Mechanism of the buffer system

Of the 15 000 to 30 000 mmol of protons delivered daily to the extracellular fluid, only 40 to 60 nmol/l are found free in the blood; the remainder are bound by the buffer system. Buffers, which are present in extracellular and intracellular fluids, are substances which are able to bind or release H +, thus preventing large changes in free H+ concentration. In general, buffers are weak acids and their ionized salts. At a given pH the relative concentrations of base (able to accept H +) and acid (able to release H+) are defined by the Henderson-Hasselbalch equation:

where [A-] and [AH] are the concentrations of dissociated base and undissociated acid respectively. The maximum efficiency of a given buffer occurs when p K= pH.

In these conditions, the concentrations of A and AH are the same, and the buffer system is equally able to bind or release H +. Also, the efficiency of a given buffer pair increases with increasing concentration.

The p K values and the concentrations of the various extracellular buffers are listed in Table 1... Three buffer systems (phosphates, proteins, and hemoglobin) have similar p K values (about 6.8). Thus they can be grouped together as a single buffer. The HCO 3--CO2 buffer pair has a less favorable p K (6.1); however, it is the most important buffer pair in the body as it can be regulated independently by the lungs (CO 2 elimination) and by the kidneys (HCO3- reabsorption).

To understand the mechanism of buffering, it is convenient first to analyze the effects of an acid load in a closed system (e.g. venous blood before it reaches the lungs). When an acid load is delivered to a closed system, buffering is almost immediate. Quantitatively, it is interesting to know how a given acid load is shared by the different buffer pairs depending on their p K. The regulation of acid-base sharing between the different buffers is based on the following equilibrium:

where Pr, Pr, Hb , HHb, HPO4-, and H2PO4 are proteins, hemoglobin, and phosphates respectively in their dissociated and undissociated forms.

Since the p K values of proteins, hemoglobin, and phosphate are similar (although not exactly the same), these three systems can be grouped together (A -AH buffer pair). Thus the equilibrium simplifies to

7 m = 1 + lop ^ I it, = -Kl ni k i = 6.x +^, (9)

of which hemoglobin is quantitatively the main component under normal conditions. Titrating the A --AH buffer pairs with H2CO3 leads to an increase in HCO3-. The in vivo HCO3- increase due to this physiochemical mechanism is approximately 1 mmol/l HCO3 for every increase of 10 mmHg (1.33 kPa) in PCO2 above 40 mmHg (5.33

kPa) (Brackettetal 1965; Weill et al. 1986). As pH is determined by the ratio of [HCO3-] to [CO2], the increase in HCO3- associated with the rise in PCO2 limits the decrease in pH. However, both the increased PCO2 and the decreased pH trigger the physiological control, which involves the central nervous system and the kidneys. The increased PCO2 and the low pH stimulate the chemosensitive regions of the respiratory center in the brainstem and the peripheral chemoreceptors in the carotid bodies (Cunningham eLal 19.8.6.). The result is an increased respiratory drive which normally leads to increased alveolar ventilation.

This mechanism is effective when the CO2 increase is due to hypermetabolism or HCO3- titration by fixed acid, with an intact pulmonary function. If the cause is primarly hypoventilation or the patient is receiving fixed mechanical ventilation, PCO2 will rise until a new equilibrium is reached. The decreased pH in the tubular kidney cells stimulates the generation of NH 3 which combines with the H+ secreted in lumen of the distal segments to form the ammonium ion NH4+ which is trapped in the lumen. As an OH- ion is produced for each H+ ion secreted (both derive from the dissociation of water catalyzed by carbonic anhydrase), new HCO 3- is generated according to

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