in Cl- plasma concentration. (13)  Again, normal AG acidosis may develop from ingestion of NH4Cl or carbonic anhydrase inhibitors; or from parenteral administration of large volumes of saline (0.9% NaCl).  In such normal AG or hyperchloremic metabolic acidosis, NaHCO3 therapy may be indicated.  Acidosis is mostly corrected by HCO3- to increase the HCO3- deficit while Na+ ions correct the strong ion difference (SID),  which equals Na+ - Cl- towards normal.
In high AG metabolic acidosis (usually due to disorders associated with endogenous or exogenous organic acids), excess anions are buffered by HCO3-, and the physician should search for the underlying etiology.(14)  In this condition, treatment of the underlying cause, rather than HCO3- therapy, is mandatory, specially when AG values exceed 25 mEq/L.
The calculated AG is often unreliable in detecting increased concentrations of the gap anions (15, 16).  It should be corrected or adjusted before categorizing low or high AG metabolic acidosis, or before diagnosing abnormally low AG acidosis. For example, in hypoalbuminemia, the correction factor for albumin was defined as 0.25 to quantify the effect of the change of albumin concentration on the AG.(17)
Adjusted AG = calculated AG + 0.25  (normal albumin – measured albumin concentration) 
It has been reported that for each gram decline in serum albumin level, 2.5-3 mEq/L decrease of AG will take place (18).  Again, the AG falls by 2-8 mEq/L for each gram % decrease in serum phosphate (11).
Given the frequency of hypo-albuminemia and dysphosphatemia in the ICU patients, some have suggested the normal AG for critically-ill patients to be calculated by the formula:
AG = 2 (albumin g/d) + 0.5 (phosphate mg/dl) (11).
As another example, in an occult neoplasm like multiple myeloma, the positively charged gamma globulin may need adjustment for the AG to be valuable (19, 20).
Mixed acid-base disorders cannot be diagnosed by simple AG calculation. In this situation, the change in AG (delta AG), should be compared to the change in HCO3- concentration (delta HCO3-) to diagnose the mixed acid-base disorder. This ratio shows the “deviation from 1: 1 correlation” (21)
                                 
 
When                 is zero, it diagnoses normal AG metabolic acidosis. When the ratio is unity, it diagnoses high AG metabolic acidosis because the ∆ AG increase equals the ∆ HCO3 decrease.  Deviation from unity signals mixed acid-base disorders.  A ratio less than unity denotes high and normal AG metabolic acidosis. A ratio exceeding unity indicates high AG acidosis and metabolic alkalosis. In this situation, the ∆ AG increase is more than the ∆ decrease of HCO3-, and this relative elevation of HCO3- denotes a coexisting metabolic alkalosis.
The clinical usefulness of the AG, in the patient with metabolic acidosis, is that it shows whether the acidosis is associated with an increase in UA (e.g. lactate) if the AG is raised, or, if normal, a hyperchloremic acidosis (3).  However, the AG has few limitations:
- Limits of normal serum Na+, HCO3-, and Cl- levels are set within 95% of normal population. This may affect the fidelity of measured ion levels used in AG calculation (22).
- About two thirds of the AG are formed by proteins (albumin).  A decrease in serum albumin, commonly encountered in critically ill patients, can affect the calculated AG (23).  So, hypoalbuminemia, can mask an increased concentration of the AG (18,20,23-26).  Significant hyperlactatemia can be also missed in septic or hepatic patients with hypoalbuminemia. (27)

1. Acidosis due to lactic acid accumulation with volume depletion and hemoconcentration may cause hyperproteinemia and hyperphosphatemia leading to high AG metabolic acidosis.
2. Variations in UC concentrations as Ca++ and Mg++ can affect the AG calculation (19, 23).  As an example, an increase in serum Ca++ due to hyperparathyroidism, would lower the AG (14).  On the other hand, an increase in serum Ca++ due to neoplasms like multiple myeloma, would show a low AG due to the positively charged gamma globulins(20, 21).
3. Mixed acid-base disorders cannot be diagnosed by simple calculation of the AG, but through the ratio of ΔAG compared to Δ HCO3- concentrations (22). 

These limitations urged the need to a further physico-chemical approach for acid-base evaluation.
III. The Physico-chemical approach
An alternative concept in the understanding of acid-base regulation is the “physico-chemical approach” based on the work of Stewart, almost two decades ago (28).
Strong electrolytes dissociate (ionize) almost completely when in solution into strong ions, and the non-ionized fraction remains negligible across the physiological PH range.  Weak electrolytes partially dissociate depending on factors such as changes in PH and temperature within the normal physiological range.
In the mathematically based Stewart approach, there are dependent and independent variables. The hydrogen ion concentration (H+) and bicarbonate (HCO3-) are dependent variables.  The strong ion difference (SID), the partial pressure of carbon dioxide (PaCO2), and the total concentration of non-volatile weak acids (ATOT) represented mainly by albumin and inorganic phosphate, are independent PH regulating variables.  This differs from the Henderson-Hasselbalch concept which defines PaCO2 and HCO3- as variables to be adjusted to correct derangement in PH. 
The dependent and independent variables should be decided as fundamental of this approach.  Carbon dioxide diffuses freely across all membranes in the body, hence, it cannot be used to regulate PH. Given a constant PaCO2, metabolic acid-base effects can be calculated, (28).  If an independent variable is altered (SID, ATOT) ,then the dependent variable will change.  If a change in a dependent variable as H+ or HCO3- is observed, then there must have been a change in one independent variable at least.  Parameters that are changed by external manoeuvers (i.e. SID or protein concentration) are independent variables, while values that respond to such change (i.e. PH) are dependent variables.  So, we must know all the independent variables in order to calculate the dependent ones, through mathematical equations.
Stewart designed a computer program to solve the resulting equations for the dependent variable (H+) for differing values of independent variables (28). This is very different from the relationship of PH to PaCO2 in the Henderson-Hasselbalch equation, which is one of association not cause (29).  
The SID, being the most important variable, is calculated as the difference between the positively charged strong base cation Na+, and negatively charged strong acid anion Cl-.  To satisfy electrical neutrality, the SID should be balanced by changes in H+ or OH-. The normal value of SID is 39 ± 1 mmol/L (30). A decrease in SID or a <38 mmol/L is associated with acidosis where the H+ is greater than the OH- ion concentration.  An increase in SID >40 mmol/L is associated with alkalosis where the OH- ion concentration is greater than the H+ ion concentration.  In both conditions the difference between calculated SID and normal SID estimates the effect of a change in SID (29).  The kidneys are the most important regulators of SID for acid-base purposes. The concentration of strong ions in plasma can be altered by adjusting their absorption or secretion. Plasma Na+ is tightly controlled for preservation of intravascular volume by tonicity and plasma K+ is also closely controlled to ensure appropriate cardiac and neuromuscular functions.  Hence, we are left with plasma cl- as the strong ion that the kidney uses to regulate the acid-base status without interfering with other important homeostatic mechanisms.  This is the major factor that changes the SID relative to a constant Na+ concentration (31).  In the compensation of acidosis, the removal of cl- ions in the urine will increase the value of the SID in plasma, and thus help to return plasma PH towards normal. In the compensation of alkalosis, reabsorption of additional cl- ions by renal tubular cells will reduce the plasma SID and therefore lower the plasma PH. This is based on the fact that in order to maintain electrical neutrality within all compartments, movement of HCO3- ion out of the cell is balanced by movement of Cl- ions from plasma into the cells (the chloride shift). This Cl- movement between compartments helps  to keep a normal plasma PH.
In a body fluid containing any collection of strong electrolytes, the H+ ion is mainly detected by the difference between positively and negatively charged strong ions.  As an advantage of the physico-chemical Stewart approach, the control of acid-base and water homeostasis are explained in terms of strong ion electrolyte regulation. Dehydration or over-hydration alters the concentrations of strong ions leading to an increase or a decrease in the SID.  The body’s normal state is on the alkaline side of neutrality.  Dehydration concentrates the alkalinity causing “contraction alkalosis”, and an increased SID. On the other hand, over-hydration dilutes the alkaline state towards neutrality causing “dilutional acidosis” and a decreased SID (32).  However, these terms may lead to the erroneous idea that a change in ECF volume alone might cause  an acid-base disturbance. As a matter of fact, Stewart approach implies that changes in plasma or ECF volume alone will not change the value of any of the three independent variables, and hence cannot affect PH. But, the Stewart approach implies that if the change in volume is accompanied by a change in the proportional water content of plasma, the SID will change. For example, if water is removed from plasma, the concentration of strong cations and strong anions is increased in equal proportions. This increases the SID by the same proportion, and so causes an increase in PH. However, this effect may be complicated by compensatory mechanisms that regulate plasma volume (33).
There are two ways to quantify the SID, termed the apparent (SIDa) and the effective (SIDe).  The SIDa measures the difference between the main strong ions neglecting other strong ions that appear in low plasma concentrations.  Strong ions are completely dissociated, and lactate is the dissociation product of lactic acid. (34)
SIDa (mEq/L) = [(Na+) + (K+) – [(Cl-  + lactate-)]
The SIDe calculates the relationship between PH, PaCO2, inorganic phosphate (Pi) and protein through a complex formula (34):
In the SIDe, the changes of other non-volatile weak acids such as phosphates and protein were included, thus ATOT was more quantified. It may also encompass strong ions other than those covered by the SIDa.
The strong ion gap (SIG), showing the presence of UA other than inorganic phosphate, is the difference between the two SID values (28):
SIG = SIDe – SIDa
The normal value of the SIG is zero, implying that there are very few strong ions other than Na+, K+, Ca++, Mg++, and cl- in the plasma of healthy subjects (35).
Increased and decreased SIG indicate the preponderance of UA and UC, respectively.  Story et al (36), suggested to improve the accuracy of the SIG by identifying and measuring more UA in patient plasma, and by making clinical chemistry assays more precise.  Unfortunately, the term SIG is a misnomer, as the term AG is in common use for a different but related quantity (37). However, once AG has been corrected for anionic contributions of albumin and phosphate, it becomes similar to the SIG (33).
The total concentration of weak acids (ATOT) includes ionized (A-) and non-ionized weak acids (HA).  ATOT can be roughly estimated by multiplying total plasma proteins (g/L) by a Van Slyke factor (38) of 0.243, and coined as Prot-.  This ATOT does not include phosphates and neglects PH effects on weak acid ionizations but proved to be clinically useful (39,40).
Albumin is responsible for up to 80% of the intravascular colloid osmotic pressure (41). In critically-ill patients, a decrease in serum albumin is associated with increased morbidity and mortality (42). Serum albumin is a negatively charged acute phase protein. Thus, in severe illness, the plasma concentration of albumin decreases, and it does not increase until the recovery phase of illness (43).
In Stewart’s terminology, weak plasma acids as albumin are incompletely dissociated substances in the plasma. As albumin is the major contributor of weak acid anions, hypoalbuminemia has an alkalinizing effect while hyperalbuminemia has an acidifying effect (34). Again, the Stewart approach is valid when the albumin/ globulin ratio is normal (1.3-2.0), and hence is not correct in situations of hypo-albuminemia and hyper-globulinemia.
Plasma HCO3-, according to Stewart approach, can be calculated from the difference between SID and weak plasma proteins, and usually proves identical with actual HCO3- calculated by the Henderson-Hasselbach equation (44).
HCO3-  = SID – Prot -
This is deduced from the equation (45):
PH = 6.1 + log 
For a particular value of PaCO2, PH is determined by a difference between SID and ATOT.  This equation enables to understand the scope of causes of PH deviation from normal, and to correct the abnormalities by adjusting the values of the three independent factors; SID, ATOT, and PaCo2.  The SID alone cannot determine the final PH value because a value of ATOT can either pronounce or suppress the effect of SID.  When ATOT is decreased, it has an alkalinizing effect. Recently, it has been proved that this approach enables to define the influence of strong ions, and weak acids on PH of body fluids (31, 46).  In this way the Stewart approach is mechanistic rather than descriptive.
