Bicarbonate buffer system

Carbon dioxide, a by-product of cellular respiration, is dissolved in the blood, where it is taken up by red blood cells and converted to carbonic acid by carbonic anhydrase. Most of the carbonic acid then dissociates to bicarbonate and hydrogen ions.
The bicarbonate buffer system is an acid-base homeostatic mechanism involving the balance of carbonic acid (H2CO3), bicarbonate ion (HCO3-), and carbon dioxide (CO2) in order to maintain pH in the blood and duodenum, among other tissues, to support proper metabolic function.[1] Catalyzed by carbonic anhydrase, carbon dioxide (CO2) reacts with water (H2O) to form carbonic acid (H2CO3), which in turn rapidly dissociates to form a bicarbonate ion (HCO3− ) and a hydrogen ion (H+) as shown in the following reaction:[2]

[3][4]

\rm CO_2 + H_2O \rightleftarrows H_2CO_3 \rightleftarrows HCO_3^- + H^+

As with any buffer system, the pH is balanced by the presence of both weak acid (i.e. H2CO3) and conjugate base (i.e. HCO3-) so that any excess acid or base introduced to the system is neutralized.

Failure of this system to function properly results in acid-base imbalance such as acidemia (pH<7.35) and alkalemia (pH>7.45) in the blood.[5] In patients with duodenal ulcers, Heliobacter pylori eradication can restore mucosal bicarbonate secretion, and reduce the risk of ulcer recurrence.[6]

Physiological Mechanism

In tissue, cellular respiration produces carbon dioxide as a waste product; as one of the primary roles of the cardiovascular system, most of this CO2 is rapidly removed from the tissues by its hydration to bicarbonate ion.[7] The bicarbonate ion present in the blood plasma is transported to the lungs, where it is dehydrated back into CO2 and released during exhalation. These hydration and dehydration conversions of CO2 and H2CO3, which are normally very slow, are facilitated by carbonic anhydrase in both the blood and duodenum.[8] While in the blood, bicarbonate ion serves to neutralize acid introduced to the blood through other metabolic processes (e.g. lactic acid, ketone bodies); likewise, any bases (e.g. urea from the catabolism of proteins) are neutralized by carbonic acid.[9]

The bicarbonate buffer system plays a vital role in other tissues as well. In the human stomach and duodenum, the bicarbonate buffer system serves to both neutralize gastric acid and stabilize the intracellular pH of epithelial cells via the secretion of bicarbonate ion into the gastric mucosa.[1]

Regulation

As calculated by the Henderson-Hasselbalch equation, in order to maintain a normal pH of 7.4 in the blood (whereby the pKa of carbonic acid is 6.1 at physiological temperature), a 20:1 bicarbonate to carbonic acid must constantly be maintained; this homeostasis is mainly mediated by the respiratory and renal systems.[10] In the blood of most animals, the bicarbonate buffer system is coupled to the lungs via respiratory compensation, the process by which the rate of breathing changes to compensate for changes in the blood concentration of CO2.[11] By Le Chȃtlier’s Principle, the release of CO2 from the lungs pushes the reaction above to the left, causing carbonic anhydrase to form CO2 until all excess acid is removed. Bicarbonate concentration is also further regulated by renal compensation, the process by which the kidneys regulate the concentration of bicarbonate ion by filtering out excess or retaining it when in low concentrations.[12]

Henderson–Hasselbalch equation

A modified version of the Henderson–Hasselbalch equation can be used to relate the pH of blood to constituents of the bicarbonate buffer system:[13]

pH = pK_{a~H_2CO_3}+ \log \left ( \frac{[HCO_3^-]}{[H_2CO_3]} \right )

, where:

This is useful in arterial blood gas, but these usually state pCO2, that is, the partial pressure of carbon dioxide, rather than H2CO3. However, these are related by the equation:[13]

[H_2CO_3] = k_{\rm H~CO_2}\, \times pCO_2

, where:

Taken together, the following equation can be used to relate the pH of blood to the concentration of bicarbonate and the partial pressure of carbon dioxide:[13]

pH = 6.1 + \log \left ( \frac{[HCO_3^-]}{0.03 \times pCO_2} \right )

, where:

Derivation of The Kassirer-Bleich Approximation

The Henderson Equation, which is derived from the Law of Mass Action, can be modified with respect to the bicarbonate buffer system to yield a simpler equation that provides a quick approximation of the H+ or HCO3- concentration without the need to calculate logarithms:[8]

\rm K_{a,H_2CO_3} = \frac{[HCO_3^-][H_3O^+]}{[H_2CO_3]}

Since the partial pressure of carbon dioxide is much easier to obtain from measurement than carbonic acid, the Henry’s Law solubility constant – which relates the partial pressure of a gas to its solubility – for CO2 in plasma is used in lieu of the carbonic acid concentration. After rearranging the equation and applying Henry’s Law, the equation becomes:[14]

\rm [H^+] = \frac{K'\cdot0.03P_{CO_2}}{[HCO_3^-]}

Where K’ is the dissociation constant from the pKa of carbonic acid, 6.1, which is equal to 800nmol/L (since K’ = 10-pKa = 10-(6.1) ≈ 8.00X10−07mol/L = 800nmol/L).

