## Clinical Correlates of pH LevelsProblem Set

### Problem 2: Bicarbonate as a biological buffer

 Tutorial to help answer this question Bicarbonate is a crucial buffer in the body and is usually present in body fluids as sodium bicarbonate (sodium being the main positive ion in extracellular fluids). What features of sodium bicarbonate contribute to its effectiveness as a biological buffer?
 A. The bicarbonate ion (HCO3-) can combine with a proton (H+) to form carbonic acid (H2CO3), thus absorbing protons from solution and raising blood pH. B. Carbonic acid, which can be formed from CO2 and water, can dissociate into H+ and HCO3- in order to provide H+ and lower blood pH. C. Carbonic acid, which can be formed from bicarbonate, is converted to CO2 and water via a very fast enzymatic reaction. D. CO2, being volatile, can be rapidly expelled from the body at varying rates by respiration.

### Tutorial

Biological buffers

Buffering is an important property in biological systems, for which rapid pH changes can have disastrous consequences. An effective biological buffer must help maintain blood in the "safe" range of pH 7.35-7.45 by resisting pH changes in either direction outside of this range. Excursions in the acid direction (i.e., below 7.35) are particularly to be feared, given the variations in production of acids such as lactic acid, pyruvic acid, acetic acid, etc., by metabolism. Production of such acids during peak exercise can lower peripheral blood pH to well below 7.0.

The bicarbonate buffering system is central to pH regulation in human blood and can respond to pH changes in several ways:

1. The bicarbonate ion is really the conjugate base of carbonic acid:
H+ + HCO3- [H2CO3] ; pKa = 6.14
[Non-enzymatic acid base reaction - nearly instantaneous]

2. Carbonic acid, however, is very rapidly interconverted with CO2 and water by by carbonic anhydrase, making it a transient species:
[H2CO3] CO2 + H2O ; pKa = 6.14
[Enzymatic reaction with very fast rate]

3. Concerning the two products of carbonic anhydrase action, water is easily absorbed into the system, while CO2 can be expelled by respiration. Moreover, the rate of CO2 loss in respiration can be controlled via neurological mechanisms.

4. [HCO3-] and [H+] can be manipulated (slowly and incompletely) by physiological mechanisms operating in the kidney.
The total of all of these features can be summarized as follows:

 CO2 + H2O [H2CO3] H+ + HCO3- produced by metabolism always available in equilibrium with species on either side produced by metabolism pre-existing blood buffer directly expelled in lung adjusted in kidney via physiologic mechanisms unrelated to pH converted to products on left by carbonic anhydrase (RBC) adjusted in kidney or reacts with bicarbonate to make products on left adjusted in kidney or reacts with H+ to make products on left

The Biology Project
Department of Biochemistry and Molecular Biophysics

The University of Arizona
January 1999
Revised: October 2004
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