So, given a constant PaCO2, metabolic acid- base effects result from changes in the independent variables: SID and Prot - (47,48).  Metabolic acidosis is the result of either a decrease in SID and/ or an increase in weak plasma acids (high SID acidosis).  A decrease in HCO3- may represent a reciprocal automatic change in response to increased Cl- concentration, whether the primary disturbance is a loss of HCO3-, or an increase in Cl- due to exogenous administration (as NH4 ingestion or saline parenteral administration) (49).  If the SID decreases due to hyperchloremia, an increase in Cl- independent negative charge, leads to a decrease in HCO3- negative charge, resulting in acidosis and vice versa. Again, a decrease in ATOT due to hypo-albuminemia leads to an increase in HCO3-, resulting in alkalosis and vice versa. So, through the Stewart approach, completely new hyperchloremic acidosis and hypo-albuminic alkalosis can be detected.
Base excess (BE) is a single variable used to quantify the metabolic component of a patient’s acid-base status (50-52).  It measures the net effect of changes in SID and weak acids (29).  Several researchers have combined the BE approach with the Stewart approach to acid-base physiology. They examined the BE effect of two of the Stewart’s independent variables: the SID, and the total weak acid concentration. This approach has been termed the Fencl-Stewart approach (51).  Gilfix et al (50) have developed the idea, initially put forward by Fencl (49), that the BE is the net result of changes to SID and Prot -.  Any deviations in Na+, Cl-, or albumin from normal will produce a base excess or deficit.  Any difference between the sum of the three BE effects and the actual BE was termed the BE-gap, indicating the presence of UA or UC (29).  The BE-gap correlated well with both SIG and AG (51).  The base excess gap may provide a good estimation of the SIG and its calculation can be performed easily at the bedside rather than requiring a computer (51).  While this approach is simple, it needs a calculator to use five equations to calculate the SID and Prot -.  Story et al (17) has recently proposed three simple equations for clinical use:
Na- Cl- effect on BE (mEq/L) = (Na+) – (Cl-) – 38

1. Albumin effect on BE (mEq/L) = 0.25 [42 – albumin (g/L)]
2. Unmeasured ion effect (mEq/L) = SBE – (Na+ - Cl- effect) – albumin effect.

A decrease in albumin leads to a decrease in Prot- inducing metabolic alkalosis. Unmeasured ion effect on BE may be due to strong ions as sulphates or weak ions as phosphates. The unmeasured ion component of the BE is the important clinical marker of mortality (40).
Classification of acid-base disorders:
Acid-base classification due to Stewart approach is based on derangements of the independent variable(s). 
Respiratory acidosis and alkalosis are those in which the first independent variable affected is the PaCO2.  A change in the plasma SID may then occur as a compensatory response.
Metabolic acidosis arises from conditions that cause either a reduction in the plasma SID or increase in ATOT.  Metabolic alkalosis arises from conditions that cause either an increase in the plasma SID or a decrease in ATOT.
Stewart approach explains the commonly occurring metabolic acidosis following the administration of large volumes of normal saline. The concentration of Cl- in plasma increases to a greater extent than that of Na+ when normal saline (unlike plasma) contains Na+ and Cl- in equal amounts. This leads to a reduction in the value of plasma SID and a consequent decrease in PH.
It follows that the changes in electrolytes would change the acid-base status. Considering changes in AG, SID and plasma weak acids with consideration of the BE, the physico-chemical Stewart approach can be a useful tool to formulate water, electrolyte and acid-base homeostasis, on the basis of electroneutrality and conservation of mass. This approach should be encouraged to accompany the every-day clinical use of the traditional Henderson-Hasselbalch approach.
Interpretation of acid-base disturbances will remain an art that combines intelligent synthesis of the clinical history, physical examination, and laboratory data, in the context of the individual patient and the nature and course of his / her illness.
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