By multiplying K’ (expressed as nmol/L) and 0.03 (800 X 0.03 = 24) and rearranging with respect to HCO3-, the equation is simplified to:

\rm [HCO_3^-] = 24\frac{P_{CO_2}}{[H^+]}

References

  1. 1 2 Krieg, Brian J.; Taghavi, Seyed Mohammad; Amidon, Gordon L.; Amidon, Gregory E. (2014-11-01). "In Vivo Predictive Dissolution: Transport Analysis of the CO2, Bicarbonate In Vivo Buffer System". Journal of Pharmaceutical Sciences 103 (11): 3473–3490. doi:10.1002/jps.24108. ISSN 1520-6017.
  2. ↑ Oxtoby, David W.; Gillis, Pat (2015). "Acid-base equilibria". Principles of Modern Chemistry (8 ed.). Boston, MA: Cengage Learning. pp. 611–753. ISBN 1305079116.
  3. ↑ Widmaier, Eric; Raff, Hershel; Strang, Kevin (2014). "The kidneys and regulation of water and inorganic ions". Vander's Human Physiology (13 ed.). New York, NY: McGraw-Hill. pp. 446–489. ISBN 0073378305.
  4. ↑ Meldrum, N. U.; Roughton, F. J. W. (1933-12-05). "Carbonic anhydrase. Its preparation and properties". The Journal of Physiology 80 (2): 113–142. ISSN 0022-3751. PMC 1394121. PMID 16994489.
  5. ↑ Rhoades, Rodney A.; Bell, David R. (2012). Medical physiology : principles for clinical medicine (4th ed., International ed.). Philadelphia, Pa.: Lippincott Williams & Wilkins. ISBN 9781451110395.
  6. ↑ Hogan, DL; Rapier, RC; Dreilinger, A; Koss, MA; Basuk, PM; Weinstein, WM; Nyberg, LM; Isenberg, JI. "Duodenal bicarbonate secretion: Eradication of Helicobacter pylori and duodenal structure and function in humans". Gastroenterology 110 (3): 705–716. doi:10.1053/gast.1996.v110.pm8608879.
  7. ↑ al.], David Sadava ... [et; Bell, David R. (2014). Life : The Science of Biology (10th ed.). Sunderland, MA: Sinauer Associates. ISBN 9781429298643.
  8. 1 2 Bear, R. A.; Dyck, R. F. (1979-01-20). "Clinical approach to the diagnosis of acid-base disorders.". Canadian Medical Association Journal 120 (2): 173–182. ISSN 0008-4409. PMC 1818841. PMID 761145.
  9. ↑ Nelson, David L.; Cox, Michael M.; Lehninger, Albert L (2008). Lehninger Principles of Biochemistry (5th ed.). New York: W.H. Freeman. ISBN 9781429212427.
  10. ↑ al.], edited by Leonard R. Johnson ; with contributions by John H. Byrne ... [et (2003). Essential medical physiology (3rd ed.). Amsterdam: Elsevier Academic Press. ISBN 9780123875846.
  11. ↑ Heinemann, Henry O.; Goldring, Roberta M. "Bicarbonate and the regulation of ventilation". The American Journal of Medicine 57 (3): 361–370. doi:10.1016/0002-9343(74)90131-4.
  12. ↑ Koeppen, Bruce M. (2009-12-01). "The kidney and acid-base regulation". Advances in Physiology Education 33 (4): 275–281. doi:10.1152/advan.00054.2009. ISSN 1043-4046. PMID 19948674.
  13. 1 2 3 page 556, section "Estimating plasma pH" in: Bray, John J. (1999). Lecture notes on human physiolog. Malden, Mass.: Blackwell Science. ISBN 978-0-86542-775-4.
  14. ↑ Kamens, Donald R.; Wears, Robert L.; Trimble, Cleve (1979-11-01). "Circumventing the Henderson-Hasselbalch equation". Journal of the American College of Emergency Physicians 8 (11): 462–466. doi:10.1016/S0361-1124(79)80061-1.

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