Body Buffers

Compensatory Mechanisms

Physiological responses to changes in [H ⁺] are char-acterized by three phases: (1) immediate chemical buffering, (2) respiratory compensation (whenever possible), and (3) a slower but more effective renal compensatory response that may nearly normalize arterial pH even if the pathological process remains present.

BODY BUFFERS

Physiologically important buffers in humans include bicarbonate (H2CO3/HCO3−), hemoglobin (HbH/ Hb−), other intracellular proteins (PrH/Pr−), phos-phates (H2PO4−/HPO42−), and ammonia (NH3/NH4+). The effectiveness of these buffers in the various fluid compartments is related to their concentration. Bicarbonate is the most important buffer in the extra-cellular fluid compartment. Hemoglobin, though restricted inside red blood cells, also functions as an important buffer in blood. Other proteins probably play a major role in buffering the intracellular fluid compartment. Phosphate and ammonium ions are important urinary buffers.

Buffering of the extracellular compartment can also be accomplished by the exchange of extracel-lular H⁺ for Na⁺ and Ca²⁺ ions from bone and by the exchange of extracellular H ⁺ for intracellular K ⁺. Acid loads can demineralize bone and release alka-line compounds (CaCO₃ and CaHPO₄). Alkaline loads (NaHCO₃) increase the deposition of carbon-ate in bone.

Buffering by plasma bicarbonate is almost immediate, whereas that due to interstitial bicar-bonate requires 15–20 min. In contrast, buffering by intracellular proteins and bone is slower (2–4 h). Up to 50% to 60% of acid loads may ultimately be buff-ered by bone and intracellular buffers.

The Bicarbonate Buffer

Although in the strictest sense, the bicarbonate buffer consists of H₂CO₃ and HCO₃⁻, CO₂ tension (Pco₂) may be substituted for H₂CO₃ because:

This hydration of CO₂ is catalyzed by carbonic anhydrase. If adjustments are made in the dissocia-tion constant for the bicarbonate buffer and if the solubility coefficient for CO₂ (0.03 mEq/L) is taken into consideration, the Henderson–Hasselbalch equation for bicarbonate can be written as follows:

where pK′ = 6.1.

Note that its pK′ is well removed from the nor-mal arterial pH of 7.40, which means that bicar-bonate would not be expected to be an efficient extracellular buffer (see above). The bicarbonate system is, however, important for two reasons: (1) bicarbonate (HCO₃⁻) is present in relatively high concentrations in extracellular fluid, and (2) more

importantly—Paco₂ and plasma [HCO₃⁻] are closely regulated by the lungs and the kidneys, respectively. The ability of these two organs to alter the [HCO₃⁻]/Paco₂ ratio allows them to exert important influences on arterial pH.

A simplified and more practical derivation of the Henderson–Hasselbalch equation for the bicarbonate buffer is as follows:

This equation is very useful clinically because pH can be readily converted to [H⁺] (Table 50–2). Note that below 7.40, [H⁺] increases 1.25 nEq/L for each 0.01 decrease in pH; above 7.40, [H⁺] decreases 0.8 nEq/L for each 0.01 increase in pH.

It should be emphasized that the bicarbonate buffer is effective against metabolic but notrespiratory acid–base disturbances. If 3 mEq/L of a strong nonvolatile acid, such as HCl, is added to extracellular fluid, the following reaction takes place:

Note that HCO ₃⁻ reacts with H ⁺ to produce CO₂. Moreover, the CO₂ generated is normally elim-inated by the lungs such that Paco₂ does not change. Consequently, [H⁺] = 24 × 40 ÷ 21 = 45.7 nEq/L, and pH = 7.34. Furthermore, the decrease in [HCO ₃⁻] reflects the amount of nonvolatile acid added.

In contrast, an increase in CO₂ tension (vola-tile acid) has a minimal effect on [HCO₃]. If, for example, Paco₂ increases from 40 to 80 mm Hg, the dissolved CO ₂ increases only from 1.2 mEq/L to 2.2 mEq/L. Moreover, the equilibrium constant for the hydration of CO ₂ is such that an increase of this magnitude minimally drives the reaction to the left:

If the valid assumption is made that [HCO₃⁻] does not appreciably change, then

 [H⁺] therefore increases by 40 nEq/L, and because HCO₃⁻ is produced in a 1:1 ratio with H⁺, [HCO₃⁻] also increases by 40 nEq/L. Thus, extracel-lular [HCO₃⁻] increases negligibly, from 24 mEq/L to 24.000040 mEq/L. Therefore, the bicarbonate buffer is not effective against increases in Paco₂, and changes in [HCO₃⁻] do not reflect the severity of a respiratory acidosis.

Hemoglobin as a Buffer

Hemoglobin is rich in histidine, which is an effec-tive buffer from pH 5.7 to 7.7 (pK_a 6.8). Hemoglobin is the most important noncarbonic buffer in extra-cellular fluid. Simplistically, hemoglobin may be thought of as existing in red blood cells in equilibrium as a weak acid (HHb) and a potassiumsalt (KHb). In contrast to the bicarbonate buf-fer, hemoglobin is capable of buffering bothcarbonic (CO2) and noncarbonic (nonvolatile) acids: