Biochemistry at The Biology Project

Clinical Correlates of pH Levels
Problem Set


Bicarbonate as a buffer

The major buffering systems in the body are proteins, particularly those with the amino acids histidine and cysteine exposed to the outside environment, phosphate, and bicarbonate. All three of these are weak acids with pKa values lower than physiological pH. As a consequence, buffering capacity increases as the pH is lowered from the physiological range. This meets the needs of most organisms because physiological pH excursions generally occur in the acid direction. Hence, the low pKa of these buffering systems is poised to respond to metabolic acidosis.

Of these three, only the bicarbonate system, which is critical for buffering extracellular fluids such as blood, is in steady-state between production and removal. Thus, pH changes via this dynamic bicarbonate system are taking place on a background provided by the more static protein and phosphate systems.

Production of Bicarbonate
Cells generate and excrete large quantities of carbon dioxide (CO2) during aerobic metabolism of glucose and fats. CO2 is subsequently converted to carbonic acid (H2CO3), which serves as the basis for the bicarbonate buffering system. Hence, the body is not dependent on ingestion of exogenous compounds or complex syntheses to maintain this buffering system.

Removal of Bicarbonate
The bicarbonate buffering system is in volatile equilibrium (via breathing) with the external environment (lungs and air). Thus it is able to respond rapidly to endogenous alterations. It can also be affected, either positively or negatively, by environmental manipulation.

Movement into and out of cells

The acid components of the bicarbonate system (i.e. H+ and CO2) cross biological membranes rapidly, thus do not depend on complex transport kinetics. The base component (HCO3-), on the other hand, is transported rapidly in all cells via anion exchange. Consequently, the bicarbonate buffering system helps to maintain both intracellular and extracellular pH.

Role of other blood components

The acid components of the bicarbonate system are transported from the tissues to the lungs by hemoglobin. Thus, this important protein participates in both the production and removal of metabolic acid.

Clinical Correlates: Acidosis & Alkalosis

CO2 produced by metabolism is normally balanced by CO2 expired from the lungs, resulting in no net production of H2CO3. However, as detailed in the table below, certain medically significant circumstances can throw the equation out of balance.

Condition Possible causes
respiratory acidosis apnea or impaired lung capacity, with a build-up of CO2 in the lungs
metabolic acidosis

ingestion of acid, production of ketoacids in uncontrolled diabetes, or kidney failure

Note: These conditions all result in build-up of H+ from sources other than excess CO2.


Condition Possible causes
respiratory alkalosis hyperventilation, with a net loss of CO2 from the blood.
metabolic alkalosis

ingestion of alkali, prolonged vomiting leading to a loss of HCl, or extreme dehydration leading to kidney retention of bicarbonate.

Note: The common thread here is the loss of H+ for reasons other than depletion of CO2.



Although a slight drop in pH from 7.4 to 7.2 does not sound 

significant, this involves an increase in H<SUP>+</SUP> concentration from 3.9 to x 10<SUP>-8</SUP> M to 6.3 x 10<SUP>-8</SUP> M, an increase of > 60%!

For respiratory problems caused by alterations in CO2, the best treatment involves ventilation. If bicarbonate is used to raise the pH in cases of respiratory acidosis, the result can be fatal, since compensation is also working to increase the blood bicarbonate concentration.

For metabolic problems that involve HCO3-, the best treatment is either bicarbonate infusion (for acidosis) or NH4Cl infusion (for alkalosis). NH4Cl dissociates into NH4+ and Cl-. The NH4+ (ammonium ion) is in equilibrium with NH3 (ammonia) and H+. Because ammonia is volatile, it is respired through the lungs, leaving behind H+ and Cl- or hydrochloric acid, which lowers the pH. Often, metabolic acidosis is found in combination with respiratory alkalosis (e.g. compensated). This is a fragile situation because the buffering power is significantly reduced.

Problem Set

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Department of Biochemistry and Molecular Biophysics

The University of Arizona
January 1999
Revised: October 2004 & June 2006

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