**8. Stewart approach**

Here H+ /proton is the preliminary determinant in acid base disturbances, not the CO2 [21]. The dependent variables are H+ , OH<sup>−</sup>, CO3 <sup>2</sup><sup>−</sup>, HA (weak acid), A<sup>−</sup>(weak anions), HCO3<sup>−</sup> and pH. The independent variables are strong ion difference (SID), total non-volatile weak acids (Atot) and PaCO2 [24]. Among them the strong ion difference has maximum effect on the hydrogen ion concentration. With that, acid base disorder can be divided into three categories: 1. respiratory (increase or decrease PaCO2), 2. SID changes (excess or deficit of strong ions or water) and 3. inorganic phosphate or albumin deficit or excess (Atot changes). In Stewart approach, a large number of variables are needed to calculate SID. Sodium, potassium, calcium and magnesium are strong positive ions, and chloride and lactate are the negative ions [25]. Bicarbonate and albumin are the balancing ion in strong ion difference. Strong ion difference (mEq/L) = [strong cations] − [strong anions]. Weak acid dissociates in body fluid (Eq. (3)).

$$\text{HA} \leftarrow \rightarrow \text{H}^\* + \text{A}^- \tag{3}$$

A<sup>−</sup> Resembles weak anions, that vary with pH. Strong ion difference is filled with this weak A<sup>−</sup>, and HCO3+<sup>−</sup>, H+ , OH<sup>−</sup>, CO3 <sup>2</sup><sup>−</sup> are also present in minute amount, but are less important. There are many unmeasured anions accounts for ion difference. For electrical neutrality, strong ion difference and the total charge of weak ions must be equal [26]. Normal SID is dominated by sodium and chloride. But other negligible, but measurable ions are present there. Here narrowing of SID from an increase in [Na+ ] has alkalizing effect, whereas an increase in [Cl<sup>−</sup>] has acidifying effect. From the ionic basis metabolic acid base disturbances are about four major types [25]: (1) The water effect, and it is produced by dilutional effect on SID. Free water intake and intravenous infusion can produce it. (2) The chloride effect is caused by chloride change, and administration of normal saline is the common cause. (3) The protein effect is produced by a change in albumin concentration. (4) There are other factors, and those are influenced by unmeasured anions, that cause a wide anion gap.
