Buffering is the ability of weak acids, present in excess, to accept H+ donated from strong acids, thus limiting the changes in free H+ concentrations and pH changes (equation ):
The principal buffer system in blood (and other extracellular fluids) is based on bicarbonate (HCO-), accounting for approximately 70% of the buffering capacity of the blood. In blood, CO2 (the major product of oxidative metabolism) reacts with water in the presence of the enzyme carbonic anhydrase (CA) to form carbonic acid (H2CO3). This compound is relatively unstable and tends to dissociate (eqn ). The rate of formation of carbonic acid is dependent on the concentration of carbon dioxide and the rate constant of reaction [i]; the dissociation of carbonic acid to generate H+ and HCO- is governed by the rate constant of reaction [ii]. In practice, these two reactions can be combined, and the relationship between pH ([H+]), carbon dioxide, and bicarbonate is described by a single equation - the Henderson-Hasselbalch equation :
pH reflects —log [H+]; 6.1 is the value of —log (1/K), K being the equilibrium constant describing the overall equation ; PCOz is the partial pressure of carbon dioxide; S is the solubility constant for carbon dioxide. K.S. is constant and equal to 0.225 when PCo is measured in kPa, 0.03 when PCOz is measured in mmHg). Table 1 shows the normal range for these parameters in humans.
From eqn  the principles of acid-base balance can be appreciated. Acidification may occur in two ways: either by the production of CO2 or by the consumption of bicarbonate (as part of the buffering of fixed acid). The excretion of CO2 (see below) is controlled by the lungs, and the excretion of fixed acid takes place in the kidney.
The Henderson-Hasselbalch equation allows basic understanding of acid-base physiology, in health and disease, but has limitations. In the presence of either metabolic or respiratory derangement of acid-base homeostasis it does not allow assessment of the severity of the metabolic derangement, analogous to the respiratory component. It also does not assess the influence of other acids other than carbonic acid. For this reason some authors propose analysis of acid-base physiology using a more complex method based on the principles of physical chemistry. This method proposes that all changes pH in plasma can be explained in terms of relative concentrations of CO2, relative electrolyte, and weak acid. This concept allows more rigorous interrogation of acid-base disorders and may permit greater insight into their pathophysiology and management.
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